Pharmaceutics

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Open AccessArticle

In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Atorvastatin: A Focus on Cervical and Head and Neck Cancers

by Hiba F. Muddather, Noémi Bózsity, György T. Balogh, Zsuzsanna Schelz and István Zupkó

Pharmaceutics 2025, 17(10), 1253; https://doi.org/10.3390/pharmaceutics17101253 - 24 Sep 2025

Abstract

Background/Objectives: In spite of substantial treatment progress, cancer persists as a leading health challenge. With the slow advancement in developing new anticancer agents, drug repurposing provides a promising strategy to enhance cancer therapy. This study investigates the antiproliferative and antimetastatic properties of [...] Read more.

Background/Objectives: In spite of substantial treatment progress, cancer persists as a leading health challenge. With the slow advancement in developing new anticancer agents, drug repurposing provides a promising strategy to enhance cancer therapy. This study investigates the antiproliferative and antimetastatic properties of two 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, atorvastatin and rosuvastatin, which represent lipophilic and hydrophilic statins, respectively. Methods: Growth inhibition was evaluated in a panel of human cancer cells using the standard MTT assay. Apoptotic effects were determined through flow cytometry, caspase-3 activity assay, mitochondrial membrane potential assessment, and Hoechst/Propidium iodide fluorescent double staining. Migration and invasion assays were conducted using wound-healing and Boyden chamber assays, respectively. Results: Atorvastatin demonstrated more pronounced growth-inhibitory effects than rosuvastatin, with the IC₅₀ values in the range of 2.57–61.01 µM. Atorvastatin exhibited both biochemical and morphological indicators of apoptosis. Flow cytometry revealed cell cycle disruptions and increased sub-G1 apoptotic populations in HPV-positive oral squamous carcinoma cells (UPCI-SCC-154) and HPV-negative cervical cancer cells (C33A). Atorvastatin also significantly inhibited cell migration and invasion in the tested cell lines. Conclusions: Our results highlight the promising anticancer potential of atorvastatin in cervical cancer and oral squamous carcinoma cells. However, these findings are limited to in vitro models and warrant further in vivo validation. Full article

(This article belongs to the Special Issue Drug Delivery Strategies and Novel Approaches for Cancer Treatment)

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Open AccessReview

A Scoping Review of Recent Developments in Cellulose-Derived Hydrogels for Dental Applications

by Smriti Aryal A C, Md Sofiqul Islam, Marwan Mansoor Mohammed, Lina Abu-Nada, Elaf Akram Abdulhameed, Sangeetha Narasimhan, Snigdha Pattanaik and Ghee Seong Lim

Pharmaceutics 2025, 17(10), 1252; https://doi.org/10.3390/pharmaceutics17101252 - 24 Sep 2025

Abstract

Application of cellulose-based hydrogels in dentistry has gained significant attention. They are emerging as novel biomaterials in the field of tissue engineering, regeneration, and drug delivery in dentistry. The objective of this scoping review is to highlight and summarize recent developments of cellulose-based [...] Read more.

Application of cellulose-based hydrogels in dentistry has gained significant attention. They are emerging as novel biomaterials in the field of tissue engineering, regeneration, and drug delivery in dentistry. The objective of this scoping review is to highlight and summarize recent developments of cellulose-based hydrogels in their designs, reported applications, and laboratory functions. Methods: Between the periods of November 2014 and November 2024 (searches completed and datasets locked on 30th Nov 2024), the comprehensive electronic database search was performed in PubMed, Science Direct, Scopus, and MyEBSCO. All the studies that are related to cellulose-based and dentistry were included in this review. This review followed the PRISMA-ScR guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews. Results: Out of 518 entries found, 13 studies were qualified for inclusion. When comparative analysis of cellulose-based hydrogel-related studies was performed, most of the included studies were conducted in vitro, and they highlighted significant advancements in their functionality, their inert properties such as mechanical adaptability, design, bioactivity, biodegradability, and clinical potential. Conclusions: Cellulose-based hydrogels show great potential in regenerative dentistry, providing a biomimetic platform for tissue regeneration and drug delivery. Addressing present challenges and exploring pathways towards clinical translation will be critical to know their potential in the future. This review critically evaluates the strengths and weaknesses that are used in the current studies and thus, it provides a resource for future research directions for innovations in the field of regenerative dentistry and tissue engineering. Full article

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research, 2nd Edition)

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Open AccessArticle

The Antidepressant Effect of Targeted Release of Ketamine-Loaded Nanodroplets Stimulated by Low-Intensity Focused Ultrasound

by Bailing Wu, Yu Xu, Yuhang Xie, Youzhuo Li, Yue Huang, Yuran Feng and Mei Zhu

Pharmaceutics 2025, 17(10), 1251; https://doi.org/10.3390/pharmaceutics17101251 - 24 Sep 2025

Abstract

Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose [...] Read more.

Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose intravenous (IV) administration in a mice model of depression. Low-intensity focused ultrasound (LIFU) was employed to induce transcranial, region-specific drug release in the lateral habenula (LHb). Methods: Ket-NDs were synthesized using a thin-film hydration method with sonication and emulsification, incorporating perfluoropentane as the core material. Characterization was performed using light microscopy, cryogenic scanning electron microscopy (cryo-SEM), transmission electron microscopy, and dynamic light scattering (DLS). Drug EE and loading efficiency (LE) were quantified by reversed-phase high-performance liquid chromatography. A chronic restraint stress model was established, and Ket-NDs were administered intravenously followed by LIFU targeting the LHb. Antidepressant efficacy and biosafety were systematically evaluated. Results: (1) Ket-NDs exhibited uniform spherical morphology and a narrow size distribution, as confirmed by DLS (particle size: 139.75 ± 9.43 nm; Polydispersity index: 0.225 ± 0.025) and cryo-SEM analysis (number-average diameter: 109.5 ± 10.4 nm). The zeta potential was −15.93 ± 5.906 mV, and the formulation remained stable under 4 °C storage. (2) Ket-NDs demonstrated high EE (78.25 ± 16.13%) and LE (15.55 ± 4.49%). (3) In depressive mice, IV administration of Ket-NDs followed by LIFU targeting the LHb significantly improved behavioral outcomes: increased locomotor activity in the open field test, elevated sucrose preference index, and reduced immobility time in the tail suspension test. (4) Safety assessments revealed no significant organ toxicity or brain tissue damage in ultrasound-exposed regions. Conclusions: In summary, this study developed stable Ket-NDs. When combined with LIFU, they enable precise regional drug delivery to the brain, showcasing a promising treatment strategy for depression with reduced systemic side effects. Full article

(This article belongs to the Special Issue Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation, 2nd Edition)

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Open AccessArticle

In Vitro Comparative Study on Oppositely Charged Donepezil-Loaded Intranasal Liposomes

by Elika Valehi, Gábor Katona, Dorina Gabriella Dobó and Ildikó Csóka

Pharmaceutics 2025, 17(10), 1250; https://doi.org/10.3390/pharmaceutics17101250 - 24 Sep 2025

Abstract

Background/Objectives: Intranasal delivery is a promising approach for targeting the central nervous system (CNS); however, most of the drugs show poor permeability through the nasal mucosa. Nanocarriers such as liposomes can improve nasal drug absorption; however, the surface charge of liposomes has [...] Read more.

Background/Objectives: Intranasal delivery is a promising approach for targeting the central nervous system (CNS); however, most of the drugs show poor permeability through the nasal mucosa. Nanocarriers such as liposomes can improve nasal drug absorption; however, the surface charge of liposomes has a key role in the nasal mucosal uptake process. Therefore, the present study aimed to formulate and compare the intranasal applicability of oppositely charged liposomes loaded with donepezil hydrochloride (DPZ) as CNS-active model compound using two different charge inducers, the negatively charged dicethyl phosphate (DCP) and the positively charged stearylamine (SA). Methods: Liposomes were prepared with a fixed phosphatidylcholine (PC)/cholesterol (CH) 7:2 molar ratio, while the effect of DCP and SA was studied in a 0.5:2 molar ratio. The most important properties for intranasal administration were studied, e.g., colloidal parameters, drug release and permeability behavior, and mucoadhesion. Results: It has been revealed that the reduction in liposome vesicle size is directly proportional to the amount of DCP, while it is inversely proportional to the amount of SA. This was also supported by the drug release studies—the lower vesicle size resulted in faster drug release. Both charge inducers increased the drug encapsulation efficiency (~60–80%) through tighter packing or increased spacing of the lipid bilayer structure. DCP also improved the in vitro nasal permeability compared to the initial DPZ solution. The positively charged SA showed more remarkable mucoadhesive properties than DCP. Conclusions: We can conclude that both charge inducers can be useful for improving nasal absorption of liposomal carriers, DCP in higher (PC:CH:DCP 7:2:2), while SA in lower concentrations (PC:CH:SA 7:2:0.5). Full article

(This article belongs to the Special Issue Advances in Colloidal Drug Delivery Systems)

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Open AccessReview

Recent Techniques to Improve Amorphous Dispersion Performance with Quality Design, Physicochemical Monitoring, Molecular Simulation, and Machine Learning

by Hari Prasad Bhatta, Hyo-Kyung Han, Ravi Maharjan and Seong Hoon Jeong

Pharmaceutics 2025, 17(10), 1249; https://doi.org/10.3390/pharmaceutics17101249 - 24 Sep 2025

Abstract

Amorphous solid dispersions (ASDs) represent a promising formulation strategy for improving the solubility and bioavailability of poorly water-soluble drugs, a major challenge in pharmaceutical development. This review provides a comprehensive analysis of the physicochemical principles underlying ASD stability, with a focus on drug–polymer [...] Read more.

Amorphous solid dispersions (ASDs) represent a promising formulation strategy for improving the solubility and bioavailability of poorly water-soluble drugs, a major challenge in pharmaceutical development. This review provides a comprehensive analysis of the physicochemical principles underlying ASD stability, with a focus on drug–polymer miscibility, molecular mobility, and thermodynamic properties. The main manufacturing techniques including hot-melt extrusion, spray drying, and KinetiSol^® dispersing are discussed for their impact on formulation homogeneity and scalability. Recent advances in excipient selection, molecular modeling, and in silico predictive approaches have transformed ASD design, reducing dependence on traditional trial-and-error methods. Furthermore, machine learning and artificial intelligence (AI)-based computational platforms are reshaping formulation strategies by enabling accurate predictions of drug–polymer interactions and physical stability. Advanced characterization methods such as solid-state NMR, IR, and dielectric spectroscopy provide valuable insights into phase separation and recrystallization. Despite these technological innovations, ensuring long-term stability and maintaining supersaturation remain significant challenges for ASDs. Integrated formulation design frameworks, including PBPK modeling and accelerated stability testing, offer potential solutions to address these issues. Future research should emphasize interdisciplinary collaboration, leveraging computational advancements together with experimental validation to refine formulation strategies and accelerate clinical translation. The scientists can unlock the full therapeutic potential with emerging technologies and a data-driven approach. Full article

(This article belongs to the Special Issue Advances in Solid and Semi-Solid Dosage Form Design for Enhanced Biopharmaceutical Performance)

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Open AccessArticle

Analgesic Effect of a Novel Intravenous Ibuprofen-Low-Dose Tramadol Combination: A Multimodal Approach to Moderate-to-Severe Postoperative Dental Pain

by M. Rosario Salas-Butrón, Leonor Laredo-Velasco, Ana B. Rivas-Paterna, Aránzazu González-Corchon, Mario F. Muñoz-Guerra, Alberto M. Borobia, Julio J. Acero-Sanz, Carla Pérez-Ingidua, Francisco Abad-Santos, Jose-Luis Cebrián, María Ángeles Gálvez-Múgica, Irene Serrano-García, Carmen Portolés-Díez, Lucia Llanos, Dolores Martínez, Nuria Sanz, Carlos Calandria, Emilio Vargas-Castrillón, Rafael Martín-Granizo and Antonio Portolés-Pérez

Pharmaceutics 2025, 17(10), 1248; https://doi.org/10.3390/pharmaceutics17101248 - 24 Sep 2025

Abstract

Background: Drug combinations with complementary mechanisms of action are able to achieve effective analgesia at lower doses, thereby reducing the risk of adverse effects (AEs). This study evaluated the analgesic efficacy and tolerability of two fixed-dose combinations (FDCs) of ibuprofen/tramadol (IBU/TRA) compared with [...] Read more.

Background: Drug combinations with complementary mechanisms of action are able to achieve effective analgesia at lower doses, thereby reducing the risk of adverse effects (AEs). This study evaluated the analgesic efficacy and tolerability of two fixed-dose combinations (FDCs) of ibuprofen/tramadol (IBU/TRA) compared with tramadol and a placebo. Methods: This multicenter, randomized, double-blind, dose-finding, pilot clinical trial compared IBU/TRA (400/37.5 mg and 400/75 mg) with 100 mg of tramadol and a placebo in patients with moderate-to-severe pain following dental surgery. The primary endpoints were pain intensity at 6 h (PI_6h) and the pain intensity difference from baseline to 6 h (PID_6h). PID_7h, the sum of pain intensity differences from baseline to 7 h (SPID_0–7h), pain relief (PAR_7h), total pain relief (TOTPAR_7h), the use of rescue medication and AEs were also assessed. Results: Seventy-two patients were randomized and evaluated. Both FDCs showed superiority over the placebo for PI_6h and PID_6h (p < 0.05) but were not significantly different from 100 mg of tramadol. The statistical superiority of FDCs over the placebo was observed for PID_7h, SPID_0–7h, PAR_7h and TOTPAR_7h. The percentage of patients receiving rescue medication was higher in the placebo (94.1%) and tramadol (52.6%) groups than the FDC groups (35.3% and 36.8% for 400/37.5 mg and 400/75 mg, respectively). A post hoc analysis showed that the FDCs had a superior analgesic efficacy to 100 mg of tramadol in the SPID_0–4h (p < 0.005). The incidence of AEs was comparable between treatment groups. Conclusions: Both FDCs of IBU/TRA provided superior analgesic efficacy compared to the placebo. We propose using SPID_0–4h as the preferred variable for evaluating the efficacy of this type of drug combination. Full article

(This article belongs to the Special Issue Emerging Drugs and Formulations for Pain Treatment)

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Open AccessArticle

Fabrication and Characterization of Curcumin-Complexed Nanoparticles Using Coconut Protein Nanoparticles

by Leila Ziaeifar, Maryam Salami, Gholamreza Askari, Zahra Emam-Djomeh, Raimar Loebenberg, Michael J Serpe and Neal M. Davies

Pharmaceutics 2025, 17(10), 1247; https://doi.org/10.3390/pharmaceutics17101247 - 24 Sep 2025

Abstract

Background/Objectives: Curcumin (Cur) has various biological properties, including anti-microbial, antioxidant, anticancer, anti-diabetic, anticarcinogenic, antitumor, and anti-inflammatory activities. However, using Cur in functional food products is challenging because of its low solubility in an aqueous environment, rapid degradation, and low bioavailability. Nanostructure delivery [...] Read more.

Background/Objectives: Curcumin (Cur) has various biological properties, including anti-microbial, antioxidant, anticancer, anti-diabetic, anticarcinogenic, antitumor, and anti-inflammatory activities. However, using Cur in functional food products is challenging because of its low solubility in an aqueous environment, rapid degradation, and low bioavailability. Nanostructure delivery systems provide a high surface area to volume ratio and sustainable release properties. Methods: Coconut protein nanoparticles (CPNPs) have been fabricated through heat treatment at 85 °C and pH 2 for 5 h. The formation of CPNP-Cur was used to improve Cur solubility, followed by antioxidant activity at neutral pH in an aqueous solution. Results: The maximum efficiency and loading capacity of Cur in CPNP were 96.6% and 19.32 µg/mg protein, respectively. Scanning electron microscopy indicated the spherical and organized shape of CPNP with a small size of 80 nm. The fluorescence quenching of CPNP-Cur confirmed the potential of Cur to bind to the tryptophane and tyrosine residues in CPNP. The structural properties of CPNP and CPNP-Cur were investigated using FTIR and X-ray diffraction. The antioxidant activity of samples, measured with the ABTS radical scavenging method, demonstrated that the antioxidant capacity of the aqueous solution of Cur was significantly enhanced through the encapsulation into CPNP. The steady release of Cur was observed in the simulated gastrointestinal tract, and the percentage of the cumulative release increased up to 29.2% after 4 h. Conclusions: Our findings suggest that CPNP was a suitable nanocarrier for Cur due to improved antioxidant activity and controlled release behavior. These results are valuable for the development of coconut protein nanoparticles to use as a novel nano-delivery system of bioactive components. Full article

(This article belongs to the Special Issue Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release)

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Open AccessSystematic Review

Skin Microbiome, Nanotoxicology, and Regulatory Gaps: Chronic Cosmetic Exposure and Skin Barrier Dysfunction—A Systematic Review

by Loredana-Elena Pîrvulescu, Sorana-Cristiana Popescu, Roman Popescu, Vlad-Mihai Voiculescu and Carolina Negrei

Pharmaceutics 2025, 17(10), 1246; https://doi.org/10.3390/pharmaceutics17101246 - 24 Sep 2025

Abstract

Background: Engineered nanoparticles (NPs)—titanium dioxide, silver, zinc oxide and silica—are widely used in cosmetics for UV protection, antimicrobial activity and texturising effects. Chronic consumer-level exposure may impair skin-barrier integrity, disturb microbiome composition and dysregulate immune signalling via the gut–skin axis. Current regulatory frameworks [...] Read more.

Background: Engineered nanoparticles (NPs)—titanium dioxide, silver, zinc oxide and silica—are widely used in cosmetics for UV protection, antimicrobial activity and texturising effects. Chronic consumer-level exposure may impair skin-barrier integrity, disturb microbiome composition and dysregulate immune signalling via the gut–skin axis. Current regulatory frameworks typically omit chronic- or microbiome-focused safety assessments, leaving potential gaps. Objectives: This study aimed to evaluate the long-term effects of cosmetic-relevant NPs (titanium dioxide, silver, zinc oxide, silica) on skin and gut microbiota, epithelial-barrier integrity and immune signalling—including telocyte- and exosome-mediated pathways—and to identify regulatory shortcomings, particularly the absence of microbiome endpoints, validated chronic models and consideration of vulnerable populations. Methods: Following PRISMA 2020, PubMed, Scopus and Web of Science were searched for English-language in vivo animal or human studies (December 2014–April 2025) meeting chronic-exposure criteria (≥90 days in rodents or >10% of lifespan in other species; for humans, prolonged, repetitive application over months to years consistent with cosmetic use). Although not registered in PROSPERO, the review adhered to a pre-specified protocol. Two independent reviewers screened studies; risk of bias was assessed using a modified SYRCLE tool (animal) or adapted NIH guidance (zebrafish). Owing to heterogeneity, findings were synthesised narratively. Results: Of 600 records, 450 unique articles were screened, 50 full texts were assessed and 12 studies were included. Oral exposure predominated and was associated with dysbiosis, barrier impairment, immune modulation and metabolic effects. Dermal models showed outcomes from minimal change to pronounced immune activation, contingent on host susceptibility. Comparative human–animal findings are summarised; telocyte and exosome pathways were largely unexplored. Regulatory reviews (EU SCCS, US FDA and selected Asian frameworks) revealed no requirements for chronic microbiome endpoints. Limitations: Evidence is limited by the small number of eligible studies, heterogeneity in NP characteristics and exposure routes, predominance of animal models and a scarcity of longitudinal human data. Conclusions: Cosmetic nanoparticles may disrupt the microbiome, compromise barrier integrity and trigger immune dysregulation—risks amplified in vulnerable users. Existing regulations lack requirements for chronic exposure, microbiome endpoints and testing in vulnerable groups, and neglect mechanistic pathways involving telocytes and exosomes. Long-term, real-world exposure studies integrating gut–skin microbiome and immune outcomes, and harmonised global nanomaterial-safety standards, are needed to ensure safer cosmetic innovation. Full article

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

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Open AccessCorrection

Correction: Bonaccorso et al. Optimization of Curcumin Nanocrystals as Promising Strategy for Nose-to-Brain Delivery Application. Pharmaceutics 2020, 12, 476

by Angela Bonaccorso, Maria Rosa Gigliobianco, Rosalia Pellitteri, Debora Santonocito, Claudia Carbone, Piera Di Martino, Giovanni Puglisi and Teresa Musumeci

Pharmaceutics 2025, 17(10), 1245; https://doi.org/10.3390/pharmaceutics17101245 - 24 Sep 2025

Abstract

In the original publication [...] Full article

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

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Open AccessArticle

Vitamin D Nanoliposomes to Improve Solubility, Stability, and Uptake Across Intestinal Barrier

by Cosimo Landi, Elisa Landucci, Costanza Mazzantini, Rebecca Castellacci and Maria Camilla Bergonzi

Pharmaceutics 2025, 17(10), 1244; https://doi.org/10.3390/pharmaceutics17101244 - 23 Sep 2025

Abstract

Background/Objectives: Vitamin D (VD) is a fat-soluble vitamin essential for bone health, and calcium and phosphorus absorption. Recently, new interesting functions are reported such as neuroprotective activity, regulatory roles in the immune system, and protective effects in cancer patients. However, the lipophilic [...] Read more.

Background/Objectives: Vitamin D (VD) is a fat-soluble vitamin essential for bone health, and calcium and phosphorus absorption. Recently, new interesting functions are reported such as neuroprotective activity, regulatory roles in the immune system, and protective effects in cancer patients. However, the lipophilic nature of VD represents a limitation, as it is associated with low solubility and poor absorption; additionally, VD exhibits poor stability. Methods: Two nanoliposomes containing VD, conventional (LP-VD) and conjugated with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, LPT-VD), were developed. The physical and chemical stability during the storage and gastrointestinal stability, the dissolution profile, the cytotoxicity and the Caco-2 cellular uptake were investigated. Nanoliposomes were fully characterized determining sizes, PdI, Zeta potential, encapsulation efficiency and recovery and they were lyophilized to improve stability. Subsequently, the freeze-dried liposomes were encapsulated in hard gelatin capsules to mimic an oral dosage form, and they were subjected to dissolution test. Results: LP-VD exhibited an average size of 85.50 ± 5.70 nm, a PdI of 0.24 ± 0.06, and a ZP of −20.90 ± 4.37 mV. LPT-VD showed an average size of 61.70 ± 3.90 nm, a PdI of 0.26 ± 0.02, and a ZP of −9.45 ± 2.99 mV. The EE% values were 95.76 ± 1.26% and 97.54 ± 3.24% for LP-VD and LPT-VD, respectively. Both nanoliposomes solubilized 2 mg/mL of VD and improved both its storage stability and stability in aqueous and gastrointestinal environment. The freeze-dried products guarantee constant chemical-physical parameters for 28 days at 25 °C. VD dissolution profile was improved. Conclusions: Nanoliposomes, in particular LPT-VD, showed the best results in terms of chemical stability, dissolution profile, and Caco-2 cellular uptake, confirming the stabilization, bioenhancer properties and P-gp inhibition capabilities of TPGS. Full article

(This article belongs to the Special Issue Liposomes Applied in Drug Delivery Systems)

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Open AccessReview

The Role of Natural Hydrogels in Enhancing Wound Healing: From Biomaterials to Bioactive Therapies

by Paula Stefana Pintilei, Roya Binaymotlagh, Laura Chronopoulou and Cleofe Palocci

Pharmaceutics 2025, 17(10), 1243; https://doi.org/10.3390/pharmaceutics17101243 - 23 Sep 2025

Abstract

Wound healing is a complex, multifaceted biological process that plays a vital role in recovery and overall quality of life. However, conventional wound care methods often prove insufficient, resulting in delayed healing, higher infection risk, and other complications. In response, biomaterials—especially hydrogels—have gained [...] Read more.

Wound healing is a complex, multifaceted biological process that plays a vital role in recovery and overall quality of life. However, conventional wound care methods often prove insufficient, resulting in delayed healing, higher infection risk, and other complications. In response, biomaterials—especially hydrogels—have gained attention for their advanced wound management capabilities, which support wound healing by maintaining moisture, mimicking the extracellular matrix (ECM), and enabling targeted drug delivery triggered by wound-specific signals. They frequently carry antimicrobial or anti-inflammatory agents, promote blood vessel and nerve regeneration, and are biocompatible with customizable properties suited to different healing stages. Natural hydrogels, derived from polysaccharides, proteins, and peptides, offer several advantages over synthetic options, including inherent bioactivity, enzymatic degradability, and cell-adhesive qualities that closely resemble the native ECM. These features facilitate cell interaction, modulate inflammation, and speed up tissue remodeling. Moreover, natural hydrogels can be engineered as delivery systems for therapeutic agents like antimicrobial compounds, nanoparticles, growth factors, and exosomes. This review discusses recent advances in the use of natural hydrogels as multifunctional wound dressings and delivery platforms, with a focus on their composition, mechanisms of action, and potential for treating chronic and infected wounds by incorporating antimicrobial and regenerative additives such as silver and zinc oxide nanoparticles. Full article

(This article belongs to the Special Issue Advances in Chemically Crosslinked Hydrogels at Different Scale Levels as Versatile Drug Delivery Systems in the Biomedical Field)

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Open AccessReview

Polymeric Nanocarrier-Based Drug Formulations for Enhancing Nose-to-Brain Delivery

by Tobeka Naki, Sijongesonke Peter and Sibusiso Alven

Pharmaceutics 2025, 17(10), 1242; https://doi.org/10.3390/pharmaceutics17101242 - 23 Sep 2025

Abstract

Neurological-related diseases are among the most debilitating and difficult to manage. Many possible pharmacological treatments for neurological diseases struggle to cross the blood–brain barrier (BBB) to achieve concentrations that can produce a therapeutic benefit. This is primarily because of the existence of the [...] Read more.

Neurological-related diseases are among the most debilitating and difficult to manage. Many possible pharmacological treatments for neurological diseases struggle to cross the blood–brain barrier (BBB) to achieve concentrations that can produce a therapeutic benefit. This is primarily because of the existence of the BBB, which poses significant hurdles for both therapeutic and diagnostic efforts by restricting the entry of most medications. Nasal-to-brain drug transportation has surfaced as an encouraging approach to tackle the difficulties linked with conventional drug administration techniques for neurological disorders. In response, innovative methods for improving drug delivery focus on breaking down the BBB via physical techniques, including optical and photothermal therapy, electrical stimulation, and acoustic or mechanical stimulation. Nanocarriers represent a promising approach for facilitating nasal systemic and brain delivery of active compounds. Hence, the achievement of therapeutically relevant concentrations of exogenous molecules within the body is significantly contingent upon the nanocarriers’ capability to surpass biological barriers. Polymers in nanocarrier formulations can result in significantly enhanced nose-to-brain drug delivery by protecting drugs from premature biodegradation, increasing permeability, improving mucoadhesion, and targeting specific cells in the brain. Polymeric nanocarriers are frequently functionalized with cell-penetrating peptides to further improve the specificity of the loaded therapeutic molecules. This review focuses on the use of nanocarrier-based therapeutic agents to enhance the efficacy of nose-to-brain delivery systems. Full article

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

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Open AccessArticle

LMT2368 (1-(4-Chlorophenyl)-3-(3-fluoro-5-(trifluoromethyl)phenyl)urea) Negatively Regulates Inflammation by Inhibiting NLRP3 Inflammasome Activation

by Thai Uy Nguyen, Su Jeong Kwon, Sunghoon Hurh, Ashok Kale, Jae Min Cho, Hossam Nada, Chang Seong Kim, Peela Induvadana, Beom Jin Park, Kyeong Lee, Yongseok Choi and Jong-Ik Hwang

Pharmaceutics 2025, 17(10), 1241; https://doi.org/10.3390/pharmaceutics17101241 - 23 Sep 2025

Abstract

Background/Objectives: The dysregulation of NLRP3 inflammasome activation has been established as a key driver of inflammatory disease pathology, which marks NLRP3 as an attractive therapeutic target. However, the clinical development of NLRP3 inhibitors such as MCC950 has been hampered by their associated [...] Read more.

Background/Objectives: The dysregulation of NLRP3 inflammasome activation has been established as a key driver of inflammatory disease pathology, which marks NLRP3 as an attractive therapeutic target. However, the clinical development of NLRP3 inhibitors such as MCC950 has been hampered by their associated toxicity profiles, highlighting an unmet clinical need. Methods: Herein, we present LMT2368, a novel urea-based NLRP3 inhibitor identified through screening of urea-based derivatives from our in-house compound library. Results: Biolayer interferometry confirmed direct binding of LMT2368 to the NLRP3 NACHT domain with a (K_D = 27.4 ± 1.2 μM which was superior to MCC950. Molecular docking studies predicted enhanced binding interactions for LMT2368, consistent with its improved biological activity. In LPS-primed macrophages, LMT2368 dose-dependently suppressed IL-1β secretion (IC50 = 0.8 μM in J774A.1 cells) and caspase-1 activation without affecting NF-κB signaling. Importantly, LMT2368 inhibited ASC oligomerization and pyroptosis while maintaining excellent safety margins (CC50 > 50 μM). In a murine model of LPS-induced acute lung injury, LMT2368 (10 mg/kg) reduced bronchoalveolar lavage fluid immune cell infiltration by 68% (p < 0.001), suppressed pro-inflammatory cytokine release (IL-1β/IL-6/TNF-α), and preserved lung histoarchitecture. Notably, LMT2368 showed selectivity for NLRP3 inhibition without affecting TNF-α/IL-6 production during TLR4 priming in monocytic cell lines. Conclusions: Together, these findings establish LMT2368 as a promising lead compound for developing safer NLRP3 inhibitors with therapeutic potential for inflammasome-driven diseases. Full article

(This article belongs to the Special Issue Recent Advances in Inhibitors for Targeted Therapies)

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Open AccessArticle

Solid Tranilast Nanocrystal-Loaded Cationic Contact Lenses for Sustained Ocular Drug Delivery

by Shinichiro Kobayakawa, Toru Matsunaga, Hiroko Otake, Shiori Hino, Fumihiko Ogata, Manju Misra, Kazutaka Kanai, Naohito Kawasaki and Noriaki Nagai

Pharmaceutics 2025, 17(10), 1240; https://doi.org/10.3390/pharmaceutics17101240 - 23 Sep 2025

Abstract

Background/Objectives Conventional eye drops are the primary therapeutic option for ocular diseases; however, their clinical utility is hindered by several drawbacks, including limited bioavailability and suboptimal patient compliance. To overcome these challenges, we designed a sustained-release contact lens (CL) device loaded with tranilast [...] Read more.

Background/Objectives Conventional eye drops are the primary therapeutic option for ocular diseases; however, their clinical utility is hindered by several drawbacks, including limited bioavailability and suboptimal patient compliance. To overcome these challenges, we designed a sustained-release contact lens (CL) device loaded with tranilast (TRA) and determined whether the TRA-laden CL could provide sustained drug delivery to the lacrimal fluid and aqueous humor. Methods TRA nanocrystals were prepared using the bead-milling approach. Using three types of CLs (nonionic, anionic, and cationic), we prepared TRA-laden CLs by employing a combination of solid TRA nanocrystals and soaking methods under high-temperature and high-pressure conditions in an autoclave (the hThP method). Male Japanese albino rabbits (2–3 kg) were used to evaluate the CLs. Results Bead milling reduced the size of the solid TRA nanoparticles (STNs) to approximately 35–180 nm. The TRA-laden cationic CLs prepared using STNs and the hThP method contained a higher amount of TRA than those prepared using the corresponding conventional soaking method. The CLs prepared using the hThP method remained transparent after drug loading. Compared with nonionic and anionic CLs, cationic CLs had the highest drug-loading capacity and allowed for sustained drug release. Moreover, STNs were observed in the released TRA, with no corneal damage or light scattering detected in the rabbits’ eyes. TRA-laden cationic CLs prepared using the hThP method achieved sustained and higher drug delivery into the lacrimal fluid and aqueous humor than those prepared using the conventional soaking method. Conclusions Our findings suggest that TRA-laden cationic CLs prepared using STNs and the hThP method can overcome the challenges associated with the conventional soaking method, including low drug uptake and high burst release. Full article

(This article belongs to the Special Issue Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release)

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Open AccessReview

Emerging Insulin Analogues: A Glimpse into How Insulin Analogues May Look in the near Future

by Ntethelelo Sibiya, Lorah Dzimwasha, Samarah Zvandasara, Amanda Zuma and Andile Khathi

Pharmaceutics 2025, 17(10), 1239; https://doi.org/10.3390/pharmaceutics17101239 - 23 Sep 2025

Abstract

The use of insulin as a treatment for diabetes mellitus has been marred by several challenges. These setbacks incurred in an attempt to better manage diabetes, together with past innovative strategies, have encouraged science and the clinical community to continue to endeavour for [...] Read more.

The use of insulin as a treatment for diabetes mellitus has been marred by several challenges. These setbacks incurred in an attempt to better manage diabetes, together with past innovative strategies, have encouraged science and the clinical community to continue to endeavour for an ideal insulin analogue that demonstrates heightened pharmacokinetic profiles and thermal stability. This review therefore seeks to provide an update on emerging insulin analogues. This review aims to update the science and clinical community of the recent developments on novel insulin analogues design and engineering. Through this exercise, we believe this review consolidates cutting-edge innovations on insulin development and diabetes management. The accelerated innovation of design and engineering in the biotechnology and peptide field has seen more insulin analogues reported in the last decade. Although the analogues are often limited to preclinical studies, Degludec, Icodec, and Efsitora have been the exceptions. The emerging insulin analogues include those with extended pharmacokinetic profile, increased thermostability, are glucose-responsive, and are hepato-preferential insulin analogues. Due to the fast pace of innovation in the design of insulin analogues, more insulin analogues are likely to emerge in the clinical space in the near future. Such innovations should be applauded and encouraged as they aim to strive for better management of diabetes mellitus. Full article

(This article belongs to the Special Issue Compounds and Drug Delivery for Diabetes Treatment)

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Open AccessArticle

Investigating the Potential of Poly(2-ethyl-2-oxazoline) and Its Polymer Blends for Enhancing Fenofibrate Amorphous Solid Dispersion Dissolution Profile

by Ziru Zhang, Rasha M. Elkanayati, Sheng Feng, Indrajeet Karnik, Sateesh Kumar Vemula and Michael A. Repka

Pharmaceutics 2025, 17(10), 1238; https://doi.org/10.3390/pharmaceutics17101238 - 23 Sep 2025

Abstract

Background/Objectives: This study aimed to develop a novel amorphous solid dispersion (ASD) platform using poly(2-ethyl-2-oxazoline) (PEtOx) for the solubility enhancement of poorly water-soluble drugs. Fenofibrate (FB), a Biopharmaceutics Classification System (BCS) Class II drug, was selected as the model drug. The novelty of [...] Read more.

Background/Objectives: This study aimed to develop a novel amorphous solid dispersion (ASD) platform using poly(2-ethyl-2-oxazoline) (PEtOx) for the solubility enhancement of poorly water-soluble drugs. Fenofibrate (FB), a Biopharmaceutics Classification System (BCS) Class II drug, was selected as the model drug. The novelty of this work lies in the formulation of dual-matrix systems by blending PEtOx of varying molecular weights (50 kDa, 200 kDa, 500 kDa) with solubility-enhancing polymers, Soluplus^® and Kollidon^® VA64, to investigate component compatibility, synergistic solubility enhancement, and the influence of PEtOx molecular weight on drug release. Methods: ASDs were prepared via hot-melt extrusion (HME) and characterized using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and Fourier transform–infrared spectroscopy (FTIR) to confirm FB amorphization and evaluate drug–polymer interactions. In vitro dissolution testing was performed to assess drug release performance, and stability studies were conducted at ambient conditions for one month to evaluate physical stability. Results: DSC, PXRD, and FTIR confirmed the successful amorphization of FB and good miscibility between PEtOx and the selected excipients. In vitro dissolution studies showed an 8–12-fold increase in FB release from ASDs compared to crystalline drug. Lower-molecular-weight PEtOx grades yielded faster release profiles, while binary blends with Soluplus^® or Kollidon^® VA64 enabled tailored drug release. Stability testing indicated that all formulations maintained their amorphous state over one month. Conclusions: PEtOx-based ASDs represent a versatile platform for enhancing the solubility and dissolution of poorly water-soluble drugs. By adjusting polymer molecular weight and combining with complementary excipients, release profiles can be optimized to achieve improved performance and stability. Full article

(This article belongs to the Special Issue Emerging Strategies to Enhance Solubility of Poorly Soluble Drugs: From Nanosystems to Molecular Innovations)

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Pharmaceutics, Volume 17, Issue 10 (October 2025) – 16 articles

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