Pharmaceutics

19 pages, 2145 KB

Open AccessArticle

Surfactant-Enriched Cross-Linked Scaffold as an Environmental and Manufacturing Feasible Approach to Boost Dissolution of Lipophilic Drugs

by Abdelrahman Y. Sherif, Doaa Hasan Alshora and Mohamed A. Ibrahim

Pharmaceutics 2025, 17(11), 1387; https://doi.org/10.3390/pharmaceutics17111387 (registering DOI) - 26 Oct 2025

Abstract

Background/Objectives: The inherent low aqueous solubility of lipophilic drugs, belonging to Class II based on Biopharmaceutical classification system, negatively impacts their oral bioavailability. However, the manufacturing of pharmaceutical dosage forms for these drugs faces challenges related to environmental impact and production complexity. [...] Read more.

Background/Objectives: The inherent low aqueous solubility of lipophilic drugs, belonging to Class II based on Biopharmaceutical classification system, negatively impacts their oral bioavailability. However, the manufacturing of pharmaceutical dosage forms for these drugs faces challenges related to environmental impact and production complexity. Herein, the surfactant-enriched cross-linked scaffold addresses the limitations of conventional approaches, such as the use of organic solvents, energy-intensive processing, and the demand for sophisticated equipment. Methods: Scaffold former (Pluronic F68) and scaffold trigger agent (propylene glycol) were used to prepare cross-linked scaffold loaded with candesartan cilexetil as a model for lipophilic drugs. Moreover, surfactants were selected based on the measured solubility to enhance formulation loading capacity. Design-Expert was used to study the impact of Tween 80, propylene glycol, and Pluronic F68 concentrations on the measured responses. In addition, in vitro dissolution study was implemented to investigate the drug release profile. The current approach was assessed against the limitations of conventional approach in terms of environmental and manufacturing feasibility. Results: The optimized formulation (59.27% Tween 80, 30% propylene glycol, 10.73% Pluronic F68) demonstrated a superior drug loading capacity (19.3 mg/g) and exhibited a solid-to-liquid phase transition at 35.5 °C. Moreover, it exhibited a rapid duration of solid-to-liquid transition within about 3 min. In vitro dissolution study revealed a remarkable enhancement in dissolution with 92.87% dissolution efficiency compared to 1.78% for the raw drug. Conclusions: Surfactant-enriched cross-linked scaffold reduced environmental impact by eliminating organic solvents usage and reducing energy consumption. Moreover, it offers significant manufacturing advantages through simplified production processing. Full article

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

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18 pages, 2266 KB

Open AccessArticle

Anti-Hyperpigmentation-Related Potential Activities in B16BL6 Cells and Chemical Composition of Essential Oil from Chamaecyparis pisifera Leaves

by Do Yoon Kim, Kyung Jong Won, Yoon Yi Kim, Da Yeon Yoo and Hwan Myung Lee

Pharmaceutics 2025, 17(11), 1386; https://doi.org/10.3390/pharmaceutics17111386 (registering DOI) - 25 Oct 2025

Abstract

Background/Objectives: Chamaecyparis pisifera (C. pisifera; family Cupressaceae) is known to have insecticidal and antibacterial activities, but its effects on skin depigmentation-related activities have not been elucidated. Thus, in the present study, we aimed to investigate the anti-hyperpigmentation potential of C. [...] Read more.

Background/Objectives: Chamaecyparis pisifera (C. pisifera; family Cupressaceae) is known to have insecticidal and antibacterial activities, but its effects on skin depigmentation-related activities have not been elucidated. Thus, in the present study, we aimed to investigate the anti-hyperpigmentation potential of C. pisifera var. filifera leaf essential oil (CPEO), specially focusing on responses related to melanogenesis and melanin transport, using B16BL6 cells. Methods: CPEO was extracted by steam distillation, and its composition was determined by GC/MS spectrometry. The biological activities of CPEO on B16BL6 melanoma cells were analyzed using the water soluble tetrazolium salt, BrdU incorporation, ELISA, and immunoblotting assays. Results: Twenty-eight components were identified in CPEO. CPEO was noncytotoxic to B16BL6 cells at 1–100 μg/mL and reduced serum-induced proliferation in B16BL6 cells. CPEO significantly inhibited α-MSH-stimulated increases in melanin synthesis and tyrosinase activity in the cells (e.g., at 100 μg/mL CPEO, melanin synthesis: 117.89 ± 0.00% vs. 571.94 ± 0.81% with α-MSH; tyrosinase activity: 73.62 ± 0.00% vs. 322.60 ± 3.10% with α-MSH). CPEO also downregulated the expression levels of melanogenesis-related proteins (MITF, tyrosinase, TRP-1 and -2) and melanosome transport-related proteins (Rab27a, melanophilin, myosin Va) in cells exposed to α-MSH. Moreover, the essential oil increased the phosphorylations of MAPKs (p38, ERK1/2, and JNK) in α-MSH-treated B16BL6 cells. In addition, CPEO reduced the ultraviolet A (UVA) induced increases in α-MSH levels in HaCaT cells. In addition, conditioned medium from HaCaT cells irradiated with UVA (CM-UVA) in the presence of CPEO reduced melanin synthesis and tyrosinase activity in B16BL6 cells (e.g., at CM-UVA with 100 μg/mL CPEO, melanin synthesis: 100.92 ± 0.99% vs. 134.44 ± 0.97% with CM-UVA; tyrosinase activity: 101.02 ± 1.81% vs. 133.77 ± 1.88% with CM-UVA). Conclusions: These findings suggest that CPEO inhibits melanin production (probably through the regulation of MAPKs) and transport-related activities in B16BL6 cells, and that CPEO may serve as a potential natural anti-hyperpigmentation or skin whitening. Full article

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

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Graphical abstract

14 pages, 5575 KB

Open AccessArticle

Generation and Purification of RANKL-Derived Small-Fragment Variants for Osteoclast Inhibition

by Hyungjun Lee, Hyungseok Park, Kabsun Kim, Youngjong Ko, Chang-Moon Lee and Wonbong Lim

Pharmaceutics 2025, 17(11), 1385; https://doi.org/10.3390/pharmaceutics17111385 (registering DOI) - 25 Oct 2025

Abstract

Background/Objectives: Osteoporosis is caused by excessive osteoclast activation via the receptor activator nuclear factor kappa B ligand (RANKL), which is released from osteoblasts or osteocytes. RANKL regulates osteoclast activity by binding to the receptor activator of nuclear factor kappa B (RANK) in the [...] Read more.

Background/Objectives: Osteoporosis is caused by excessive osteoclast activation via the receptor activator nuclear factor kappa B ligand (RANKL), which is released from osteoblasts or osteocytes. RANKL regulates osteoclast activity by binding to the receptor activator of nuclear factor kappa B (RANK) in the canonical pathway or leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) in the non-canonical pathway. In this study, we attempted to develop an intact small-fragment protein based on RANKL by removing the RANK-binding site and transforming the amino acid residues at crucial sites to inhibit osteoclast activity and treat osteoporosis. Methods: We expressed a small-fragment variant of RANKL as a soluble glutathione S-transferase (GST) or 6x histidine (His)-tagged fusion protein using a GST- or His-binding domain tag expression vector system. To generate an intact form of small-fragment RANKL, ribosome-inactivating protein–His-fusion RANKL was purified using HisTrap affinity chromatography and treated with tobacco etch virus nuclear inclusion endopeptidase to remove the His-tag fusion protein. Tartrate-resistant acid phosphatase (TRAP) and bone resorption pit formation assays were performed to analyze the inhibitory effects on osteoclast differentiation and activation. Results: The intact forms of 225RANKL295P and 225RANKL295A showed the strongest inhibitory effects on TRAP activity and bone resorption pit formation. Conclusions: Using an optimal construct design, a large and diverse range of small RANKL fragments could be generated. This suggests that the generation of small-fragment RANKL provides a promising avenue for the advancement of novel therapeutic approaches to osteoporosis. Full article

(This article belongs to the Section Gene and Cell Therapy)

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41 pages, 3900 KB

Open AccessReview

Therapeutic and Formulation Advances of Ivermectin in Veterinary and Human Medicine

by Nicezelle Gernandt, Chanri Wentzel, Daniélle van Staden, Wilna Liebenberg, Hendrik J. R. Lemmer and Minja Gerber

Pharmaceutics 2025, 17(11), 1384; https://doi.org/10.3390/pharmaceutics17111384 (registering DOI) - 25 Oct 2025

Abstract

The treatment of parasitic infections has evolved in terms of effectiveness and the prevention of drug resistance. This is highlighted by the discovery of ivermectin (IVM), a macrocyclic lactone and broad-spectrum antiparasitic agent. IVM garnered scientific attention by presenting a therapeutic alternative in [...] Read more.

The treatment of parasitic infections has evolved in terms of effectiveness and the prevention of drug resistance. This is highlighted by the discovery of ivermectin (IVM), a macrocyclic lactone and broad-spectrum antiparasitic agent. IVM garnered scientific attention by presenting a therapeutic alternative in the field of veterinary medicine due to its control of multiple parasite species, including nematodes and soil-transmitted helminths. Shortly after its discovery, IVM was approved for human use by the World Health Organization (WHO) and United States Food and Drug Administration (FDA) for combating head lice, onchocerciasis, rosacea, scabies, and worm infestations within the gastrointestinal tract (GIT). In veterinary medicine, IVM is available in a range of formulations and can be administered via different routes (i.e., oral, topical, and parenteral), whereas for humans, IVM is only approved as a single oral dose and dermal cream. Establishing a comprehensive overview of IVM’s applications in both human and veterinary medicine is necessary, particularly in light of its repurposing potential as a treatment for various conditions and emerging diseases. Given its primary application in veterinary medicine, there is a need to enhance the development of dosage forms suitable for human use. Therefore, this review details the discovery, mechanisms, and applications of IVM, while also examining the challenges of resistance, side-effects, and controversy surrounding its use, to ultimately emphasize the importance of targeted, optimized IVM delivery via tailored dosage form development in animals and humans as part of the One Health approach to interlink innovations across veterinary and human medicine fields. Full article

(This article belongs to the Special Issue Novel Therapeutic Agents and Innovative Delivery Systems Against Infectious Diseases)

30 pages, 5963 KB

Open AccessReview

Engineering Inorganic Nanoparticles to Induce Cuproptosis: A New Strategy for Cancer Therapy

by Zhenxing Jiang, Jianwei Dai, Juanjuan Jiang, Shenghe Deng, Junnan Gu, Jun Wang, Mian Chen, Wentai Cai, Ke Wu, Kaixiong Tao, Ke Liu and Kailin Cai

Pharmaceutics 2025, 17(11), 1383; https://doi.org/10.3390/pharmaceutics17111383 (registering DOI) - 24 Oct 2025

Abstract

Cuproptosis is a newly identified type of copper (Cu)-dependent programmed cell death (PCD), triggered when Cu directly interacts with the lipoylated components of the tricarboxylic acid (TCA) cycle, and it has shown significant antitumor potential. However, challenges such as insufficient Cu accumulation in [...] Read more.

Cuproptosis is a newly identified type of copper (Cu)-dependent programmed cell death (PCD), triggered when Cu directly interacts with the lipoylated components of the tricarboxylic acid (TCA) cycle, and it has shown significant antitumor potential. However, challenges such as insufficient Cu accumulation in tumor cells, systemic toxicity, and the lack of specific carriers for effectively inducing cuproptosis hinder its practical application. Inorganic nanoparticles (INPs) present a promising solution due to their unique ability to target specific areas, potential for multifunctional modification, and controlled release capabilities. Their distinctive physicochemical properties also enable the integration of synergistic multimodal cancer therapies. Therefore, utilizing INPs to induce cuproptosis represents a promising strategy for cancer treatment. This review systematically elucidates the regulatory mechanisms of Cu homeostasis and the molecular pathways underlying cuproptosis, thoroughly discusses current INP-based strategies designed to trigger cuproptosis, and comprehensively examines the multi-modal synergistic antitumor mechanisms based on cuproptosis. Finally, we also address the current challenges and future perspectives in developing clinically applicable nanoplatforms aimed at harnessing cuproptosis for effective cancer therapy. Full article

(This article belongs to the Special Issue Inorganic Nanomaterials for the Development of Drug Delivery and Biomedical Applications)

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25 pages, 1665 KB

Open AccessReview

Hydrogel-Based Therapeutic Strategies for Periodontal Tissue Regeneration: Advances, Challenges, and Future Perspectives

by Bowen Wang, Fengxin Ge, Wenqing Wang, Bo Wang, Cory J. Xian and Yuankun Zhai

Pharmaceutics 2025, 17(11), 1382; https://doi.org/10.3390/pharmaceutics17111382 (registering DOI) - 24 Oct 2025

Abstract

Periodontitis, a prevalent chronic infectious disease triggered by oral biofilm microbiota, results in progressive destruction of periodontal supporting tissues, and conventional treatments have limited therapeutic effects on it. Hydrogels, due to their excellent biocompatibility, three-dimensional extracellular matrix-like structure, and localized sustained-release properties, can [...] Read more.

Periodontitis, a prevalent chronic infectious disease triggered by oral biofilm microbiota, results in progressive destruction of periodontal supporting tissues, and conventional treatments have limited therapeutic effects on it. Hydrogels, due to their excellent biocompatibility, three-dimensional extracellular matrix-like structure, and localized sustained-release properties, can provide support for cell attachment, promote cell proliferation and differentiation, and improve drug utilization efficiency, showing great promise for applications in treating periodontitis as well as promoting periodontal tissue regeneration. This article first introduces the limitations of current periodontitis treatments and the unique advantages of hydrogels in periodontitis treatment and periodontal tissue regeneration, and then provides an overview of the classifications of hydrogels, the active substances they can load, and the characteristics and functions of these active substances. Subsequently, the article introduces the latest advances in the application of several common natural polymer hydrogels in periodontal tissue regeneration. Finally, the article discusses the current limitations of hydrogels in terms of structure and properties, and proposes potential solutions and future development directions in periodontal tissue regeneration. Full article

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

19 pages, 1774 KB

Open AccessArticle

Photodynamic Therapy with 5-Aminolevulinic Acid Versus Topical Corticosteroids in the Treatment of Oral Lichen Planus: A Randomized Clinical Trial with Lesion Site-Specific Analysis

by Aleksandra Pietruska, Magdalena Sulewska, Patryk Wiśniewski, Jagoda Tomaszuk, Emilia Szymańska, Katarzyna Winnicka, Joanna Narolewska and Małgorzata Pietruska

Pharmaceutics 2025, 17(11), 1381; https://doi.org/10.3390/pharmaceutics17111381 (registering DOI) - 24 Oct 2025

Abstract

Objective: Oral lichen planus (OLP) is a chronic immune-mediated condition of the oral mucosa, commonly associated with pain and burning sensations that impair quality of life. This study aimed to compare the efficacy of photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) and topical [...] Read more.

Objective: Oral lichen planus (OLP) is a chronic immune-mediated condition of the oral mucosa, commonly associated with pain and burning sensations that impair quality of life. This study aimed to compare the efficacy of photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) and topical glucocorticosteroids (CT) in the treatment of OLP, considering lesion location on keratinized and non-keratinized mucosa. Materials and Methods: A randomized clinical trial was conducted on 90 patients with histologically confirmed OLP. Participants were allocated to receive either ALA-PDT in addition to novel oromucosal emulgel containing 5% ALA (five weekly sessions) or clobetasol propionate applied twice daily for two weeks. Lesion area, clinical severity (Reticulation, Erythema, Ulceration—REU index), and subjective symptoms (Visual Analog Scale—VAS) were evaluated before treatment, immediately after, and six months after therapy. Results: ALA-PDT achieved significantly greater and more durable reductions in lesion area, REU scores, and VAS values compared to CT, particularly on non-keratinized mucosa (mean lesion reduction from 2.64 to 0.56 cm² at six months; p < 0.0001). CT therapy showed initial improvement but was followed by relapse at six months. Both treatments were well tolerated, with only mild transient adverse effects reported. Conclusions: ALA-PDT, especially when applied to non-keratinized oral mucosa, provides superior and longer-lasting therapeutic outcomes than topical CT. The application of novel ALA-loaded emulgel enhances treatment efficacy and tolerability, supporting PDT as a promising alternative for OLP management. Full article

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

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13 pages, 2925 KB

Open AccessArticle

Volatile Compounds as Upcoming Antigiardial Agents: In Vitro Action of Carvacrol, Thymol and p-Cymene on Giardia lamblia Trophozoites

by Marisa Machado, Ana Silva, Rui Linhares, Carlos Cavaleiro and Maria C. Sousa

Pharmaceutics 2025, 17(11), 1380; https://doi.org/10.3390/pharmaceutics17111380 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: Carvacrol and thymol are monoterpenes present in phenolic-rich essential oils extracted from aromatic plants that exhibit antimicrobial activity. This study evaluates the antiprotozoal effect of carvacrol, thymol and their precursor, p-Cymene, against Giardia lamblia and investigates their mechanism of action and cytotoxicity [...] Read more.

Background/Objectives: Carvacrol and thymol are monoterpenes present in phenolic-rich essential oils extracted from aromatic plants that exhibit antimicrobial activity. This study evaluates the antiprotozoal effect of carvacrol, thymol and their precursor, p-Cymene, against Giardia lamblia and investigates their mechanism of action and cytotoxicity profile. Methods: G. lamblia susceptibility, cell viability, swelling and adhesion abilities following application of carvacrol, thymol and p-Cymene were assessed. Ultrastructural changes were evaluated using electron microscopy. Cytotoxicity was determined in mammalian cell lines (murine macrophages RAW 264.7 and bovine aortic endothelial cells) exposed to the same IC₅₀ concentrations effective against G. lamblia. Results: Carvacrol and thymol led to significant inhibition of G. lamblia trophozoite proliferation (IC₅₀ ≅ 50 µg/mL). After 7 h of incubation, total cell number decreased by 30% (p < 0.01) with carvacrol and by 50% (p < 0.001) with thymol, accompanied by reduced motility and adhesion (<20% attached cells). At IC₅₀ concentrations, G. lamblia trophozoites exposed to carvacrol and thymol underwent considerable ultrastructural alterations (e.g., aberrant-shaped cells, mitochondrial swelling and autophagosomal structures). Reduced trophozoite motility and adhesion capacity were also observed. In mammalian cells, thymol showed no significant cytotoxicity, whereas carvacrol significantly reduced viability in both cell lines. In contrast, p-Cymene showed no antigiardial activity. Conclusions: Our data suggests that carvacrol and thymol disrupt G. lamblia trophozoite integrity, possibly through alterations in membrane permeability and osmoregulatory processes. In conclusion, these compounds reveal in vitro antigiardial activity, supporting their potential as antigiardial drugs. Full article

(This article belongs to the Special Issue Natural Products with Antimicrobial Activity and Their Pharmaceutical Delivery Systems)

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26 pages, 7095 KB

Open AccessArticle

How Do Cryo-Milling and Lyophilization Affect the Properties of Solid Dispersions with Etodolac?

by Anna Czajkowska-Kośnik, Radosław A. Wach, Eliza Wolska and Katarzyna Winnicka

Pharmaceutics 2025, 17(11), 1379; https://doi.org/10.3390/pharmaceutics17111379 (registering DOI) - 24 Oct 2025

Abstract

Background: Solid dispersions (SDs) of etodolac (ETD), a poorly water-soluble drug model, were developed to enhance its solubility and dissolution rate by employing various preparation methods and hydrophilic or amphiphilic polymers. Methods: Polyvinylpyrrolidone-poly(vinyl acetate) copolymers (PVP/VA), hydroxypropyl methylcellulose (HPMC) and poloxamer were used [...] Read more.

Background: Solid dispersions (SDs) of etodolac (ETD), a poorly water-soluble drug model, were developed to enhance its solubility and dissolution rate by employing various preparation methods and hydrophilic or amphiphilic polymers. Methods: Polyvinylpyrrolidone-poly(vinyl acetate) copolymers (PVP/VA), hydroxypropyl methylcellulose (HPMC) and poloxamer were used as carriers, while cryo-milling and lyophilization were utilized as routine methods to SDs preparation. Obtained SDs were characterized by drug content, solubility, dissolution rate and moisture content. The physical structure of SDs was estimated via scanning electron microscopy (SEM), whereas differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were employed to assess the potential drug-carrier interactions. Results: SD formulations demonstrated enhanced solubility of ETD in aqueous media, including water and buffers (pH 5.5 and 7.4). DSC analysis confirmed that PVP/VA and poloxamer ensured better ETD dissolution and protection against recrystallization. Furthermore, FTIR indicated the formation of hydrogen bonds between ETD and polymer, particularly in lyophilized dispersions. Conclusions: The optimized SD formulation for ETD contained PVP/VA and/or poloxamer as carriers and was obtained via lyophilization. This SD formulation exhibited the most favorable properties, enhanced the solubility and dissolution of ETD in aqueous media and effectively reduced its crystallinity. Full article

(This article belongs to the Special Issue Solid Dispersions for Drug Delivery: Development, Preparation and In Vitro/In Vivo Characterization)

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12 pages, 2247 KB

Open AccessReview

A Review on the Structure-Response-Efficacy Optimization of Ultrasound-Responsive Micro/Nanobubbles for Cancer Therapy

by Yuting Yang, Yuan Cheng, Zhiguang Chen and Yanjun Liu

Pharmaceutics 2025, 17(11), 1378; https://doi.org/10.3390/pharmaceutics17111378 (registering DOI) - 24 Oct 2025

Abstract

Ultrasound-responsive micro/nanobubbles (MNBs) are promising tools for targeted cancer therapy due to their controllable acoustic activation and real-time imaging. Despite extensive research, the quantitative relationship between bubble structure, acoustic response, and therapeutic efficacy remains poorly understood. This knowledge gap hinders parametric design and [...] Read more.

Ultrasound-responsive micro/nanobubbles (MNBs) are promising tools for targeted cancer therapy due to their controllable acoustic activation and real-time imaging. Despite extensive research, the quantitative relationship between bubble structure, acoustic response, and therapeutic efficacy remains poorly understood. This knowledge gap hinders parametric design and clinical standardization. This review summarizes recent advances from an engineering perspective, highlighting how structural parameters—such as size, shell, gas core, and ligand density—affect acoustic sensitivity and drug release. Furthermore, the roles of microfluidic electroporation and cell membrane coating are discussed in terms of controllable fabrication and preservation of biological functions, highlighting their significance for reproducible and predictable therapies. In conclusion, this review establishes a “Structure-Response-Efficacy (S-R-E)” framework to summarize the core relationships between structural design and acoustic modulation. We propose an engineering strategy based on a standardized parameter system to guide the predictable design and clinical translation of ultrasound-based theranostic platforms. Full article

(This article belongs to the Special Issue Combining Ultrasound and Microbubbles/Nanobubbles for Enhancing the Effects of Cancer Therapies)

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Graphical abstract

33 pages, 1762 KB

Open AccessReview

Advances in Oral Drug Delivery Systems for Natural Polyunsaturated Fatty Acids: Enhancing Bioavailability and Therapeutic Potential

by Matheus Felipe Zazula, Roberta Pozzan, Guilherme Anacleto dos Reis, Mônica Maciel, Thomas Horlem, Tayná Nery Banckes, Josilene Lima Serra Pereira, Ceci Sales-Campos, Luiz Claudio Fernandes, Walter José Martinez-Burgos and Katya Naliwaiko

Pharmaceutics 2025, 17(11), 1377; https://doi.org/10.3390/pharmaceutics17111377 (registering DOI) - 24 Oct 2025

Abstract

Omega-3 and omega-6 fatty acids play essential roles in human health, being widely used in the prevention and treatment of various conditions, such as cardiovascular diseases, inflammation, and metabolic disorders. However, their oral administration faces significant challenges, including low solubility, rapid oxidation, and [...] Read more.

Omega-3 and omega-6 fatty acids play essential roles in human health, being widely used in the prevention and treatment of various conditions, such as cardiovascular diseases, inflammation, and metabolic disorders. However, their oral administration faces significant challenges, including low solubility, rapid oxidation, and low bioavailability, which limit their therapeutic efficacy. This article explores recent advances in oral drug delivery systems designed for polyunsaturated fatty acids, highlighting how innovative technologies, such as nanoemulsions, liposomes, microencapsulation, and solid lipid nanoparticles (SLNs/NLCs), can improve their stability, absorption and clinical performance. In addition, the main natural sources of these compounds, as well as their extraction and purification methods, and the challenges related to their absorption and metabolism are discussed. This narrative review was based mainly on a comprehensive search of peer-reviewed literature published between 2015 and 2025 in PubMed, Scopus, and Web of Science. The therapeutic benefits of these emerging approaches are analyzed by comparing conventional methods with modern delivery strategies to optimize the use of omega-3 and omega-6 in the body. Finally, the article outlines future perspectives and regulatory challenges associated with these technologies, highlighting their potential to revolutionize the administration of essential fatty acids and broaden their applications in medicine and nutrition. Full article

(This article belongs to the Special Issue Drug Delivery for Natural Extract Applications)

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2 pages, 1329 KB

Open AccessCorrection

Correction: Badea et al. Carboxyl-Functionalized Carbon Nanotubes Loaded with Cisplatin Promote the Inhibition of PI3K/Akt Pathway and Suppress the Migration of Breast Cancer Cells. Pharmaceutics 2022, 14, 469

by Madalina Andreea Badea, Mihaela Balas, Mariana Prodana, Florentina Gina Cojocaru, Daniela Ionita and Anca Dinischiotu

Pharmaceutics 2025, 17(11), 1376; https://doi.org/10.3390/pharmaceutics17111376 (registering DOI) - 24 Oct 2025

Abstract

Error in Figure [...] Full article

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19 pages, 873 KB

Open AccessArticle

Extended Stability of Ascorbic Acid in Pediatric TPN Admixtures: The Role of Storage Temperature and Emulsion Integrity

by Rafał Chiczewski, Żaneta Sobol, Alicja Pacholska and Dorota Wątróbska-Świetlikowska

Pharmaceutics 2025, 17(11), 1375; https://doi.org/10.3390/pharmaceutics17111375 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: This study assessed the chemical and physical stability of ascorbic acid in pediatric total parenteral nutrition (TPN) admixtures under conditions reflecting both hospital compounding and home administration. Methods: Two storage protocols were examined: (A) refrigerated storage (15 days, 4 ± 2 °C) [...] Read more.

Background/Objectives: This study assessed the chemical and physical stability of ascorbic acid in pediatric total parenteral nutrition (TPN) admixtures under conditions reflecting both hospital compounding and home administration. Methods: Two storage protocols were examined: (A) refrigerated storage (15 days, 4 ± 2 °C) followed by addition of ascorbic acid and a 24-h period of storage at room temperature, and (B) vitamin supplementation within 24 h after composing and storage at 21 ± 2 °C. A validated high-performance liquid chromatography (HPLC) method was used to quantify ascorbic acid degradation. Physical stability was evaluated via optical microscopy, dynamic light scattering (DLS), laser diffraction (LD), zeta potential, and pH measurement. Results: Ascorbic acid content remained above 90% of the declared value in both protocols, although gradual degradation was observed with increasing storage time and temperature. Emulsion droplet sizes remained within pharmacopeial limits (<500 nm), and no coalescence or phase separation was detected. Zeta potential values (−20 to −40 mV) confirmed kinetic stability, while pH ranged from 5.8 to 6.2, remaining within acceptable safety margins. Conclusions: Vitamin C in pediatric TPN admixtures is stable under refrigerated conditions for up to 15 days. However, the additional 24 h at room temperature resulted in measurable loss of ascorbic acid content, suggesting a need for improved guidance in home-based parenteral nutrition, particularly regarding transport and handling. The study underscores the importance of strict cold-chain maintenance and highlights the role of emulsion matrix and packaging in protecting labile vitamins. This research provides practical implications for hospital pharmacists and caregivers, supporting better formulation practices and patient safety in pediatric home TPN programs. Full article

(This article belongs to the Section Clinical Pharmaceutics)

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18 pages, 4483 KB

Open AccessArticle

Simian Immunodeficiency Virus-Derived Extracellular Vesicles Induce a Chronic Inflammatory Phenotype in Healthy Astrocytes Unresolved by Anti-Retroviral Therapy

by Alison R. Van Zandt, Miranda D. Horn, Ryan P. McNamara, Tiffany A. Peterson, Nicholas J. Maness, Blake Schoest, Elise M. Frost, Yijun Zhou, Matilda J. Moström, Dirk P. Dittmer and Andrew G. MacLean

Pharmaceutics 2025, 17(11), 1374; https://doi.org/10.3390/pharmaceutics17111374 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: Extracellular vesicles (EVs) are key mediators of intercellular communication and are implicated in the neuropathogenesis of HIV-associated brain injury (HABI). However, their direct effects on glial cells, particularly in the context of antiretroviral therapy (ART), remain incompletely understood. Methods: In this study, [...] Read more.

Background/Objectives: Extracellular vesicles (EVs) are key mediators of intercellular communication and are implicated in the neuropathogenesis of HIV-associated brain injury (HABI). However, their direct effects on glial cells, particularly in the context of antiretroviral therapy (ART), remain incompletely understood. Methods: In this study, we investigated how EVs from naïve, Simian Immunodeficiency Virus (SIV)-infected, and SIV-infected ART-treated rhesus macaques impact primary mixed glial cultures. Results: Through multiple, sequential applications mimicking chronic exposure, we found that EVs from SIV-infected animals significantly reduced glial expansion and induced a simplified, reactive astrocyte morphology indicative of neuroinflammatory stress. In contrast, EVs from naïve animals supported glial health. EVs derived from ART-treated animals provided partial protection from SIV-induced effects, yet still suppressed glial proliferation and failed to fully restore normal morphology. Furthermore, cytokine profiling revealed that both SIV and SIV + ART EVs induced a sustained proinflammatory secretory phenotype, characterized by elevated IL-6, IL-8, and IFN-γ. Conclusions: Our findings demonstrate that systemically circulating EVs in SIV infection are potential drivers of glial dysfunction. The persistence of these pathogenic EV effects despite ART suggests a vesicle-mediated mechanism that may contribute to chronic neuroinflammation and cognitive impairment in virally suppressed individuals. Full article

(This article belongs to the Special Issue Gene- and Peptide-Based Therapeutics for Neurodegenerative Disorders)

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4 pages, 177 KB

Open AccessEditorial

Pharmaceutical Applications of Metal Complexes and Derived Materials

by Pedro Ivo da Silva Maia

Pharmaceutics 2025, 17(11), 1373; https://doi.org/10.3390/pharmaceutics17111373 (registering DOI) - 24 Oct 2025

Abstract

Medicinal Inorganic Chemistry has demonstrated incomparable potential in the design and development of metal complexes and related materials for a wide spectrum of pharmaceutical applications, including those for therapeutic, diagnostic, and theranostic purposes [...] Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Metal Complexes and Derived Materials)

46 pages, 2002 KB

Open AccessReview

Advances in 3D-Printed Drug Delivery and Screening Platforms for Bone Disease Therapy

by Iosif-Aliodor Timofticiuc, Alex-Gabriel Grigore, Elena-Teodora Tomescu, Teona-Maria Vlaicu, Serban Dragosloveanu, Andreea-Elena Scheau, Ana Caruntu, Christiana Diana Maria Dragosloveanu, Ioana Anca Badarau, Andreea Cristiana Didilescu, Constantin Caruntu and Cristian Scheau

Pharmaceutics 2025, 17(11), 1372; https://doi.org/10.3390/pharmaceutics17111372 - 23 Oct 2025

Abstract

Bone diseases such as osteomyelitis, osteosarcoma, and osteoarthritis, as well as conditions caused by metabolic imbalances, including osteoporosis, require more efficient and optimized therapies. Systemic drug administration entails major disadvantages like cytotoxicity and adverse reactions, which can lead to serious complications or death. [...] Read more.

Bone diseases such as osteomyelitis, osteosarcoma, and osteoarthritis, as well as conditions caused by metabolic imbalances, including osteoporosis, require more efficient and optimized therapies. Systemic drug administration entails major disadvantages like cytotoxicity and adverse reactions, which can lead to serious complications or death. Therefore, local drug administration alternatives are currently under investigation for different pharmacological therapies. New vectors were created to improve control over administration, and 3D-printed and patient-specific drug delivery systems have been tested, revealing great potential. Moreover, 3D-printed platforms that mimic human tissues for drug testing are innovative solutions emerging for the pharmaceutical industry. Situated between in vitro and in vivo testing on human patients, they offer the advantage of reproducing functional architecture, providing results that are closer to those encountered in clinical trials performed on patients. In our article, we present the two categories of 3D systems, from the perspective of main drug groups (antibiotics, anticancer, and anti-inflammatory) as well as other categories, alongside their advantages, limitations, and their adaptations to 3D printing technologies. This article also highlights the technological drawbacks encountered in both delivery and screening systems, as well as the printing methods and materials used, including their physical and biological properties. Full article

(This article belongs to the Special Issue Cutting-Edge 3D Printing Technology for Drug Delivery and Tissue Engineering)

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27 pages, 9862 KB

Open AccessArticle

Post-Synthesis Modulation of the Physicochemical Properties of Green-Synthesized Iron Oxide Nanoparticles with Tween 80 to Enhance Their Antibacterial Activity and Biocompatibility

by Marwa R. Bakkar, Alaa M. Ali, Gehad E. Elkhouly, Nermeen R. Raya, Terry W. Bilverstone, Nicholas P. Chatterton, Gary R. McLean and Yasmin Abo-Zeid

Pharmaceutics 2025, 17(11), 1371; https://doi.org/10.3390/pharmaceutics17111371 - 23 Oct 2025

Abstract

Background: Iron oxide nanoparticles (IONPs) have broad-spectrum antimicrobial activity, with negligible potential for resistance development, excellent biocompatibility, and therefore, could be promising alternatives to conventional antimicrobials. However, their industrial-scale production relies on chemical synthesis that involves toxic reagents, imposing potential environmental hazards. [...] Read more.

Background: Iron oxide nanoparticles (IONPs) have broad-spectrum antimicrobial activity, with negligible potential for resistance development, excellent biocompatibility, and therefore, could be promising alternatives to conventional antimicrobials. However, their industrial-scale production relies on chemical synthesis that involves toxic reagents, imposing potential environmental hazards. In contrast, green synthesis offers an eco-friendly alternative, but our previous study found that green-synthesized IONPs (IONPs-G) exhibited a lower antibacterial activity and a higher cytotoxicity compared to chemically synthesized counterparts, likely due to nanoparticle aggregation. Objectives: To address this challenge, the current study presents a simple, effective, economic, scalable, and eco-friendly strategy to optimize the physicochemical properties of IONPs-G post-production without requiring extensive modifications to synthesis parameters. Methods: IONPs-G were dispersed in a solvent mixture containing Tween 80 (Tw80). Subsequently, in vitro antimicrobial and in vivo cytotoxicity studies on rabbits’ skin and eye were conducted. Results: The formed nanoparticles’ dispersion (IONPs-GTw80) had a particle size of 9.7 ± 2.1 nm, a polydispersity index of 0.111 ± 0.02, and a zeta potential of −11.4 ± 2.4 mV. MIC of IONPs-GTw80 values against S. aureus and E. coli were reduced by more than ten-fold compared to IONPs-G. MBC was twice MIC, confirming the bactericidal activity of IONPs-GTw80. In vivo studies of IONPs-GTw80 confirmed their biocompatibility with intact/abraded skin and eyes; this was further confirmed by histopathological and biochemical analyses. Conclusions: IONPs-GTw80 might be recommended as a disinfectant in healthcare settings or a topical antimicrobial agent for treatment of infected wounds. Nevertheless, further studies are required for their clinical translation. Full article

(This article belongs to the Special Issue Advanced Metal-Based Nano-Drug Delivery Systems for Antimicrobial Therapy)

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15 pages, 4863 KB

Open AccessArticle

Estimated Glomerular Filtration Rate Variability in Patients with Diabetes Receiving SGLT2 Inhibitors Versus DPP4 Inhibitors

by Yi-Wei Kao, Tze-Fan Chao, Yu-Wen Cheng, Shao-Wei Chen and Yi-Hsin Chan

Pharmaceutics 2025, 17(11), 1370; https://doi.org/10.3390/pharmaceutics17111370 - 23 Oct 2025

Abstract

Background: Major clinical trials regarding sodium–glucose cotransporter 2 inhibitors (SGLT2is) have focused on estimated glomerular filtration rate (eGFR) slope and composite kidney outcomes, with limited evaluation of eGFR variability as a kidney outcome or its long-term implications in patients receiving SGLT2i versus placebo. [...] Read more.

Background: Major clinical trials regarding sodium–glucose cotransporter 2 inhibitors (SGLT2is) have focused on estimated glomerular filtration rate (eGFR) slope and composite kidney outcomes, with limited evaluation of eGFR variability as a kidney outcome or its long-term implications in patients receiving SGLT2i versus placebo. Methods: This retrospective study analyzed 3777 propensity score-matched patients with type 2 diabetes receiving either SGLT2i or dipeptidyl peptidase-4 inhibitor (DPP4i) between June 2016 and December 2021. Each patient had eGFR data at three time points before (−15, −9, and −3 months) and after (3, 9, and 15 months) the drug-index date. eGFR variability was assessed using the coefficient of variation (COV) and standard deviation (SD) of eGFR values. Results: SGLT2i therapy was associated with a significant reduction in eGFR variability by both COV (from 0.072 (0.001) to 0.069 (0.001); p = 0.014) and SD (mL/min/1.73 m²) (from 5.34 (0.07) to 4.82 (0.07); p < 0.001). In contrast, DPP4i therapy resulted in increased COV (from 0.072 (0.001) to 0.080 (0.001); p < 0.001) and no significant improvement in SD (from 5.06 (0.07) to 5.22 (0.07); p = 0.082). Greater reduction in eGFR variability was observed in SGLT2i relative to DPP4i with high pre-treatment eGFR variability, pre-existing chronic kidney disease, or rapid pre-treatment eGFR decline. Greater pre-treatment eGFR variability predicted risk of major adverse kidney events (MAKEs) and abrupt kidney decline in DPP4i-treated patients, but not in those on SGLT2is. SGLT2i consistently reduced the risk of MAKE and abrupt kidney decline across the spectrum of pre-treatment eGFR variability, with a greater risk reduction on the MAKE for SGLT2i versus DPP4i therapy with a higher pre-treatment eGFR variability estimated by SD (p interaction = 0.014). Conclusions: SGLT2i therapy improved eGFR variability and reduced the risk of adverse kidney outcomes compared to DPP4i, particularly in patients with higher pre-treatment eGFR variability. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring as a Useful Tool in Therapy Improvement, 3rd Edition)

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15 pages, 1556 KB

Open AccessArticle

In-Situ Forming Polyester Implants for Sustained Intravesical Oxybutynin Release

by Michael Uwe Hartig, Jan Appelhaus, Marc Vollenbröker and Alf Lamprecht

Pharmaceutics 2025, 17(11), 1369; https://doi.org/10.3390/pharmaceutics17111369 - 23 Oct 2025

Abstract

Background/Objectives: Neurogenic detrusor overactivity (NDO), caused by spinal cord injury or multiple sclerosis, is marked by involuntary bladder contractions and reduced urine volume. Current therapy requires frequent catheterization with oxybutynin hydrochloride. This work investigates a novel in situ forming implant (ISFI) with PLGA [...] Read more.

Background/Objectives: Neurogenic detrusor overactivity (NDO), caused by spinal cord injury or multiple sclerosis, is marked by involuntary bladder contractions and reduced urine volume. Current therapy requires frequent catheterization with oxybutynin hydrochloride. This work investigates a novel in situ forming implant (ISFI) with PLGA as a sustained-release formulation for the urinary bladder by quantifying drug release, polymer degradation, and solvent release in vitro. Methods/Results: Various formulation parameters were investigated, of which the drug load and PLGA termination were found to have the highest impact on drug release and polymer degradation. An increase in drug load from 1.5% to 7.5% for implants with the ester-terminated PLGA enhanced the degradation from 0% to around 20% after 7 d. Oxybutynin base catalyzed the polymer degradation, as implants with PLGA 502 and 15% drug load exhibited a degradation of 33% compared to 0% for 1.5% drug load. In the case of 1.5% drug load, the degradation could be increased by the use of an acid-terminated PLGA, compared to an ester-terminated. Conclusion: In summary, the feasibility of a biodegradable ISFI for NDO patients was shown, which could allow a single administration up to approx. one week, improving the quality of life for NDO patients. Additionally, this work provided insight to which formulation parameters can help to parallel drug release and polymer degradation. Full article

(This article belongs to the Special Issue PLGA Implants for Controlled Drug Release)

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