Pharmaceutics最新文献

{"title":"Colon-Specific Delivery of Febuxostat via an Amino Acid Conjugate Enhances Anti-Colitis Efficacy and Limits Systemic Exposure.","authors":"Suji Kim, Sanghyun Ju, Yunjin Jung","doi":"10.3390/pharmaceutics18091187","DOIUrl":"10.3390/pharmaceutics18091187","url":null,"abstract":"<p><p><b>Background/objectives:</b> Febuxostat (FBXT), a xanthine oxidase (XO) inhibitor, is a urate-lowering drug commonly used to treat gout. XO is also a promising therapeutic target for inflammatory bowel disease (IBD). This study aimed to improve the efficacy and safety of FBXT repurposed for the treatment of IBD. <b>Methods:</b> FBXT was conjugated with the acidic amino acids aspartic acid (Asp) and glutamic acid (Glu) via amide linkages to yield the colon-specific conjugates FBXT-Asp and FBXT-Glu. <b>Results:</b> The results revealed that amino acid conjugation decreased the distribution coefficient of FBXT from 1.451 to -1.217 for FBXT-Asp and -0.859 for FBXT-Glu. In parallel, conjugation retarded FBXT transport across the small intestinal wall, with a more pronounced effect observed with Glu conjugation than with Asp conjugation. The conjugates were converted to FBXT in cecal contents under a nitrogen atmosphere while remaining intact in pH 1.2 buffer and small intestinal contents. The cecal conversion percentages at 8 and 24 h were 7.1% and 22%, respectively, for FBXT-Asp and 17% and 54.8%, respectively, for FBXT-Glu. Consistent with these in vitro results, oral gavage of FBXT-Glu resulted in greater FBXT accumulation in the rat cecum than that observed with free FBXT. In rats with 2,4-dinitrobenzenesulfonic acid-induced colitis, oral gavage of FBXT-Glu at a dose equivalent to 20 mg of FBXT ameliorated colonic damage and inflammation. This effect was more potent than that of FBXT at the same dose or sulfasalazine (SSZ), a currently used anti-IBD drug. Additionally, FBXT-Glu did not produce detectable blood levels of FBXT, whereas FBXT was detected at concentrations of up to 6.7 μM at 2 h after oral gavage of FBXT at the corresponding dose. <b>Conclusions</b>: FBXT-Glu may serve as an anti-colitis agent with therapeutic and toxicological advantages over FBXT and could be a viable alternative to SSZ.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of In Vitro Permeation and Human Pharmacokinetic Data for a Bioadhesive Vaginal Tablet as a Potential Clinical Approach for Bacterial Vaginosis.","authors":"Monika Kłosińska, Anna Kiryluk, Bartłomiej Kubiak, Emilia Szymańska","doi":"10.3390/pharmaceutics18091183","DOIUrl":"10.3390/pharmaceutics18091183","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Reformulating oral drugs for vaginal delivery is a current therapeutic strategy for genitourinary tract infections. Bioadhesive delivery systems, by interacting with the mucosal epithelium, improve drug deposition at the application site and are promising carriers for drugs with poor bioavailability. This study compares an in vitro permeation test (IVPT) in excised human vaginal epithelium and a first-in-human (FIH) pharmacokinetic (PK) study for a bioadhesive vaginal tablet developed as a potential clinical approach for bacterial vaginosis (BV). <b>Methods:</b> A Phase 1, single-dose, open-label, crossover study in 24 healthy volunteers evaluated PK differences after ascending doses of the vaginal tablet and an oral comparator, with a 7-day wash-out between administrations. The IVPT examined drug permeation and deposition in excised human vaginal epithelium for the pure drug and drug-loaded tablet. <b>Results:</b> IVPT showed limited penetration of the antimicrobial agent across human vaginal epithelium. Tablet excipients reduced drug accumulation in the ectocervical tissue, further hindering absorption. Single vaginal administration resulted in low plasma drug levels (C_max 0.084-0.127 ng/mL), irrespective of dose. Mean AUC₍₀_-t) after vaginal tablet administration did not exceed 1.560 h·ng/mL (100 mg) and was significantly lower than for the oral comparator (824.147 h·ng/mL, 100 mg). The IVPT data with human vaginal epithelium supported the FIH data, demonstrating low systemic absorption following single-dose vaginal application and potential for local drug performance. <b>Conclusions:</b> A single dose of the bioadhesive vaginal tablet appears to be a potentially safe alternative for BV treatment, with minimal systemic drug exposure, supporting further research on clinical efficacy and local pharmacodynamics of bioadhesive tablets for BV.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-Printing of Magnetoactive Gelatin-Alginate Scaffolds.","authors":"Sofía Municoy, Exequiel Giorgi, María Edith Farías, Romina B Currá, Hina N Chaudhari, Rajshree B Jotania, Robert C Pullar, Mauricio De Marzi, Martín F Desimone","doi":"10.3390/pharmaceutics18091186","DOIUrl":"10.3390/pharmaceutics18091186","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Magnetically responsive biomaterials have emerged as promising platforms for tissue engineering as they allow remote stimulation of cells and improved control over tissue regeneration. Although gelatin-alginate hydrogels incorporating iron oxide nanoparticles have been reported, the use of U-type hexaferrite particles, particularly Al³⁺-substituted compositions, remains largely unexplored. This study aimed to develop and characterize extrusion-based 3D-printed gelatin-alginate scaffolds containing U-type hexaferrite particles and to evaluate the influence of particle composition and loading on the rheological, physicochemical and magnetic properties of the resulting biomaterials, as well as their in vitro compatibility with macrophages. <b>Methods:</b> Gelatin-alginate inks containing two U-type hexaferrite compositions (Ba₄Co₂Fe₃₆-<i>_x</i>Al<i>_x</i>O₆₀; <i>x</i> = 0.0 and <i>x</i> = 1.0) at two particle loadings (20 and 200 mg) were prepared and processed by extrusion-based 3D printing. The scaffolds were characterized by rheological analysis, SEM-EDS, FTIR, swelling measurements, magnetic responsiveness, and in vitro biological evaluation using RAW264.7 macrophages. <b>Results:</b> The inks exhibited suitable shear-thinning behavior and viscoelastic properties for extrusion-based printing. Increasing particle loading enhanced the thermal resistance of the network, whereas Al³⁺ substitution modified the viscoelastic response of the polymeric network. The 3D scaffolds successfully responded to an external magnetic field and SEM-EDS confirmed the homogeneous incorporation of hexaferrite particles. The magnetic scaffolds did not compromise macrophage metabolic activity. <b>Conclusions:</b> U-type hexaferrite particles provide an effective strategy for producing 3D-printed magnetically responsive scaffolds with tunable rheological properties without inducing an inflammatory response. The combined modulation of particle composition and loading represents a versatile approach for designing multifunctional inks with potential applications in tissue engineering.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Honokiol-Loaded β-D-Glucan/Chitosan Nanoparticles with Antibacterial and Anti-Inflammatory Activities for Promoting MRSA-Infected Wound Healing.","authors":"Shouli Yi, Ming Guan, Hongjuan Zhang, Ping Qiu, Shengyi Wang, Tingjun Hu","doi":"10.3390/pharmaceutics18091184","DOIUrl":"10.3390/pharmaceutics18091184","url":null,"abstract":"<p><p><b>Background:</b> Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) wound infections are a major clinical concern due to their high prevalence and the growing risk of antimicrobial resistance. Therefore, it is imperative to develop safe and effective therapeutic strategies. <b>Methods</b>: Herein, we fabricated a novel antibiotic-free nanodrug delivery system (HNK/DG-COS NPs) by loading honokiol (HNK), a hydrophobic natural antimicrobial agent, onto a dual-polysaccharide carrier composed of chitosan (COS) and β-D-glucan (DG), for the treatment of MRSA-infected wounds. COS endows the nanoparticles with synergistic antibacterial activity together with HNK, while DG improves their anti-inflammatory and tissue repair capacities. The physicochemical characteristics of nanoparticles, as well as their in vitro antibacterial and anti-inflammatory activities, were systematically evaluated. Furthermore, an MRSA-infected wound model was constructed to verify their therapeutic efficacy. <b>Results</b>: HNK/DG-COS NPs exhibited a spherical morphology with a uniform particle size of approximately 200 nm. In vitro experiments have shown that HNK/DG-COS NPs can significantly kill MRSA and inhibit biofilm formation. Scanning electron microscopy further revealed that the nanoparticles exerted antibacterial effects by disrupting the integrity of bacterial cell membranes. In LPS-stimulated RAW264.7 macrophages, treatment with HNK/DG-COS NPs significantly mitigated pro-inflammatory cytokine levels. Cell migration assays confirmed that nanoparticles effectively enhanced L929 cell migration. In vivo, treatment with HNK/DG-COS NPs significantly accelerated MRSA-infected wound healing in mice, mitigated inflammatory damage, stimulated collagen production and repaired damaged tissues. <b>Conclusions</b>: HNK/DG-COS NPs represent a promising antibiotic-free candidate for intervention against early-stage MRSA-infected wounds.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced Ophthalmic Drug Delivery in Homocystinuria Type CblC: A Translational Review of Ophthalmic Pathologies and Therapeutic Opportunities.","authors":"Selene Cuello-Rodríguez, Martina Sanna, Imelda Lecoeuche, Bruno Sarmento, Francisco J Otero-Espinar, Victoria Díaz-Tomé","doi":"10.3390/pharmaceutics18091182","DOIUrl":"10.3390/pharmaceutics18091182","url":null,"abstract":"<p><p>Homocystinuria type CblC is a congenital error in cobalamin metabolism characterized by increased homocysteine and methylmalonic acid levels, together with a reduced methionine availability. This metabolic imbalance leads to multisystemic pathologies, including ophthalmic pathologies that cause damage to the photoreceptors and oculomotor disorders, such as pigmentary retinopathy and nystagmus, respectively. Current commercial treatment (Megamilbedoce^®) is mainly based on intramuscular hydroxocobalamin administration. Although this approach may improve systemic manifestations, it is ineffective at the ophthalmic level. Given the ophthalmic complications, there is a clear need for new therapeutic strategies capable of significantly reaching the eyeball, improving visual function and patient quality of life. The most convenient and acceptable route for patients is topical-ophthalmic administration. However, treatments administered by this route have significant limitations due to anatomical and physiological ophthalmic barriers. In this context, advanced ophthalmic drug delivery systems have gained increasing interest as strategies to address the low ocular bioavailability of conventional treatments. By increasing ocular residence time, limiting drug loss through tear turnover and nasolacrimal drainage, and improving interaction with ocular tissues, these platforms may enhance local drug availability and therapeutic performance. Nanoparticles, lipid-based carriers, hydrogels, in situ gelling systems, surfactant-based formulations and other multifunctional delivery approaches have shown potential to improve drug retention, tissue penetration and controlled release within the ocular environment. Although reaching posterior ocular tissues through topical administration remains a major pharmacological challenge, these technologies open new possibilities for developing less invasive and more effective treatments for the ocular manifestations of CblC-type homocystinuria.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative 3D-Printed Devices with Modified Prednisolone Release for Colon-Targeted Drug Delivery Systems.","authors":"Dareena Jaiseri, Supusson Pengnam, Praneet Opanasopit, Theerada Taesotikul, Boonnada Pamornpathomkul, Chaiyakarn Pornpitchanarong, Phuvamin Suriyaamporn, Theerasak Rojanarata, Teeratas Kansom, Thapakorn Charoenying","doi":"10.3390/pharmaceutics18091185","DOIUrl":"10.3390/pharmaceutics18091185","url":null,"abstract":"<p><p><b>Background</b>: Prednisolone conventional tablet is a drug commonly used to treat inflammatory bowel disease (IBD). However, the long-term use of high doses of prednisolone can lead to gastric irritation, risk of infection, and other systemic complications. These limitations of the drug can be overcome by using three-dimensional (3D) printing technology with pH-dependent approaches. <b>Objectives</b>: This study aimed to develop 3D-printed devices containing prednisolone tablets and gel with an enteric coating for colon-targeted modified release. <b>Methods</b>: 3D-printed drug-containing devices (CDDs) were designed and divided into two classifications, including devices for prednisolone tablets (PTDs) and devices for prednisolone gel (PGDs). CDDs were fabricated using fused deposition modeling (FDM). The morphology of the CDDs was assessed using a microscope. The tablets and gel of prednisolone were loaded into CDDs depending on the type of device, and the CDDs were coated by Eudragit^® S100. In vitro drug release studies were investigated using dissolution apparatus II in simulated gastric medium (pH 1.2) for 2 h, simulated intestinal medium (pH 6.8) for 2 h, and simulated colonic medium (pH 7.4) for 20 h. <b>Results</b>: The prednisolone-loaded CDDs with enteric coating were protected from drug release before reaching the colon. The dissolution profile of prednisolone from CDDs showed no drug release in the simulated gastric and simulated intestinal medium, with drug release initiated under simulated colonic medium and sustained release maintained for up to 24 h. <b>Conclusions</b>: These findings showed that CDDs have potential for delivering prednisolone to the colon with controlled drug release under simulated in vitro gastrointestinal conditions. Furthermore, these CDDs could be adapted for other drugs.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Characterization of a Hydrogel Incorporating Protamine-Hyaluronic Acid Nanoparticles Co-Loaded with Disulfiram and Coumarin for Diabetic Wound Healing.","authors":"Zainab Lafi, Mohammad I A Ahmad, Shreen Deeb Nusair, Razan Madi, Alaa Al-Sanabrah, Somaya Ahmad, Qout Qtashat, Maisrh Ali Alrubaye, Sara Yousef Asha","doi":"10.3390/pharmaceutics18091180","DOIUrl":"10.3390/pharmaceutics18091180","url":null,"abstract":"<p><p><b>Background:</b> Diabetes-associated wound healing is frequently impaired due to persistent hyperglycemia, which causes vascular dysfunction and neuropathy, thereby delaying tissue repair. <b>Objectives:</b> In this study, hyaluronic acid and protamine nanoparticles (HA-PRO-NPs) were developed and optimized to encapsulate disulfiram (DSF) and coumarin (COM) for potential application in diabetic wound healing. <b>Methods:</b> The nanoparticles were prepared using a simple ionic interaction method and characterized for their particle size, zeta potential, morphology and encapsulation efficiency. Then, HA-PRO-NPs were incorporated into a hydrogel that contains carboxymethyl cellulose (CMC) and propylene glycol (PG). The hydrogel formulations were evaluated for swelling behavior, spreadability and DSF and COM release kinetics. <b>Results:</b> The prepared formulations were safe against human dermal fibroblasts (HDFs), with cell viability remaining above 70% over the concentration ranges tested. In the scratch assay, HA-PROT-DSF-COM-NPs improved HDF migration, achieving approximately 81% wound closure. An in vivo study was conducted using streptozotocin-induced diabetic mice. Topical application of Gel-HA-PROT-DSF-COM-NPs promoted wound closure. The study monitored wound contraction on Days 0, 3, 7, and 12. By Day 12, topical administration of the dual-cargo system (Gel-HA-PROT-DSF-COM NPs, n = 6) achieved 78.2 ± 4.1% wound closure. This was significantly higher than the single-drug formulation (Gel-HA-PROT-DSF-NPs: 59.5 ± 4.8%) and the untreated Control (Diabetic) group (55.4 ± 5.2%, <i>p</i> < 0.01), while the non-diabetic Control group (non diabetic) reached 97.6 ± 3.5% closure. Semi-quantitative histopathological evaluation showed that the Gel-HA-PROT-DSF-COM NPs achieved a healing score of 4/5, characterized by optimized epidermal regeneration with preserved adnexal structures and moderate dermal remodeling. <b>Conclusions:</b> In conclusion, Gel-HA-PROT-DSF-COM-NPs demonstrated promising potential as a topical formulation for improving wound healing under diabetic conditions.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR-Targeted Nanoparticle Delivery of Osimertinib for Triple-Negative and Metastatic Breast Cancer Therapy.","authors":"Iman M Alfagih, Maryam Alfagih, Alanood Almurshedi, Basmah Aldosari, Bushra Alquadeib, Baraa Hajjar, Shahad Almogheerah, Rund Alzahrani","doi":"10.3390/pharmaceutics18091179","DOIUrl":"10.3390/pharmaceutics18091179","url":null,"abstract":"<p><p><b>Background/objective:</b> Osimertinib, an EGFR-targeted agent approved for metastatic NSCLC, shows promise for triple-negative breast cancer due to EGFR overexpression in aggressive tumors. However, oral administration limits tumor delivery and causes systemic side effects. This study aimed to develop chitosan-coated PLGA nanoparticles loaded with osimertinib (CH-P-NPs) to enhance its anticancer efficacy in breast cancer cell lines (MDA-MB-231, MCF-7) by promoting apoptosis and reducing migration in vitro. <b>Methods:</b> CH-P-NPs were synthesized via single-emulsion solvent evaporation and characterized for particle size, zeta potential, encapsulation efficiency, and in vitro release. Anticancer activity was evaluated in MDA-MB-231 and MCF-7 cell lines through in vitro cellular uptake, cytotoxicity, apoptosis induction, and migration inhibition assays. <b>Results:</b> CH-P-NPs exhibited a particle size less than 200 nm, high encapsulation efficiency and a positive zeta potential. Moreover, sustained drug release was achieved with 59.62 ± 1.9% at 24 h. In vitro anticancer studies demonstrated that osimertinib and its nanoparticle formulations showed concentration-dependent cytotoxicity in MDA-MB-231 and MCF-7 cells. CH-P-NPs enhanced cytotoxicity compared with uncoated PLGA nanoparticles (IC₅₀: 1.56 vs. 6 µg/mL). CH-P-NPs enhanced cellular uptake in MDA-MB-231 cells, whereas its effect on MCF-7 cellular uptake was cell line-dependent. Annexin V/PI assay showed that CH-P-NPs significantly enhanced apoptosis compared to free osimertinib in both cell lines. In MDA-MB-231 cells, CH-P-NPs induced ~52.5% total apoptosis versus 3.3% with free drug. In MCF-7 cells, CH-P-NPs induced ~16.6% apoptosis versus 1.5% with free drug. Late apoptosis predominated, indicating irreversible cell death. Wound healing assay showed that CH-P-NPs significantly inhibited migration in both cell lines compared to free osimertinib and control. In MDA-MB-231 cells, CH-P-NPs exhibited greater inhibition at 48 and 72 h, while free osimertinib showed minimal effect. In MCF-7 cells, CH-P-NPs reduced migration at all time points. <b>Conclusions:</b> CH-P-NPs markedly enhanced osimertinib's anticancer activity by improving cellular uptake, cytotoxicity, inducing apoptosis, and inhibiting migration. This nanoformulation offers a promising strategy to boost efficacy and reduce systemic toxicity in breast cancer treatment.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoformulations for Ocular Drug Delivery in Glaucoma: From Metal-Based Nanoparticles to Advanced Nanocarriers.","authors":"Ionut Iulian Lungu, Liviu Stafie, Alina Stefanache, David-Constantin Stefan, Andreea Lungu, Georgiana-Elena Sarbu, Liliana Savin, Andreea Guraliuc, Francesca Cristiana Dohotariu, Nicoleta Anton","doi":"10.3390/pharmaceutics18091181","DOIUrl":"10.3390/pharmaceutics18091181","url":null,"abstract":"<p><p>Glaucoma is a chronic and progressive optic neuropathy in which sustained intraocular pressure (IOP) reduction remains the main therapeutic objective, while increasing attention is being directed toward neuroprotective strategies and improved ocular drug delivery. Conventional topical therapies are frequently limited by short precorneal residence time, poor ocular bioavailability, and the need for frequent administration. This narrative review examines nanoformulation-based strategies investigated for ocular drug delivery in glaucoma, ranging from metal-based nanoparticles, including gold, silver, zinc-, copper-, and iron-based systems, to advanced nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, nanosuspensions, dendrimers, cyclodextrin-based systems, and hydrogels. Particular attention is given to the relationship between nanocarrier composition, physicochemical characteristics, drug-loading and release properties, ocular retention and penetration, therapeutic effects, and the level of experimental evidence. The review further compares metal-based nanoparticles with non-metal-based nanocarriers, highlighting their respective advantages and limitations in terms of drug delivery, sustained ocular exposure, therapeutic potential, biocompatibility, toxicity, and translational relevance. Although several nanoformulation platforms have demonstrated promising results in preclinical studies, the available evidence remains heterogeneous and predominantly preclinical. Further research is needed to establish long-term ocular safety, optimize formulation characteristics, standardize evaluation methods, and determine the clinical relevance of these emerging delivery systems.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Anti-VEGF: Toward Integrated Precision Care in Diabetic Retinal Disease.","authors":"Jesus H Gonzalez-Cortes, Jesus E Gonzalez-Cantu, Alper Bilgic, Francesc March de Ribot, Aditya Sudhalkar, Laurent Kodjikian, David Pelayes, Thibaud Mathis, Jesus Mohamed-Hamsho","doi":"10.3390/pharmaceutics18091178","DOIUrl":"10.3390/pharmaceutics18091178","url":null,"abstract":"<p><p>Diabetic retinal disease (DRD) remains one of the leading causes of preventable vision loss worldwide and continues to represent a major global public health challenge despite remarkable therapeutic advances over the past two decades. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the management of diabetic macular edema and proliferative diabetic retinopathy, significantly improving visual outcomes and reducing vision-threatening complications. Nevertheless, a substantial proportion of patients exhibit incomplete anatomical or functional responses, require frequent lifelong intravitreal injections, or experience disease progression despite adequate VEGF suppression, underscoring the biological heterogeneity of DRD. Growing evidence recognizes DRD as a chronic neurovascular disorder extending beyond a purely microvascular disease. Inflammation, oxidative stress, mitochondrial dysfunction, neurodegeneration, vascular instability, and progressive retinal ischemia interact throughout disease progression. Concurrently, advances in multimodal retinal imaging-including optical coherence tomography (OCT), OCT angiography (OCTA), ultra-widefield imaging, and artificial intelligence-assisted image analysis-have enabled the identification of imaging biomarkers that improve diagnosis, prognostication, and individualized therapeutic decision-making. The therapeutic landscape has expanded considerably beyond conventional anti-VEGF therapy. Corticosteroid implants, dual-pathway inhibitors, sustained drug-delivery systems, vitreoretinal surgery, laser photocoagulation, and emerging pharmacological approaches have broadened treatment options. Increasing evidence supports tailoring therapy according to retinal phenotype, imaging biomarkers, inflammatory status, ischemic burden, and systemic metabolic factors rather than relying on uniform treatment algorithms. This review summarizes recent advances in the understanding and management of DRD, emphasizing pathophysiology, multimodal imaging biomarkers, pharmacological therapies and delivery systems, vitreoretinal surgery, systemic risk-factor optimization, artificial intelligence, and emerging therapeutic strategies. Finally, we introduce Integrated Precision Care (IPC) as a proposed conceptual and research framework that integrates conventional disease staging with multimodal retinal imaging, biological phenotyping, systemic risk assessment, treatment burden, and patient-specific characteristics. IPC is not intended to replace established stage-specific guidelines or to function as a prospectively validated therapeutic algorithm; rather, it provides a hypothesis-generating structure for testing whether multidimensional integration can improve risk stratification, therapeutic selection, durability, patient-centered outcomes, and long-term vision.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}