{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T03:28:05Z","timestamp":1786678085738,"version":"build-2736575974"},"reference-count":113,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"crossref","award":["PNURSP2026R944"],"award-info":[{"award-number":["PNURSP2026R944"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Keratitis is an ocular disease caused by microbial infection or by non-infectious damage due to UV light exposure, chemical exposure, or eye injuries. Methods: Moxifloxacin-loaded ufasomes (MOX-UFAs) were optimized using a full factorial design (12.23) after being prepared by the vortex mixing method. The study evaluated the effects of the oleic acid amount, surface active agent (SAA) amount, and SAA type as independent factors on the entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount released after 6 h (Q6h%). Results: The optimized ufasomes (UFAs) formulation was spherical, with an EE% of 78.37 \u00b1 3.91%, PS of 203.13 \u00b1 20.31 nm, PDI of 0.334 \u00b1 0.016, and ZP of \u221225.42 \u00b1 1.27 mV. The in vitro release of moxifloxacin (MOX) from the UFAs was maintained for more than 6 h in the range of 40.0\u201375.0%. The optimum MOX-UFAs formulation was incorporated into an in situ gel (Pluronic F-127\/HPMC K4M). The ex vivo studies (corneal permeation and confocal laser scanning microscopy) proved the successful retention of the MOX-UFAs-laden in situ gel. Furthermore, the in vitro and in vivo antimicrobial studies revealed their significant antimicrobial effect against Pseudomonas aeruginosa. In addition, the Draize test proved the tolerability of MOX-UFAs-laden in situ gel in animals. Conclusions: The incorporation of MOX-UFAs into Pluronic F-127\/HPMC K4M in situ gel could successfully provide sustained ocular delivery and improve the bioavailability of MOX for the management of keratitis.<\/jats:p>","DOI":"10.3390\/ph19020313","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T16:09:32Z","timestamp":1770998972000},"page":"313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sustained Ocular Delivery of Moxifloxacin\u2013Ufasomes-Laden In Situ Gel for Keratitis Management"],"prefix":"10.3390","volume":"19","author":[{"given":"Ghadeer","family":"El-Fadaly","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City 12566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia M.","family":"Ghorab","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba M. El","family":"Sorogy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City 12566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salwa Seif","family":"Eldin","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9557-1153","authenticated-orcid":false,"given":"Marwa A.","family":"Sabet","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Sphinx University, New Assiut 71684, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda E.","family":"Teba","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City 12566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.ophtha.2017.05.012","article-title":"Update on the management of infectious keratitis","volume":"124","author":"Austin","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/ceo.14113","article-title":"Infectious keratitis: A review","volume":"50","author":"Khoo","year":"2022","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.micpath.2016.12.013","article-title":"Pathogenesis of microbial keratitis","volume":"104","author":"Lakhundi","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1016\/j.ophtha.2015.06.007","article-title":"Multidrug-resistant Pseudomonas aeruginosa keratitis: Risk factors, clinical characteristics, and outcomes","volume":"122","author":"Vazirani","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2147\/OPTH.S181997","article-title":"Treatment-resistant bacterial keratitis: Challenges and solutions","volume":"14","author":"Egrilmez","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Shehata, M., Fekry, A.M., and Walcarius, A. (2020). Moxifloxacin hydrochloride electrochemical detection at gold nanoparticles modified screen-printed electrode. Sensors, 20.","DOI":"10.3390\/s20102797"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1016\/j.xphs.2019.04.005","article-title":"An ex vivo evaluation of moxifloxacin nanostructured lipid carrier enriched in situ gel for transcorneal permeation on goat cornea","volume":"108","author":"Gade","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.colsurfb.2009.03.028","article-title":"Effect of polymer viscosity on physicochemical properties and ocular tolerance of FB-loaded PLGA nanospheres","volume":"72","author":"Vega","year":"2009","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Souto, E.B., Dias-Ferreira, J., L\u00f3pez-Machado, A., Ettcheto, M., Cano, A., Espuny, A.C., Espina, M., Garcia, M.L., and S\u00e1nchez-L\u00f3pez, E. (2019). Advanced formulation approaches for ocular drug delivery: State-of-the-art and recent patents. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11090460"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0378-5173(97)00419-5","article-title":"Characterization of a new ocular delivery system based on a dispersion of liposomes in a thermosensitive gel","volume":"162","author":"Bochot","year":"1998","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/j.2042-7158.1991.tb03534.x","article-title":"Improvement of ocular penetration of amikacin sulphate by association to poly(butylcyanoacrylate) nanoparticles","volume":"43","author":"Losa","year":"1991","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0928-0987(03)00178-7","article-title":"The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa","volume":"20","author":"Gref","year":"2003","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ijpharm.2019.01.070","article-title":"Mucoadhesive olaminosomes: A novel prolonged release nanocarrier of agomelatine for the treatment of ocular hypertension","volume":"560","author":"ElKasabgy","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nair, A.B., Shah, J., Jacob, S., Al-Dhubiab, B.E., Sreeharsha, N., Morsy, M.A., Gupta, S., Attimarad, M., Shinu, P., and Venugopala, K.N. (2021). Experimental design, formulation and in vivo evaluation of a novel topical in situ gel system to treat ocular infections. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248857"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"130457","DOI":"10.1016\/j.ijbiomac.2024.130457","article-title":"Cationized gelatin-sodium alginate polyelectrolyte nanoparticles encapsulating moxifloxacin as an eye drop to treat bacterial keratitis","volume":"264","author":"Ch","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3797\/scipharm.1204-08","article-title":"An improvement of the efficacy of moxifloxacin HCl for the treatment of bacterial keratitis by the formulation of ocular mucoadhesive microspheres","volume":"81","author":"Dandagi","year":"2012","journal-title":"Sci. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5247","DOI":"10.2147\/IJN.S316326","article-title":"Tailoring terpesomes and leciplex for the effective ocular conveyance of moxifloxacin hydrochloride (Comparative assessment): In-vitro, ex-vivo, and in-vivo evaluation","volume":"16","author":"Albash","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.3109\/10717544.2014.987333","article-title":"Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel","volume":"23","author":"Kesarla","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shah, J., Nair, A.B., Jacob, S., Patel, R.K., and Shah, H. (2019). Nanoemulsion based vehicle for effective ocular delivery of moxifloxacin using experimental design and pharmacokinetic study in rabbits. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11050230"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e42436","DOI":"10.1016\/j.heliyon.2025.e42436","article-title":"Development of sustained-release extemporaneous moxifloxacin loaded commercial soft hydrogel contact lenses","volume":"11","author":"Toan","year":"2025","journal-title":"Heliyon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1021\/la0100338","article-title":"Electron spin resonance study of the pH-induced transformation of micelles to vesicles in an aqueous oleic acid\/oleate system","volume":"17","author":"Fukuda","year":"2001","journal-title":"Langmuir"},{"key":"ref_22","first-page":"32","article-title":"Review on ufasomes and vesicular drug delivery system","volume":"9","author":"Patel","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hashem, S.M., Gad, M.K., Anwar, H.M., Saleh, N.M., Shamma, R.N., and Elsherif, N.I. (2023). Itraconazole-loaded ufasomes: Evaluation, characterization, and anti-fungal activity against candida albicans. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010026"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1016\/j.bpj.2018.04.011","article-title":"Mechanism of Long-Chain Free Fatty Acid Protonation at the Membrane-Water Interface","volume":"114","author":"Pashkovskaya","year":"2018","journal-title":"Biophys. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1080\/10717544.2022.2120926","article-title":"Pronounced capping effect of olaminosomes as nanostructured platforms in ocular candidiasis management","volume":"29","author":"Ahmed","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jconrel.2022.10.011","article-title":"Oleic acid-based vesicular nanocarriers for topical delivery of the natural drug thymoquinone: Improvement of anti-inflammatory activity","volume":"352","author":"Bruno","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.3109\/02713683.2014.904361","article-title":"Effects of oleic acid on the corneal permeability of compounds and evaluation of its ocular irritation of rabbit eyes","volume":"39","author":"Gao","year":"2014","journal-title":"Curr. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s43094-020-00143-w","article-title":"Preparation and characterizations of glyceryl oleate ufasomes of terbinafine hydrochloride: A novel approach to trigger Candida albicans fungal infection","volume":"7","author":"Bhattacharya","year":"2021","journal-title":"Futur. J. Pharm. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kumar, P., Singh, S.K., Handa, V., and Kathuria, H. (2018). Acid Nanovesicles of Minoxidil for Enhanced Follicular Delivery. Medicines, 5.","DOI":"10.3390\/medicines5030103"},{"key":"ref_30","first-page":"680580","article-title":"Ufasomes mediated cutaneous delivery of dexamethasone: Formulation and evaluation of anti-inflammatory activity by carrageenin-induced rat paw edema model","volume":"2013","author":"Mittal","year":"2013","journal-title":"J. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rossello, S., Mandrone, M., Cerchiara, T., Chiocchio, I., Rossi, M., Chinnici, F., Sallustio, V., Aponte, M., Blaiotta, G., and Luppi, B. (2024). A New wound-healing tool based on glycyrrhiza glabra extract-loaded ufasomes on spanish broom dressings. Molecules, 29.","DOI":"10.3390\/molecules29163811"},{"key":"ref_32","first-page":"873653","article-title":"Formulation and in vitro evaluation of ufasomes for dermal administration of methotrexate","volume":"2012","author":"Sharma","year":"2012","journal-title":"Int. Sch. Res. Not."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Aboud, H.M., Ali, A.A., Mohammed, N.H., Hassan, A.H.E., Roh, E.J., and El Menshawe, S.F. (2024). Investigating the potential of ufasomes laden with nintedanib as an optimized targeted lung nanoparadigm for accentuated tackling of idiopathic pulmonary fibrosis. Pharmaceuticals, 17.","DOI":"10.3390\/ph17121605"},{"key":"ref_34","first-page":"706","article-title":"Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of cinnarizine: Preparation, optimization, ex-vivo histopathological safety assessment and mucosal confocal imaging","volume":"21","author":"Salama","year":"2015","journal-title":"Pharm. Dev. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1023\/A:1016368714631","article-title":"Effect of oleic acid vesicles on intestinal absorption of carboxyfluorescein in rats","volume":"3","author":"Murakami","year":"1986","journal-title":"Pharm. Res."},{"key":"ref_36","first-page":"511","article-title":"Preparation and in vivo evaluation of in situ gel system as dual thermo-\/pH-responsive nanocarriers for sustained ocular drug delivery","volume":"32","author":"Davaran","year":"2015","journal-title":"J. Microencapsul."},{"key":"ref_37","unstructured":"Scherlund, M. (2014). In Situ Gelling Drug Delivery Systems for Periodontal Anaesthesia. [Doctoral Dissertation, Acta Universitatis Upsaliensis]. Available online: http:\/\/uu.diva-portal.org\/smash\/get\/diva2:160625\/FULLTEXT01.pdf."},{"key":"ref_38","first-page":"1","article-title":"Research progress of in-situ gelling ophthalmic drug delivery system","volume":"14","author":"Wu","year":"2019","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101736","DOI":"10.1016\/j.jddst.2020.101736","article-title":"Nanoparticles laden In situ gel for sustained drug release after topical ocular administration","volume":"57","author":"Shivam","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1021\/bm0496965","article-title":"In situ gelling of alginate\/Pluronic solutions for ophthalmic delivery of pilocarpine","volume":"5","author":"Lin","year":"2004","journal-title":"Biomacromolecules"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2174\/1874126600802010061","article-title":"Designing of a thermosensitive chitosan\/poloxamer in situ gel for ocular delivery of ciprofloxacin","volume":"2","author":"Varshosaz","year":"2008","journal-title":"Open Drug Deliv. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0378-5173(02)00234-X","article-title":"El In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate","volume":"241","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.molliq.2014.09.021","article-title":"Role of Pluronic F127 micelles in enhancing ocular delivery of ciprofloxacin","volume":"199","author":"Taha","year":"2014","journal-title":"J. Mol. Liq."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bachu, R.D., Chowdhury, P., Al-Saedi, Z.H.F., Karla, P.K., and Boddu, S.H.S. (2018). Ocular drug delivery barriers\u2014Role of nanocarriers in the treatment of anterior segment ocular diseases. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10010028"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Giuliano, E., Paolino, D., Fresta, M., and Cosco, D. (2018). Mucosal applications of poloxamer 407-based hydrogels: An overview. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030159"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"103327","DOI":"10.1016\/j.jddst.2022.103327","article-title":"Recent progress in colloidal nanocarriers loaded in situ gel in ocular therapeutics","volume":"71","author":"Chaudhari","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jcis.2016.08.018","article-title":"Moxifloxacin loaded gelatin nanoparticles for ocular delivery: Formulation and in-vitro, in-vivo evaluation","volume":"483","author":"Mahor","year":"2016","journal-title":"J. Colloid Interface Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.2174\/1567201815666180619105419","article-title":"Implementing central composite design for developing transdermal diacerein-loaded niosomes: Ex vivo permeation and in vivo deposition","volume":"15","author":"Aziz","year":"2018","journal-title":"Curr. Drug Deliv."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3109\/21691401.2013.794351","article-title":"Oleic acid vesicles: A new approach for topical delivery of antifungal agent","volume":"42","author":"Verma","year":"2014","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"424","DOI":"10.4172\/jbb.1000336","article-title":"Optimization and evaluation of oleic acid based unsaturated fatty acid liposomes gel","volume":"9","author":"N","year":"2017","journal-title":"J. Bioequiv. Availab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1208\/s12249-010-9480-2","article-title":"Formulation and optimization of zidovudine niosomes","volume":"11","author":"Ruckmani","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ijpharm.2017.09.017","article-title":"Designing lipid nanoparticles for topical ocular drug delivery","volume":"532","author":"Diebold","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"105735","DOI":"10.1016\/j.ejps.2021.105735","article-title":"A grafted copolymer-based nanomicelles for topical ocular delivery of everolimus: Formulation, characterization, ex-vivo permeation, in-vitro ocular toxicity, and stability study","volume":"159","author":"Mehra","year":"2021","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Atef, B., Ishak, R.A.H., Badawy, S.S., and Osman, R. (2023). 10-Hydroxy Decanoic Acid-Based Vesicles as a Novel Topical Delivery System: Would It Be a Better Platform Than Conventional Oleic Acid Ufasomes for Skin Cancer Treatment?. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15051461"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1111\/jocd.13960","article-title":"Increase adapalene delivery using chemical and herbal enhancers","volume":"20","author":"Salimi","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/08982100802312762","article-title":"Entrapment of ovalbumin into liposomes\u2014Factors affecting entrapment efficiency, liposome size, and zeta potential","volume":"18","author":"Brgles","year":"2008","journal-title":"J. Liposome Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/BF02530898","article-title":"Novel fatty acids from the royal jelly of honeybees (Apis mellifera, L.) NEVIN","volume":"3","author":"Weaver","year":"1968","journal-title":"Lipids"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Aziz, D., Mohamed, S.A., Tayel, S., and Makhlouf, A. (2022). Enhanced ocular anti-aspergillus activity of tolnaftate employing novel cosolvent-modified spanlastics: Formulation, statistical optimization, kill kinetics, ex vivo trans-corneal permeation, in vivo histopathological and susceptibility study. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14081746"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ahmed, Y.M., Orfali, R., Hamad, D.S., Rateb, M.E., and Farouk, H.O. (2022). Sustainable release of propranolol hydrochloride laden with biconjugated-ufasomes chitosan hydrogel attenuates cisplatin-induced sciatic nerve damage in in vitro\/in vivo evaluation. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14081536"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0005-2736(96)00167-8","article-title":"Effect of sterical stabilization on macrophage uptake in vitro and on thickness of the fixed aqueous layer of liposomes made from alkylphosphocholines","volume":"1285","author":"Zeisig","year":"1996","journal-title":"Biochim. Biophys. Acta-Biomembr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1080\/10717544.2022.2057619","article-title":"Fenticonazole nitrate loaded trans-novasomes for effective management of tinea corporis: Design characterization, in silico study, and exploratory clinical appraisal","volume":"29","author":"Albash","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Cort\u00e9s, H., Hern\u00e1ndez-Parra, H., Bernal-Ch\u00e1vez, S.A., Del Prado-Audelo, M.L., Caballero-Flor\u00e1n, I.H., Borbolla-Jim\u00e9nez, F.V., Gonz\u00e1lez-Torres, M., Maga\u00f1a, J.J., and Leyva-G\u00f3mez, G. (2021). Non-ionic surfactants for stabilization of polymeric nanoparticles for biomedical uses. Materials, 14.","DOI":"10.3390\/ma14123197"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"590","DOI":"10.3390\/pharmaceutics4040590","article-title":"Composition influence on pulmonary delivery of rifampicin liposomes","volume":"4","author":"Manca","year":"2012","journal-title":"Pharmaceutics"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Bolla, P.K., Meraz, C.A., Rodriguez, V.A., Deaguero, I., Singh, M., Yellepeddi, V.K., and Renukuntla, J. (2019). Clotrimazole loaded ufosomes for topical delivery: Formulation development and in-vitro studies. Molecules, 24.","DOI":"10.3390\/molecules24173139"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1080\/10717544.2021.1989090","article-title":"Novel cubosome based system for ocular delivery of acetazolamide","volume":"28","author":"Teba","year":"2021","journal-title":"Drug Deliv."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jcis.2023.05.050","article-title":"Non-ionic surfactant-assisted controlled release of oxyresveratrol on dendritic fibrous silica for topical applications","volume":"646","author":"Kerdmuanglek","year":"2023","journal-title":"J. Colloid Interface Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.2147\/IJN.S196771","article-title":"Use of transethosomes for enhancing the transdermal delivery of olmesartan medoxomil: In vitro, ex vivo, and in vivo evaluation","volume":"14","author":"Albash","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"959741","DOI":"10.1155\/2014\/959741","article-title":"Formulation and characterization of drug loaded nonionic surfactant vesicles (Niosomes) for oral bioavailability enhancement","volume":"2014","author":"Kamboj","year":"2014","journal-title":"Sci. World J."},{"key":"ref_69","first-page":"830","article-title":"Rapamycin-loaded, capryoltm 90 and oleic acid mediated nanoemulsions: Formulation development, characterization and toxicity assessment","volume":"17","author":"Sobhani","year":"2018","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.ijpharm.2015.08.011","article-title":"Long-circulating lipoprotein-mimic nanoparticles for smart intravenous delivery of a practically-insoluble antineoplastic drug: Development, preliminary safety evaluations and preclinical pharmacokinetic studies","volume":"493","author":"Tadros","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ijpharm.2015.03.033","article-title":"Investigating the potential of employing bilosomes as a novel vesicular carrier for transdermal delivery of tenoxicam","volume":"485","author":"Abdelbary","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.3109\/10717544.2015.1013587","article-title":"Nanotransfersomes of carvedilol for intranasal delivery: Formulation, characterization and in vivo evaluation","volume":"23","author":"Aboud","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3109\/03639045.2011.592529","article-title":"Development and evaluation of nanosized niosomal dispersion for oral delivery of Ganciclovir","volume":"38","author":"Akhter","year":"2012","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0005-2736(01)00400-X","article-title":"Self-assembled vesicles of monocarboxylic acids and alcohols: Conditions for stability and for the encapsulation of biopolymers","volume":"1559","author":"Apel","year":"2002","journal-title":"Biochim. Biophys. Acta-Biomembr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2478\/v10007-012-0002-5","article-title":"Design and evaluation of moxifloxacin hydrochloride ocular inserts","volume":"62","author":"Pawar","year":"2012","journal-title":"Acta Pharm."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Vigani, B., Rossi, S., Sandri, G., Bonferoni, M.C., Caramella, C.M., and Ferrari, F. (2020). Recent advances in the development of in situ gelling drug delivery systems for non-parenteral administration routes. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090859"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1080\/10717544.2020.1858997","article-title":"Statistical optimization of hyaluronic acid enriched ultradeformable elastosomes for ocular delivery of voriconazole via Box-Behnken design: In vitro characterization and in vivo evaluation","volume":"28","author":"Fahmy","year":"2021","journal-title":"Drug Deliv."},{"key":"ref_78","first-page":"e17511","article-title":"Development and in vitro\/in vivo evaluation of thermo-sensitive in situ gelling systems for ocular allergy","volume":"55","author":"Berkman","year":"2010","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2162159","DOI":"10.1080\/10717544.2022.2162159","article-title":"Syringeable atorvastatin loaded eugenol enriched PEGylated cubosomes in-situ gel for the intra-pocket treatment of periodontitis: Statistical optimization and clinical assessment","volume":"30","author":"Elgendy","year":"2023","journal-title":"Drug Deliv."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ijpharm.2016.04.021","article-title":"Ketoroloac tromethamine loaded nanodispersion incorporated into thermosensitive in situ gel for prolonged ocular delivery","volume":"506","author":"Morsi","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/s13346-015-0275-6","article-title":"In vitro and ex vivo corneal penetration and absorption models","volume":"6","author":"Agarwal","year":"2016","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1016\/j.survophthal.2005.07.001","article-title":"Ocular pharmacokinetics of moxifloxacin after topical treatment of animals and humans","volume":"50","author":"Robertson","year":"2005","journal-title":"Surv. Ophthalmol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"119552","DOI":"10.1016\/j.ijpharm.2020.119552","article-title":"Development of besifloxacin HCl loaded nanofibrous ocular inserts for the treatment of bacterial keratitis: In vitro, ex vivo and in vivo evaluation","volume":"585","author":"Polat","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2217\/nnm-2018-0297","article-title":"Noninvasive biodegradable nanoparticles-in-nanofibers single-dose ocular insert: In vitro, ex vivo and in vivo evaluation","volume":"14","author":"Khalil","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jconrel.2005.04.007","article-title":"Ethosomes for skin delivery of ammonium glycyrrhizinate: In vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers","volume":"106","author":"Paolino","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"122621","DOI":"10.1016\/j.ijpharm.2023.122621","article-title":"Integration of terpesomes loaded Levocetrizine dihydrochloride gel as a repurposed cure for Methicillin-Resistant Staphylococcus aureus (MRSA)-Induced skin infection; D-optimal optimization, ex-vivo, in-silico, and in-vivo studies","volume":"633","author":"Teaima","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1080\/10717544.2022.2100514","article-title":"Utilization of propranolol hydrochloride mucoadhesive invasomes as a locally acting contraceptive: In-vitro, ex-vivo, and in-vivo evaluation","volume":"29","author":"Teaima","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1177\/147323000903700322","article-title":"Influence of borneol on in vitro corneal permeability and on in vivo and in vitro corneal toxicity","volume":"37","author":"Yang","year":"2009","journal-title":"J. Int. Med. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jconrel.2012.06.024","article-title":"Objective assessment of nanoparticle disposition in mammalian skin after topical exposure","volume":"162","author":"Campbell","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"78","DOI":"10.4103\/2230-973X.100042","article-title":"Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride","volume":"2","author":"Mandal","year":"2012","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0169-409X(02)00228-4","article-title":"Biodegradable nanoparticles for drug and gene delivery to cells and tissue","volume":"55","author":"Panyam","year":"2003","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1080\/21691401.2017.1307209","article-title":"Enhancement of antimicrobial activity by liposomal oleic acid-loaded antibiotics for the treatment of multidrug-resistant Pseudomonas aeruginosa","volume":"46","author":"Nellore","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"111643","DOI":"10.1016\/j.msec.2020.111643","article-title":"Interaction between mucoadhesive cellulose derivatives and Pluronic F127: Investigation on the micelle structure and mucoadhesive performance","volume":"119","author":"Braga","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1080\/17435889.2024.2359364","article-title":"Chitosan decorated oleosomes loaded propranolol hydrochloride hydrogel repurposed for Candida albicans -vaginal infection","volume":"19","author":"Eltabeeb","year":"2024","journal-title":"Nanomedicine"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Hassan, D.H., Shohdy, J.N., El-Setouhy, D.A., El-Nabarawi, M., and Naguib, M.J. (2022). Compritol-based nanostrucutured lipid carriers (NLCs) for augmentation of zolmitriptan bioavailability via the transdermal route: In vitro optimization, ex vivo permeation, in vivo pharmacokinetic study. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14071484"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.ijpharm.2014.06.041","article-title":"Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: In-vitro optimization, ex-vivo permeation studies, and in-vivo assessment","volume":"472","author":"Khowessah","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Akbar, N., Gul, J., Siddiqui, R., Shah, M.R., and Khan, N.A. (2021). Moxifloxacin and sulfamethoxazole-based nanocarriers exhibit potent antibacterial activities. Antibiotics, 10.","DOI":"10.3390\/antibiotics10080964"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1128\/AAC.03503-14","article-title":"Thermosensitive and mucoadhesive pluronic-hydroxypropylmethylcellulose hydrogel containing the mini-CD4 M48U1 is a promising efficient barrier against HIV diffusion through macaque cervicovaginal mucus","volume":"59","author":"Bouchemal","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jddst.2017.12.002","article-title":"Investigation of effectiveness of some extensively used polymers on thermoreversible properties of Pluronic\u00ae tri-block copolymers","volume":"44","author":"Rarokar","year":"2018","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.jsps.2018.01.005","article-title":"Ocular administration of acetazolamide microsponges in situ gel formulations","volume":"26","author":"Obiedallah","year":"2018","journal-title":"Saudi Pharm. J."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Gugleva, V., Michailova, V., Mihaylova, R., Momekov, G., Zaharieva, M.M., Najdenski, H., Petrov, P., Rangelov, S., Forys, A., and Trzebicka, B. (2022). Formulation and evaluation of hybrid niosomal in situ gel for intravesical co-delivery of curcumin and gentamicin sulfate. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14040747"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"78","DOI":"10.4274\/tjps.galenos.2022.00334","article-title":"Thermosensitive in situ gelling system for dermal drug delivery of rutin","volume":"20","author":"Polat","year":"2023","journal-title":"Turk. J. Pharm. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1208\/s12249-009-9261-y","article-title":"In vitro and in vivo characteristics of a thermogelling rectal delivery system of etodolac","volume":"10","author":"Barakat","year":"2009","journal-title":"AAPS PharmSciTech"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"118684","DOI":"10.1016\/j.ijpharm.2019.118684","article-title":"Concentration of a microemulsion influences the mechanical properties of ibuprofen in situ microgels","volume":"570","author":"Hamed","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1080\/10717544.2022.2115164","article-title":"Fabrication of nanostructured lipid carriers ocugel for enhancing Loratadine used in treatment of COVID-19 related symptoms: Statistical optimization, in-vitro, ex-vivo, and in-vivo studies evaluation","volume":"29","author":"Abdelmonem","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7947","DOI":"10.2147\/IJN.S150366","article-title":"Tailored nanostructured platforms for boosting transcorneal permeation: Box-behnken statistical optimization, comprehensive in vitro, ex vivo and in vivo characterization","volume":"12","author":"Elsayed","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2147\/DDDT.S293127","article-title":"Development and characterization of PLGA nanoparticle-laden hydrogels for sustained ocular delivery of norfloxacin in the treatment of pseudomonas keratitis: An experimental study","volume":"15","author":"Gebreel","year":"2021","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jpha.2015.11.005","article-title":"Methods for in vitro evaluating antimicrobial activity: A review","volume":"6","author":"Balouiri","year":"2016","journal-title":"J. Pharm. Anal."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"617","DOI":"10.2147\/DDDT.S295874","article-title":"Treatment of severe acute bacterial keratitis in rabbits using continuous topical ocular instillation with norvancomycin treatment of severe acute bacterial keratitis in rabbits using continuous topical ocular instillation with norvancomycin","volume":"15","author":"Lin","year":"2021","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"120271","DOI":"10.1016\/j.ijpharm.2021.120271","article-title":"Sterilization methods of liposomes: Drawbacks of conventional methods and perspectives","volume":"597","author":"Delma","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_111","first-page":"732","article-title":"The estimation of the bactericidal power of the blood","volume":"38","author":"Miles","year":"1931","journal-title":"J. Hyg."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0168-3659(02)00284-5","article-title":"Clinical evaluation of bioadhesive ophthalmic drug inserts (BODI\u00ae) for the treatment of external ocular infections in dogs","volume":"85","author":"Baeyens","year":"2002","journal-title":"J. Control. Release"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.ijpharm.2013.11.043","article-title":"Acetazolamide encapsulated dendritic nano-architectures for effective glaucoma management in rabbits","volume":"461","author":"Mishra","year":"2014","journal-title":"Int. J. Pharm."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/2\/313\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T05:13:13Z","timestamp":1771132393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/2\/313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,13]]},"references-count":113,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ph19020313"],"URL":"https:\/\/doi.org\/10.3390\/ph19020313","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,13]]}}}