Previous Issue
Volume 17, June
 
 

Pharmaceutics, Volume 17, Issue 7 (July 2025) – 107 articles

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Select all
Export citation of selected articles as:
23 pages, 2078 KiB  
Article
Antioxidant and Anti-Inflammatory Activities of Thai Traditional Hand and Foot Soaking Formulary and Its Bioactive Compounds
by Jaenjira Angsusing, Weerasak Samee, Supachoke Mangmool, Usma Dortae, Pranot Keawthip, Surakameth Mahasirimongkol, Somsak Kreechai, Kulthanit Wanaratna, Chuda Chittasupho and Nopparut Toolmal
Pharmaceutics 2025, 17(7), 907; https://doi.org/10.3390/pharmaceutics17070907 (registering DOI) - 13 Jul 2025
Abstract
Background/Objectives: This study aimed to investigate the antioxidant and anti-inflammatory properties of a Hand and Foot Soaking Formulary composed of ten medicinal plants, with curcumin as a major bioactive marker, to provide scientific validation for its traditional use. Methods: The formulation was [...] Read more.
Background/Objectives: This study aimed to investigate the antioxidant and anti-inflammatory properties of a Hand and Foot Soaking Formulary composed of ten medicinal plants, with curcumin as a major bioactive marker, to provide scientific validation for its traditional use. Methods: The formulation was evaluated for total phenolic and flavonoid contents, with curcumin quantified using HPLC. Antioxidant activity was assessed using DPPH, ABTS, and FRAP assays. Cytotoxicity was evaluated in RAW264.7 cells using the MTT assay. Anti-inflammatory activity was determined by measuring nitric oxide (NO), PGE2, TNF-α, IL-1β, and IL-6 levels in LPS-stimulated RAW264.7 macrophages using ELISA. Results: The Hand and Foot Soaking Formulary exhibited promising antioxidant and anti-inflammatory properties, consistent with its traditional use. Phytochemical analysis confirmed the presence of bioactive compounds, with measurable levels of total phenolics, flavonoids, and significant curcumin content. Antioxidant activity was demonstrated through free radical scavenging and ferric-reducing assays, while cytotoxicity testing in RAW264.7 macrophages indicated low toxicity (IC50 = 48.61 ± 3.80 µg/mL). The formulary significantly reduced LPS-induced nitric oxide, PGE2, TNF-α, IL-1β, and IL-6 production. These effects were comparable to turmeric extract and curcumin, though curcumin displayed higher potency. Conclusions: The Hand and Foot Soaking Formulary demonstrates antioxidant and anti-inflammatory properties in vitro, supporting its traditional use. Its polyherbal composition may offer synergistic effects and holds promise as a safe, natural topical remedy. Full article
(This article belongs to the Special Issue Natural Compounds in Drug Delivery Systems)
Show Figures

Figure 1

15 pages, 3800 KiB  
Article
A Novel Temozolomide-Myricetin Drug-Drug Cocrystal: Preparation, Characterization, Property Evaluations
by Hai-Xin Qin, Jie Wang, Jia-Hui Peng, Xia-Lin Dai, Cai-Wen Li, Tong-Bu Lu and Jia-Mei Chen
Pharmaceutics 2025, 17(7), 906; https://doi.org/10.3390/pharmaceutics17070906 (registering DOI) - 13 Jul 2025
Abstract
Objectives: Drug-drug cocrystals with improved properties can be used to facilitate the development of synergistic therapeutic combinations. The goal of the present study is to obtain novel drug-drug cocrystals involving two anti-glioma agents, temozolomide (TMZ) and myricetin (MYR). Methods: The novel [...] Read more.
Objectives: Drug-drug cocrystals with improved properties can be used to facilitate the development of synergistic therapeutic combinations. The goal of the present study is to obtain novel drug-drug cocrystals involving two anti-glioma agents, temozolomide (TMZ) and myricetin (MYR). Methods: The novel TMZ-MYR cocrystal was prepared via slurry and solvent evaporation techniques and characterized by X-ray diffraction, thermal analysis, infrared spectroscopy, and dynamic vapor sorption measurements. The stability, compaction, and dissolution properties were also evaluated. Results: Crystal structure analysis revealed that the cocrystal lattice contains two TMZ molecules, one MYR molecule, and four water molecules, which are linked by hydrogen bonding interactions to produce a three-dimensional network. The cocrystal hydrate exhibited favorable stability and tabletability compared to pure TMZ. A dissolution study showed that the maximum solubility of MYR in the cocrystal (176.4 μg/mL) was approximately 6.6 times higher than that of pure MYR·H2O (26.9 μg/mL), while the solubility of TMZ from the cocrystal (786.7 µg/mL) was remarkably lower than that of pure TMZ (7519.8 µg/mL). The solubility difference between MYR and TMZ was diminished from ~280-fold to ~4.5-fold. Conclusions: Overall, the TMZ-MYR cocrystal optimizes the stability and tabletability of TMZ and the dissolution behavior of both drugs, offering a promising approach for synergistic anti-glioma therapy with improved clinical potential. Full article
Show Figures

Graphical abstract

22 pages, 3848 KiB  
Article
Electroporation- and Liposome-Mediated Co-Transfection of Single and Multiple Plasmids
by Uday K. Baliga, Anthony Gurunian, Aitor Nogales, Luis Martinez-Sobrido and David A. Dean
Pharmaceutics 2025, 17(7), 905; https://doi.org/10.3390/pharmaceutics17070905 (registering DOI) - 12 Jul 2025
Abstract
Background/Objectives: Co-transfection of multiple DNAs is important to many research and therapeutic applications. While the optimization of single plasmid transfection is common, multiple plasmid co-transfection analyses are limited. Here we provide empirical data regarding multiple plasmid co-transfection while altering the number of species [...] Read more.
Background/Objectives: Co-transfection of multiple DNAs is important to many research and therapeutic applications. While the optimization of single plasmid transfection is common, multiple plasmid co-transfection analyses are limited. Here we provide empirical data regarding multiple plasmid co-transfection while altering the number of species of plasmids transfected (up to four different plasmids) and the amount of plasmids/cell using the two most common non-viral techniques, electroporation and lipofection. Methods: A549 human lung epithelial cells were transfected using lipofectamine 2000 or electroporation with combinations of plasmids, each expressing one of four different fluorescent proteins from the CAGG promoter. Twenty-four hours later, cells were analyzed by spectral flow cytometry to determine the number of cells expressing each fluorescent protein and the amount of fluorescent signal of each protein in a cell. Results and Conclusions: For electroporation, while the fraction of cells expressing plasmids increased with increasing amounts of DNA, increasing the number of plasmid species did not alter the fraction of expressing cells and had no effect on levels of expression in individual cells. By contrast, for lipofection, the fraction of cells expressing plasmids was not affected by the amount of DNA added but both the fraction of cells expressing and the level of protein produced in these cells decreased for each plasmid species as the number of delivered species increased. For both lipofection and electroporation after single plasmid transfection, the expressing cells had greater numbers of plasmid copies/cell than non-expressing cells. Multiple plasmid lipofection resulted in more plasmid copies/cell in co-expressing than non-expressing cells. Multiple plasmid electroporation was the inverse of this with fewer plasmid copies/cell in co-expressing than non-expressing cells. Full article
(This article belongs to the Special Issue Electroporation-Mediated Drug and Gene Delivery)
Show Figures

Figure 1

17 pages, 2505 KiB  
Article
Distinct In Vitro Effects of Liposomal and Nanostructured Lipid Nanoformulations with Entrapped Acidic and Neutral Doxorubicin on B16-F10 Melanoma and Walker 256 Carcinoma Cells
by Roxana Pop, Mădălina Nistor, Carmen Socaciu, Mihai Cenariu, Flaviu Tăbăran, Dumitriţa Rugină, Adela Pintea and Mihai Adrian Socaciu
Pharmaceutics 2025, 17(7), 904; https://doi.org/10.3390/pharmaceutics17070904 (registering DOI) - 12 Jul 2025
Abstract
Background: Liposomes and, more recently, structured nanolipid particles have demonstrated effectiveness as carriers for delivering hydrophilic or lipophilic anticancer agents, enhancing their biocompatibility, bioavailability, and sustained release to target cells. Objective: Herein, four doxorubicin formulations—comprising either the acidic or neutral form—were encapsulated into [...] Read more.
Background: Liposomes and, more recently, structured nanolipid particles have demonstrated effectiveness as carriers for delivering hydrophilic or lipophilic anticancer agents, enhancing their biocompatibility, bioavailability, and sustained release to target cells. Objective: Herein, four doxorubicin formulations—comprising either the acidic or neutral form—were encapsulated into liposomes (Lipo) or nanostructured lipid carriers (NLCs) and characterized in terms of size, entrapment efficiency, morphology, and effects on two cancer cell lines (melanoma B16-F10 and breast carcinoma Walker 256 cells). Methods and Results: While liposomal formulations containing acidic doxorubicin displayed IC50 values ranging from 1.33 to 0.37 µM, NLC-based formulations, particularly NLC-Doxo@Ac, demonstrated enhanced cytotoxicity with IC50 values as low as 0.58 µM. Neutral Doxorubicin demonstrated lower cytotoxicity in both the nanoformulations and cell lines. Differences were also observed in their internalization patterns, cell-cycle impact, and apoptotic/necrotic effects. Compared to liposomes, NLCs exhibited distinct internalization patterns and induced stronger cell-cycle arrest and necrosis, especially in melanoma cells. Notably, NLC-Doxo@Ac outperformed liposomal counterparts in melanoma cells, while liposomal formulations showed slightly higher efficacy in Walker cells. Early and late apoptosis were more pronounced in Walker cells, whereas necrosis was more prominent in melanoma B16-F10 cells, particularly with the nanolipid formulations. Conclusions: These results correlated positively with cell-cycle measurements, highlighting the potential of NLCs as an alternative to liposomes for the delivery of neutral or acidic doxorubicin, particularly in tumor types that respond poorly to conventional formulations. Full article
46 pages, 2676 KiB  
Review
Trends and Commonalities of Approved and Late Clinical-Phase RNA Therapeutics
by Maxime Tufeu, Christophe Herkenne and Yogeshvar N. Kalia
Pharmaceutics 2025, 17(7), 903; https://doi.org/10.3390/pharmaceutics17070903 (registering DOI) - 12 Jul 2025
Abstract
Background/Objectives: After many years of research and the successful development of therapeutic products by a few industrial actors, the COVID-19 vaccines brought messenger RNAs, as well as other nucleic acid modalities, such as antisense oligonucleotides, small interfering RNA, and aptamers, into the spotlight, [...] Read more.
Background/Objectives: After many years of research and the successful development of therapeutic products by a few industrial actors, the COVID-19 vaccines brought messenger RNAs, as well as other nucleic acid modalities, such as antisense oligonucleotides, small interfering RNA, and aptamers, into the spotlight, eliciting renewed interest from both academia and industry. However, owing to their structure, relative “fragility”, and the (usually) intracellular site of action, the delivery of these therapeutics has frequently proven to be a key limitation, especially when considering endosomal escape, which still needs to be overcome. Methods: By compiling delivery-related data on approved and late clinical-phase ribonucleic acid therapeutics, this review aims to assess the delivery strategies that have proven to be successful or are emerging, as well as areas where more research is needed. Results: In very specific cases, some strategies appeared to be quite effective, such as the N-acetylgalactosamine moiety in the case of liver delivery. Surprisingly, it also appears that for some modalities, efforts in molecular design have led to more “drug-like” properties, enablingthe administration of naked nucleic acids, without any form of encapsulation. This appears to be especially true when local administration, i.e., by injection, is possible, as this provides de facto targeting and a high local concentration, which can compensate for the small proportion of nucleic acids that reach the cytoplasm. Conclusions: Nucleic acid-based therapeutics have come a long way in terms of their physicochemical properties. However, due to their inherent limitations, targeting appears to be crucial for their efficacy, even more so than for traditional pharmaceutical modalities. Full article
Show Figures

Graphical abstract

15 pages, 3148 KiB  
Article
Development of an Antimicrobial Coating Film for Denture Lining Materials
by Kumiko Yoshihara, Takeru Kameyama, Noriyuki Nagaoka, Yukinori Maruo, Yasuhiro Yoshida, Bart Van Meerbeek and Takumi Okihara
Pharmaceutics 2025, 17(7), 902; https://doi.org/10.3390/pharmaceutics17070902 (registering DOI) - 11 Jul 2025
Abstract
Background/Objectives: Denture hygiene is essential for the prevention of oral candidiasis, a condition frequently associated with Candida albicans colonization on denture surfaces. Cetylpyridinium chloride (CPC)-loaded montmorillonite (CPC-Mont) has demonstrated antimicrobial efficacy in tissue conditioners and demonstrates potential for use in antimicrobial coatings. In [...] Read more.
Background/Objectives: Denture hygiene is essential for the prevention of oral candidiasis, a condition frequently associated with Candida albicans colonization on denture surfaces. Cetylpyridinium chloride (CPC)-loaded montmorillonite (CPC-Mont) has demonstrated antimicrobial efficacy in tissue conditioners and demonstrates potential for use in antimicrobial coatings. In this study, we aimed to develop and characterize CPC-Mont-containing coating films for dentures, focusing on their physicochemical behaviors and antifungal efficacies. Methods: CPC was intercalated into sodium-type montmorillonite to prepare CPC-Mont; thereafter, films containing CPC-Mont were fabricated using emulsions of different polymer types (nonionic, cationic, and anionic). CPC loading, release, and recharging behaviors were assessed at various temperatures, and activation energies were calculated using Arrhenius plots. Antimicrobial efficacy against Candida albicans was evaluated for each film using standard microbial assays. Results: X-ray diffraction analysis confirmed the expansion of montmorillonite interlayer spacing by approximately 3 nm upon CPC loading. CPC-Mont showed temperature-dependent release and recharging behavior, with higher temperatures enhancing its performance. The activation energy for CPC release was 38 kJ/mol, while that for recharging was 26 kJ/mol. Nonionic emulsions supported uniform CPC-Mont dispersion and successful film formation, while cationic and anionic emulsions did not. CPC-Mont-containing coatings maintained antimicrobial activity against Candida albicans on dentures. Conclusions: CPC-Mont can be effectively incorporated into nonionic emulsion-based films to create antimicrobial coatings for denture applications. The films exhibited temperature-responsive, reversible CPC release and recharging behaviors, while maintaining antifungal efficacy, findings which suggest the potential utility of CPC-Mont-containing films as a practical strategy to prevent denture-related candidiasis. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
Show Figures

Figure 1

16 pages, 999 KiB  
Article
Insulin-Enhanced Biological Visual Rehabilitation in Neuroretinal Degeneration Patients Treated with Mesenchymal Cell-Derived Secretome
by Paolo Giuseppe Limoli, Celeste Limoli and Marcella Nebbioso
Pharmaceutics 2025, 17(7), 901; https://doi.org/10.3390/pharmaceutics17070901 - 11 Jul 2025
Abstract
Objectives: Insulin plays a crucial role in neuronal survival and oxidative stress modulation, making it a potential therapeutic target. This study investigates the effects of insulin in combination with a mesenchymal cell-derived secretome in patients with degenerative neuroretinal diseases. Methods: Sixty-four patients with [...] Read more.
Objectives: Insulin plays a crucial role in neuronal survival and oxidative stress modulation, making it a potential therapeutic target. This study investigates the effects of insulin in combination with a mesenchymal cell-derived secretome in patients with degenerative neuroretinal diseases. Methods: Sixty-four patients with severe neuroretinal diseases who had previously undergone the Limoli Retinal Restoration Technique (LRRT) were included in this longitudinal study and divided into groups: group 1 received a single injection of 5 units of insulin lispro into the suprachoroidal space of the worse-seeing eye; group 2 received insulin injection in the better-seeing eye. Retinal function was assessed using microperimetry (MY) before and after treatment (approximately 1 year for eye drops). Group 3 consisted of patients who demonstrated improvement in MY after insulin injection. These patients continued treatment with daily insulin eye drops. Results: In group 1, insulin-treated eyes showed a significant increase in retinal sensitivity from 10.09 dB to 10.75 dB (p = 0.0067), while untreated eyes declined from 12.35 dB to 11.92 dB (p = 0.0448). In group 2, insulin-treated eyes improved from 10.8 dB to 11.63 dB (p = 0.05), whereas untreated eyes exhibited a decline from 8.68 dB to 8.50 dB (p = 0.6771). In group 3, patients using insulin eye drops showed a stabilization or mild increase in retinal sensitivity, from 11.39 dB to 11.73 dB (p = 0.231). Conclusions: The addition of insulin in patients previously treated with the LRRT was associated with improved sensitivity and a stabilizing effect on neuroretinal function. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Ocular Diseases)
Show Figures

Figure 1

22 pages, 13140 KiB  
Article
Development and Characterization of Optimized Drug-Loaded Niosomes for Delivery of 5-FU and Irinotecan
by Kafilat O. Agbaje, Simeon K. Adesina and Amusa S. Adebayo
Pharmaceutics 2025, 17(7), 900; https://doi.org/10.3390/pharmaceutics17070900 - 11 Jul 2025
Abstract
Background/Objectives: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the [...] Read more.
Background/Objectives: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the synergism of 5-FU-IRT has provided incremental improvements in clinical outcomes, the short elimination half-life and off-target binding to healthy cells remain significant challenges. We postulated that nanoencapsulation of a combination of 5-FU and IRT in niosomes would prolong the drugs’ half-lives, while over-encapsulation lyophilized powder in Targit® oral capsules would passively the CRC microenvironment and avoid extensive systemic distribution. Methods: Ranges of formulation and process variables were input into design of experiment (DOE Fusion One) software, to generate screening experiments. Niosomes were prepared using the thin-film hydration method and characterized by size, the polydispersity index (PDI), morphology and intrastructure, and drug loading. Blank niosomes ranged in size from 215 nm to 257 nm. Results: After loading with the 5-FU-IRT combination, the niosomes averaged 251 ± 2.20 nm with a mean PDI of 0.293 ± 0.01. The surfactant-to-cholesterol ratio significantly influenced the niosome size and the PDI. The hydrophilic 5-FU exhibited superior loading compared to the lipophilic IRT molecules, which probably competed with other lipophilic niosome components in niosomes’ palisade layers. In vitro dissolution in biorelevant media showed delayed release until lower intestinal region (IRT) or colonic region (5-FU). Conclusions: Thus, co-nanoencapsulation of 5-FU/IRT in niosomes, lyophilization, and over-encapsulation of powder in colon-specific capsules could passively target the CRC cells in the colonic microenvironment. Full article
(This article belongs to the Special Issue Combination Therapy Approaches for Cancer Treatment)
Show Figures

Figure 1

40 pages, 1203 KiB  
Review
Overview of Preclinical and Clinical Trials of Nanoparticles for the Treatment of Brain Metastases
by Muhammad Izhar, Mohamed Al Gharyani, Ahed H. Kattaa, Juan J. Cardona, Ruchit P. Jain, Elaheh Shaghaghian, Yusuke S. Hori, Fred C. Lam, Deyaaldeen Abu Reesh, Sara C. Emrich, Louisa Ustrzynski, Armine Tayag, Maciej S. Lesniak, Steven D. Chang and David J. Park
Pharmaceutics 2025, 17(7), 899; https://doi.org/10.3390/pharmaceutics17070899 - 11 Jul 2025
Abstract
Brain metastases (BM), which most commonly originate from lung, breast, or skin cancers, remain a major clinical challenge, with standard treatments such as stereotactic radiosurgery (SRS), surgical resection, and whole-brain radiation therapy (WBRT). The prognosis for patients with BM remains poor, with a [...] Read more.
Brain metastases (BM), which most commonly originate from lung, breast, or skin cancers, remain a major clinical challenge, with standard treatments such as stereotactic radiosurgery (SRS), surgical resection, and whole-brain radiation therapy (WBRT). The prognosis for patients with BM remains poor, with a median overall survival (OS) of just 10–16 months. Although recent advances in systemic therapies, including small molecule inhibitors, monoclonal antibodies, chemotherapeutics, and gene therapies, have demonstrated success in other malignancies, their effectiveness in central nervous system (CNS) cancers is significantly limited by poor blood–brain barrier (BBB) permeability and subtherapeutic drug concentrations in the brain. Nanoparticle-based drug delivery systems have emerged as a promising strategy to overcome these limitations by enhancing CNS drug penetration and selectively targeting metastatic brain tumor cells while minimizing off-target effects. This review summarizes recent preclinical and clinical developments in nanoparticle-based therapies for BM. It is evident from these studies that NPs can carry with them a range of therapeutics, including chemotherapy, immunotherapy, small molecule inhibitors, gene therapies, radiosensitizers, and modulators of tumor microenvironment to the BM. Moreover, preclinical studies have shown encouraging efficacy in murine models, highlighting the potential of these platforms to improve therapeutic outcomes. However, clinical translation remains limited, with few ongoing trials. To close this translational gap, future work must address clinical challenges such as trial design, regulatory hurdles, and variability in BBB permeability while developing personalized nanoparticle-based therapies tailored to individual tumor characteristics. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles, 2nd Edition)
Show Figures

Figure 1

17 pages, 593 KiB  
Review
Patent-Based Technological Overview of Propolis–Cyclodextrin Inclusion Complexes with Pharmaceutical Potential
by Salvana Costa, Ighor Costa Barreto, Nataly Gama, Kathylen Santos, Cleomárcio Miguel de Oliveira, Isabela Silva Costa, Monique Vila Nova, Ruane Santos, Arthur Borges, José Marcos Teixeira de Alencar Filho and Ticiano Gomes do Nascimento
Pharmaceutics 2025, 17(7), 898; https://doi.org/10.3390/pharmaceutics17070898 - 11 Jul 2025
Abstract
Background/objectives: Propolis, known for its medicinal properties, faces challenges in pharmaceutical applications due to its low aqueous solubility, attributed to its resinous and hydrophobic nature. This limits oral administration, reducing its bioavailability and pharmacological activities. To overcome these barriers, cyclodextrins (CDs), cyclic oligosaccharides, [...] Read more.
Background/objectives: Propolis, known for its medicinal properties, faces challenges in pharmaceutical applications due to its low aqueous solubility, attributed to its resinous and hydrophobic nature. This limits oral administration, reducing its bioavailability and pharmacological activities. To overcome these barriers, cyclodextrins (CDs), cyclic oligosaccharides, are widely studied as carrier systems that enhance the solubility and bioavailability of propolis and other nonpolar compounds. This study aimed to review patents that developed innovative therapeutic approaches to improve the physicochemical and biological properties of propolis through complexation with CDs. Methods: Active and application patents registered over the last 17 years were searched across multiple databases, resulting in the selection of eight inventions for detailed analysis. Results: These patents highlight therapeutic applications of propolis–CD systems for conditions such as diabetes and skin and gastrointestinal cancers, as well as antimicrobial, immunostimulant, and antioxidant effects. Additionally, novel extraction processes free of organic solvents, including nanometric-scale powder extracts, are described. Conclusions: Findings from scientific articles support the patent data, demonstrating that CD complexation significantly enhances the solubility and therapeutic efficacy of propolis. Thus, these patents present an innovative and promising strategy for developing propolis-based pharmaceutical products. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
Show Figures

Graphical abstract

22 pages, 1305 KiB  
Review
Hydrogel Conjugation: Engineering of Hydrogels for Drug Delivery
by Linh Dinh, Sung-Joo Hwang and Bingfang Yan
Pharmaceutics 2025, 17(7), 897; https://doi.org/10.3390/pharmaceutics17070897 - 10 Jul 2025
Abstract
Background: Hydrogels are 3D networks of hydrophilic polymers with various biomedical applications, including tissue regeneration, wound healing, and localized drug delivery. Hydrogel conjugation links therapeutic agents to a hydrogel network, creating a delivery system with adjustable and flexible hydrogel properties and drug [...] Read more.
Background: Hydrogels are 3D networks of hydrophilic polymers with various biomedical applications, including tissue regeneration, wound healing, and localized drug delivery. Hydrogel conjugation links therapeutic agents to a hydrogel network, creating a delivery system with adjustable and flexible hydrogel properties and drug activity, allowing for controlled release and enhanced drug stability. Conjugating therapeutic agents to hydrogels provides innovative delivery formats, including injectable and sprayable dosage forms, which facilitate localized and long-lasting delivery. This approach enables non-viral therapeutic methods, such as insertional mutagenesis, and minimally invasive drug administration. Scope and Objectives: While numerous reviews have analyzed advancements in hydrogel synthesis, characterization, properties, and hydrogels as a drug delivery vehicle, this review focuses on hydrogel conjugation, which enables the precise functionalization of hydrogels with small molecules and macromolecules. Subsequently, a description and discussion of several bio-conjugated hydrogel systems, as well as binding motifs (e.g., “click” chemistry, functional group coupling, enzymatic ligation, etc.) and their potential for clinical translation, are provided. In addition, the integration of therapeutic agents with nucleic acid-based hydrogels can be leveraged for sequence-specific binding, representing a leap forward in biomaterials. Key findings: Special attention was given to the latest conjugation approaches and binding motifs that are useful for designing hydrogel-based drug delivery systems. The review systematically categorizes hydrogel conjugates for drug delivery, focusing on conjugating hydrogels with major classes of therapeutic agents, including small-molecule drugs, nucleic acids, proteins, etc., each with distinct conjugation challenges. The design principles were discussed along with their properties and drug release profiles. Finally, future opportunities and current limitations of conjugated hydrogel systems are addressed. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
Show Figures

Figure 1

18 pages, 4976 KiB  
Article
Mechanistic Insights into Cytokine Antagonist-Drug Interactions: A Physiologically Based Pharmacokinetic Modelling Approach with Tocilizumab as a Case Study
by Xian Pan, Cong Liu, Felix Stader, Abdallah Derbalah, Masoud Jamei and Iain Gardner
Pharmaceutics 2025, 17(7), 896; https://doi.org/10.3390/pharmaceutics17070896 - 10 Jul 2025
Abstract
Background: Understanding interactions between cytokine antagonists and drugs is essential for effective medication management in inflammatory conditions. Recent regulatory authority guidelines emphasise a systematic, risk-based approach to evaluating these interactions, underscoring the need for mechanistic insight. Proinflammatory cytokines, such as interleukin-6 (IL-6), modulate [...] Read more.
Background: Understanding interactions between cytokine antagonists and drugs is essential for effective medication management in inflammatory conditions. Recent regulatory authority guidelines emphasise a systematic, risk-based approach to evaluating these interactions, underscoring the need for mechanistic insight. Proinflammatory cytokines, such as interleukin-6 (IL-6), modulate cytochrome P450 (CYP) enzymes, reducing the metabolism of CYP substrates. Cytokine antagonists (such as IL-6 receptor antagonists) can counteract this effect, restoring CYP activity and increasing drug clearance. However, quantitative prediction of cytokine-mediated drug interactions remains challenging, as existing models often lack the mechanistic detail needed to capture the dynamic relationship between cytokine signalling, receptor engagement, and downstream modulation of drug metabolism. Methods: A physiologically based pharmacokinetic (PBPK) framework incorporating cytokine–receptor binding, subsequent downregulation of CYP expression, and blockade of the cytokine signalling by a therapeutic protein antagonist was developed to simulate and investigate cytokine antagonist-drug interactions. Tocilizumab, a humanised IL-6 receptor antagonist used to treat several inflammatory conditions associated with elevated IL-6 levels, was selected as a model drug to demonstrate the utility of the framework. Results: The developed PBPK model accurately predicted the pharmacokinetics profiles of tocilizumab and captured clinically observed dynamic changes in simvastatin exposure before and after tocilizumab treatment in rheumatoid arthritis (RA) patients. Simulated IL-6 dynamics aligned with observed clinical profiles, showing transient elevation following receptor blockade and associated restoration of CYP3A4 activity. Prospective simulations with commonly co-administered CYP substrates (celecoxib, chloroquine, cyclosporine, ibuprofen, prednisone, simvastatin, and theophylline) in RA patients revealed dose regimen- and drug-dependent differences in interaction magnitude. Conclusions: This study demonstrated the utility of PBPK models in providing a mechanistic understanding of cytokine antagonist-drug interactions, supporting enhanced therapeutic decision-making and optimising patient care in inflammatory conditions. Full article
Show Figures

Figure 1

22 pages, 4797 KiB  
Article
Silver Nanoparticles Synthesized from Enicostemma littorale Exhibit Gut Tight Junction Restoration and Hepatoprotective Activity via Regulation of the Inflammatory Pathway
by Hiral Aghara, Simran Samanta, Manali Patel, Prashsti Chadha, Divyesh Patel, Anamika Jha and Palash Mandal
Pharmaceutics 2025, 17(7), 895; https://doi.org/10.3390/pharmaceutics17070895 - 9 Jul 2025
Viewed by 121
Abstract
Background: Alcohol-associated liver disease (ALD) is a primary global health concern, exacerbated by oxidative stress, inflammation, and gut barrier dysfunction. Conventional phytocompounds exhibit hepatoprotective potential but are hindered by low bioavailability. This study aimed to evaluate the hepatoprotective and gut-barrier-restorative effects of green-synthesized [...] Read more.
Background: Alcohol-associated liver disease (ALD) is a primary global health concern, exacerbated by oxidative stress, inflammation, and gut barrier dysfunction. Conventional phytocompounds exhibit hepatoprotective potential but are hindered by low bioavailability. This study aimed to evaluate the hepatoprotective and gut-barrier-restorative effects of green-synthesized silver nanoparticles (AgNPs) derived from Enicostemma littorale, a medicinal plant known for its antioxidant and anti-inflammatory properties. Methods: AgNPs were synthesized using aqueous leaf extract of E. littorale and characterized using UV-Vis, XRD, FTIR, DLS, and SEM. HepG2 (liver) and Caco-2 (colon) cells were exposed to 0.2 M ethanol, AgNPs (1–100 µg/mL), or both, to simulate ethanol-induced toxicity. A range of in vitro assays was performed to assess cell viability, oxidative stress (H2DCFDA), nuclear and morphological integrity (DAPI and AO/EtBr staining), lipid accumulation (Oil Red O), and gene expression of pro- and anti-inflammatory, antioxidant, and tight-junction markers using RT-qPCR. Results: Ethanol exposure significantly increased ROS, lipid accumulation, and the expression of inflammatory genes, while decreasing antioxidant enzymes and tight-junction proteins. Green AgNPs at lower concentrations (1 and 10 µg/mL) restored cell viability, reduced ROS levels, preserved nuclear morphology, and downregulated CYP2E1 and SREBP expression. Notably, AgNPs improved the expression of Nrf2, HO-1, ZO-1, and IL-10, and reduced TNF-α and IL-6 expression in both cell lines, indicating protective effects on both liver and intestinal cells. Conclusions: Green-synthesized AgNPs from E. littorale exhibit potent hepatoprotective and gut-barrier-restoring effects through antioxidant, anti-inflammatory, and antilipidemic mechanisms. These findings support the therapeutic potential of plant-based nanoparticles in mitigating ethanol-induced gut–liver axis dysfunction. Full article
(This article belongs to the Special Issue Nanoparticles for Liver Diseases Therapy)
Show Figures

Figure 1

4 pages, 166 KiB  
Editorial
An Editorial on the Special Issue “Where Are We Now and Where Is Cell Therapy Headed?”
by Andrea Papait and Paola Chiodelli
Pharmaceutics 2025, 17(7), 894; https://doi.org/10.3390/pharmaceutics17070894 - 9 Jul 2025
Viewed by 91
Abstract
Cell-based therapies have swiftly transitioned from experimental modalities to core components of modern translational medicine [...] Full article
(This article belongs to the Special Issue Where Are We Now and Where Is Cell Therapy Headed?)
39 pages, 4547 KiB  
Review
Inhalable Nanotechnology-Based Drug Delivery Systems for the Treatment of Inflammatory Lung Diseases
by Doaa Elsayed Mahmoud, Seyedeh Hanieh Hosseini, Hassaan Anwer Rathore, Alaaldin M. Alkilany, Andreas Heise and Abdelbary Elhissi
Pharmaceutics 2025, 17(7), 893; https://doi.org/10.3390/pharmaceutics17070893 - 9 Jul 2025
Viewed by 81
Abstract
This review explores recent advancements in inhaled nanoparticle formulations and inhalation devices, with a focus on various types of nanoparticles used for inhalation to treat inflammatory lung diseases and the types of devices used in their delivery. Medical nebulizers have been found to [...] Read more.
This review explores recent advancements in inhaled nanoparticle formulations and inhalation devices, with a focus on various types of nanoparticles used for inhalation to treat inflammatory lung diseases and the types of devices used in their delivery. Medical nebulizers have been found to be the most appropriate type of inhalation devices for the pulmonary delivery of nanoparticles, since formulations can be prepared using straightforward techniques, with no need for liquefied propellants as in the case of pressurized metered dose inhalers (pMDIs), or complicated preparation procedures as in the case of dry powder inhalers (DPIs). We demonstrated examples of how formulations should be designed considering the operation mechanism of nebulizers, and how an interplay of factors can affect the aerosol characteristics of nanoparticle formulations. Overall, nanoparticle-based formulations offer promising potential for the treatment of inflammatory lung diseases due to their unique physicochemical properties and ability to provide localized drug delivery in the lung following inhalation. Full article
(This article belongs to the Special Issue Recent Advances in Pulmonary Inhalation of Nanoformulations)
Show Figures

Figure 1

27 pages, 3554 KiB  
Article
Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and Proliferation
by Karina Torres Pomini, Júlia Carolina Ferreira, Laira Mireli Dias da Silva, Paulo Gabriel Friedrich Totti, Monique Gonçalves Alves, Eliana de Souza Bastos Mazuqueli Pereira, Marcelo Melo Soares, Durvanei Augusto Maria and Rose Eli Grassi Rici
Pharmaceutics 2025, 17(7), 892; https://doi.org/10.3390/pharmaceutics17070892 - 9 Jul 2025
Viewed by 90
Abstract
Background/Objectives: Although the nanocomposite of poly(L-lactic acid) with graphene oxide (PLLA-GO) shows promise for tissue engineering, its specific bioactive interactions with diverse cell lineages during early tissue regeneration remain unclear. This study comprehensively investigated the in vitro multifaceted biocompatibility of PLLA-GO using human [...] Read more.
Background/Objectives: Although the nanocomposite of poly(L-lactic acid) with graphene oxide (PLLA-GO) shows promise for tissue engineering, its specific bioactive interactions with diverse cell lineages during early tissue regeneration remain unclear. This study comprehensively investigated the in vitro multifaceted biocompatibility of PLLA-GO using human fibroblasts (FN1 cells), murine mesenchymal stem cells (mBMSCs), and human umbilical vein endothelial cells (HUVECs). Methods: Morphological analyses were performed using optical and scanning electron microscopy, while proliferation dynamics were assessed via CFSE staining. Cell cycle progression was evaluated using flow cytometry, mitochondrial activity was examined through TMRE staining, and inflammatory cytokine profiling was performed via Cytometric Bead Array (CBA). Results: PLLA-GO exhibited primary biocompatibility across all evaluated cell lines, characterized by efficient adhesion and proliferation. However, significant cell-type-dependent modulations were observed. The FN1 cells exhibited proliferative adaptation but induced accelerated scaffold degradation, as evidenced by a substantial increase in cellular debris (5.93% control vs. 34.38% PLLA-GO; p = 0.03). mBMSCs showed a transient initial proliferative response and a significant 21.66% increase in TNF-α production (179.67 pg/mL vs. 147.68 pg/mL in control; p = 0.03). HUVECs demonstrated heightened mitochondrial sensitivity, exhibiting a 32.19% reduction in mitochondrial electrical potential (97.07% control vs. 65.82% PLLA-GO; p ≤ 0.05), alongside reductions in pro-inflammatory cytokines TNF-α (8.73%) and IL-6 (12.47%). Conclusions: The PLLA-GO processing method is crucial for its properties and subsequent cellular interactions. Therefore, rigorous and specific preclinical evaluations—considering both cellular contexts and fabrication—are indispensable to ensure the safety and therapeutic potential of PLLA-GO in tissue engineering and regenerative medicine. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
Show Figures

Figure 1

2 pages, 610 KiB  
Correction
Correction: Balas et al. Photodynamic Activity of TMPyP4/TiO2 Complex under Blue Light in Human Melanoma Cells: Potential for Cancer-Selective Therapy. Pharmaceutics 2023, 15, 1194
by Mihaela Balas, Simona Nistorescu, Madalina Andreea Badea, Anca Dinischiotu, Mihai Boni, Andra Dinache, Adriana Smarandache, Ana-Maria Udrea, Petronela Prepelita and Angela Staicu
Pharmaceutics 2025, 17(7), 891; https://doi.org/10.3390/pharmaceutics17070891 - 9 Jul 2025
Viewed by 69
Abstract
In the original publication [...] Full article
Show Figures

Figure 8

13 pages, 2107 KiB  
Article
Unlocking the Bioactivity of Sweet Wormwood (Artemisia annua L., Asteraceae) Ethanolic Extract: Phenolics, Antioxidants, and Cytotoxic Effects
by Neda Gavarić, Milica Aćimović, Nebojša Kladar, Maja Hitl, Jovana Drljača Lero, Nataša Milić and Katarina Radovanović
Pharmaceutics 2025, 17(7), 890; https://doi.org/10.3390/pharmaceutics17070890 - 9 Jul 2025
Viewed by 145
Abstract
Objectives: The aim of this work was to determine the phenolic composition of sweet wormwood (Artemisia annua L., Asteraceae) from controlled cultivation in Serbia and to assess the potential antioxidant effects and cytotoxicity. Methods: High-performance liquid chromatography was used to [...] Read more.
Objectives: The aim of this work was to determine the phenolic composition of sweet wormwood (Artemisia annua L., Asteraceae) from controlled cultivation in Serbia and to assess the potential antioxidant effects and cytotoxicity. Methods: High-performance liquid chromatography was used to determine the phenolic composition of Artemisia annua ethanolic extract. The antioxidant activity was studied using in vitro tests of inhibition of the neutralization of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), and nitroso (NO) radicals, as well as the process of inhibiting lipid peroxidation and the ferric reducing antioxidant power (FRAP). The cytotoxicity was evaluated by the effect on three cell lines (the rat pancreatic insulinoma cell line (Rin-5F), the rat hepatoma cell line (H4IIE), and human hepatocellular carcinoma (Hep G2)) using the MTT test of viability. Results: Ethanol extract showed the highest potency in inhibiting the DPPH radical, and the half maximal inhibitory concentration (IC50) was 5.17 μg/mL. Chlorogenic acid was the dominant phenolic compound with an amount of 651 μg/g of dry extract. The results of the MTT viability test showed that the extract has the potential to inhibit the growth of the Rin-5F and Hep G2 cell lines, while no growth inhibition was observed on the H4IIE cell line. Conclusions: Undoubtedly, Artemisia annua is a powerful plant and a rich source of phenolic compounds. Inhibitory activity on causes of oxidative stress shows that the plant has a good antioxidant effect. Also, the anticancer activity shown through the inhibition of cell growth is not negligible. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
Show Figures

Graphical abstract

21 pages, 1170 KiB  
Review
Innovative Controlled-Release Systems for Fucoxanthin: Research Progress and Applications
by Shiyan Wang, Mengran Guo and Zhaohui Jin
Pharmaceutics 2025, 17(7), 889; https://doi.org/10.3390/pharmaceutics17070889 - 8 Jul 2025
Viewed by 152
Abstract
Fucoxanthin, a marine-derived carotenoid primarily sourced from algae and microalgae, holds significant potential for pharmaceutical and nutraceutical applications. However, its highly unsaturated structure presents critical challenges, including structural instability, poor aqueous solubility, and limited bioavailability. These restrict its application despite its abundant natural [...] Read more.
Fucoxanthin, a marine-derived carotenoid primarily sourced from algae and microalgae, holds significant potential for pharmaceutical and nutraceutical applications. However, its highly unsaturated structure presents critical challenges, including structural instability, poor aqueous solubility, and limited bioavailability. These restrict its application despite its abundant natural availability. Recently, various controlled-release nanotechnologies have been applied to improve the properties of fucoxanthin formulations. In this review, we systematically summarized the bioactivities of fucoxanthin and highlighted recent advancements in controlled-release systems designed to address the limitations. These controlled-release systems mainly use natural or synthetic organic materials and are employed to develop various formulations, including emulsions, nanoparticles, nanofibers, and nanostructured lipid carriers. In addition, the emerging bioinspired drug delivery systems, particularly extracellular vesicles and cell-membrane-derived biomimetic systems, have gained prominence for their immunocompatibility and ability to penetrate physiological barriers, which is regarded as superior encapsulation vesicles for fucoxanthin. Focusing on innovations, we discussed the state-of-the-art delivery systems for fucoxanthin encapsulation and emphasized their roles in improving biosafety, enhancing bioavailability, preserving bioactivity, and optimizing therapeutic performance across various disease models. These insights will provide promising guidance for engineering controlled-release platforms and will aim to unlock fucoxanthin’s full potential in drug development and dietary supplement formulations. Full article
Show Figures

Figure 1

12 pages, 926 KiB  
Review
Nanotechnology Approaches for Mitigating Biologic Immunogenicity: A Literature Review
by Jouri Alanazi, Fadilah Sfouq Aleanizy and Fulwah Yahya Alqahtani
Pharmaceutics 2025, 17(7), 888; https://doi.org/10.3390/pharmaceutics17070888 - 7 Jul 2025
Viewed by 278
Abstract
Biologic therapeutics, particularly monoclonal antibodies (mAbs), have revolutionized disease treatment paradigms; however, their clinical success is often hindered by immunogenicity. Host immune recognition of these biologics can induce anti-drug antibody (ADA) formation, leading to reduced therapeutic efficacy, altered pharmacokinetics and serious adverse events, [...] Read more.
Biologic therapeutics, particularly monoclonal antibodies (mAbs), have revolutionized disease treatment paradigms; however, their clinical success is often hindered by immunogenicity. Host immune recognition of these biologics can induce anti-drug antibody (ADA) formation, leading to reduced therapeutic efficacy, altered pharmacokinetics and serious adverse events, such as infusion reactions and loss of response. Overcoming these immunogenicity challenges is essential to maximize the clinical effect of biologics and ensure patient safety. This paper offers an overview of the mechanisms underlying the formation of anti-drug antibodies and explores potential nanotechnology-based strategies to reduce or eliminate these responses. Specifically, the review examines how the immune system recognizes biologics and develops ADAs, which can impact drug efficacy and safety. The review then investigates various nanotechnology approaches aimed at mitigating ADA formation, potentially improving the therapeutic outcomes of biologic drugs. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
Show Figures

Figure 1

17 pages, 2146 KiB  
Article
Synthesis and Antiviral Activity of Nanowire Polymers Activated with Ag, Zn, and Cu Nanoclusters
by Thomas Thomberg, Hanna Bulgarin, Andres Lust, Jaak Nerut, Tavo Romann and Enn Lust
Pharmaceutics 2025, 17(7), 887; https://doi.org/10.3390/pharmaceutics17070887 - 6 Jul 2025
Viewed by 301
Abstract
Background/Objectives: Airborne viral diseases pose a health risk, due to which there is a growing interest in developing filter materials capable of capturing fine particles containing virions from the air and that also have a virucidal effect. Nanofiber membranes made of poly(vinylidene fluoride) [...] Read more.
Background/Objectives: Airborne viral diseases pose a health risk, due to which there is a growing interest in developing filter materials capable of capturing fine particles containing virions from the air and that also have a virucidal effect. Nanofiber membranes made of poly(vinylidene fluoride) dissolved in N,N-dimethylacetamide and functionalized with copper, silver, and zinc nanoclusters were fabricated via electrospinning. This study aims to evaluate and compare the virucidal effects of nanofibers functionalized with metal nanoclusters against the human influenza A virus A/WSN/1933 (H1N1) and SARS-CoV-2. Methods: A comprehensive characterization of materials, including X-ray diffraction, scanning electron microscopy, microwave plasma atomic emission spectroscopy, thermogravimetric analysis, contact angle measurements, nitrogen sorption analysis, mercury intrusion porosimetry, filtration efficiency, and virucidal tests, was used to understand the interdependence of the materials’ physical characteristics and biological effects, as well as to determine their suitability for application as antiviral materials in air filtration systems. Results: All the filter materials tested demonstrated very high particle filtration efficiency (≥98.0%). The material embedded with copper nanoclusters showed strong virucidal efficacy against the SARS-CoV-2 alpha variant, achieving an approximately 1000-fold reduction in infectious virions within 12 h. The fibrous nanowire polymer functionalized with zinc nanoclusters was the most effective material against the human influenza A virus strain A/WSN/1933 (H1N1). Conclusions: The materials with Cu nanoclusters can be used with high efficiency to passivate and kill the SARS-CoV-2 alpha variant virions, and Zn nanoclusters modified activated porous membranes for killing human influenza A virus A7WSN/1933 (H1N1) virions. Full article
Show Figures

Figure 1

26 pages, 3269 KiB  
Review
ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer Immunotherapy
by Yuan-Yuan Fan, Hong Wu and Chuan Xu
Pharmaceutics 2025, 17(7), 886; https://doi.org/10.3390/pharmaceutics17070886 - 5 Jul 2025
Viewed by 279
Abstract
Despite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained in solid tumors due to the immunosuppressive tumor microenvironment (TME). Reactive oxygen species (ROS), which exhibit dual regulatory roles in the TME by regulating immunogenic cell death (ICD) and reprogramming immune cell [...] Read more.
Despite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained in solid tumors due to the immunosuppressive tumor microenvironment (TME). Reactive oxygen species (ROS), which exhibit dual regulatory roles in the TME by regulating immunogenic cell death (ICD) and reprogramming immune cell functionality, have emerged as a pivotal therapeutic target. Nano-enabled drug delivery systems present distinct advantages for TME modulation due to their structural versatility, tumor-specific targeting precision, and spatiotemporally controlled drug release. In particular, ROS-responsive nanoplatforms demonstrate multifaceted immunomodulatory potential by synergistically restoring ICD and remodeling immunosuppressive immune cell phenotypes within the TME. These platforms further amplify the therapeutic outcomes of conventional modalities including chemotherapy, radiotherapy, and photodynamic therapy (PDT) through ROS-mediated sensitization mechanisms. This review comprehensively examines recent breakthroughs in ROS-responsive nanosystems for antitumor immunotherapy, emphasizing their mechanistic interplay with TME components and clinical translation potential. Herein, we provide a framework for developing integrated therapeutic strategies to overcome the current limitations in cancer immunotherapy. Full article
(This article belongs to the Special Issue ROS-Mediated Nano Drug Delivery for Antitumor Therapy)
Show Figures

Figure 1

17 pages, 3316 KiB  
Review
Advances in Liposomal Drug Delivery: Multidirectional Perspectives on Overcoming Biological Barriers
by Żaneta Sobol, Rafał Chiczewski and Dorota Wątróbska-Świetlikowska
Pharmaceutics 2025, 17(7), 885; https://doi.org/10.3390/pharmaceutics17070885 - 5 Jul 2025
Viewed by 328
Abstract
Liposomes represent a cornerstone of modern drug delivery systems due to their unique structural and physicochemical characteristics. Extensive research has refined their formulation, stability, and targeting capabilities, leading to numerous clinical applications, particularly in oncology. A key clinical feature is their ability to [...] Read more.
Liposomes represent a cornerstone of modern drug delivery systems due to their unique structural and physicochemical characteristics. Extensive research has refined their formulation, stability, and targeting capabilities, leading to numerous clinical applications, particularly in oncology. A key clinical feature is their ability to accumulate in malignant tissues via the enhanced permeability and retention effect, offering improved pharmacokinetics and reduced systemic toxicity. Advances in liposomal engineering, including PEGylation and ligand-based targeting, have significantly enhanced pharmacokinetic profiles and tissue specificity, minimizing off-target toxicity. The modern approach to nanocarrier-based drugs offers multidirectional perspectives on targeted therapy. Liposomes can bypass drug resistance mechanisms and provide controlled or stimuli-responsive drug release. Current trends in liposome research focus on hybrid nanocarriers, personalized medicine applications, and combination therapies. Full article
(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)
Show Figures

Figure 1

15 pages, 1142 KiB  
Article
Prediction of Monoclonal Antibody Pharmacokinetics in Pediatric Populations Using PBPK Modeling and Simulation
by Chiara Zunino, Virginie Gualano, Haiying Zhou, Viera Lukacova and Maxime Le Merdy
Pharmaceutics 2025, 17(7), 884; https://doi.org/10.3390/pharmaceutics17070884 - 5 Jul 2025
Viewed by 318
Abstract
Background: Accurately determining pediatric dosing is essential prior to initiating clinical trials or administering medications in routine clinical settings. In children, ethical considerations demand careful evaluation of both safety and effectiveness. Typically, dosing recommendations for therapeutic proteins, such as monoclonal antibodies (mAbs), [...] Read more.
Background: Accurately determining pediatric dosing is essential prior to initiating clinical trials or administering medications in routine clinical settings. In children, ethical considerations demand careful evaluation of both safety and effectiveness. Typically, dosing recommendations for therapeutic proteins, such as monoclonal antibodies (mAbs), are derived from adult dosages using body weight as a scaling factor. However, this method overlooks key physiological and biochemical distinctions between pediatric and adult patients. Therefore, this could lead to the underexposure of mAbs, limiting their efficacy in this population. Additional methods are necessary to predict pediatric doses mechanistically. For small molecules, physiologically based pharmacokinetic (PBPK) models have been extensively used to predict pediatric doses based on physiological age-related changes and enzymes/transporters ontogeny. This study aims to evaluate the ability of PBPK models to predict mAbs’ pediatric exposure. Methods: Three mAbs were used for model development and validation: bevacizumab, infliximab, and atezolizumab. The PBPK models were built using GastroPlus© Biologics module. For each mAb, the PBPK model was developed based on observed data in healthy and/or patient adults. Then, the physiological parameters were scaled to describe the pediatric physiology to predict exposure to the pediatric populations. Predicted plasma concentration–time courses were overlaid with reported observed data to assess the ability of the PBPK model to predict pediatric exposure. Results: Results showed that PBPK models accurately predicted pediatric pharmacokinetics for mAbs. Conclusions: This research marks a significant step in validating mechanistic extrapolation methods for biologics exposure prediction in children using PBPK models. Full article
Show Figures

Figure 1

28 pages, 9146 KiB  
Review
Nanoscale Porphyrin-Based Metal–Organic Frameworks for Enhanced Radiotherapy–Radiodynamic Therapy: A Comprehensive Review
by Bin Gong, Qiuyun Zhang, Yijie Qu, Xiaohua Zheng and Weiqi Wang
Pharmaceutics 2025, 17(7), 883; https://doi.org/10.3390/pharmaceutics17070883 - 4 Jul 2025
Viewed by 352
Abstract
The phototherapeutic applications of porphyrin-based nanoscale metal–organic frameworks (nMOFs) are limited by the poor penetration of conventional excitation light sources into biological tissues. Radiodynamic therapy (RDT), which directly excites photosensitizers using X-rays, can overcome the issue of tissue penetration. However, RDT faces the [...] Read more.
The phototherapeutic applications of porphyrin-based nanoscale metal–organic frameworks (nMOFs) are limited by the poor penetration of conventional excitation light sources into biological tissues. Radiodynamic therapy (RDT), which directly excites photosensitizers using X-rays, can overcome the issue of tissue penetration. However, RDT faces the problems of low energy conversion efficiency, requiring a relatively high radiation dose, and the potential to cause damage to normal tissues. Researchers have found that by using some metals with high atomic numbers (high Z) as X-ray scintillators and coordinating them with porphyrin photosensitizers to form MOF materials, the excellent antitumor effect of radiotherapy (RT) and RDT can be achieved under low-dose X-ray irradiation, which can not only effectively avoid the penetration limitations of light excitation methods but also eliminate the defect issues associated with directly using X-rays to excite photosensitizers. This review summarizes the relevant research work in recent years, in which researchers have used metal ions with high Z, such as Hf4+, Th4+, Ta5+, and Bi3+, in coordination with carboxyl porphyrins to form MOF materials for combined RT and RDT toward various cancer cells. This review compares the therapeutic effects and advantages of using different high-Z metals and introduces the application of the heavy atom effect. Furthermore, it explores the introduction of a chemodynamic therapy (CDT) mechanism through iron coordination at the porphyrin center, along with optimization strategies such as oxygen delivery using hemoglobin to enhance the efficacy of these MOFs as radiosensitizers. This review also summarizes the potential of these materials in preclinical applications and highlights the current challenges they face. It is expected that the summary and prospects outlined in this review can further promote preclinical biomedical research into and the development of porphyrin-based nMOFs. Full article
(This article belongs to the Special Issue Advanced Nanotechnology for Combination Therapy and Diagnosis)
Show Figures

Graphical abstract

24 pages, 8040 KiB  
Article
Development of Modified Drug Delivery Systems with Metformin Loaded in Mesoporous Silica Matrices: Experimental and Theoretical Designs
by Mousa Sha’at, Maria Ignat, Florica Doroftei, Vlad Ghizdovat, Maricel Agop, Alexandra Barsan (Bujor), Monica Stamate Cretan, Fawzia Sha’at, Ramona-Daniela Pavaloiu, Adrian Florin Spac, Lacramioara Ochiuz, Carmen Nicoleta Filip and Ovidiu Popa
Pharmaceutics 2025, 17(7), 882; https://doi.org/10.3390/pharmaceutics17070882 - 4 Jul 2025
Viewed by 496
Abstract
Background/Objectives: Mesoporous silica materials, particularly KIT-6, offer promising features, such as large surface area, tunable pore structures, and biocompatibility, making them ideal candidates for advanced drug delivery systems. The aims of this study were to develop and evaluate an innovative modified-release platform for [...] Read more.
Background/Objectives: Mesoporous silica materials, particularly KIT-6, offer promising features, such as large surface area, tunable pore structures, and biocompatibility, making them ideal candidates for advanced drug delivery systems. The aims of this study were to develop and evaluate an innovative modified-release platform for metformin hydrochloride (MTF), using KIT-6 mesoporous silica as a matrix, to enhance oral antidiabetic therapy. Methods: KIT-6 was synthesized using an ultrasound-assisted sol-gel method and subsequently loaded with MTF via adsorption from alkaline aqueous solutions at two concentrations (1 and 3 mg/mL). The structural and morphological characteristics of the matrices—before and after drug loading—were assessed using SEM-EDX, TEM, and nitrogen adsorption–desorption isotherms (the BET method). In vitro drug release profiles were recorded in simulated gastric and intestinal fluids over 12 h. Kinetic modeling was performed using seven classical models, and a multifractal theoretical framework was used to further interpret the complex release behavior. Results: The loading efficiency increased with increasing drug concentration but nonlinearly, reaching 56.43 mg/g for 1 mg/mL and 131.69 mg/g for 3 mg/mL. BET analysis confirmed significant reductions in the surface area and pore volume upon MTF incorporation. In vitro dissolution showed a biphasic release: a fast initial phase in an acidic medium followed by sustained release at a neutral pH. The Korsmeyer–Peppas and Weibull models best described the release profiles, indicating a predominantly diffusion-controlled mechanism. The multifractal model supported the experimental findings, capturing nonlinear dynamics, memory effects, and soliton-like transport behavior across resolution scales. Conclusions: The study confirms the potential of KIT-6 as a reliable and efficient carrier for the modified oral delivery of metformin. The combination of experimental and multifractal modeling provides a deeper understanding of drug release mechanisms in mesoporous systems and offers a predictive tool for future drug delivery design. This integrated approach can be extended to other active pharmaceutical ingredients with complex release requirements. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
Show Figures

Figure 1

16 pages, 3597 KiB  
Article
Towards a Customized Oral Drug Therapy for Pediatric Applications: Chewable Propranolol Gel Tablets Printed by an Automated Extrusion-Based Material Deposition Method
by Kristiine Roostar, Andres Meos, Ivo Laidmäe, Jaan Aruväli, Heikki Räikkönen, Leena Peltonen, Sari Airaksinen, Niklas Sandler Topelius, Jyrki Heinämäki and Urve Paaver
Pharmaceutics 2025, 17(7), 881; https://doi.org/10.3390/pharmaceutics17070881 - 4 Jul 2025
Viewed by 275
Abstract
Background: Automated semi-solid extrusion (SSE) material deposition is a promising new technology for preparing personalized medicines for different patient groups and veterinary applications. The technology enables the preparation of custom-made oral elastic gel tablets of active pharmaceutical ingredient (API) by using a semi-solid [...] Read more.
Background: Automated semi-solid extrusion (SSE) material deposition is a promising new technology for preparing personalized medicines for different patient groups and veterinary applications. The technology enables the preparation of custom-made oral elastic gel tablets of active pharmaceutical ingredient (API) by using a semi-solid polymeric printing ink. Methods: An automated SSE material deposition method was used for generating chewable gel tablets loaded with propranolol hydrochloride (-HCl) at three different API content levels (3.0 mg, 4.0 mg, 5.0 mg). The physical appearance, surface morphology, dimensions, mass and mass variation, process-derived solid-state changes, mechanical properties, and in-vitro drug release of the gel tablets were studied. Results: The inclusion of API (1% w/w) in the semi-solid CuraBlendTM printing mixture decreased viscosity and increased fluidity, thus promoting the spreading of the mixture on the printed (material deposition) bed and the printing performance of the gel tablets. The printed gel tablets were elastic, soft, jelly-like, chewable preparations. The mechanical properties of the gel tablets were dependent on the printing ink composition (i.e., with or without propranolol HCl). The maximum load for the final deformation of the CuraBlend™-API (3.0 mg) gel tablets was very uniform, ranging from 73 N to 80 N. The in-vitro dissolution test showed that more than 85% of the drug load was released within 15–20 min, thus verifying the immediate-release behavior of these drug preparations. Conclusions: Automated SSE material deposition as a modified 3D printing method is a feasible technology for preparing customized oral chewable gel tablets of propranolol HCl. Full article
Show Figures

Figure 1

20 pages, 4947 KiB  
Article
Novel Micellar Formulation of Silymarin (Milk Thistle) with Enhanced Bioavailability in a Double-Blind, Randomized, Crossover Human Trial
by Chuck Chang, Yiming Zhang, Yun Chai Kuo, Min Du, Kyle Roh, Roland Gahler, Afoke Ibi and Julia Solnier
Pharmaceutics 2025, 17(7), 880; https://doi.org/10.3390/pharmaceutics17070880 - 4 Jul 2025
Viewed by 341
Abstract
Background: Silymarin, a flavonoid complex, and the main bioactive component of milk thistle (Silybum marianum), is known for its hepatoprotective properties but suffers from poor bioavailability due to its low solubility and extensive first-pass metabolism. Method: This study aimed to evaluate [...] Read more.
Background: Silymarin, a flavonoid complex, and the main bioactive component of milk thistle (Silybum marianum), is known for its hepatoprotective properties but suffers from poor bioavailability due to its low solubility and extensive first-pass metabolism. Method: This study aimed to evaluate the pharmacokinetics and tolerability of a novel micellar milk thistle formulation designed to enhance silymarin absorption, compared to an unformulated/standard milk thistle product, in a small-scale human bioavailability trial. In a randomized, double-blinded, crossover study, 16 healthy participants received a single dose of either the micellar formulation (LipoMicel Milk Thistle; LMM) or the standard formulation (STD) at a total daily dose of 130 mg silymarin. Blood concentrations were measured over 24 h, and key pharmacokinetic parameters—maximum plasma concentration (Cmax), time to reach maximum concentration (Tmax), and area under the curve (AUC)—were calculated. Tolerability and safety were assessed through adverse event monitoring during the study period. Results: Results demonstrated a significant increase in bioavailability with the micellar formulation, with 18.9-fold higher Cmax (95% CI: 1.9–30.7 ng/mL vs. 74.4–288.3 ng/mL; p = 0.007) and 11.4-fold higher AUC0–24 (95% CI: 7.40–113.5 ng·h/mL vs. 178–612.5 ng·h/mL; p = 0.015). Tmax was 0.5 (95% CI: 0.5–4.0) hours for the micellar formulation versus 2.5 (95% CI: 0.5–8.0) hours for the standard product (p = 0.015) indicating faster absorption of LMM. The standard formulation exhibited a significantly longer mean residence time compared to the LMM formulation (95% CI: 4.4–7.5 h vs. 2.8–4.2 h; p = 0.015). Conclusions: No adverse events or significant safety concerns were observed in either group. Compared to the standard, the micellar formulation showed superior pharmacokinetic outcomes, suggesting it may enhance silymarin’s clinical efficacy in liver health. Full article
(This article belongs to the Collection Pharmaceutical Sciences in Canada)
Show Figures

Graphical abstract

15 pages, 4132 KiB  
Article
Crotoxin-Loaded Silica Nanoparticles: A Nanovenom Approach
by Florencia Silvina Conti, Exequiel Giorgi, Laura Montaldo, Juan Pablo Rodríguez, Mauricio Cesar De Marzi and Federico Gastón Baudou
Pharmaceutics 2025, 17(7), 879; https://doi.org/10.3390/pharmaceutics17070879 - 4 Jul 2025
Viewed by 277
Abstract
Background: Ophidism is a globally neglected health problem. In Argentina, Crotalus durissus terrificus (C.d.t., South American rattlesnake) is one of the species of greatest medical importance since its venom contains mainly crotoxin (CTX), a potent enzyme–toxin with PLA2 activity, [...] Read more.
Background: Ophidism is a globally neglected health problem. In Argentina, Crotalus durissus terrificus (C.d.t., South American rattlesnake) is one of the species of greatest medical importance since its venom contains mainly crotoxin (CTX), a potent enzyme–toxin with PLA2 activity, which is responsible for its high lethality. Objective: In this work, we aimed to generate nanovenoms (NVs), complexes formed by CTX adsorbed onto 150 nm silica nanoparticles (SiNPs), and to study their physicochemical, biological, and immunomodulatory activities for potential use as adjuvants (ADJs) in antivenom (AV) production. Methods: CTX was isolated and corroborated by SDS-PAGE. Then, CTX was adsorbed on the synthetized Stöber SiNPs’ surfaces, forming a monolayer and retaining its biological activity (as observed by the MTT cell proliferation assay using the THP-1 cell line). Results: Immunomodulatory activity revealed a high pro-inflammatory (IL-1β) response induced by SiNPs followed by NVs. In the case of the anti-inflammatory response, NVs presented significant differences for TGF-β only after cell activation with LPS. No significant differences were observed in IL-10 levels. Conclusions: Thus, these results suggest that NVs together with SiNPs could increase immunogenicity and enhance immune response, turning them into potential tools for the generation of new antivenoms. Full article
(This article belongs to the Special Issue Delivery System for Biomacromolecule Drugs: Design and Application)
Show Figures

Figure 1

16 pages, 2915 KiB  
Article
Extrusion-Based 3D Printing of Rutin Using Aqueous Polyethylene Oxide Gel Inks
by Oleh Koshovyi, Jyrki Heinämäki, Alina Shpychak, Andres Meos, Niklas Sandler Topelius and Ain Raal
Pharmaceutics 2025, 17(7), 878; https://doi.org/10.3390/pharmaceutics17070878 - 3 Jul 2025
Viewed by 312
Abstract
Background/Objectives. Flavonoids are a vast class of phenolic substances. To date, approximately 6000 plant-origin flavonoids have been discovered, with many of them being used in drug therapy. Therapeutic flavonoids are commonly formulated to conventional “one-size-fits-all” dosage forms, such as conventional tablets or hard [...] Read more.
Background/Objectives. Flavonoids are a vast class of phenolic substances. To date, approximately 6000 plant-origin flavonoids have been discovered, with many of them being used in drug therapy. Therapeutic flavonoids are commonly formulated to conventional “one-size-fits-all” dosage forms, such as conventional tablets or hard capsules. However, the current trends in pharmacy and medicine are centred on personalised drug therapy and drug delivery systems (DDSs). Therefore, 3D printing is an interesting technique for designing and preparing novel personalised pharmaceuticals for flavonoids. The aim of the present study was to develop aqueous polyethylene oxide (PEO) gel inks loaded with rutin for semisolid extrusion (SSE) 3D printing. Methods. Rutin (a model substance for therapeutic flavonoids), Tween 80, PEO (MW approx. 900,000), ethanol, and purified water were used in PEO gels at different proportions. The viscosity and homogeneity of the gels were determined. The rutin–PEO gels were printed with a bench-top Hyrel 3D printer into lattices and discs, and their weight and effective surface area were investigated. Results. The key SSE 3D-printing process parameters were established and verified. The results showed the compatibility of rutin as a model flavonoid and PEO as a carrier polymer. The rutin content (%) and content uniformity of the 3D-printed preparations were assayed by UV spectrophotometry and high-performance liquid chromatography (HPLC). Conclusions. The most feasible aqueous PEO gel ink formulation for SSE 3D printing contained rutin 100 mg/mL and Tween 80 50 mg/mL in a 12% aqueous PEO gel. The 3D-printed dosage forms are intended for the oral administration of flavonoids. Full article
(This article belongs to the Special Issue 3D Printing of Drug Delivery Systems)
Show Figures

Graphical abstract

Previous Issue
Back to TopTop