Pharmaceutics

36 pages, 4305 KB

Open AccessArticle

Chemical Characterization and Evaluation of Antimicrobial, Antioxidant, and Synergistic Activities of Teucrium polium L.: An Integrated Experimental and In Silico Approach

by Khalid Zibouh, Brahim Ed-Damsyry, Aziz Drioiche, Mohamed Ed-Dahmouny, Noorah A. Alkubaisi, Mourad A. M. Aboul-Soud, Firdaous Remok, Chaimae Ibbur, Mohamed Radi, Atika Ailli, Sevser Sahpaz and Touriya Zair

Pharmaceutics 2026, 18(3), 397; https://doi.org/10.3390/pharmaceutics18030397 - 23 Mar 2026

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Abstract

Background/Objectives: Teucrium polium L. is widely used in traditional medicine and has been proposed as a source of antimicrobial adjuvants in the context of antimicrobial resistance. Here, we characterized the essential oil (EO) and polar extracts of T. polium and evaluated their antioxidant [...] Read more.

Background/Objectives: Teucrium polium L. is widely used in traditional medicine and has been proposed as a source of antimicrobial adjuvants in the context of antimicrobial resistance. Here, we characterized the essential oil (EO) and polar extracts of T. polium and evaluated their antioxidant activity, antimicrobial potency against clinical multidrug-resistant (MDR) isolates, and the interaction of the EO with conventional antibiotics using a chequerboard assay (FICI); further, we investigated in silico molecular interactions with some targets related to resistance. Methods/Results: The EO, which was hydrodistilled and subsequently analyzed by GC–MS, is characterized by dominant limonene content (24.13%) and contents of oxygenated sesquiterpenes such as β-eudesmol (10.48%) and α-muurolol (8.10%). HPLC/UV–ESI–MS characterization of the extracts (decoction and Soxhlet) demonstrated that they were rich in polyphenolic compounds and flavonoids, which matched the standard phytochemical characteristics of this species. The extracts exhibited significant reducing capabilities, and the hydroethanolic extract exhibited the highest antioxidant activity (DPPH IC₅₀ = 15.41 μg/mL; FRAP EC₅₀ = 30.65 μg /mL), while the EO revealed at most moderate capacity in these tests. In antimicrobial assays, the EO inhibited fungi more effectively than the extracts (MIC of 1.17 mg/mL against Aspergillus niger; 4.69 mg/mL against Candida spp.), while antibacterial MICs for both the EO and extracts were generally high (up to 50 mg/mL). Combination testing nevertheless identified synergistic or additive effects of the EO with selected antibiotics, notably with ceftazidime against ESBL-producing Escherichia coli (FICI = 0.141) and Staphylococcus aureus (FICI = 0.039) and with amikacin against Klebsiella pneumoniae (FICI = 0.313); the EO–ceftriaxone pairing against ESBL E. coli was additive (FICI = 0.516). Docking simulations further supported these observations by showing the favorable predicted binding of oxygenated sesquiterpenes, most notably β-eudesmol and α-muurolol (up to −8.6 kcal/mol), to resistance-related targets such as RND efflux pumps, β-lactamases, and porins. Conclusions: Taken together, the in vitro and in silico data suggest that T. polium could be explored as a natural antimicrobial option and as an adjuvant to enhance antibiotic activity against multidrug-resistant pathogens. Full article

(This article belongs to the Special Issue Essential Oils: From Biological Activity to Pharmaceutical Applications)

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26 pages, 4262 KB

Open AccessArticle

Predicting Drug Loading Capacity for PLA-Amorphous Drug System Using Hansen Solubility Parameters

by Artūrs Paulausks, Artjoms Iljičevs, Jurga Bernatoniene, Līga Pētersone and Konstantīns Logviss

Pharmaceutics 2026, 18(3), 396; https://doi.org/10.3390/pharmaceutics18030396 - 23 Mar 2026

Viewed by 481

Abstract

Objective: In this work, we look at Hansen solubility parameters (HSPs) to predict drug miscibility with polymers, in order to create a saturated amorphous drug phase. Methods: We used the Yamamoto molecular break (Y-MB) group contribution method (GCM) and solvent experiments to establish [...] Read more.

Objective: In this work, we look at Hansen solubility parameters (HSPs) to predict drug miscibility with polymers, in order to create a saturated amorphous drug phase. Methods: We used the Yamamoto molecular break (Y-MB) group contribution method (GCM) and solvent experiments to establish HSPs for PLA and 12 model drugs. Drug-loaded samples were made using solvent casting (SC) and vacuum compression moulding (VCM) in incremental drug concentrations until a saturated amorphous drug load was achieved. The amorphous drug phase was confirmed by X-ray diffraction after 24 h. These amorphous samples were further analysed by HPLC to confirm drug concentration. These drug concentrations were expressed as volume concentration in PLA, and they correlate with linearised HSP distance between drug and polymer. Results: This gives a statistically significant linear correlation between drug concentration and HSPs with R² values ranging from 0.85 to 0.93 for SC and VCM methods. Conclusions: This work entails a possible concept for novel application of HSPs to predict miscible drug–polymer pairs and to estimate amorphous saturation concentration. Full article

(This article belongs to the Section Physical Pharmacy and Formulation)

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15 pages, 1314 KB

Open AccessReview

Improvement of Adeno-Associated Virus (AAV)-Based Technologies by Cell-Penetrating Penta-Peptides (CPP5s)

by Charles W. Guo, Anastasia Diener and Shigemi Matsuyama

Pharmaceutics 2026, 18(3), 395; https://doi.org/10.3390/pharmaceutics18030395 - 22 Mar 2026

Viewed by 592

Abstract

Adeno-associated viruses (AAVs) are a promising gene therapy technology, but major technical challenges remain. One problem is that commonly used AAVs have a low efficiency in penetrating the blood–brain barrier (BBB) and the blood–retina barrier (BRB). Consequently, gene delivery to the nervous system [...] Read more.

Adeno-associated viruses (AAVs) are a promising gene therapy technology, but major technical challenges remain. One problem is that commonly used AAVs have a low efficiency in penetrating the blood–brain barrier (BBB) and the blood–retina barrier (BRB). Consequently, gene delivery to the nervous system has limitations. Another problem is that AAVs induce immune reactions that cause serious side effects. To avoid immune reactions, the AAV dose must be reduced to lower levels that may result in insufficient gene delivery. Researchers have been modifying viral capsid protein sequences and searching for effective peptide sequences to solve these problems. As a result, Cell-Penetrating Penta-Peptides (CPP5s) have been shown to be effective in improving the BBB/BRB penetration of AAVs and suppressing immune reactions against AAVs. CPP5s were originally developed from peptide sequences of the Bax (a pro-apoptotic protein) binding domain of Ku70 (a DNA repair protein) and from negative control cell-penetrating peptides without Bax-binding activity. This article will discuss the background science of CPP5s and future directions of CPP5s for AAV-mediated gene delivery to the nervous system as well as other organs. Full article

(This article belongs to the Special Issue Recent Advances in Adeno-Associated Virus-Mediated Gene Therapy and Vaccine Development)

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13 pages, 3785 KB

Open AccessArticle

pH-Responsive ZIF-8 Precisely Induces Apoptosis of Oral Squamous Cell Carcinoma over Orofacial Mesenchymal Stem Cells

by Jessica Hao, Mehrnaz Zakershahrak, Peter Ly, Xiaobin Huang, Kunfeng Sun, Shilan Zhang, Fusun Ozer and Chider Chen

Pharmaceutics 2026, 18(3), 394; https://doi.org/10.3390/pharmaceutics18030394 - 22 Mar 2026

Viewed by 495

Abstract

Objectives: pH-responsive zeolite imidazolate framework-8 (ZIF-8) enables selective release of 5-fluorouracil (5-FU) within the acidic tumor microenvironment. However, the direct effects of ZIF-8 itself on cancer cells or surrounding tissues remain unclear. Since oral cancer involves interactions between epithelial tumor cells and [...] Read more.

Objectives: pH-responsive zeolite imidazolate framework-8 (ZIF-8) enables selective release of 5-fluorouracil (5-FU) within the acidic tumor microenvironment. However, the direct effects of ZIF-8 itself on cancer cells or surrounding tissues remain unclear. Since oral cancer involves interactions between epithelial tumor cells and stromal cells, comparing the effects of ZIF-8 on epithelial cancer cells and orofacial mesenchymal stem/stromal cells (OMSCs) is critical to understanding its broader biological impact. Methods: The effects of ZIF-8 on SCC7 epithelial cancer cells and OMSCs, including periodontal ligament stem cells (PDLSCs) and dental pulp stem cells (DPSCs), were evaluated using RNA sequencing, nuclear staining, live/dead assays, and immunocytochemistry. Cells were treated with 0, 1, 10, or 100 μg/mL ZIF-8. Based on nuclear staining results, live/dead viability assays were conducted on SCC7 and DPSCs treated with 0 or 100 μg/mL ZIF-8. Apoptosis-related markers (Bax, caspase-3, caspase-6, and caspase-10) were assessed following exposure to 100 μg/mL ZIF-8. Results: Transcriptomic analysis revealed that ZIF-8 not only facilitates selective 5-FU release but also directly induces apoptosis in SCC7 cells compared with 5-FU alone. At 100 μg/mL ZIF-8, SCC7 viability was significantly reduced, whereas OMSC viability was preserved. Nonviable SCC7 cells increased markedly compared with controls, while DPSCs showed no significant change. Apoptosis-related signaling was also elevated in SCC7 cells compared with DPSCs. Conclusions: ZIF-8 at 100 μg/mL selectively inhibits SCC7 growth while sparing OMSC viability and apoptosis. Full article

(This article belongs to the Special Issue Nanocomposites as Implantable Devices or Drug Delivery Platforms: A New Insight into Treat Dental and Oral Diseases)

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24 pages, 3525 KB

Open AccessArticle

Exploring Key Factors Affecting the Encapsulation Efficiency of Ligusticum Chuanxiong–Vinegar Cyperus Rotundus Essential Oil Based on QbD Principles

by Zhongcheng Tang, Wenting Chen, Ting Zhang, Yu He and Haitong Wan

Pharmaceutics 2026, 18(3), 393; https://doi.org/10.3390/pharmaceutics18030393 - 22 Mar 2026

Viewed by 427

Abstract

Objective: The objective is to investigate and optimize the β-cyclodextrin inclusion process for volatile oils in Ligusticum Chuanxiong–Vinegar cyperus rotundus based on Quality by Design (QbD) principles. Methods: First, ligustilide and α-cyperone were selected as inclusion process indicator components using high-performance [...] Read more.

Objective: The objective is to investigate and optimize the β-cyclodextrin inclusion process for volatile oils in Ligusticum Chuanxiong–Vinegar cyperus rotundus based on Quality by Design (QbD) principles. Methods: First, ligustilide and α-cyperone were selected as inclusion process indicator components using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS). Single-factor experiments were conducted to preselect the inclusion speed based on ligustilide and α-cyperone content as evaluation criteria. Subsequently, using the inclusion rates of ligustilide and α-cyperone as evaluation criteria, a factorial design was employed to investigate the inclusion temperature, inclusion time, and the volume ratio of β-cyclodextrin solution to essential oil, thereby optimizing the inclusion process parameters. Finally, the inclusion process parameters were validated, and the inclusion rates were determined. The obtained inclusion complexes were characterized by microscopic analysis, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC). Furthermore, phase dissolution studies and molecular docking were employed for confirmation. Results: The optimal process parameters were determined as follows: encapsulation speed of 300 rpm, β-cyclodextrin solution excess of 6, encapsulation time of 2.5~3 h, and encapsulation temperature of 30~35 °C. The encapsulation rates for ligustilide and α-cyperone in the resulting inclusion complex were 63.15~64.74% and 71.33~76.89%, respectively. Structural characterization confirmed the formation of the inclusion complex. Conclusions: This inclusion process is reliable and provides a reference for preparing β-cyclodextrin inclusion complexes of volatile oils in formulations containing the Chuanxiong–Vinegar cyperus rotundus drug pair. Full article

(This article belongs to the Section Physical Pharmacy and Formulation)

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19 pages, 3262 KB

Open AccessArticle

Gelatin/Ascorbic Acid Scaffolds for Controlled Release of Allantoin: A Fully Natural Approach for Skin Tissue Regeneration Through Pro-Regenerative, Antimicrobial, and Keratinocyte-Supportive Properties

by Marija M. Babić Radić, Marija Vukomanović, Martina Žabčić, Lea Gazvoda, Dubravka Živanović and Simonida Tomić

Pharmaceutics 2026, 18(3), 391; https://doi.org/10.3390/pharmaceutics18030391 - 22 Mar 2026

Viewed by 523

Abstract

Background/Objectives: Nature-inspired therapeutic strategies that promote biological regenerative mechanisms and replicate the native structural microenvironment conductive to formation of healthy tissue are increasingly recognized as a promising platform for skin tissue regeneration and wound healing. This study proposes an innovative design of [...] Read more.

Background/Objectives: Nature-inspired therapeutic strategies that promote biological regenerative mechanisms and replicate the native structural microenvironment conductive to formation of healthy tissue are increasingly recognized as a promising platform for skin tissue regeneration and wound healing. This study proposes an innovative design of novel multifunctional scaffolds composed entirely of natural components—gelatin, L-ascorbic (ASA) acid and allantoin—as a bioinspired approach for skin tissue regeneration through pro-regenerative, antimicrobial, and keratinocyte-supportive properties. Methods: The biocompatible, skin-adhesive scaffolds were prepared via a simple and environmentally friendly heat-induced crosslinking of gelatin with varying ASA contents, and by enriching the system with allantoin. The influence of ASA content on scaffold properties was investigated through characterization of their morphology, porosity, swelling behavior, skin tissue adhesion, and allantoin release potential. Biocompatibility was evaluated in vitro using human keratinocyte (HaCaT) cells, while antibacterial activity was assessed against Escherichia coli and Staphylococcus epidermidis. Results: The scaffolds revealed a highly porous, interconnected structure with tunable porosity (87.37–92.39%) and soft-tissue-matched mechanical properties (0.81–1.47 MPa). Incorporation of allantoin into the scaffolds enhanced their mechanical performance and swelling capacity. All scaffolds demonstrated antibacterial activity against both tested bacteria, supported keratinocyte viability and provided sustained release of allantoin for up to 76 h, confirming their multifunctional pro-regenerative potential. Conclusions: The novel gelatin/ascorbic acid scaffolds enriched with allantoin combine a porous replicated structure of native extracellular matrix, fluid absorption capacity, soft-tissue-like mechanical properties, stable skin tissue adhesion, cytocompatibility and antibacterial functionality with the pro-regenerative properties of allantoin, thereby representing a multifunctional and biologically inspired platform for advanced skin tissue regeneration and wound-healing applications. Full article

(This article belongs to the Special Issue Multifunctional Natural Polymer-Based Therapeutic Systems: Drug Delivery Meets Tissue Engineering)

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22 pages, 5547 KB

Open AccessArticle

Pain Outcome Determines the Sensitivity to Peripheral Opioid Antagonism of Morphine, Ibuprofen, and Their Combination in Laparotomized Mice

by Makeya A. Hasoun, Miriam Santos-Caballero, Miguel Á. Huerta, María Robles-Funes, Amada Puerto-Moya, M. Carmen Ruiz-Cantero, Enrique J. Cobos and Rafael González-Cano

Pharmaceutics 2026, 18(3), 392; https://doi.org/10.3390/pharmaceutics18030392 - 21 Mar 2026

Viewed by 583

Abstract

Background/Objectives: Postoperative pain pharmacology is complex. We investigated the sensitivity of analgesic-like effects induced by morphine, ibuprofen, and their combination to peripheral opioid antagonism in a mouse laparotomy model. Methods: Mechanical hypersensitivity was assessed using von Frey filaments, and ongoing pain (abdominal [...] Read more.

Background/Objectives: Postoperative pain pharmacology is complex. We investigated the sensitivity of analgesic-like effects induced by morphine, ibuprofen, and their combination to peripheral opioid antagonism in a mouse laparotomy model. Methods: Mechanical hypersensitivity was assessed using von Frey filaments, and ongoing pain (abdominal licking and facial expressions) was evaluated using artificial intelligence algorithms. We tested the sensitivity of the analgesic treatments to the opioid antagonist naloxone or its peripherally restricted analog, naloxone methiodide. We also tested the effects of neutrophil depletion using an anti-Ly6G antibody. Gastrointestinal transit and pupillary diameter were measured to assess non-analgesic opioid effects. Results: Morphine reversed all pain-related behaviors; its effect on mechanical hypersensitivity was reversed by peripheral opioid antagonism, whereas its effects on ongoing pain were not. Ibuprofen reduced mechanical hypersensitivity and facial expressions but failed to alter licking. Interestingly, the ibuprofen effect on mechanical hypersensitivity depended on peripheral opioid receptors and neutrophils at the injury site. The morphine–ibuprofen combination produced synergistic analgesia across all endpoints without enhancing opioid-induced gastrointestinal inhibition or mydriasis. Peripheral opioid antagonism reversed the effect of the combination on mechanical hypersensitivity and facial expressions but not on licking. Conclusions: Our results replicate the key clinical phenomena relevant to the postoperative pain context, including the potentiation of morphine analgesia by ibuprofen without the exacerbation of adverse effects. Our results suggest that drug effects on different postoperative pain measures rely on distinct neurobiological mechanisms and are not interchangeable. Therefore, the use of a battery of complementary pain endpoints in preclinical pharmacology studies is advisable. Full article

(This article belongs to the Section Clinical Pharmaceutics)

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29 pages, 8875 KB

Open AccessArticle

Biofabrication of Leucas aspera-Mediated Chitosan–Zinc Oxide Nanocomposites for In Vitro Antioxidant, Antibacterial, Anti-Inflammatory and Wound-Healing Properties

by Karuppuchamy Poorani, Manickam Rajkumar, Bhupendra G. Prajapati, Sundar Velmani, Parappurath Narayanan Sudha, Alagarsamy Shanmugarathinam and Himanshu Paliwal

Pharmaceutics 2026, 18(3), 390; https://doi.org/10.3390/pharmaceutics18030390 - 21 Mar 2026

Viewed by 493

Abstract

Background/Objectives: Nanostructured biomaterials based on natural polymers have gained increasing attention in pharmaceutics due to their biocompatibility, multifunctionality, and diverse biomedical applications. This novel study aimed to biofabricate chitosan-doped zinc oxide nanocomposites (CS-ZnONCs) using Leucas aspera leaf extract and to evaluate their [...] Read more.

Background/Objectives: Nanostructured biomaterials based on natural polymers have gained increasing attention in pharmaceutics due to their biocompatibility, multifunctionality, and diverse biomedical applications. This novel study aimed to biofabricate chitosan-doped zinc oxide nanocomposites (CS-ZnONCs) using Leucas aspera leaf extract and to evaluate their physicochemical properties and in vitro biomedical performance. Methods: CS-ZnONCs were synthesized using L. aspera leaf extract through a green precipitation approach, and the resulting nanocomposites were characterized by various spectroscopic techniques. The in vitro antioxidant, antibacterial, and anti-inflammatory activities were evaluated, while wound-healing potential was assessed using L929 fibroblast cell migration assays. Results: UV–visible analysis confirmed the formation of CS-ZnONCs, with a characteristic absorption peak at 362 nm, and FTIR spectra indicated the presence of various important functional groups. XRD results demonstrated the crystalline nature of ZnO within the chitosan matrix. Well-dispersed, quasi-spherical nanoparticles with an average size of 44 ± 3.1 nm were identified by HR-TEM, and a positive zeta potential (+9 mV) suggested considerable colloidal stability. CS-ZnONCs showed a high swelling capacity (88 ± 2.75% for 2%) and significant phytocompound release (65.38 ± 2.79% at pH 7.4). The CS-ZnONCs showed significant antioxidant activity (ABTS of 88.19 ± 1.59%), notable antibacterial efficacy against Staphylococcus aureus (18.78 ± 0.98 mm) and Escherichia coli (17.14 ± 0.96 mm), and significant anti-inflammatory activity (82.12 ± 1.47% membrane stabilization). In vitro biocompatibility and wound-healing assays revealed significant cytocompatibility in Vero cells, with 98.75 ± 1.17% cell viability observed, whereas the fibroblast migration assay demonstrated near-complete wound closure (96.55 ± 6.46%). Conclusions: The green-synthesized CS-ZnONCs exhibit favorable physicochemical properties, biocompatibility, and multifunctional biological activities, supporting their potential as a promising sustainable biomaterial nanomedicine for pharmaceutical formulations, wound healing, and regenerative medicine applications. Full article

(This article belongs to the Special Issue Advanced Nanomaterials and Drug Delivery Systems for Wound Healing and Antimicrobial Therapy)

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14 pages, 2531 KB

Open AccessArticle

Differentiating Resistance from Formulation Failure: Isoniazid Instability and Poor Dissolution in Crushed Multi-Drug Paediatric Preparations

by Halima Samsodien, Jana Winkler, Marique Aucamp and Anthony J. Garcia-Prats

Pharmaceutics 2026, 18(3), 389; https://doi.org/10.3390/pharmaceutics18030389 - 21 Mar 2026

Viewed by 471

Abstract

Background: Bedside manipulation of adult anti-tuberculosis tablets for paediatric dosing is common in low-resource settings, yet it can compromise drug stability. This study investigated how grinding and multi-drug co-suspension affect the supramolecular organisation, thermal stability, and dissolution of isoniazid (INH). Methods: INH [...] Read more.

Background: Bedside manipulation of adult anti-tuberculosis tablets for paediatric dosing is common in low-resource settings, yet it can compromise drug stability. This study investigated how grinding and multi-drug co-suspension affect the supramolecular organisation, thermal stability, and dissolution of isoniazid (INH). Methods: INH raw, INH branded tablets (whole and ground), and multi-drug combination mixtures (MCMs) that simulate paediatric multi-drug-resistant tuberculosis (MDR-TB) regimens were assessed. Samples were analysed as solids and aqueous suspensions using hot-stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman spectroscopy, FTIR-ATR, USP dissolution, and HPLC (LOD 0.0015 mg mL⁻¹; LOQ 0.005 mg mL⁻¹). Results: Grinding and co-mixing lowered melting points and masked typical INH events. Spectroscopy revealed the broadening and shifting of OH/NH and pyridine-ring bands, consistent with the formation of new hydrogen-bonding networks, correlative with supramolecular rearrangements. In multi-drug suspensions, INH fell below the HPLC quantification limit in both pH 1.2 and 6.8 media, despite visible residue, suggesting the formation of non-dissociable supramolecular complexes. Using a validated HPLC assay, no quantifiable INH was detected from the crushed multi-drug suspensions in either pH 1.2 or pH 6.8, whereas intact API/tablets showed measurable release. Conclusions: Co-suspension of INH with companion tuberculosis (TB) drugs disrupts its supramolecular integrity, leading to pre-administration degradation and a loss of quantifiable drug. Dissolution testing showed minimal INH release at pH 1.2 and none at pH 6.8, contrasting with intact tablets/API. These observations highlight that converting an immediate-release tablet into an aqueous suspension fundamentally alters its physicochemical environment and requires rational formulation design to preserve molecular stability, differentiating true resistance from formulation failure. Full article

(This article belongs to the Special Issue Pharmaceutical Solid Dosage Forms: Manufacturing, Design, Development, and Biomedical Applications)

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20 pages, 6462 KB

Open AccessArticle

Mechanistic Modulation of Lipopolysaccharide-Induced Hepatic Injury by Chitosan-Coated Selenium Nanoparticles: Targeting the STEAP-3/TLR-4 and IL-17/TRAF-6/HSP-90 Axes

by Asmaa Ramadan, Eman Hamza, Eman Ali Elkordy, Eslam E. Abd El Fattah, Amr Yehia and Ahmed S.G. Srag El-Din

Pharmaceutics 2026, 18(3), 388; https://doi.org/10.3390/pharmaceutics18030388 - 20 Mar 2026

Viewed by 554

Abstract

Background/Objectives: The aim of the current study was to investigate the mechanistic hepatoprotective efficacy of selenium (SE) and chitosan-coated selenium nanoparticles (CS-SENPs) using a rat model induced by lipopolysaccharide (LPS). Methods: CS-SENP was prepared and characterized for particle size, polydispersity index [...] Read more.

Background/Objectives: The aim of the current study was to investigate the mechanistic hepatoprotective efficacy of selenium (SE) and chitosan-coated selenium nanoparticles (CS-SENPs) using a rat model induced by lipopolysaccharide (LPS). Methods: CS-SENP was prepared and characterized for particle size, polydispersity index (PDI), zeta potential, transmission electron microscope (TEM), and Fourier transform infrared spectroscopy (FTIR). Male albino rats (n = 40) were divided into four groups: control, LPS, SE, and CS-SENP. SE and CS-SENPs (5 mg/kg orally for 14 days) were given before LPS injection. Tissue architecture was assessed using histopathological analysis. HSP-47 and STEAP-3 protein expression levels were measured using ELISA, and oxidative stress markers were quantitatively evaluated. The expression of HO-1, TLR-4, STAT-3, TRAF-6, and IL-17A was measured using immunohistochemical analysis. Furthermore, HSP-90 expression was evaluated by immunofluorescence labeling. Results: CS-SENP characterization revealed uniform (PDI = 0.125 ± 0.04) nanoparticle size (108.54 ± 2.24 nm), with high zeta potential (+63.92 ± 6.287 mV), attributed to the CS layer, which was confirmed by FTIR and TEM as an electron-lucent halo enveloping the individual SENP cores. CS-SENPs significantly reduced lipid peroxidation (MDA) and restored glutathione (GSH) more effectively than SE. CS-SENPs improved redox (upregulated HO-1) and iron balance (downregulated STEAP-3), and also increased the anti-inflammatory effect (suppressed TLR-4, IL-17A, TRAF-6, and STAT-3). CS-SENPs showed superior antifibrotic efficacy (suppresses stress proteins, HSP-47 and HSP-90). Rats treated with CS-SENPs had nearly normal liver structure. Conclusions: The results concluded that CS-SENPs had superior and multi-targeted hepatoprotection against LPS-induced liver damage. Full article

(This article belongs to the Special Issue Advanced Nano-Formulations for Drug Delivery and Cancer Immunotherapy)

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38 pages, 1303 KB

Open AccessReview

Bacteriophages as Therapeutic Agents for Pulmonary Infections: From Biological Principles to Clinical Applications

by Abdullah A. Alshehri, Alhassan H. Aodah, Ibrahim A. Alradwan, Meshal K. Alnefaie, Majed S. Nassar, Ibtihal S. Alduhaymi, Ahmad M. Aldossary, Nojoud Al Fayez, Essam A. Tawfik and Fahad A. Almughem

Pharmaceutics 2026, 18(3), 387; https://doi.org/10.3390/pharmaceutics18030387 - 20 Mar 2026

Viewed by 687

Abstract

Respiratory infections remain a significant global health concern, especially as multidrug-resistant (MDR) respiratory pathogens reduce the effectiveness of conventional antibiotics. Patients with chronic lung diseases face persistent biofilm-related infections that are difficult to treat, underscoring the urgency for new solutions. This challenge has [...] Read more.

Respiratory infections remain a significant global health concern, especially as multidrug-resistant (MDR) respiratory pathogens reduce the effectiveness of conventional antibiotics. Patients with chronic lung diseases face persistent biofilm-related infections that are difficult to treat, underscoring the urgency for new solutions. This challenge has renewed focus on bacteriophage therapy as a promising alternative in respiratory antimicrobial management. Bacteriophages are viruses that selectively infect and lyse bacteria, showing strong potential as a precise and effective therapy for resistant pulmonary infections. This review focuses on the mechanisms of phage biology and therapy in lung infections, highlighting their unique interactions with mucus, surfactants, and immune defenses—all of which are central to their clinical promise. The review examines advances in phage engineering, delivery strategies, and inhaled formulations aimed at maximizing phage stability and targeting within the airways. It summarizes recent preclinical and clinical progress targeting MDR respiratory pathogens and discusses regulatory, manufacturing, and safety considerations key to integrating phage therapy into mainstream respiratory care. Full article

(This article belongs to the Section Biopharmaceutics)

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24 pages, 5142 KB

Open AccessReview

Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates in Oncology

by Keon Niles Jafari, Charlene Chai, Shelby Kim and Kamaljit Kaur

Pharmaceutics 2026, 18(3), 386; https://doi.org/10.3390/pharmaceutics18030386 - 20 Mar 2026

Viewed by 739

Abstract

Targeted drug delivery (TDD), specifically through targeting ligand–drug conjugates, has reshaped oncology by enabling selective delivery of cytotoxic payloads to cancer cells while minimizing uptake by normal tissues. A key approach relies on exploiting overexpressed cell surface receptors (CSRs) to enable selective uptake [...] Read more.

Targeted drug delivery (TDD), specifically through targeting ligand–drug conjugates, has reshaped oncology by enabling selective delivery of cytotoxic payloads to cancer cells while minimizing uptake by normal tissues. A key approach relies on exploiting overexpressed cell surface receptors (CSRs) to enable selective uptake of drug conjugates via receptor-mediated endocytosis. This review delineates four clinically validated CSRs (HER2, Trop-2, Nectin-4, and SSTR2) with several FDA-approved drug conjugates. Furthermore, emerging CSRs (EGFR, DLL3, and keratin 1) that may support next-generation TDD platforms for cancer treatment are also highlighted. We discuss how CSR type, density on cancer cells, and its mechanism of endocytosis, as well as the conjugate design for cellular uptake, tissue distribution, ligand size, and linker stability, collectively determine tumor drug accumulation and therapeutic efficacy. From representative examples, we elucidate the rationale for judicious refinement of these parameters, guiding the development of more potent ligands and drug conjugates to enhance the therapeutic efficacy of cytotoxic agents. Full article

(This article belongs to the Special Issue Peptide–Drug Conjugates for Targeted Delivery)

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16 pages, 3096 KB

Open AccessArticle

Protein Kinase Inhibitors and Oxidative Stress Modulate In Vivo Phosphorylation of Trypanosoma cruzi DNA Polymerase β

by Edio Maldonado, Matías Oyarce, Paz Canobra, Emilia Rojas, Fabiola Urbina, Julio C. Tapia, Lilian Jara, Vicente J. Miralles, Christian Castillo and Aldo Solari

Pharmaceutics 2026, 18(3), 385; https://doi.org/10.3390/pharmaceutics18030385 - 20 Mar 2026

Viewed by 467

Abstract

Background/Objectives: Protein kinases play crucial roles in signal transduction pathways that regulate growth and differentiation in Trypanosoma cruzi. These protein kinases are attractive targets to develop new drugs to treat Chagas disease. Methods: We used several protein kinase inhibitors targeting the [...] Read more.

Background/Objectives: Protein kinases play crucial roles in signal transduction pathways that regulate growth and differentiation in Trypanosoma cruzi. These protein kinases are attractive targets to develop new drugs to treat Chagas disease. Methods: We used several protein kinase inhibitors targeting the p38 MAPK, MEK, and ERK pathways to evaluate their effects on the in vivo phosphorylation status of T. cruzi proteins, particularly DNA polymerase beta (TcPolβ). We also used Genistein, a protein tyrosine kinase inhibitor, to assess its effects on global protein phosphorylation and TcPolβ phosphorylation. Also, we investigated the effect of oxidative stress on global tyrosine phosphorylation. Finally, we determined the phosphorylation sites on TcPolβ by the protein kinases TcPKC2 and TcWee570 in vitro. Results: p38 MAPK and MEK protein kinase inhibitors inhibited approximately 50% of the Ser/Thr phosphorylation of TcPolβ. Genistein inhibited both Ser/Thr and Tyr phosphorylation of several polypeptides in epimastigotes. Oxidative stress increases global Tyr phosphorylation by about twofold and also TcPolβ phosphorylation. TcPKC2 and TcWee570 were able to phosphorylate TcPolβ at both Ser/Thr and Tyr residues. Conclusions: Small-molecule protein kinase inhibitors can affect the phosphorylation status of TcPolβ in vivo. Since Genistein can inhibit both Ser/Thr and Tyr protein phosphorylation, and TcPKC2 and TcWee570 can phosphorylate both Ser/Thr and Tyr residues, it suggests the existence of dual protein kinases in T. cruzi. However, this possibility must be further studied. Full article

(This article belongs to the Section Drug Targeting and Design)

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16 pages, 288 KB

Open AccessArticle

Descriptor-Guided Selection of Extracellular Vesicle Loading Strategies for Small-Molecule Drug Delivery: A Mechanistically Interpretable Decision-Support Framework

by Romána Zelkó and Adrienn Kazsoki

Pharmaceutics 2026, 18(3), 384; https://doi.org/10.3390/pharmaceutics18030384 - 20 Mar 2026

Viewed by 378

Abstract

Background: Extracellular vesicles (EVs) are increasingly explored as nanocarriers in drug delivery; however, selecting an appropriate loading strategy for a given small-molecule cargo still relies largely on empirical, resource-intensive parallel screening within EV formulation workflows. Despite the widespread application of passive incubation, electroporation, [...] Read more.

Background: Extracellular vesicles (EVs) are increasingly explored as nanocarriers in drug delivery; however, selecting an appropriate loading strategy for a given small-molecule cargo still relies largely on empirical, resource-intensive parallel screening within EV formulation workflows. Despite the widespread application of passive incubation, electroporation, saponin-mediated permeabilization, freeze–thaw cycling, and sonication, there is currently no mechanistically grounded, descriptor-informed framework that enables rational prioritization of loading methods during the early design stage of EV-based dosage forms, leading to inefficient trial-and-error experimentation. Methods: We assembled a chemically diverse dataset of 21 compounds with experimentally determined loading efficiencies across five EV loading methods and calculated seven mechanistically motivated physicochemical descriptors (LogP, molecular weight, aqueous solubility, hydrogen bond donors/acceptors, polar surface area, and formal charge) for each drug. Separate Elastic Net regression models were trained for each loading strategy. Model performance was evaluated using leave-one-out cross-validation, a predefined external validation set (n = 4), and 50 repeated random train–test splits. The analysis emphasized decision-level ranking of loading methods rather than the precise prediction of absolute efficiencies. The applicability domain was assessed via leverage analysis to define the supported chemical space for prospective implementation in EV-based formulation development. Results: As anticipated for biologically heterogeneous EV systems, continuous regression performance remained modest (LOOCV R² = 0.06–0.41). In contrast, decision-level accuracy for identifying the experimentally optimal loading method was consistently high across validation schemes (internal: 76.5%; predefined external: 75%; repeated random validation: 80.5 ± 16.8%). Mechanical disruption methods (freeze–thaw and sonication) demonstrated comparatively greater predictive stability, while misclassification patterns suggested potential nonlinear behavior for highly polar, ionizable cargos. All compounds resided within the leverage-defined applicability domain, confirming adequate descriptor-space representation. Conclusions: This study establishes a mechanistically interpretable, descriptor-based decision-support framework capable of reliably prioritizing EV loading strategies for small-molecule cargos beyond empirical chance without altering standard protocols. By reframing the modeling objective from high-precision efficiency prediction to robust ranking of candidate methods, the approach offers a practical tool to triage between commonly used techniques, thereby reducing experimental burden in early-stage EV formulation development. The framework provides a quantitative basis for integrating molecular-descriptor-guided method selection into rational EV-based drug delivery design and can be expanded with membrane-specific descriptors and larger datasets. Full article

(This article belongs to the Section Drug Delivery and Controlled Release)

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21 pages, 2220 KB

Open AccessArticle

Analytical Physicochemical and Functional Studies to Compare AryoTrust, a Follow-On Biologics, with the Originator Trastuzumab (Herceptin)

by Khalid Kadhem Al-Kinani, Hussein Kadhum Alkufi and Salam Shanta Taher

Pharmaceutics 2026, 18(3), 383; https://doi.org/10.3390/pharmaceutics18030383 - 20 Mar 2026

Viewed by 462

Abstract

Background: Trastuzumab is a blockbuster monoclonal antibody that has revolutionized the treatment of HER2-positive breast and gastric cancers. With the increasing availability of biosimilar monoclonal antibodies in clinical practice, independent verification of biosimilarity using products sampled from a real-world supply chain is [...] Read more.

Background: Trastuzumab is a blockbuster monoclonal antibody that has revolutionized the treatment of HER2-positive breast and gastric cancers. With the increasing availability of biosimilar monoclonal antibodies in clinical practice, independent verification of biosimilarity using products sampled from a real-world supply chain is important to assure clinicians and the patients to use these products confidently. Objective: The aim of this study is to assess the biosimilarity of AryoTrust, a trastuzumab biosimilar, in comparison with the reference product Herceptin. AryoTrust and Herceptin products were randomly withdrawn from Iraqi hospitals to reflect medicines administered in real clinical settings. Methods: AryoTrust and Herceptin were compared using an extensive set of orthogonal analytical techniques which included SDS-PAGE, ion-exchange chromatography, capillary isoelectric focusing, peptide mapping, N-glycan profiling, circular dichroism, differential scanning calorimetry, and surface plasmon resonance. In addition to these teste, functional comparability was also tested using an HER2-dependent cell-based proliferation inhibition bioassay. Results: The results showed that both products have highly comparable profiles in all assessed attributes. The analysis showed similar molecular integrity and purity, identical primary structure, comparable charge heterogeneity, similar isoelectric points (pI) of the main isoform, close glycosylation patterns (mainly, by core-fucosylated complex-type glycans), similar higher-order structural features, and thermal stability. The receptor binding studies exhibited comparable binding affinities with Fcγ receptors and FcRn. Finally, the cell-based bioassay revealed comparable dose–response curves with similar EC₅₀ values and relative potency. Conclusions: The integrated analytical and functional data support the biosimilarity of AryoTrust to the reference product Herceptin, which has been marketed and used in Iraq. This study provides real-world scientific evidence supporting confidence in the quality and comparability of this trastuzumab biosimilar and reduces any doubt in the product and at the same time emphasizes the value of independent post-marketing biosimilarity assessments. Full article

(This article belongs to the Special Issue Medical Applications of Biologic Drugs)

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27 pages, 7495 KB

Open AccessArticle

Comparative Stability and Quality Assessment of Powder–Liquid Double-Chamber Bag Versus Traditional Meropenem Infusions: Implications for Critical Care and Individualized Dosing

by Xiaokai Ren, Xiao Li, Liting Zhang, Xiaofei Zhao, Lei Zhang and Zhanjun Dong

Pharmaceutics 2026, 18(3), 382; https://doi.org/10.3390/pharmaceutics18030382 - 20 Mar 2026

Viewed by 442

Abstract

Background: Maintaining therapeutic meropenem plasma concentrations requires prolonged infusion, but stability concerns exist between preparation and administration. This study compared the stability and operability of ready-to-use powder–liquid double-chamber bag (DCB) infusions versus traditional powder-for-injection (PFI) meropenem under clinical conditions. Methods: Infusions [...] Read more.

Background: Maintaining therapeutic meropenem plasma concentrations requires prolonged infusion, but stability concerns exist between preparation and administration. This study compared the stability and operability of ready-to-use powder–liquid double-chamber bag (DCB) infusions versus traditional powder-for-injection (PFI) meropenem under clinical conditions. Methods: Infusions at clinically relevant concentrations were stored at 2–8 °C, 25 ± 5 °C, and 40 ± 2 °C for 12 h. Stability assessments included appearance, pH, osmolality, insoluble particle count, meropenem content (HPLC), and impurity A level. Results: DCBs demonstrated superior content uniformity, significantly fewer insoluble particles (p < 0.05), and greater operational simplicity compared to PFI. Refrigeration maintained meropenem content > 95% and effectively suppressed impurity formation for up to 12 h. However, at both room temperature and elevated temperature, impurity A exceeded pharmacopoeial limits within 2 h, particularly at higher concentrations. An innovative bedside solvent volume adjustment method enabled DCBs to deliver high-concentration infusions, facilitating individualized critical care dosing. Conclusions: Compared with traditional powder injection formulations, the Meropenem powder–liquid dual-chamber bag offers more convenient operation under routine preparation conditions and poses a lower risk of contamination during the preparation process. Its stability is more sensitive to storage temperature, requiring strict adherence to refrigeration conditions. When stored under standardized conditions, the dual-chamber bag can better ensure drug efficacy stability and medication safety, making it particularly suitable for clinical emergency use and standardized workflow management. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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14 pages, 1688 KB

Open AccessArticle

Oral Islatravir in Macaques Decreases Lymphocytes and Monocytes and Is Associated with Immune Alterations

by Michele B. Daly, Daniel Kim, Seidu Inusah, Dawn Little, Jiyoung S. Kim, Natalia Makarova, Tiancheng E. Edwards, James Mitchell, Walid Heneine, Yi Pan, Charles W. Dobard and J. Gerardo García-Lerma

Pharmaceutics 2026, 18(3), 381; https://doi.org/10.3390/pharmaceutics18030381 - 20 Mar 2026

Viewed by 465

Abstract

Background: Islatravir (ISL) is a first-in-class nucleoside reverse transcriptase translocation inhibitor with high potency and long half-life in peripheral blood mononuclear cells (PBMCs). However, treatment and prevention of HIV with oral ISL in humans has been associated with decreases in total lymphocytes, CD4 [...] Read more.

Background: Islatravir (ISL) is a first-in-class nucleoside reverse transcriptase translocation inhibitor with high potency and long half-life in peripheral blood mononuclear cells (PBMCs). However, treatment and prevention of HIV with oral ISL in humans has been associated with decreases in total lymphocytes, CD4 T-cells, and B-cells in a dose-dependent manner. We investigated in macaques the effects of oral ISL on lymphocytes, monocytes, granulocytes, and gene expression in PBMCs. Methods: Female pig-tailed macaques (n = 5) received an HIV pre-exposure prophylaxis dose of oral ISL adjusted allometrically once a week for 12 weeks. Complete blood counts and B- and T-cells were monitored prior to, during, and after ISL treatment, and changes in counts were evaluated by using a repeated measures model. Changes in gene expression were investigated in PBMCs during treatment and following treatment discontinuation. Results: ISL treatment was associated with declines in lymphocytes (11.9%, p = 0.0015) and monocytes (22.4%, p = 0.0003), but not granulocytes (0.3%, p = 0.9781). Total lymphocytes and monocytes returned to pre-treatment levels 6 weeks after treatment cessation (p = 0.8244 and p = 0.4620, respectively). Lymphocyte subpopulation analyses showed a significant decline in CD8 (−18.4%, p = 0.0364) and CD20 (−35.3%; p = 0.0002) cells but not CD4 cells (−7.4%; p = 0.3470). Gene set enrichment analysis showed negative enrichment (p_adj < 0.05) of gene pathways associated with immune regulation, cell proliferation, and inflammation. Conclusions: ISL treatment resulted in significant reductions in lymphocytes reproducing clinical toxicity. This effect was reversed after treatment cessation as observed in humans. Our results highlight the value of the macaque model to study immune alterations at the preclinical stage. Full article

(This article belongs to the Special Issue Advancing HIV Prevention and Treatment: Pharmacokinetics, Pharmacodynamics, Toxicokinetics, Formulation and Delivery of Antiretroviral Drugs)

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14 pages, 1649 KB

Open AccessArticle

Anti-Psoriatic Effects of J2H-1802, a Mycophenolate Mofetil and 5-Aminosalicylic Acid Hybrid, in an Imiquimod-Induced Psoriasis-like Mouse Model

by Sung-Hoon Park, Ji Hwan Lee, Kyeong-No Yoon, Gabsik Yang, Jason Kim, Ju Young Lee, Kwanghyun Choi, Kiwon Jung, Sumi Lee, Woo-Chan Son and Ki Sung Kang

Pharmaceutics 2026, 18(3), 380; https://doi.org/10.3390/pharmaceutics18030380 - 19 Mar 2026

Viewed by 420

Abstract

Background/Objectives: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and systemic inflammatory responses, which are primarily driven by the interleukin (IL)-23/Th17 axis. Although current therapies effectively suppress inflammation, their long-term use is often limited by adverse systemic effects, [...] Read more.

Background/Objectives: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and systemic inflammatory responses, which are primarily driven by the interleukin (IL)-23/Th17 axis. Although current therapies effectively suppress inflammation, their long-term use is often limited by adverse systemic effects, underscoring the need for safe immunomodulatory agents. This study investigated the anti-psoriatic efficacy of J2H-1802, a novel hybrid compound combining mycophenolate mofetil (MMF) and 5-aminosalicylic acid (5-ASA), in an imiquimod (IMQ)-induced psoriasis-like mouse model. Methods: J2H-1802 was orally administered at doses of 125 and 250 mg/kg during IMQ treatment, and its effects were evaluated by conducting clinical assessments, histological analyses, and inflammatory cytokine measurements in the serum and skin tissues. Results: J2H-1802 treatment reduced Psoriasis Area and Severity Index (PASI) scores, skin and ear thickness, and splenomegaly in a dose-dependent manner. Histological examination revealed IMQ-induced epidermal hyperplasia attenuation and dermal collagen organization improvement. In addition, J2H-1802 significantly reduced serum tumor necrosis factor-α (TNF-α) levels and suppressed pro-inflammatory cytokine expression, including IL-1β, IL-6, IL-17, and TNF-α, in psoriatic skin. Conclusions: J2H-1802 alleviates both local and systemic inflammatory features of psoriasis, suggesting its potential as a therapeutic candidate for targeting IL-23/Th17-mediated inflammatory pathways. Full article

(This article belongs to the Special Issue Skin Care Products for Healthy and Diseased Skin, 2nd Edition)

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18 pages, 3759 KB

Open AccessArticle

Effects of Proglumide with Chemotherapy on the Pancreatic Tumor Microenvironment: Phase 1 PROGEM Trial

by Jill P. Smith, Gakiza C. Nkulikiyimana, Hong Cao, Wenqiang Chen, Bhaskar Kallakury, John Kwagyan, Anju Duttargi and Benjamin A. Weinberg

Pharmaceutics 2026, 18(3), 379; https://doi.org/10.3390/pharmaceutics18030379 - 19 Mar 2026

Viewed by 513

Abstract

Background: The primary aim of this Phase 1 clinical trial was to study the safety and dose of a cholecystokinin receptor antagonist, proglumide, in combination with gemcitabine/nab-paclitaxel (GEM-NAB-P) in patients with metastatic pancreatic cancer. The secondary aim was to study the effects [...] Read more.

Background: The primary aim of this Phase 1 clinical trial was to study the safety and dose of a cholecystokinin receptor antagonist, proglumide, in combination with gemcitabine/nab-paclitaxel (GEM-NAB-P) in patients with metastatic pancreatic cancer. The secondary aim was to study the effects of proglumide with GEM-NAB-P on the tumor microenvironment (TME) with tumor biopsies and a blood biomarker assay. An exploratory aim studied the effects of proglumide treatment on cancer-related pain. Methods: Gemcitabine-naïve patients were treated with GEM-NAB-P plus proglumide 1200 mg/day. Tumor biopsies and a liquid biopsy serum sample for analysis of a microRNA biomarker panel were collected pre- and on-treatment to study the TME. McGill pain surveys were done at baseline, week 8 and at the end of treatment. The study was approved and registered (NCT05827055). Results: The mean age of the patients was 68.2 years (range 54–74 years). The starting dose was well-tolerated with no unexpected treatment-related adverse events observed. Multiplex immunohistochemical analysis of tumor biopsies at baseline and week 8 revealed a significant reduction in Ki67+ cells, collagen1α1, and M2-polarized tumor-associated macrophages (TAMs). Week 8 tumor biopsies demonstrated a significant increase in CD8+ T-cells and natural killer cells compared to baseline. The blood biomarker panel showed a significant inverse change in microRNAs associated with decreasing fibrosis and metastasis. The McGill pain scores showed less pain at week 24 or end-of-treatment compared to baseline. Conclusions: Proglumide demonstrates a favorable safety profile when combined with standard chemotherapy for metastatic pancreatic cancer. Its unique ability to remodel TME and alleviate cancer-related pain highlights its potential, warranting further research. Full article

(This article belongs to the Special Issue Advances in Drug Delivery, Diagnostics, and Therapeutics for Cancer: Toward Personalized Oncology)

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20 pages, 10890 KB

Open AccessArticle

Development of Stearic Acid Nanoemulsion for Therapeutic Delivery of Talazoparib Against Breast Cancer

by Jingjing Zhang, Zhongkun Zhang, Xiaohan Xia, Kaixin Feng, Siyu Yao, Yufei Wang and Min Wu

Pharmaceutics 2026, 18(3), 378; https://doi.org/10.3390/pharmaceutics18030378 - 19 Mar 2026

Viewed by 418

Abstract

Objectives: Talazoparib (TZL) is a potent PARP inhibitor but suffers from poor aqueous solubility, dissolution-limited absorption, and dose-limiting systemic toxicities, which together restrict its antitumor efficacy in some breast cancer settings. This study aimed to develop a stearic acid-based nanoemulsion (SANE) to [...] Read more.

Objectives: Talazoparib (TZL) is a potent PARP inhibitor but suffers from poor aqueous solubility, dissolution-limited absorption, and dose-limiting systemic toxicities, which together restrict its antitumor efficacy in some breast cancer settings. This study aimed to develop a stearic acid-based nanoemulsion (SANE) to improve the delivery of TZL and enhance its antitumor activity and preliminarily explore its impact on DNA damage response-related pathways. Methods: SANE-TZL was prepared using a high-pressure homogenization method, and its physicochemical properties were characterized. MCF-7 and MDA-MB-231 breast cancer cells were used to evaluate cellular uptake, cytotoxicity, and changes in key DNA damage response markers. In vivo therapeutic efficacy and safety were assessed in an MDA-MB-231 xenograft mouse model. Results: SANE-TZL exhibited a uniform particle size of approximately 118 nm with excellent stability. In MCF-7 cells, SANE-TZL significantly enhanced drug internalization, resulting in an 8.4-fold reduction in IC₅₀ compared to free TZL. Consistently, in MDA-MB-231 cells, SANE-TZL also showed markedly increased antiproliferative activity. At the molecular level, SANE-TZL modulated the expression of several DNA damage response-related genes, including BRCA1, RAD51, and SLFN11, in a manner consistent with impaired DNA repair capacity. In vivo, high-dose SANE-TZL achieved a tumor growth inhibition (TGI) rate of 58.55%, which was higher than that of the free TZL group (41.86%) and the blank eSANE group (17.59%). No evident hematological or organ toxicities were observed in the SANE-TZL-treated groups. Conclusions: SANE-TZL markedly improves the delivery efficiency and antitumor activity of TZL in breast cancer models while maintaining a favorable safety profile. By combining a functional stearic acid carrier with TZL, this nanoemulsion formulation represents a safe and potent strategy to enhance PARP inhibitor-based chemotherapy in breast cancer, and it may provide a basis for further mechanistic studies on DNA damage response modulation. Full article

(This article belongs to the Special Issue Advanced Nano-Formulations for Drug Delivery and Cancer Immunotherapy)

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15 pages, 915 KB

Open AccessArticle

Accurate and Sensitive UHPLC–Tandem Mass Spectrometry Sequential Methods for Therapeutic Drug Monitoring of Aztreonam/Avibactam in Human Plasma

by Ilaria Trozzi, Beatrice Giorgi, Riccardo De Paola, Milo Gatti and Federico Pea

Pharmaceutics 2026, 18(3), 377; https://doi.org/10.3390/pharmaceutics18030377 - 19 Mar 2026

Viewed by 429

Abstract

Background/Objectives: The aztreonam/avibactam combination represents a promising therapeutic option for severe infections caused by multidrug-resistant Gram-negative pathogens, particularly in critically ill patients. Due to marked pharmacokinetic variability and the need to achieve joint pharmacokinetic/pharmacodynamic (PK/PD) targets of both agents, therapeutic drug monitoring [...] Read more.

Background/Objectives: The aztreonam/avibactam combination represents a promising therapeutic option for severe infections caused by multidrug-resistant Gram-negative pathogens, particularly in critically ill patients. Due to marked pharmacokinetic variability and the need to achieve joint pharmacokinetic/pharmacodynamic (PK/PD) targets of both agents, therapeutic drug monitoring (TDM) may play a pivotal role in optimizing treatment. This study aimed to develop and validate two rapid, accurate, and sensitive UHPLC–qTOF MS/MS sequential methods for quantifying aztreonam and avibactam in human plasma, suitable for routine clinical TDM. Methods: Plasma concentrations were determined by means of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC–qTOF MS/MS), operating in positive and negative electrospray ionization modes for aztreonam and avibactam, respectively. Sample preparation consisted of protein precipitation with isotopically labeled internal standards. The method’s validation was performed according to the European Medicines Agency guidelines, by assessing selectivity, linearity, precision, accuracy, recovery, matrix effects, carry-over, and stability. Clinical applicability was evaluated by reprocessing plasma samples, which were already previously collected for routine clinical practice from 20 hospitalized patients undergoing treatment with ceftazidime-avibactam plus aztreonam. Results: The methods showed excellent linearity (R² ≥ 0.999) over ranges of 0.2–100 µg/mL for aztreonam and 0.1–50 µg/mL for avibactam. Lower limits of quantification were 0.2 µg/mL and 0.1 µg/mL, respectively. Intra- and inter-day precision and accuracy met the EMA criteria at all of the quality control levels. Extraction recovery exceeded 90% for both analytes, and matrix effects were effectively compensated by internal standards. Stability testing highlighted the need for careful sample handling, particularly for aztreonam under repeated freeze–thaw conditions. Clinical application revealed substantial inter-individual variability in steady-state concentrations. Conclusions: The validated UHPLC–qTOF MS/MS assays provide robust and sensitive sequential quantification of aztreonam and avibactam in human plasma, supporting TDM-guided dose optimization in clinical practice. Full article

(This article belongs to the Section Clinical Pharmaceutics)

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23 pages, 2072 KB

Open AccessArticle

Sexual Function and Depressive Symptoms in Metformin-Treated Women with Drug-Induced Hyperprolactinemia and Different Vitamin D Status: A Pilot Study

by Robert Krysiak, Witold Szkróbka, Karolina Kowalcze and Bogusław Okopień

Pharmaceutics 2026, 18(3), 376; https://doi.org/10.3390/pharmaceutics18030376 - 18 Mar 2026

Viewed by 447

Abstract

Background: Elevated prolactin levels are associated with disturbances in female sexual function. While long-term therapy with dopamine agonists has been shown to improve these disturbances, the therapeutic benefits appear to be reduced in the presence of vitamin D deficiency or insufficiency. Therefore, the [...] Read more.

Background: Elevated prolactin levels are associated with disturbances in female sexual function. While long-term therapy with dopamine agonists has been shown to improve these disturbances, the therapeutic benefits appear to be reduced in the presence of vitamin D deficiency or insufficiency. Therefore, the present study aimed to examine whether vitamin D status modulates the effects of metformin—a medication with less pronounced prolactin-lowering properties—on sexual function and depressive symptoms. Methods: The study cohort comprised three groups of reproductive-age women with drug-induced hyperprolactinemia and prediabetes, matched for age, glycated hemoglobin, and prolactin concentrations. Group I included 25 women with normal vitamin D status who were not receiving vitamin D supplementation. Group II consisted of 25 women with vitamin D deficiency or insufficiency that was adequately corrected through supplementation, while group III included 25 women with untreated vitamin D deficiency or insufficiency. All participants received metformin throughout the six-month study period. Female sexual function and depressive symptoms were assessed before and after metformin therapy using the Female Sexual Function Index (FSFI) and the Beck Depression Inventory-II (BDI-II), respectively. Additional outcome measures included plasma 25-hydroxyvitamin D, fasting plasma glucose, glycated hemoglobin (HbA_1c), the homeostatic model assessment of insulin resistance (HOMA-IR), prolactin, gonadotropins, and sex hormones. Results: Improvements in glucose homeostasis were observed across all groups; however, these changes were more pronounced in groups I and II than in group III. Reductions in prolactin concentrations (total and monomeric), accompanied by increases in gonadotropins, estradiol, and testosterone, were observed exclusively in women with normal vitamin D status. In groups I and II, metformin therapy resulted in significant improvements in total FSFI scores as well as in all individual domain scores. In contrast, in group III, the effects of metformin were limited to increases in the domain scores for lubrication and sexual satisfaction. Improvements in sexual function were positively associated with baseline 25-hydroxyvitamin D levels, reductions in prolactin concentrations, and, to a lesser extent, treatment-related changes in HbA_1c and increases in testosterone. A treatment-induced reduction in total BDI-II scores was observed only among women with normal vitamin D status. Conclusions: Low vitamin D status diminishes the beneficial effects of metformin on sexual function and depressive symptoms in reproductive-age women with iatrogenic hyperprolactinemia. Full article

(This article belongs to the Special Issue Drug–Drug Interactions—New Perspectives)

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40 pages, 2001 KB

Open AccessReview

Botanical and Upcycled Bioactives for Advanced Topical Formulations: Mechanistic Pathways, Cutaneous Delivery, and Sustainability-by-Design

by Salvatore Panza, Beatrice Pellegrini, Dorotea Fiore, Martine Tarsitano, Antonia Mancuso, Maria Chiara Cristiano and Donatella Paolino

Pharmaceutics 2026, 18(3), 375; https://doi.org/10.3390/pharmaceutics18030375 - 18 Mar 2026

Viewed by 444

Abstract

Natural and sustainable cosmetics represent a rapidly evolving frontier in dermatological science, integrating plant-derived bioactive compounds with advanced delivery technologies and environmentally conscious formulation design. Botanical ingredients, including polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides, modulate key biological pathways involved in oxidative stress, inflammation, [...] Read more.

Natural and sustainable cosmetics represent a rapidly evolving frontier in dermatological science, integrating plant-derived bioactive compounds with advanced delivery technologies and environmentally conscious formulation design. Botanical ingredients, including polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides, modulate key biological pathways involved in oxidative stress, inflammation, extracellular matrix remodeling, pigmentation, and immune responses, thereby supporting skin regeneration, protection, and homeostasis. To overcome limitations related to instability, compositional variability, and limited skin penetration, these compounds are increasingly incorporated into advanced delivery systems such as nanoemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), vesicular systems, microneedle platforms, three-dimensional matrices, and plant-derived extracellular vesicles (PDEVs). These technologies enhance cutaneous bioavailability, enable controlled release, and improve tissue targeting, linking formulation design to exposure–response relationships. In parallel, sustainability has become a critical component of product development. Circular economy strategies, including the upcycling of agro-industrial by-products, green extraction technologies, biodegradable packaging, and life cycle assessment, are reshaping cosmetic innovation. Regulatory frameworks are also evolving to address safety, efficacy, and transparency of natural claims, as well as the challenges of botanical standardization. This narrative review, conducted through a structured literature search, provides a mechanistically oriented analysis of botanical ingredients in dermatology, emphasizing molecular pathways, skin delivery science, and safety considerations. Rather than cataloguing ingredients, it proposes a translational framework linking phytochemistry, delivery science, safety-by-design principles, and sustainability to support the rational development of effective and safe dermatological formulations. Full article

(This article belongs to the Special Issue 3D Printing and Personalized Medicine: Advancing Drug Delivery Systems)

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19 pages, 1311 KB

Open AccessArticle

Tranexamic Acid for Reduction of Blood Loss in Patients with Extracapsular Proximal Femur Fractures: Systematic Review and Meta-Analysis of Randomized Clinical Trials

by Irena Ilic, Ivan Stojadinovic, Branko Ristic and Milena Ilic

Pharmaceutics 2026, 18(3), 374; https://doi.org/10.3390/pharmaceutics18030374 - 18 Mar 2026

Viewed by 388

Abstract

Background/Objectives: Blood loss is a major concern in elderly patients undergoing hip fracture surgery. Tranexamic acid (TXA) is used to improve bleeding outcomes; however, randomized clinical trials (RCTs) report mixed findings, with some studies finding no improvements. This meta-analysis was conducted to [...] Read more.

Background/Objectives: Blood loss is a major concern in elderly patients undergoing hip fracture surgery. Tranexamic acid (TXA) is used to improve bleeding outcomes; however, randomized clinical trials (RCTs) report mixed findings, with some studies finding no improvements. This meta-analysis was conducted to evaluate the effectiveness of intravenous TXA in patients with extracapsular proximal femur fractures undergoing surgery. Methods: A systematic literature review was performed to identify relevant RCTs. Evaluated outcomes were total blood loss (TBL), hidden blood loss (HBL), change in hemoglobin (Hb), change in hematocrit (Hct), risk for transfusion and number of transfused units per patient. Review Manager 5.3 was used. Results: Twenty-five RCTs were included. TXA administration was associated with significant reductions in TBL (MD = −255.59 mL, 95% CI −306.50 to −204.68) and HBL (MD = −219.28 mL, 95% CI −286.93 to −151.62) compared with control. Patients receiving TXA had significantly smaller changes in Hb (MD = 0.65 g/dL, 95% CI 0.39–0.90) and Hct (MD = 4.22%, 95% CI 2.04–6.40). TXA significantly reduced the risk of transfusion (RR = 0.55, 95% CI 0.43–0.70) and number of transfused units per patient (SMD = −0.66, 95% CI −1.15 to −0.17). Subgroup analyses showed consistent effects. Sensitivity analyses confirmed robustness of results, except for the significance in reducing the number of transfused units when studies with ‘liberal’ transfusion thresholds were excluded. Conclusions: These findings show statistically significant improvements in bleeding outcomes with the use of intravenous TXA in patients with extracapsular proximal femur fractures undergoing surgery. Further high-quality RCTs are needed to standardize TXA timing and dosing. Full article

(This article belongs to the Section Clinical Pharmaceutics)

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26 pages, 6215 KB

Open AccessArticle

Modified Chitosan-Based Hemostatic Dressings Incorporating Heparin-Loaded Nanoparticles for Enhanced Hemostatic Activity

by Despoina Meimaroglou, Evi Christodoulou, Rizos Evangelos Bikiaris, Ioanna Koumentakou, Michiel Jan Noordam, Amalia Oikonomou, Ioannis Taitzoglou, Ioannis Tsamesidis, Eleana Kontonasaki, Zoi Terzopoulou, Lysimachos G. Papazoglou, George Z. Kyzas and Dimitrios N. Bikiaris

Pharmaceutics 2026, 18(3), 373; https://doi.org/10.3390/pharmaceutics18030373 - 18 Mar 2026

Viewed by 451

Abstract

Background/Objectives: Achieving effective hemostasis is a vital step in wound healing, particularly in cases of severe bleeding caused by surgical procedures or trauma. This study focuses on the development of chitosan-based dressings enriched with Heparin (hep)-loaded poly(butylene succinate) (PBSu) nanoparticles to combine [...] Read more.

Background/Objectives: Achieving effective hemostasis is a vital step in wound healing, particularly in cases of severe bleeding caused by surgical procedures or trauma. This study focuses on the development of chitosan-based dressings enriched with Heparin (hep)-loaded poly(butylene succinate) (PBSu) nanoparticles to combine hemostatic and anticoagulant properties. Methods: Chitosan, a biocompatible and biodegradable carbohydrate with inherent antibacterial and hemostatic properties, was chemically modified with 2-(N-morpholino)ethanesulfonic acid (MES) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) to enhance its swelling ability and hemostatic activity. PBSu nanoparticles were synthesized using an oil-in-water emulsification method and loaded with Hep to achieve controlled anticoagulant release. The dressings of the modified chitosan derivatives with the nanoparticles which were systematically characterized for morphology, chemical structure, swelling ability, loading capacity, and Hep release kinetics. Results: This dual-function system is designed to decouple local surface hemostasis from thrombotic processes: the chitosan matrix provides rapid topical hemostasis, while controlled heparin release from the nanoparticles aims to modulate excessive fibrin deposition, support microvascular perfusion, and exploit the pro-healing benefits of low-dose heparin reported in advanced wound dressings, particularly in high-risk or thrombotic-prone patients. In vitro and in vivo studies demonstrated their potential for promoting rapid hemostasis. Conclusions: These findings suggest that the integration of modified chitosan and Hep-loaded nanoparticles is a promising strategy for advancing wound care and hemostatic technologies. Full article

(This article belongs to the Section Drug Delivery and Controlled Release)

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19 pages, 4669 KB

Open AccessArticle

In Vitro and In Vivo Effects of a Copper(II)-Hydrazone Complex Against Human Osteosarcoma

by Lucía Santa Maria de la Parra, Matías H. Assandri, Luisina M. Solernó, María de los A. Serradell, Daniel F. Alonso, Juan Garona, Lucía M. Balsa and Ignacio E. León

Pharmaceutics 2026, 18(3), 372; https://doi.org/10.3390/pharmaceutics18030372 - 17 Mar 2026

Viewed by 568

Abstract

Introduction: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults, with poor prognosis due to relapse, metastasis, and chemoresistance. The search for novel metal-based therapeutics has highlighted copper complexes as promising candidates. Here, we report the in [...] Read more.

Introduction: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults, with poor prognosis due to relapse, metastasis, and chemoresistance. The search for novel metal-based therapeutics has highlighted copper complexes as promising candidates. Here, we report the in vitro and in vivo antitumor activity of a tetranuclear Cu(II)-hydrazone complex (Cu₄L₄) derived from (E)-5-chloro-N′-(2-hydroxy-3-methoxybenzylidene)thiophene-2-carbohydrazide. Results: Cytotoxic assays on MG-63 OS cells revealed potent activity with an IC₅₀ of 0.50 ± 0.04 µM, significantly surpassing its free ligand (IC₅₀ = 13.9 ± 1.6 µM) and cisplatin (IC₅₀ = 39.0 ± 1.8 µM). This tetranuclear complex outperforms mononuclear Cu-hydrazones analogs (e.g., 4-fold vs. CuHL1, 2-fold vs. CuHL2, 5-fold vs. CuHL3, 17-fold vs. CuHL4,), and Cu₄L₄ also exhibits reduced clonogenic survival, induces reactive oxygen species production, and promotes late apoptosis as a main mechanism, being the main mechanism of action involved in anticancer activity. In multicellular tumor spheroids, the complex maintained strong cytotoxicity (IC₅₀ = 4.11 ± 0.12 µM), impaired spheroid integrity, and markedly inhibited cell migration at sub-IC₅₀ concentrations. The tetranuclear architecture confers markedly enhanced antitumor activity relative to the corresponding mononuclear Cu–hydrazone complexes (e.g., 2-fold vs. CuHL1, 4-fold vs. CuHL2, 2-fold vs. CuHL3). In a xenograft model, sustained administration of Cu₄L₄ (2 mg/kg, i.p., twice weekly) inhibited tumor growth by 43.6%, reduced mitotic index, and increased necrotic area without significant systemic toxicity. Conclusions: Overall, Cu₄L₄ displayed potent and selective antitumor activity against OS cells in 2D, 3D, and in vivo models, underscoring copper–hydrazone complexes as promising scaffolds for the development of new therapies against OS. Full article

(This article belongs to the Special Issue A New Generation of Metal Anticancer Drugs)

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18 pages, 1087 KB

Open AccessArticle

Selective Human-Milk-Inspired Antimicrobial Peptides for the Treatment of Bacterial Vaginosis

by Ishita M. Shah, Carlito B. Lebrilla, J. Bruce German and David A. Mills

Pharmaceutics 2026, 18(3), 371; https://doi.org/10.3390/pharmaceutics18030371 - 17 Mar 2026

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Abstract

Background: Antimicrobial resistance (AMR) is a global healthcare threat. Traditional largely non-selective antibiotics produce side effects due to the natural host microbiome being modified creating a loss in homeostasis. In women, AMR is a cause of acute generational impact. For example, bacterial vaginosis [...] Read more.

Background: Antimicrobial resistance (AMR) is a global healthcare threat. Traditional largely non-selective antibiotics produce side effects due to the natural host microbiome being modified creating a loss in homeostasis. In women, AMR is a cause of acute generational impact. For example, bacterial vaginosis (BV), the most common gynecological infection in reproductive-age women, is a serious public health concern due to its high rates of recurrence, secondary infections, and reproductive issues; and two currently prescribed antibiotics for BV do not fully resolve the symptoms. Objective: The strong need for innovative, potent, safe, and selective therapeutics has prompted a search for such bioactive molecules in milk. Resulting from 200 million years of evolutionary pressure, mammalian lactation not only nourishes infants, but it has also been under relentless Darwinian selective pressure to provide protection from a variety of infections. Methods: Computationally designed human-milk-inspired peptides (AMPs) were tested in standard microbicidal assays for activity against BV pathogens, and evaluated for stability and safety. Results: Several AMPs are bactericidal towards Gardnerella vaginalis, a major BV-associated pathogen, and other BV-associated pathogens. Some novel AMPs do not impact the viability of key lactobacilli linked to a healthy vaginal microbiome. These stable, membrane-acting cationic AMPs reduce inflammation during an infection assay and are safe in EpiVag organoid tissues. Conclusions: AMPs can address concerns like non-selectivity and antibiotic resistance—thereby addressing AMR. Lead AMPs from this study offer a promising solution for the development of novel therapeutics for the treatment of BV, which may reduce the burden of AMR. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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23 pages, 11154 KB

Open AccessArticle

Oxidized Dextran/Carboxymethyl Chitosan Dynamic Schiff-Base Hydrogel for Sustained Hydrogen Sulfide Delivery and Burn Wound Microenvironment Remodeling

by Zhishan Liu, Ying Zhu, Zhuoya Ma, Xuyang Ning, Ziqiang Zhou, Jinchang Liu, Youfu Xie, Gang Li and Ping Hu

Pharmaceutics 2026, 18(3), 370; https://doi.org/10.3390/pharmaceutics18030370 - 17 Mar 2026

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Abstract

Background: Polysaccharide-based dynamic hydrogels are promising for wound management due to their biocompatibility, injectability, and tunable biofunctionality. The integration of therapeutic gasotransmitter donors offers a strategy to modulate the wound microenvironment. Objectives: This study aimed to develop an injectable, self-healing carbohydrate [...] Read more.

Background: Polysaccharide-based dynamic hydrogels are promising for wound management due to their biocompatibility, injectability, and tunable biofunctionality. The integration of therapeutic gasotransmitter donors offers a strategy to modulate the wound microenvironment. Objectives: This study aimed to develop an injectable, self-healing carbohydrate hydrogel capable of sustained hydrogen sulfide (H₂S) release for burn wound therapy, and to evaluate its physicochemical properties, in vivo efficacy, and mechanism of action. Methods: A dynamic hydrogel (ACMOD) was fabricated via Schiff-base crosslinking between oxidized dextran (OD) and carboxymethyl chitosan (CMCS), incorporating the H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH). Rheological and recovery tests characterized its mechanical and self-healing properties. Efficacy and mechanisms were assessed in a rat full-thickness burn model, analyzing wound closure, histology, oxidative stress, macrophage polarization, angiogenesis, and collagen deposition. Results: ACMOD exhibited shear-thinning, rapid self-healing, and strong tissue adherence. Sustained H₂S release from ACMOD significantly accelerated wound closure and improved tissue regeneration compared to controls. Mechanistically, H₂S attenuated oxidative stress, promoted a pro-regenerative M2 macrophage phenotype, enhanced angiogenesis via VEGF upregulation, and fostered organized collagen deposition and extracellular matrix remodeling. Conclusions: This work demonstrates a versatile, carbohydrate-based dynamic hydrogel platform that synergizes polymer network dynamics with bioactive H₂S delivery to effectively promote burn wound healing. The findings underscore the potential of polysaccharide hydrogels with integrated gasotransmitter release for regenerative therapy and biomaterials applications. Full article

(This article belongs to the Section Drug Delivery and Controlled Release)

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34 pages, 6483 KB

Open AccessArticle

Myrrh Oil-Based Nanoemulsion Loaded with Curcumin and Insulin: Development, Characterization, and Evaluation of Enhanced Antibacterial and Diabetic Wound-Healing Activity

by Ayman Salama, Mona Qushawy, Nehal Elsherbiny, Helal F. Hetta, Saleh F. Alqifari, Mohamed A. Safwat, Wael M. Elsaed, Mahmoud Elsabahy, Yasmin N. Ramadan and Ghareb M. Soliman

Pharmaceutics 2026, 18(3), 369; https://doi.org/10.3390/pharmaceutics18030369 - 16 Mar 2026

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Abstract

Background/Objectives: Curcumin (CUR) has shown promising potential as a wound-healing agent for diabetic wounds; however, its efficacy is hindered by poor aqueous solubility and limited skin permeability. To overcome these limitations, CUR was loaded into myrrh oil-based nanoemulsions (NEs). Methods: The [...] Read more.

Background/Objectives: Curcumin (CUR) has shown promising potential as a wound-healing agent for diabetic wounds; however, its efficacy is hindered by poor aqueous solubility and limited skin permeability. To overcome these limitations, CUR was loaded into myrrh oil-based nanoemulsions (NEs). Methods: The NEs were optimized using a three-factor two-level D-optimal mixture design, and characterized for droplet size, polydispersity index, and zeta potential. The optimized NE was subjected to various stability testing and incorporated into a gel base containing insulin (INS) to form CUR-INS nanoemulgel (CUR-INS-NEG). The antibacterial efficacy of CUR-INS-NEG was tested against various bacterial strains, while its wound-healing effects were evaluated in a diabetic rat wound model. Results: The surfactant/co-surfactant concentration had a greater influence on the NE properties than the oil and aqueous phase concentrations. The optimal NE had a droplet size of 155.2 ± 0.8 nm, a polydispersity index of 0.28, and a zeta potential of −31.4 ± 0.8 mV. It demonstrated sustained drug release, with further release control upon incorporation into the gel base. CUR-INS-NEG demonstrated higher in vitro antibacterial efficacy compared with blank NEG, CUR gel, and INS gel. It also showed 2- and 4-fold reduction in the MIC against S. aureus and E. coli, respectively, compared with CUR gel. In a diabetic wound model, CUR-INS-NEG outperformed both CUR gel and INS gel by enhancing anti-inflammatory and antioxidant effects, as well as collagen deposition and endothelial cell proliferation. Conclusions: The CUR-INS-NEG emerges as an effective system for diabetic wound management, delivering complementary anti-inflammatory, antioxidant, and tissue-regenerative effects of myrrh oil, CUR, and INS. Full article

(This article belongs to the Special Issue Nanoemulsions for Pharmaceutical and Biomedical Applications)

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22 pages, 975 KB

Open AccessReview

Green Nanodrugs: Research Progress and Challenges of Plant-Derived Nanovesicles in Tumor Treatment

by Junsong Zhu, Xingyu Zhou, Qiong Lan and Jian He

Pharmaceutics 2026, 18(3), 368; https://doi.org/10.3390/pharmaceutics18030368 - 16 Mar 2026

Viewed by 458

Abstract

Background: Plant-derived nanovesicles (PDNVs), a class of naturally occurring nanoparticles with a phospholipid bilayer structure, have attracted significant attention in biomedicine, particularly in anti-tumor research, due to their broad source availability, low production cost, high biocompatibility, and low immunogenicity. Methods: This [...] Read more.

Background: Plant-derived nanovesicles (PDNVs), a class of naturally occurring nanoparticles with a phospholipid bilayer structure, have attracted significant attention in biomedicine, particularly in anti-tumor research, due to their broad source availability, low production cost, high biocompatibility, and low immunogenicity. Methods: This review systematically summarizes and analyzes the isolation methods, composition, anti-tumor mechanisms, and clinical translation potential of PDNVs based on literature retrieved from PubMed and Web of Science, with clinical trials identified and categorized using ClinicalTrials.gov. Results: Current research has made impressive progress in the application of PDNVs, both as direct therapeutic agents and as drug delivery systems. Their remarkable stability, ability to cross physiological barriers (e.g., the gastrointestinal tract and blood–brain barrier), and engineerability underpin their versatile potential. Conclusions: This review comprehensively outlines the compositional characteristics of PDNVs and explores their multi-dimensional mechanisms and application prospects as natural therapeutics and drug delivery platforms in cancer therapy. Despite challenges such as standardization in preparation, PDNVs represent a highly promising class of novel nanobiomaterials. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

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Pharmaceutics, Volume 18, Issue 3 (March 2026) – 118 articles

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