International Journal of Pharmaceutics最新文献

{"title":"In vivo skin uptake of piroctone olamine in human subjects assessed by confocal Raman spectroscopy and tape stripping.","authors":"Annisa Rahma, Chun Fung Tang, Paul D A Pudney, Majella E Lane","doi":"10.1016/j.ijpharm.2026.127594","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127594","url":null,"abstract":"<p><p>In vivo human studies are considered the gold standard for assessing skin penetration of actives. Tape stripping (TS) is a widely used method for investigating uptake of actives following topical application to the skin of human subjects. The results of TS studies have been shown to be influenced by a number of factors, including the variability in the amount of stratum corneum (SC) removed during the stripping process. This has stimulated much interest in the development of alternative non-invasive techniques for assessing skin penetration of compounds, such as confocal Raman spectroscopy (CRS). In the present work, in vivo skin delivery of piroctone olamine (PO) in human subjects was investigated from multiple solvent systems using CRS and TS. Vehicles were prepared with propylene glycol (PG), diethylene glycol monoethyl ether - Transcutol® (TC), isopropyl myristate (IPM), caprylic/capric triglycerides - Labrafac™ Lipophile WL 1349 (LAB) and propylene glycol monolaurate - Lauroglycol™ 90 (PGML). Analysis of CRS depth profiles, expressed as the area under the signal intensity-depth curve (AUC), showed higher PO uptake for PG:TC:IPM compared with PG:TC and PG:TC:LAB (p < 0.05). TS studies indicated higher total uptake of PO for PG:TC:IPM compared with PG:TC (p < 0.05). Across all formulations, linear correlations were observed between CRS-derived AUC values and TS-measured PO uptake (R² = 0.79-0.99 for absolute uptake; 0.88-0.99 after protein normalization). To our knowledge, this is the first direct in vivo - in vivo correlation between CRS and TS for topical penetration of an active. It is also the first to investigate the in vivo skin uptake of PO using both CRS and TS, and to demonstrate correlations between these methods for profiling PO distribution within the SC.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127594"},"PeriodicalIF":6.0,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced strategies for enhancing mRNA-lipid nanoparticles stability: molecular insights, stabilization techniques, and clinical applications.","authors":"Ken Ninez Nurpramesti Prinindya, Shaligram Pokharel, Elsadig Mahdi","doi":"10.1016/j.ijpharm.2026.127561","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127561","url":null,"abstract":"<p><p>Advancements in mRNA formulation and delivery systems have transformed biomedical research, with the recent success of mRNA vaccines highlighting the technology's immense clinical potential. Despite their clinical success, the global reach of these vaccines is hindered by the necessity for ultracold storage, which restricts accessibility in resource-constrained regions. Improving the stability of mRNA-Lipid Nanoparticles (LNPs) at higher temperatures could be crucial for mass vaccination efforts in future outbreaks. This review evaluates the molecular assembly of mRNA-LNP systems, specifically how electrostatic complexation, hydrophobic interactions, and Van der Waals forces govern internal architectural organization and physicochemical integrity. This dual framework reveals how optimizing molecular coordination enhances the stability necessary for clinical viability. Beyond initial assembly, advanced stabilization technologies (e.g., lyophilization, spray-freeze drying (SFD), and thin-film freeze-drying) are evaluated for their ability to preserve LNP structural integrity during long-term storage. Incorporating these thermostable formulations into microneedle arrays and targeted pulmonary delivery platforms establishes non-invasive routes that enhance mucosal and transdermal bioavailability and clinical efficacy. Bridging nanoscale biophysics and macro-scale stability, this review connects electrostatic complexation, lipid architecture, and hydrophobic interactions to enhanced mRNA-LNP efficacy and extended shelf-life across biopharmaceutical applications.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127561"},"PeriodicalIF":6.0,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated aerosol deposition and epithelial transport in intranasal antiemetic dry powders.","authors":"Patrick He, Chun Yuen Jerry Wong, Nicole Leung, Genevieve Long, Maria Wilson, Louise Rawcliffe, Hui Xin Ong, Daniela Traini","doi":"10.1016/j.ijpharm.2026.127596","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127596","url":null,"abstract":"<p><p>Intranasal dry powder delivery offers a non-invasive route for rapid systemic drug absorption and may be particularly beneficial for antiemetic therapy when oral administration is compromised. However, conventional in vitro tools typically assess aerosol deposition or epithelial permeability in isolation, limiting their ability to discriminate formulation-dependent transport behaviour. Two spray-dried formulations, differing only in the presence or absence of a non-ionic surfactant, were characterised for physicochemical properties and aerosol performance, followed by biological evaluation using an air liquid interface (ALI) RPMI-2650 nasal epithelial model. Aerosol delivery was performed using a nasal powder device coupled to a modified expansion chamber and cascade impactor, enabling direct deposition onto epithelial cell layers. Cytocompatibility, epithelial barrier integrity, and transepithelial drug transport were assessed alongside quantitative mass balance. Both formulations exhibited comparable solid-state properties, high emitted-dose reproducibility, and similar regional nasal deposition profiles. Neither formulation induced cytotoxicity nor disrupted epithelial barrier integrity, as evidenced by unchanged transepithelial electrical resistance and paracellular permeability. Despite similar deposition behaviour, the surfactant-containing formulation demonstrated faster initial transport and consistently higher transepithelial transport trends, without evidence of barrier compromise. These differences are consistent with formulation-dependent processes following deposition, such as differences in surface wetting and dissolution behaviour at the air-liquid interface. Overall, this study demonstrates that aerosol deposition alone may not fully predict epithelial transport for intranasal dry powders. The integrated deposition-transport platform provides a robust in vitro tool for formulation screening and optimisation, supporting the development of intranasal antiemetic therapies and other nasal drug products requiring rapid and reliable systemic delivery.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127596"},"PeriodicalIF":6.0,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered hydrogels for boosting chimeric antigen receptor (CAR)-cell therapy: strategies and biomedical applications.","authors":"Chenjun Huang, Shuyun Liu, Xiangyu Zhou, Jingping Liu","doi":"10.1016/j.ijpharm.2026.127589","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127589","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-cell therapy has emerged as a revolutionary approach to treat various diseases, including cancers and non-cancer diseases. However, as a type of living drug, the therapeutic performance and persistence of CAR cells can be markedly affected by multiple factors, from in vitro manufacturing to in vivo conditions. In recent years, bioactive materials, especially hydrogel-based strategies, have emerged as powerful tools to improve ex vivo and in vivo CAR-cell therapy. In brief, engineered hydrogels might regulate CAR-cell expansion or activation states during manufacturing and as models for cell functional assessments in vitro; in vivo, hydrogels might preserve CAR cells and regulate their retention, release and tissue infiltration while reprogramming adverse disease microenvironments. Despite promising advances, the progress, limitations and future directions of this field have not been comprehensively evaluated. In this mini-review, we evaluate the framework of hydrogel-based strategies in boosting CAR-cell therapy over the past five years, from cell manufacturing to functional improvement. Together, current findings suggest that engineered hydrogels provide spatial and temporal cues to enhance CAR-cell manufacturing and therapeutic capacity. This review might provide insights into design principles for developing tailored hydrogels to improve CAR-cell therapies to treat diverse types of diseases.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127589"},"PeriodicalIF":6.0,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid nanoparticles for precision nucleic acid delivery: linking cellular engineering to organ-specific targeting.","authors":"Yongseop Shin, Sangmin Lee, Nhung Trần Nguyễn Ánh, Minsub Chung","doi":"10.1016/j.ijpharm.2026.127585","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127585","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) represent clinically validated non-viral platforms for nucleic acid delivery, yet expanding their application toward precision gene therapy demands more than efficient particle formulation or tissue accumulation. Functional delivery requires navigating a sequential biological cascade: establishing biological access to target tissues, undergoing cell-specific uptake, escaping endosomal entrapment, and releasing intact cargo into the cytosol. Because each stage presents a distinct rate-limiting barrier, success at one step does not guarantee downstream therapeutic activity. This review provides a multiscale evaluation of LNP-mediated delivery, bridging ex vivo cellular engineering and organ-specific in vivo targeting. We first analyze how lipid composition, physicochemical properties, and cargo architecture dictate self-assembly and intracellular fate. For ex vivo applications-highlighting hematopoietic stem/progenitor cells and natural killer cells-we address the balance between high transfection efficiency and the preservation of cell viability, phenotype, and cytotoxic function. For in vivo platforms, we examine how administration routes, physiological barriers, and cellular accessibility govern delivery to the liver, spleen, pancreas, lung, kidney, and brain, emphasizing that bulk organ accumulation often masks poor intracellular bioavailability-particularly given that only 1-4% of internalized cargo reaches the cytosol. Finally, we organize these insights into a route-barrier-cell framework that evaluates biological access, cellular uptake, endosomal escape, and cytosolic activity as interconnected yet distinct performance metrics. Overcoming current translational hurdles-including species-dependent tropism, biological variability, repeated-dose immunogenicity, and manufacturing scalability-will be essential to transition LNPs from broad nucleic acid carriers into precision targeted therapeutics.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127585"},"PeriodicalIF":6.0,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytosol-hydrogelled Chlorella enabling intestinal-targeted budesonide delivery for ulcerative colitis treatment.","authors":"Kaijie Qian, Hongda Chen, Hao Bai, Dongming Liu, Min Zhou, Tianhua Zhou, Xiangrui Liu","doi":"10.1016/j.ijpharm.2026.127590","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127590","url":null,"abstract":"<p><p>Current oral enteric sustained-release formulations largely rely on polymer-based surface coatings and multi-matrix technologies, which increase manufacturing complexity and overall production costs. Here, we report a cytosol-hydrogelled Chlorella pyrenoidosa (CP) delivery system, named BUD-gel@CP, for sustained release of budesonide (BUD) in the intestinal tract. Unlike conventional microalgae-based drug delivery strategies, this system requires neither surface modification nor enteric coating. We find for the first time that the intrinsic proteins of CP, such as chlorophyll protein 47 (CP47), physically entrap BUD in aggregates under acidic gastric conditions, enabling the enteric release of BUD. Importantly, BUD is easily loaded into the cytosol of lyophilized CP in the presence of two FDA-approved excipients, which are Labrasol® as a solubilizer and Soluplus® to form a thermosensitivein situgel. Following oral administration, BUD-gel@CP showed prolonged drug retention in the intestinal tract and elevated BUD concentrations in intestinal tissues. In a DSS-induced colitis mouse model, BUD-gel@CP restored colon length and reduced TNF-α and IL-6 levels, showing improved therapeutic effects compared with non-hydrogelled control groups. Our findings suggest a novel paradigm for preparing an enteric sustained-release oral drug delivery system that utilizes natural food ingredients and commercially approved pharmaceutical excipients without surface coating or modification.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127590"},"PeriodicalIF":6.0,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poly(vinyl alcohol) dissolving microneedles for transdermal semaglutide delivery and anti-obesity therapy in rats.","authors":"Xueqing Cheng, Fei Wang, Hongwei Liu, Feifei Li, Tongle Li, Chaoyong Liu","doi":"10.1016/j.ijpharm.2026.127576","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127576","url":null,"abstract":"<p><p>Semaglutide is an effective anti-obesity peptide, but repeated subcutaneous injections may reduce its acceptability for long-term therapy. We prepared semaglutide-loaded poly(vinyl alcohol) (PVA) dissolving microneedles (Sema-MNs) by sequential vacuum-assisted molding and room-temperature drying. The 15 × 15 arrays concentrated Cy5-labelled semaglutide toward the needle tips, resisted axial compression, penetrated rat skin, and partially dissolved within 5 min; skin barrier function approached baseline within 4-6 h. Sema-MNs contained 29 ± 2 μg semaglutide per patch, with an apparent delivered amount of 18 ± 2 μg (63 ± 3%; n = 3), and released more than 90% of the Sema-Cy5-associated cargo within 30 min. In high-fat-diet-induced obese rats, once-daily Sema-MN treatment for 7 days reduced food intake and body weight. Treatment also decreased adipocyte size and hepatic lipid accumulation, improved glucose tolerance and serum metabolic indices, and reduced hypothalamic neuropeptide Y immunofluorescence relative to the disease and unloaded-microneedle controls. No evident renal biochemical or major-organ histopathological abnormalities were observed during the study. These findings support the feasibility of a compositionally simple, rapid-release PVA microneedle system for transdermal semaglutide administration.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127576"},"PeriodicalIF":6.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-aptamer conjugate for shear-triggered tissue plasminogen activator release and thrombolysis.","authors":"Esraa Ismail, Fan Gong, X Frank Zhang, Xuanhong Cheng","doi":"10.1016/j.ijpharm.2026.127587","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127587","url":null,"abstract":"<p><p>Pathological blood clots cause life-threatening events, including ischemic stroke and myocardial infarction. Tissue plasminogen activator (TPA), a clinically approved fibrinolytic agent, remains a frontline therapy for clot dissolution. However, its short plasma half-life and requirement for high systemic doses pose serious risks, particularly hemorrhagic complications. To address these limitations, a shear-responsive delivery platform was engineered for controlled TPA release under pathological high-shear conditions. This system, termed Single-MOlecule-based materials with structures and functions REsponsive to Shear (SMORES), consists of a shear-amplifying microparticle conjugated to a TPA-binding aptamer and functionalized with a monoclonal antibody against integrin αIIbβ3 as a platelet-targeting element. Under elevated shear conditions, the immobilized aptamer undergoes mechanical unfolding, triggering TPA release. Optical tweezers-based single-molecule force measurements probing aptamer unfolding and refolding under constant force and varied relaxation periods revealed a narrow range of threshold forces (4-10 pN) governing the transition between folded and unfolded states. Under defined flow conditions in a microfluidic channel, single-molecule flow experiments demonstrated a flow-dependent TPA release profile, with the maximum mean release observed at 50 µL/min. COMSOL-based fluid dynamics simulations estimated a corresponding tether force of 4.76 pN and a shear rate of 3,512.9 s^-1, consistent with pathological shear levels observed in stenotic vessels and aligning with optical tweezers predictions. The enzymatic activity of released TPA was confirmed by a clot dissolution assay, with the highest mean functional TPA-equivalent activity observed under the same flow condition. Together, these results demonstrate that TPA-SMORES enables mechanistically controlled, shear-triggered release of functional TPA, supporting its potential as a strategy for improving the spatial control of thrombolytic therapy.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127587"},"PeriodicalIF":6.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxcarbazepine-loaded nanoemulsions in thermosensitive nasal gels for epilepsy: in-vitro and in-vivo evaluation in status epilepticus rat model.","authors":"Mina S Mikhail, Reham M Essam, Mohamed Salah, Donia E Hafez, Ahmed R Fares, Mohammad Abdel-Halim, Afaf A Ramadan, Mohamed H H AbouGhaly","doi":"10.1016/j.ijpharm.2026.127575","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127575","url":null,"abstract":"<p><p>To overcome the low aqueous solubility of oxcarbazepine (OXC), a BCS Class II drug, and to enhance brain exposure following intranasal administration, OXC was formulated into a self-nanoemulsifying drug delivery system (SNEDDS) incorporated within a thermosensitive nasal gel. The optimized SNEDDS (SNE.O2), comprising rose oil, Tween 80, and Transcutol® P, exhibited a droplet size of 10.38 nm, a zeta potential of -15.3 mV, and 97.24% drug content. SNE.O2 was dispersed into a hydrogel containing 16% Poloxamer 407, 1% Poloxamer 188, and 1.5% sodium carboxymethyl cellulose, yielding the optimum nanogel NG3.6. The nanogel had a gelation temperature of 30.9 °C, and viscosities of 600 and 720 cP at 25 and 31 °C, respectively. Ex-vivo buffalo mucosal permeation from NG3.6 showed a 1.67-fold enhancement compared to OXC control gel. in-vivo pharmacokinetics demonstrated 7.7 and 13.0-fold improvements for NG3.6 over the oral suspension, and 1.6-fold and 1.9 improvements over C3, for C_max and AUC_0-last, respectively. Brain-to-plasma ratios were 2.55 for NG3.6 compared to 1.67 and 0.26 for C3 and the oral suspension, respectively, demonstrating enhanced brain delivery. In status epilepticus rat model, NG3.6 significantly suppressed NF-κB, IL-1β and reduced the median Racine score when compared to Li/Pil group. However, NG3.6 did not show significant score compared to C3. Moreover, no overt short term histological abnormalities were observed. Ultimately, NG3.6 provides a promising brain delivery system with the potential to improve oxcarbazepine delivery to CNS. Further studies are needed to establish its therapeutic advantage and whether it can reduce dosage requirements and systemic side effects.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127575"},"PeriodicalIF":6.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trehalose-modulated poloxamer 407 thermosensitive hydrogel: sol-gel transition regulation and sustained low-dose pilocarpine nitrate delivery.","authors":"Huihui Shao, Heying Jin, Yumei Hao, Jie Chen, Suyong Ma, Liya Nie, Shuangqing Wang, Shanshan Ma, Zhonggao Gao","doi":"10.1016/j.ijpharm.2026.127577","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127577","url":null,"abstract":"<p><p>Traditional ophthalmic solutions and viscous gels are limited by insufficient precorneal residence time, inaccurate dosing administration, and inconvenient sterile filtration. Pilocarpine, originally a classic muscarinic acetylcholine receptor agonist for glaucoma management, has been recently repurposed for presbyopia treatment; however, its clinical application is greatly restricted by frequent severe ocular adverse reactions, including xerophthalmia and conjunctival hyperemia. Herein, trehalose was adopted to modify poloxamer 407 thermosensitive hydrogel, on the basis of its dual functions of tuning gel physicochemical properties and enhancing cellular desiccation resistance. The incorporation of trehalose lowered the critical gelation threshold concentration of poloxamer 407 without impairing the intrinsic physicochemical properties of the hydrogel. The optimized formulation exists as a low-viscosity aqueous solution (approximately 50 mPa·s) at ambient temperature, which allows convenient sterilization via 0.22 μm filtration, and rapidly undergoes in-situ sol-gel transition on the ocular surface to form isotonic hydrogel. This hydrogel protects loaded pilocarpine against hydrolytic degradation and improves corneal hydration. In vivo rabbit ocular irritation tests verified that the formulation effectively alleviates pilocarpine-induced ocular irritation. Benefiting from excellent thermal stability and industrial processability, this delivery system exhibits promising translational prospects and lays a solid foundation for follow-up clinical research on presbyopia treatment.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127577"},"PeriodicalIF":6.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}