Pharmaceutics

13 pages, 1576 KB

Open AccessArticle

Leishmanicidal Action of the Peptides 19-4LF, 19-2.5 and 19-2.5LF Topically Administered on Cutaneous Lesions Caused by Leishmania major

by Rima El-Dirany, Paolo Ginatta, Celia Fernández-Rubio, Aroia Burguete-Mikeo, Esther Larrea, Guillermo Martinez-de-Tejada and Paul A. Nguewa

Pharmaceutics 2026, 18(3), 332; https://doi.org/10.3390/pharmaceutics18030332 (registering DOI) - 7 Mar 2026

Abstract

Background/Objectives: Antimicrobial peptides (AMPs) represent a promising class of therapeutics with diverse biological functions, including antibacterial, anti-fungal, anti-parasitic and anti-tumoral activities. Previous works demonstrated the successful repurposing of the two synthetic AMPs 19-2.5 and 19-4LF for cutaneous leishmaniasis, when the compounds were administered [...] Read more.

Background/Objectives: Antimicrobial peptides (AMPs) represent a promising class of therapeutics with diverse biological functions, including antibacterial, anti-fungal, anti-parasitic and anti-tumoral activities. Previous works demonstrated the successful repurposing of the two synthetic AMPs 19-2.5 and 19-4LF for cutaneous leishmaniasis, when the compounds were administered in solution on skin lesions caused by Leishmania major in a BALB/c mouse model. In this research project, we assessed the activity of 19-4LF, 19-2.5, and their hybrid 19-2.5LF derivative when formulated as a cream for topical administration in the same animal model. Methods: The peptides were formulated in DAC cream and applied to the wound of BALB/C mice for 30 days. Lesion progression was monitored using a digital caliper. Parasite burden was measured by qPCR. Parasite viability was assessed using MTT and microscopy imaging assays. Results: The three peptides in cream formulation succeeded in reducing the skin lesion. Peptide 19-4LF was the most potent, followed by 19-2.5LF and then 19-2.5. In addition, 19-4LF was able to significantly reduce the parasite burden in the skin lesions of infected mice, as measured by quantifying L. major Lm18S ribosomal gene mRNA levels using qPCR. Moreover, when combined, the peptides exhibited synergistic effects on L. major promastigotes and significantly reduced the number of amastigotes in infected macrophages. Conclusions: These studies support the approach of repurposing these AMPs as antileishmanial drugs and identify 19-4LF as a lead candidate for further studies. While historical barriers to peptide therapeutics included high production costs, recent advancements in biological fermentation and synthesis strategies have significantly improved their economic viability. Furthermore, the use of nanotechnology delivery systems can reduce the required dosage, further making peptide therapy a sustainable option for neglected diseases, including leishmaniasis. Full article

(This article belongs to the Special Issue Antimicrobial Peptides as Promising Therapeutic Agents)

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25 pages, 6250 KB

Open AccessArticle

Design and In Vitro Evaluation of Cyclodextrin-Functionalized Albumin Nanoparticles for Intranasal Carbamazepine Brain Delivery

by Hanan Mohammad, Maher Darwish, Mária Budai-Szűcs, Maryana Salamah, Rita Ambrus, György Tibor Balogh, Gábor Katona and Ildikó Csóka

Pharmaceutics 2026, 18(3), 331; https://doi.org/10.3390/pharmaceutics18030331 - 6 Mar 2026

Abstract

Background/Objectives: Poor aqueous solubility and limited nasal permeability remain key challenges in the intranasal delivery of carbamazepine. In this study, biocompatible bovine serum albumin nanoparticles functionalized with sulfobutyl-β-cyclodextrin (SβCD-BSA NPs), comprising individually cytocompatible components with confirmed physical interactions), were formulated for intranasal [...] Read more.

Background/Objectives: Poor aqueous solubility and limited nasal permeability remain key challenges in the intranasal delivery of carbamazepine. In this study, biocompatible bovine serum albumin nanoparticles functionalized with sulfobutyl-β-cyclodextrin (SβCD-BSA NPs), comprising individually cytocompatible components with confirmed physical interactions), were formulated for intranasal delivery of carbamazepine (CBZ). Methods: The ethanolic desolvation method was utilised for the preparation of the nanoparticles, with the functional moiety incorporated during nanoparticle preparation. The effects of different molar ratios of SβCD-BSA and different ethanol volume ratios were studied. For crosslinking, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), a non-toxic crosslinker, was utilised. To determine the role of the SβCD, two preparation samples were formulated, with and without SβCD. Results: The formulation without SβCD incorporation had a mean particle size of 125 ± 0.64 nm, polydispersity index (PDI) of 0.34, encapsulation efficiency (EE%) of 61.5 ± 1.40%, and drug-loading ratio (DL%) of 31.9 ± 1.50%. Conversely, the SβCD-functionalized formulation showed a mean particle size of 128 ± 2.12 nm, PDI of 0.21 ± 0.03, EE of 64.6 ± 0.35%, and DL of 34.28 ± 1.60%. Statistical analysis revealed that the incorporation of SβCD resulted in a statistically significant increase in both DL% and EE% (p < 0.05). Conversely, the observed differences in particle size and PDI were not statistically significant (p > 0.05). This addition provides precise context regarding the comparability of the formulations while highlighting SβCD’s functional benefits in solubility and permeation. The interaction between CBZ and SβCD-BSA was confirmed using Fourier-transform infrared spectroscopy. Lastly, the prepared formulations were characterised by their physicochemical attributes and in vitro biopharmaceutical studies. It was discovered that SβCD plays a dual role, enhancing the solubility of CBZ in one scenario while promoting its nasal permeation, suggesting its potential use in epilepsy treatment. Conclusions: These findings highlight the potential of SβCD-BSA NPs as a versatile pharmaceutics platform for the intranasal delivery of poorly soluble CNS drugs. Full article

(This article belongs to the Special Issue Nanoparticle-Based Drug Formulation for Enhancing Nose-to-Brain Delivery)

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23 pages, 2583 KB

Open AccessSystematic Review

From Pathology to Formulation: Designing Biodegradable Polymers for Personalized Drug Delivery

by Mariann Dinya, Elek Dinya and Gábor M. Mórotz

Pharmaceutics 2026, 18(3), 330; https://doi.org/10.3390/pharmaceutics18030330 - 6 Mar 2026

Abstract

Background/Objectives: Selection of polymer carriers for targeted drug delivery is typically guided by material availability or trigger responsiveness rather than disease-specific evidence. However, successful preclinical formulations may already encode implicit design rules linking polymer composition to particular pathological environments. This study aimed to [...] Read more.

Background/Objectives: Selection of polymer carriers for targeted drug delivery is typically guided by material availability or trigger responsiveness rather than disease-specific evidence. However, successful preclinical formulations may already encode implicit design rules linking polymer composition to particular pathological environments. This study aimed to identify reproducible material-disease associations across biodegradable polymer systems and to derive formulation-oriented guidance for disease-calibrated carrier selection. Methods: A structured synthesis of 65 preclinical in vivo studies (2020–2025) covering inflammatory bowel disease, arthritis, cardiovascular inflammation, and solid tumors was performed. Extracted variables included polymer family, backbone chemistry, stimulus responsiveness, disease model, and reported therapeutic benefit relative to controls. Associations between polymer composition, trigger mechanisms, and disease categories were analyzed using cross-tabulation, chi-square statistics, Cramér’s V, and direction-of-effect synthesis. Results: Distinct material-disease clustering patterns emerged. Ionizable polysaccharide and methacrylate systems (e.g., alginate, chitosan, Eudragit) were strongly associated with intestinal inflammatory models, reflecting reliance on pH- and ion-mediated mechanisms. Enzyme-degradable hyaluronic acid matrices were concentrated in joint and cartilage disorders characterized by protease overexpression. Oxidation-sensitive polyether systems (e.g., PEG-PPS) and redox-active hybrid platforms predominated in atherosclerosis and tumor models, where oxidative stress is a defining pathological feature. Composite and multi-responsive systems were disproportionately represented in tumors, consistent with microenvironmental heterogeneity. Across studies, therapeutic improvement was consistently reported when polymer functional motifs aligned with dominant biochemical drivers of the disease. Conclusions: Successful biodegradable polymer carriers exhibit disease-specific compatibility patterns rather than universal applicability. These recurring associations suggest that polymer selection can be guided by pathological context even in the absence of direct outcome comparisons. The resulting formulation-oriented framework supports rational carrier choice for personalized drug delivery based on disease-specific microenvironment signatures. Full article

(This article belongs to the Section Biopharmaceutics)

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23 pages, 940 KB

Open AccessReview

AI-Driven Drug Discovery: Focus on Targets for Solid Tumors

by Jialong Wu, Jide He, Qianyang Ni, Zi’ang Li, Xiushi Lin, Zhenkun Zhao, Lei Qiu, Hongyin Wang, Sijie Li, Chengdong Shi, Yunyi Zhang, Huile Gao and Jian Lu

Pharmaceutics 2026, 18(3), 329; https://doi.org/10.3390/pharmaceutics18030329 - 6 Mar 2026

Abstract

In the field of anti-tumor drug development, target identification remains a key component of innovative therapeutic strategies. Solid malignancies have posed significant challenges to conventional target discovery approaches due to their distinct genetic heterogeneity, complex tumor microenvironment, and highly individualized evolutionary trajectories. In [...] Read more.

In the field of anti-tumor drug development, target identification remains a key component of innovative therapeutic strategies. Solid malignancies have posed significant challenges to conventional target discovery approaches due to their distinct genetic heterogeneity, complex tumor microenvironment, and highly individualized evolutionary trajectories. In recent years, artificial intelligence (AI) has emerged as a revolutionary force in drug discovery. The technological advances from machine learning and deep learning to large language models (LLMs) has enabled the comprehensive integration and analysis of multi-omics biological data and real-world evidence, thereby promoting every stage of the drug discovery process. Thus, this article begins with an overview of the biological characteristics of tumors and the limitations of traditional strategies. It then delves into recent advances particularly in the past three years in the application of AI to drug discovery, especially LLMs. The main focus is on the current landscape of AI-assisted target identification. Furthermore, the article examines key challenges such as multimodal data integration and the interpretability of AI models, and envisions the future path towards integrated AI systems in precision oncology. Full article

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

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30 pages, 2046 KB

Open AccessArticle

Natural Extract Combination Modulates Intestinal Barrier and Hepatic Cholesterol via the Gut–Liver Axis In Vitro

by Francesca Uberti, Simone Mulè, Francesca Parini, Matteo Musu and Rebecca Galla

Pharmaceutics 2026, 18(3), 328; https://doi.org/10.3390/pharmaceutics18030328 - 5 Mar 2026

Abstract

Background/Objectives: The gut–liver axis plays a central role in cholesterol homeostasis, linking intestinal absorption, microbial metabolites, and hepatic lipid regulation. Dysregulation of this axis contributes to hypercholesterolemia and cardiometabolic risk, beyond classical cholesterol synthesis pathways. This study evaluated a novel multi-botanical formulation (MIX) [...] Read more.

Background/Objectives: The gut–liver axis plays a central role in cholesterol homeostasis, linking intestinal absorption, microbial metabolites, and hepatic lipid regulation. Dysregulation of this axis contributes to hypercholesterolemia and cardiometabolic risk, beyond classical cholesterol synthesis pathways. This study evaluated a novel multi-botanical formulation (MIX) that combines Gastrodia elata, Black Garlic, Primula veris, and Emblica officinalis (AMLA) to integrate modulation of cholesterol metabolism through intestinal and hepatic mechanisms. Methods: Individual extracts were chemically characterised for polyphenols, flavonoids, polysaccharides, S-allyl-L-cysteine (SAC), and tannins. Caco-2 cells were treated with varying doses to determine optimal concentrations and for viability, transepithelial electrical resistance, and permeability analysis. Supernatants post-intestinal passage were applied to HepG2 cells under high-glucose conditions to assess viability, oxidative stress, SRC/ERK-MAPK signalling, cholesterol synthesis (HMGR), LDL uptake, PCSK9–LDLR–SREBP-2 axis, and bile acid production. Results: MIX enhanced intestinal barrier integrity (TEER, tight junctions, permeability) and preserved cell viability compared with single extracts. In HepG2 cells, MIX demonstrated synergistic effects: it reduced HMGR expression by 83–90% relative to individual extracts, increased LDLR expression by 43–97%, suppressed PCSK9 by up to 92%, and lowered total cholesterol and LDL uptake more effectively than RYRF. MIX also amplified bile acid production and free cholesterol excretion, indicating improved hepatic clearance pathways. SRC and ERK-MAPK signalling were favourably modulated, supporting hepatocyte survival under metabolic stress. Conclusions: The multi-botanical formulation exerts complementary and synergistic effects on intestinal absorption and hepatic cholesterol regulation, integrating suppression of cholesterol synthesis, enhanced LDL clearance, and stimulated elimination via bile acids. These findings highlight the potential of the MIX formulation to modulate metabolically induced cholesterol dysregulation, supporting further in vivo and clinical investigation. Full article

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

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23 pages, 5239 KB

Open AccessArticle

Polymeric Matrix Mini-Tablets Based on Eudragit^® S 100 and HPMC for Controlled Release of Pantoprazole

by Hugo Pardo, Mª Ángeles Peña, Borja Martínez-Alonso, Carlos Torrado-Salmerón and Víctor Guarnizo-Herrero

Pharmaceutics 2026, 18(3), 327; https://doi.org/10.3390/pharmaceutics18030327 - 5 Mar 2026

Abstract

Background: Pantoprazole is a widely used proton pump inhibitor that is highly unstable under acidic conditions. This limits the performance of conventional formulations and typically requires enteric-coated dosage forms or alternative modified-release approaches. This study reports the development of polymeric matrix mini-tablets designed [...] Read more.

Background: Pantoprazole is a widely used proton pump inhibitor that is highly unstable under acidic conditions. This limits the performance of conventional formulations and typically requires enteric-coated dosage forms or alternative modified-release approaches. This study reports the development of polymeric matrix mini-tablets designed to protect pantoprazole during gastric exposure and to enable pH-dependent release under intestinal conditions. The formulations combine Eudragit^® S 100, a pH-dependent polymer, with HPMC, a hydrophilic matrix former that modulates drug release through hydration and swelling. Methods: Matrix mini-tablets were prepared by blending pantoprazole with selected excipients at optimised proportions and compressing the blends by direct compression using an eccentric tablet press. Powder blends and mini-tablets were characterised according to pharmacopoeial specifications. Analytical techniques—including High-Performance Liquid Chromatography (HPLC), Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Absorption Spectroscopy (FT-IR), Powder X-Ray Diffraction (PXRD), and Scanning Electron Microscopy (SEM)—were employed to evaluate drug content uniformity, thermal behaviour, and potential drug–excipient interactions. In vitro dissolution studies were performed under sequential pH conditions, and the release kinetics were analysed using mathematical models. Results: Dissolution testing identified formulations F2 and F6 as providing the most suitable gastro-resistant performance in the acidic stage, together with sustained release up to 24 h. Kinetic modelling supported formulation-dependent release mechanisms, and multivariate analysis (PCA) highlighted relationships between physico-mechanical attributes and drug-release behaviour. Conclusions: The proposed matrix system shows potential as a robust, coating-free platform for the modified delivery of acid-labile drugs using direct compression, simplifying manufacturing. These findings support the rational design of oral modified-release formulations based on polymeric matrices. Full article

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

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40 pages, 11475 KB

Open AccessArticle

Next-Generation Minimally Invasive Anti-Aging Therapy: Incorporation of Resveratrol-Nicotinamide Cerosomes into PLGA Microneedles for Enhanced Skin Permeation

by Sammar Fathy Elhabal, Mai S. Shoela, Fatma E. Hassan, Suzan Awad AbdelGhany Morsy, Amal M. Elsharkawy, Amany Ali Khalil Nawar, Mona Mohamed Ahmed, Shady Allam, Marwa A. Fouad, Amal Anwar Taha, Ahmed Mohsen Faheem, Hanan Mohamed Abd Elmoneim and Ahmed Mohsen Elsaid Hamdan

Pharmaceutics 2026, 18(3), 326; https://doi.org/10.3390/pharmaceutics18030326 - 4 Mar 2026

Abstract

Background/Objectives: Skin aging and wrinkle formation are primarily driven by ultraviolet (UV)-induced oxidative stress and inflammation. Resveratrol (RSV) and nicotinamide (NCT) possess potent anti-aging properties but suffer from poor skin penetration. This study aimed to develop an advanced transdermal delivery system incorporating [...] Read more.

Background/Objectives: Skin aging and wrinkle formation are primarily driven by ultraviolet (UV)-induced oxidative stress and inflammation. Resveratrol (RSV) and nicotinamide (NCT) possess potent anti-aging properties but suffer from poor skin penetration. This study aimed to develop an advanced transdermal delivery system incorporating RSV/NCT-loaded cerosomes within poly(lactic-co-glycolic acid) (PLGA) microneedles to enhance skin permeation and anti-aging performance. Methods: RSV/NCT-loaded cerosomes were formulated using thin-film hydration of phosphatidylcholine, ceramides (III, IIIB, and VI), and poloxamer surfactants, subsequently optimized via a D-optimal mixture design. PLGA microneedles with optimized cerosomes were tested for their mechanical strength, penetration, drug loading, and release. Ex vivo permeation and in vivo evaluations were performed using a UVA-induced skin wrinkling model. Results: Optimized cerosomes exhibited high entrapment efficiency for RSV and NCT (91 ± 0.56% and 85 ± 0.56%, respectively), nanoscale size (195 ± 0.78 nm), low polydispersity (0.23 ± 0.01), and a negative zeta potential (−22 ± 0.45 mV). PLGA microneedles exhibited sufficient mechanical integrity and effective penetrability through Parafilm^® layers. Microneedle-loaded cerosomes enabled sustained drug release (approximately 65–70% over 48 h) and enhanced ex vivo permeation, approximately for NCT and RSV (1450 μg/cm² and 1000 μg/cm², respectively). In vivo investigations revealed improved skin appearance, restoration of epidermal thickness and collagen architecture, reduced levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, NLRP3), reduced oxidative stress biomarkers (GSH, GPx, MDA, SOD), and genetic upregulation of VEGF, TGF-β1, and β-Catenin. Conclusions: The RSV/NCT cerosome-encapsulated PLGA microneedle system offers a promising, minimally invasive approach with superior transdermal delivery, sustained efficacy, and significant anti-aging benefits. Full article

(This article belongs to the Special Issue Recent Advances in Drug Delivery Through Microneedle-Based Systems)

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30 pages, 11001 KB

Open AccessArticle

Cricket Oil-Based Sunscreen Systems: Formulation Design, Ultraviolet Protection Performance, and Preclinical Safety Evaluation

by Wantida Chaiyana, Guijun Liang, Jirasit Inthorn and Pratthana Chomchalao

Pharmaceutics 2026, 18(3), 325; https://doi.org/10.3390/pharmaceutics18030325 - 4 Mar 2026

Abstract

Background/Objectives: Insect oils have gained attention as sustainable cosmetic ingredients due to their bioactive lipid content. This study aimed to characterize oils from cricket and to evaluate their safety, biological activities, and performance in sunscreen formulations. Methods: Oils were extracted from Gryllus bimaculatus [...] Read more.

Background/Objectives: Insect oils have gained attention as sustainable cosmetic ingredients due to their bioactive lipid content. This study aimed to characterize oils from cricket and to evaluate their safety, biological activities, and performance in sunscreen formulations. Methods: Oils were extracted from Gryllus bimaculatus, Teleogryllus mitratus, and Acheta domesticus by cold pressing following hot-air drying. Fatty acid composition was determined using gas chromatography–mass spectrometry. Safety was assessed by cytotoxicity testing in normal human dermal fibroblasts (NHDF) and the hen’s egg chorioallantoic membrane (HET-CAM) assay. Antioxidant and anti-inflammatory activities were evaluated by intracellular reactive oxygen species (ROS) and nitric oxide (NO^•) assays. Based on biological performance, T. mitratus oil (TMO) was incorporated into sunscreen creams containing physical and chemical ultraviolet (UV) filters. Physical stability, viscosity, pH, sun protection factor (SPF), persistent pigment darkening/ultraviolet A protection factor (PPD/UVA-PF), and blue light protection were evaluated. Results: All cricket oils were non-cytotoxic to NHDF cells and were classified as non-irritating in the HET-CAM assay. TMO exhibited the strongest antioxidant activity, reducing intracellular ROS and significantly inhibiting NO^• production in lipopolysaccharide-stimulated cells. Only TMO showed measurable UVA protection (PPD/UVA-PF = 12.1, PA+++). Sunscreen creams formulated with TMO achieved higher photoprotective efficacy than olive oil-based creams, with SPF values up to 40.51 and PPD/UVA-PF up to 39.17. The inclusion of foundation pigments further increased SPF to 43.09 and enhanced blue light protection to 35.1%. Conclusions: TMO is a safe and effective multifunctional ingredient that enhances sunscreen performance and supports sustainable cosmetic formulation. Full article

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

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20 pages, 8263 KB

Open AccessArticle

Arecoline as a Novel Scaffold Targeting the ATAD2 Bromodomain for Cell Cycle Modulation

by Ting-Syuan Lin, Jingting Wan, Jingjin He, Shidong Cui, Yun Huang, Bojian Zhang, Hsi-Yuan Huang, Kexin Zhu, Jihang Chen, Tao Zhang, Shangfu Li, Liao Hu, Yongfei Wang, Hsien-Da Huang, Ping Tang and Yang-Chi-Dung Lin

Pharmaceutics 2026, 18(3), 324; https://doi.org/10.3390/pharmaceutics18030324 - 3 Mar 2026

Abstract

Background/Objectives: ATPase family AAA domain-containing protein 2 (ATAD2) is an oncogenic chromatin regulator that amplifies E2F/MYC transcriptional programs, yet direct modulators remain scarce. Arecoline (ARE), the primary alkaloid of the areca nut, is a known carcinogen but paradoxically exhibits context-dependent anti-proliferative activities. [...] Read more.

Background/Objectives: ATPase family AAA domain-containing protein 2 (ATAD2) is an oncogenic chromatin regulator that amplifies E2F/MYC transcriptional programs, yet direct modulators remain scarce. Arecoline (ARE), the primary alkaloid of the areca nut, is a known carcinogen but paradoxically exhibits context-dependent anti-proliferative activities. In this study, we resolve this paradox by defining ARE’s anti-cancer mechanism. Methods: Breast cancer cell proliferation and colony formation assays were performed to evaluate the anti-proliferative effects of ARE. Cell-cycle distribution was analyzed to determine phase-specific effects. Transcriptomic profiling was conducted to identify affected gene networks. An unbiased Cellular Thermal Shift Assay–Mass Spectrometry (CETSA-MS) screening was used to identify direct protein targets, followed by CETSA–Western blotting for validation. Finally, in silico structure-based design was applied to generate novel derivatives with improved predicted properties. Results: ARE suppressed breast cancer cell proliferation and colony formation by inducing G1/S phase arrest. Transcriptomic analysis revealed that this phenotype was driven by profound suppression of the E2F/Cell Cycle gene network. CETSA-MS identified ATAD2 through multi-omics convergence, as the 67 direct targets were collectively most significantly enriched in the E2F pathway. CETSA–Western blotting confirmed that ARE binds and thermally stabilizes ATAD2. Mechanistically, ARE engagement of ATAD2 led to downregulation of key downstream proteins, including MYC and Cyclin D1, directly linking target modulation to G1/S arrest. Structure-based design further yielded novel derivatives with predicted enhanced ATAD2 binding and substantially reduced toxicity. Conclusions: Together, these findings uncover ATAD2 as a druggable target of ARE, establish proof-of-concept for repurposing this scaffold, and provide a rational framework for developing safer ATAD2-targeted therapies. Full article

(This article belongs to the Special Issue Novel Approaches in the Search for Active Compounds in Drug Discovery and Development)

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28 pages, 18564 KB

Open AccessArticle

An Injectable Thermosensitive Chitosan/Astaxanthin/Ibuprofen Hydrogel Mitigates High-Voltage, Low-Current Electrical Burn Injury Through Inhibition of ROS–NF-κB Signaling-Mediated Inflammation

by Xiao Yang, Hui Wang, Wenjuan Zhang, Peng Gao, Xudong Yu, Weijia Qing, Ping Deng, Jingdian Li, Yan Luo, Li Tian, Jia Xie, Mengyan Chen, Zhengping Yu, Huifeng Pi, Ting Liu and Shenglin Luo

Pharmaceutics 2026, 18(3), 323; https://doi.org/10.3390/pharmaceutics18030323 - 3 Mar 2026

Abstract

Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive [...] Read more.

Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive chitosan hydrogel engineered with an antioxidant agent (astaxanthin) and an anti-inflammatory agent (ibuprofen) for the treatment of high-voltage, low-current electrical burn injuries. Methods: The proposed CS/AST/IBU hydrogel was prepared and its thermosensitivity was characterized. Subsequently, the hydrogel was injected into the wounds of male Sprague–Dawley (SD) rats subjected to electrical burn injury (20 kV, 3 mA). Finally, a series of experiments were performed to elucidate the dynamics of wound healing and the mechanisms by which the hydrogel promotes wound repair. Results: The injectable hydrogel, through its thermally responsive gelation effect at 37 °C, adapts to the complex irregularities of the wound surface. This facilitates the release of astaxanthin and ibuprofen throughout the wound, which collectively diminish the formation of reactive oxygen species and MDA. Furthermore, it enhances the synthesis of endogenous antioxidants such as SOD, CAT, and GSH; encourages collagen deposition; stimulates the development of dermal appendages; and fosters neovascularization. It interrupts the deleterious cycle of oxidative stress and inflammation mediated by the NF-κB signaling pathway, thereby suppressing the expression of pro-inflammatory markers such as TNF-α, CD11b, and IL-1β while upregulating CD163, an anti-inflammatory receptor. Conclusions: The use of this multipronged, contour-adaptive hydrogel represents an effective strategy for complex wound management and demonstrates broad therapeutic potential for superficial second-degree electrical burns caused by high-voltage, low-current discharge. Full article

(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)

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19 pages, 606 KB

Open AccessSystematic Review

Optimizing Vancomycin Dosing in Continuous Renal Replacement Therapy: A Systematic Review of Population Pharmacokinetic Studies in Adult Critically Ill Patients

by Nursel Sürmelioğlu, Sevgin Memili, Karel Allegaert and Nadir Yalçın

Pharmaceutics 2026, 18(3), 322; https://doi.org/10.3390/pharmaceutics18030322 - 3 Mar 2026

Abstract

Background: Vancomycin dosing during continuous renal replacement therapy (CRRT) remains challenging due to profound pharmacokinetic (PK) variability and lack of standardized guidance. Population pharmacokinetic (PopPK) models provide a quantitative framework to identify covariates affecting drug disposition and support individualized dosing. Methods: This systematic [...] Read more.

Background: Vancomycin dosing during continuous renal replacement therapy (CRRT) remains challenging due to profound pharmacokinetic (PK) variability and lack of standardized guidance. Population pharmacokinetic (PopPK) models provide a quantitative framework to identify covariates affecting drug disposition and support individualized dosing. Methods: This systematic review, registered in PROSPERO (CRD420250655157), comprehensively identified PopPK studies evaluating vancomycin in critically ill adults undergoing CRRT. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to 28 February 2025. Eligible studies reported PopPK analyses or simulations providing PK parameters and/or dosing recommendations. Data were extracted on study characteristics, CRRT settings, PK findings, and dose optimization strategies. In addition, covariates were categorized based on whether they were merely explored or statistically confirmed within the respective PopPK models, as commonly reported in similar pharmacometrics studies. Due to the methodological nature of population pharmacokinetic model development studies, no standardized risk-of-bias tool was applied; instead, a structured descriptive methodological appraisal was performed. Results were synthesized narratively given the heterogeneity in structural models, covariate strategies, and CRRT modalities. Results: Twelve PopPK studies published between 2013 and 2023 met the inclusion criteria. Considerable heterogeneity was observed across study designs, CRRT modalities, and dosing strategies. Reported vancomycin clearance ranged from 0.7 to 3.0 L/h, and volume of distribution from 0.8 L/kg to >100 L. Effluent rate consistently emerged as the primary determinant of clearance, while residual diuresis, albumin concentration, and vasopressor use acted as relevant covariates. Loading doses of 25–30 mg/kg (up to 35 mg/kg at high effluent rates) and effluent-adjusted maintenance regimens achieved therapeutic AUC24/MIC targets more consistently when supported by early and repeated therapeutic drug monitoring (TDM). Conclusions: Vancomycin PK during CRRT is highly variable and driven by effluent intensity and patient-specific factors. Fixed regimens are inadequate; individualized dosing guided by effluent flow, renal function, and TDM is essential for optimal exposure. Prospective, multicenter PopPK studies integrating pharmacodynamic targets and clinical outcomes are warranted to refine and validate CRRT-specific dosing strategies. Full article

(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)

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24 pages, 2820 KB

Open AccessArticle

Phosphatidylcholine-Polysorbate 20-Based Mixed Micelles: A New Option to Prevent Protein Aggregation?

by Johanna Weber, Tim Diederichs, Lukas Bollenbach, Patrick Garidel and Karsten Mäder

Pharmaceutics 2026, 18(3), 321; https://doi.org/10.3390/pharmaceutics18030321 - 2 Mar 2026

Abstract

Background/Objectives: Surfactants are commonly used to protect proteins from denaturation and particle formation, thereby ensuring the long-term stability of biopharmaceuticals. Polysorbates (PS) 20 and 80 are the most widely used surfactants in the pharmaceutical industry. However, alternative excipients such as poloxamers are currently [...] Read more.

Background/Objectives: Surfactants are commonly used to protect proteins from denaturation and particle formation, thereby ensuring the long-term stability of biopharmaceuticals. Polysorbates (PS) 20 and 80 are the most widely used surfactants in the pharmaceutical industry. However, alternative excipients such as poloxamers are currently under investigation. In this study, mixed micelles (MMs) composed of phospholipids (PL) and polysorbate 20 (PS20) were explored as a novel stabilisation strategy, aiming to reduce the PS content in protein formulations by partial substitution with PL. Despite their favourable properties, including thermodynamic stability and small particle size, MMs have seen limited application, and no reports exist on their use for stabilising antibody solutions. Results: In a first step, PS20/PL ratios were identified, which are advantageous to form stable MM solutions, followed by an optimization of the formulation process by introducing a second heating step using the direct dispersion method. Successful MM formation was confirmed via transmission and dynamic light scattering analyses at total surfactant concentrations of up to 20 mg·mL⁻¹ and 50 mg·mL⁻¹, with PL contents of 50% and up to 40%, respectively. These surfactant concentrations of up to 20 mg·mL⁻¹ and 50 mg·mL⁻¹ are substantially higher than the surfactant concentrations that are typically used in final biopharmaceutical formulations (0.01–2 mg·mL⁻¹). Consequently, the mixed micellar system enables operation even at concentrations substantially above practical formulation limits. In the ensuing study, the stabilizing potential of the PL/PS20 micellar system was appraised through agitation studies. Methods: In these studies, bovine serum albumin was employed as a model protein, while a monoclonal antibody was used as a candidate therapeutic molecule. Stability was assessed through visual inspection, turbidity measurements, particle analysis, and size-exclusion chromatography. Conclusions: A protective effect comparable to that of PS20 alone was observed for both model proteins, demonstrating for the first time that MMs can effectively stabilise biologics. Full article

(This article belongs to the Section Biologics and Biosimilars)

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15 pages, 2559 KB

Open AccessArticle

2,3,4-Trihydroxybenzophenone Disassembles Amyloid β Aggregates and Ameliorates Synaptic Deficits

by Eunbi Cho, Kumju Youn, Huiyoung Kwon, Ho Jung Bae, Minho Moon, Mira Jun and Dong Hyun Kim

Pharmaceutics 2026, 18(3), 320; https://doi.org/10.3390/pharmaceutics18030320 - 2 Mar 2026

Abstract

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which no disease-modifying therapy that halts or substantially slows disease progression is currently available. Although antibody therapies targeting amyloid β (Aβ) have recently received FDA approval, their high cost, limited efficacy, and [...] Read more.

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which no disease-modifying therapy that halts or substantially slows disease progression is currently available. Although antibody therapies targeting amyloid β (Aβ) have recently received FDA approval, their high cost, limited efficacy, and potential adverse effects highlight the need for alternative solutions. Therefore, the development of low-molecular-weight compounds capable of reducing toxic Aβ aggregates is of considerable interest. In this study, we investigated the effects of 2,3,4-trihydroxybenzophenone (THB) on the inhibition and disassembly of Aβ_1–42 aggregates through in vitro and in vivo experiments. Methods: In vitro assays were performed to evaluate the effects of THB on Aβ_1–42 aggregation and fibril disassembly. Cell viability assays and hippocampal slice electrophysiology were conducted to assess neurotoxicity and synaptic function. In vivo effects were examined in Aβ_1–42 aggregate-injected mice and in 5 Familial AD mutations (5XFAD) mice using behavioral, histological, and electrophysiological analyses. Results: THB inhibited Aβ_1–42 aggregation in a concentration-dependent manner and promoted the disassembly of preformed fibrils. THB attenuated Aβ_1–42-induced Neuro2a cell death and restored Aβ_1–42 aggregate-associated long-term potentiation (LTP) deficits in hippocampal slices. In Aβ_1–42 aggregate-injected and 5XFAD mice, THB reduced amyloid pathology and neuroinflammatory markers and improved synaptic function and memory performance. Conclusions: These findings suggest that THB modulates pathogenic Aβ_1–42 assemblies and provides a structural basis for the development of small-molecule modulators of Aβ_1–42 aggregation with potential preventive or disease-modifying applications in AD. Full article

(This article belongs to the Special Issue Targeted Therapies and Drug Delivery for Neurodegenerative Diseases)

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15 pages, 4873 KB

Open AccessFeature PaperArticle

Repurposing Conventional Magnetic Functional Agents: A Novel Strategy for Long-Acting, Safe, Magnetically Mediated Precision Oncology

by Zihan Lv, Yue Wang, Yimin Su, Albert Yu, Rouye He, Zhongjian Xie and Yao Zhu

Pharmaceutics 2026, 18(3), 319; https://doi.org/10.3390/pharmaceutics18030319 - 2 Mar 2026

Abstract

Background: Although conventional magnetic functional agents provide a material basis for magnetically mediated tumor therapy, they have long been restricted by the application framework of magnetic resonance imaging (MRI) or magnetic thermal ablation. Methods: This study proposed a repurposing strategy of [...] Read more.

Background: Although conventional magnetic functional agents provide a material basis for magnetically mediated tumor therapy, they have long been restricted by the application framework of magnetic resonance imaging (MRI) or magnetic thermal ablation. Methods: This study proposed a repurposing strategy of two mature magnetic functional agents, Fe₃O₄ nanoparticles and gadopentetic acid (GA), by applying their unique magnetic response properties to enhance magnetic field therapy for glioma. Results: Both magnetic materials, when combined with an external magnetic field (MF), showed a synergistic effect to amplify the therapeutic effect. In the CT-2A glioma-bearing mice model, it resulted in marked suppression of tumor growth, with the growth inhibition (TGI) rate increasing from ~27% after MF therapy alone to 64% and 55% after the Fe₃O₄- and GA-potentiated MF therapy, respectively. It was proposed that the MF effect on impairing tumor angiogenesis was enhanced, as evidenced by significant reductions in CD31 expression and microvessel density. It disrupted nutrient supply to the tumor, augmenting the tumor suppression efficiency. The reduced infiltration of CD4+ and CD8+ T cells into tumors further confirmed the effective blockade of tumor perfusion. Conclusions: This study established a new paradigm of conventional magnetic materials to enhance the non-thermal physical effects and biological regulatory effects of magnetic field for glioma therapy, instead of only as the imaging agents or magnetic hyperthermia agents. Full article

(This article belongs to the Special Issue Magnetic Materials for Biomedical Applications)

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42 pages, 1112 KB

Open AccessReview

Targeting Intratumoral Bacteria for Enhanced Tumor Suppression with Nano-Based Therapeutics: A Scoping Review

by Tianxiang Yi, Zhiyou Dong and Sharon Shui Yee Leung

Pharmaceutics 2026, 18(3), 318; https://doi.org/10.3390/pharmaceutics18030318 - 2 Mar 2026

Abstract

Background: Increasing evidence identifies intratumoral bacteria as key modulators of tumor progression, chemoresistance, and immunosuppression, presenting major obstacles to conventional cancer therapies. Recent advances in nanotechnology have enabled new strategies for selective targeting bacteria within the tumor microenvironment, potentially improving anticancer efficacy. [...] Read more.

Background: Increasing evidence identifies intratumoral bacteria as key modulators of tumor progression, chemoresistance, and immunosuppression, presenting major obstacles to conventional cancer therapies. Recent advances in nanotechnology have enabled new strategies for selective targeting bacteria within the tumor microenvironment, potentially improving anticancer efficacy. Methods: A scoping review was conducted to outline the current landscape of nano-based therapeutic approaches aimed at the simultaneous elimination of intratumoral bacteria and cancer. Preclinical research publications involving in vivo antitumor efficacy evaluations were retrieved from three databases, Web of Science, PubMed, and Scopus, using the key words “(kill* OR eradicate* OR eliminate*) AND intratumoral AND (bacteria OR infection)”. Key information from the eligible studies was extracted and analyzed. Results: The diversity of bacterial species, cancer models, and evaluation methodologies employed in these preclinical studies were summarized, followed by critical examination of the design principles, therapeutic outcomes, and translational challenges of various nanomedicine platforms, including passive and active targeting drug delivery systems, phototherapy, phage therapy, and emerging modalities. Nano-based therapeutics functionalized with both antibacterial and anticancer properties were shown to effectively overcome bacteria-induced treatment resistance. Conclusions: Targeting intratumoral bacteria may significantly enhance the efficacy of existing treatments and contribute to the evolution of precision oncology. The insights gained from this review are expected to guide future systematic reviews and inform research directions in the development of dual-functional nanomedicines for cancer therapy. Full article

(This article belongs to the Special Issue Nanotechnology in Antibacterial Drug Delivery)

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21 pages, 2523 KB

Open AccessArticle

Extracellular Vesicles from Osteotropic Triple-Negative Breast Cancer Cells Transfer miRNAs to Bone Cells Reducing Collagen Expression and Bone Matrix Mineralisation

by Luca Giacchi, Argia Ucci, Elisa Pucci, Loreto Lancia, Fanny Pulcini, Simona Delle Monache, Nadia Rucci and Marco Ponzetti

Pharmaceutics 2026, 18(3), 317; https://doi.org/10.3390/pharmaceutics18030317 - 2 Mar 2026

Abstract

Background/Objectives: Bone metastases are a common complication of breast cancer. In our previous study, we reported that extracellular vesicles released by osteotropic human (MDA-MB-231) and murine (4T1) breast cancer cells disrupt bone homeostasis by enhancing osteoclast differentiation and impairing osteoblast function. Based [...] Read more.

Background/Objectives: Bone metastases are a common complication of breast cancer. In our previous study, we reported that extracellular vesicles released by osteotropic human (MDA-MB-231) and murine (4T1) breast cancer cells disrupt bone homeostasis by enhancing osteoclast differentiation and impairing osteoblast function. Based on these findings, we investigated whether microRNAs contained within tumour-derived EVs could mediate these bone-altering effects. Methods: MDA-MB-231- and 4T1-EVs were tagged with the RNA-specific fluorophore SYTORNA and employed to treat mouse primary bone marrow macrophages (BMMs) and osteoblasts (OBs). We also performed RNAseq on MDA-MB-231- and 4T1-EVs to assess their miRNAs content. Finally, we evaluated the effect of selected miRNA-mimics on OBs, BMMs and HUVEC cells. Results: Fluorescence microscopy demonstrated EV-RNAs shuttling to recipient cells, while RNA sequencing on MDA-MB-231- and 4T1-EVs revealed that, of the top 20 expressed miRNAs, 10 were common. Among them, we first focused on the following four: miR-26a-5p, miR-24-3p, miR-29a-3p, and miR-29b-3p, which were linked to bone biology. We confirmed their presence in MDA-MB-231-/4T1-EVs by qPCR. Then, we evaluated their EV-mediated shuttling to BMMs and OBs using affinity tags. Among all the conditions tested, miR-29a and miR-29b were the best-shuttled miRNAs, with efficiency between 50–100% in both OBs and BMMs, both for MDA-MB-231- and 4T1-EVs. Finally, to test whether miR-29a and miR-29b could have a functional role in bone cells, OBs were transfected with miR-29a and 29b-mimics, discovering that this treatment reduced collagen1α1 and 1α2 mRNA as well as the OBs’ mineralisation ability, while the same miRNA mimics were found to have no effect on osteoclastogenesis or on in vitro angiogenesis. Conclusions: MDA-MB-231- and 4T1-EVs shuttle miRNAs to bone cells, which likely contributes to OBs’ activity impairment. Full article

(This article belongs to the Special Issue Extracellular Vesicles for Targeted Delivery)

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18 pages, 2447 KB

Open AccessArticle

The Protective Effect of Quercetin on Hydrogen Peroxide-Induced Oxidative Damage in Caco-2 Cells Is Enhanced by Its Loading in Mesoporous Silica Nanoparticles

by Alexis Matadamas-Ortiz, Prospero Di Pierro, Angela Sorrentino, Ivana Caputo, Gaetana Paolella, Antonio Montefusco and Carlos Regalado-González

Pharmaceutics 2026, 18(3), 316; https://doi.org/10.3390/pharmaceutics18030316 - 1 Mar 2026

Abstract

Background: Quercetin (Q) can reduce cellular oxidative stress, though it is susceptible to degradation in physiological conditions. Through adsorption and protection of Q, mesoporous silica nanoparticles (MSNs) could enhance its bioactivity. This work aimed to determine the effect of Q loading in MSN [...] Read more.

Background: Quercetin (Q) can reduce cellular oxidative stress, though it is susceptible to degradation in physiological conditions. Through adsorption and protection of Q, mesoporous silica nanoparticles (MSNs) could enhance its bioactivity. This work aimed to determine the effect of Q loading in MSN and in its aminated (A-MSN), carboxylated (C-MSN) or thiolated (T-MSN) derivatives on its Caco-2-cytoprotective effect against H₂O₂-induced oxidative stress. Methods: The mesoporous silica materials were characterized (FT-IR, ζ-potential, TGA), and their cytotoxicity was assessed; then, they were loaded with Q and incubated with Caco-2 cells prior to oxidative stress induction, and the cytoprotective effect was evaluated through measurement of cell viability. Results: None of the nanoparticles showed toxicity to Caco-2 cells. A-MSN showed the highest Q loading capacity (5.26% ± 0.06%), due to hydrogen-bonding interactions. C-MSN clearly enhanced the Q cellular uptake compared to the other nanoparticles. Oxidative stress decreased Caco-2 cell viability, which was prevented by 100 µM free Q after 18 h incubation. In contrast, higher cell viability than in non-stressed cells was observed with the same Q concentration loaded across all nanoparticle types. Conclusions: Despite the high instability of free quercetin under cell culture conditions, it exerted a time-dependent cytoprotective effect against H₂O₂-induced oxidative stress that was enhanced upon loading into nanoparticles. Prior release of the Q molecule in the medium is ineffective, and the presence of the loaded material is required. Full article

(This article belongs to the Special Issue Advances in Bioactive Compounds and Nanotechnology: Sustainable Approaches for Pharmaceutical Applications)

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21 pages, 2515 KB

Open AccessArticle

Dose Recommendation of Remimazolam Tosilate for General Anesthesia in Children and Adolescents: Synergistic Combination of PopPK and PBPK Approaches

by Qiong-Yue Liang, Hui-Hui Hu, Nassim Djebli, Yuan-Yuan Huang and Hao Jiang

Pharmaceutics 2026, 18(3), 315; https://doi.org/10.3390/pharmaceutics18030315 - 1 Mar 2026

Abstract

Background: Remimazolam tosilate is a novel, ultra-short-acting benzodiazepine. To address the unmet clinical need for safe and controllable general anesthetic options in children and adolescents, both top-down (i.e., population pharmacokinetics—PopPK) and bottom-up (i.e., physiologically based PK—PBPK) modeling approaches were combined to leverage their [...] Read more.

Background: Remimazolam tosilate is a novel, ultra-short-acting benzodiazepine. To address the unmet clinical need for safe and controllable general anesthetic options in children and adolescents, both top-down (i.e., population pharmacokinetics—PopPK) and bottom-up (i.e., physiologically based PK—PBPK) modeling approaches were combined to leverage their respective strengths for dose selection in children and adolescents aged 3–18 years. Methods: Pooled PK data from adult studies were used to develop and verify the adult PopPK and PBPK models. The PopPK model included allometric scaling to describe body weight effects, while the PBPK modeling incorporated the age-dependent physiological and metabolic ontogeny. Potential covariates and intrinsic factors influencing remimazolam exposure were assessed. Both models were then applied to simulate PK and derive exposure metrics in 3–18-year-old children and adolescents. The predictions from both approaches were used to support pediatric dose selection using an adult-matching exposure approach. Results: The PopPK and PBPK model simulations yielded consistent exposure predictions and converged on the same recommended dosing regimens for the pediatric population, providing mutual confirmation of model reliability. Both models indicated that the proposed regimens of remimazolam would achieve systemic exposures in children and adolescents (3–18 years) comparable to those in adults receiving an induction dose of 0.3 mg/kg followed by maintenance infusions of 1.0 or 3.0 mg/kg/h. Two pediatric dosing regimens were recommended: 1. Lower dose group: induction 0.2 mg/kg, initial maintenance 1.0 mg/kg/h, titratable as needed, with a maximum rate of 3.0 mg/kg/h (up to 4.0 mg/kg/h for individuals ≤ 30 kg). 2. Higher dose group: induction 0.3 mg/kg, initial maintenance 2.0 mg/kg/h, titratable as needed, with a maximum rate of 3.0 mg/kg/h (up to 4.0 mg/kg/h for individuals ≤ 30 kg). The model-informed dosing regimens have received regulatory approval from the Center for Drug Evaluation (CDE) in China and are currently being evaluated in an ongoing clinical trial. Conclusions: The integrated PopPK–PBPK approach supports evidence-based dosing recommendations of remimazolam for general anesthesia in children and adolescents aged 3–18 years and provides a reference for dose selection in future clinical studies. Full article

(This article belongs to the Special Issue Recent Advances in Physiologically Based Pharmacokinetics)

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26 pages, 65276 KB

Open AccessArticle

Matrix-Dependent Stability and Antibacterial Efficacy of Silver Nanoparticles: A Comparative Study of Anionic Carbopol vs. Non-Ionic Pluronic Hydrogels

by Amane A. Alaroud, Suhad Bani Melhim, Fahmy Banat, Arshiya Husaini, Suha M. Abudoleh, Mahmoud Y. Alkawareek and Alaaldin M. Alkilany

Pharmaceutics 2026, 18(3), 314; https://doi.org/10.3390/pharmaceutics18030314 - 1 Mar 2026

Abstract

Background/Objectives: Hydrogels infused with silver nanoparticles (AgNPs) are widely used for their antibacterial properties, yet their stability, specifically upon contact with solid growth media (agar), remains poorly explored. This study compared two hydrogel matrices, anionic Carbopol 934 and non-ionic Pluronic F127, incorporating AgNPs [...] Read more.

Background/Objectives: Hydrogels infused with silver nanoparticles (AgNPs) are widely used for their antibacterial properties, yet their stability, specifically upon contact with solid growth media (agar), remains poorly explored. This study compared two hydrogel matrices, anionic Carbopol 934 and non-ionic Pluronic F127, incorporating AgNPs of three different sizes. The evaluation focused on colloidal stability and antibacterial efficacy against Gram-positive and Gram-negative bacteria. Methods: In this study AgNPs (~20, ~55, and ~65 nm) were synthesised via a wet-chemical method and characterised by UV–visible spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). AgNPs were incorporated into Carbopol 934 and Pluronic F127 hydrogel matrices. Colloidal stability was monitored over four months of storage and upon contact with tryptic soy agar (TSA). Antibacterial activity was assessed using agar diffusion assays. Results: Showed that both hydrogel systems maintained AgNP stability during storage, comparable to aqueous suspensions. However, upon contact with TSA, aggregation of Carbopol–AgNP hydrogels occurred, whereas Pluronic–AgNP hydrogels remained stable. In antibacterial assays, both hydrogels produced larger zones of inhibition (ZOI) than AgNP suspensions against Gram-negative bacteria (E. coli, P. aeruginosa), with Carbopol–AgNP hydrogels demonstrating superior efficacy in an inverse size-dependent manner. Against Gram-positive bacteria (S. aureus, S. epidermidis), Pluronic–AgNP hydrogels initially showed larger ZOIs due to the polymer’s intrinsic antibacterial activity. However, after correcting for this baseline, Carbopol–AgNP hydrogels exhibited superior net efficacy, with S. epidermidis showing greater susceptibility than S. aureus. Conclusions: While both Carbopol 934 and Pluronic F127 stabilise AgNPs during storage, the matrix type significantly influences behaviour at the biological interface. Carbopol–AgNP hydrogels aggregate upon contact with solid agar yet deliver superior, size-dependent antibacterial activity compared to the stable but less potent Pluronic systems. Full article

(This article belongs to the Section Nanomedicine and Nanotechnology)

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