{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:43:02Z","timestamp":1785548582007,"version":"3.56.0"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSPD2024R1008"],"award-info":[{"award-number":["RSPD2024R1008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Itraconazole (ITZ) is a potent antifungal agent. Its oral administration is associated with systemic toxicity, and its efficacy in ocular formulations is limited. This study aims to enhance ITZ\u2019s ocular permeation and antifungal efficacy by loading it into deformable liposomes (DLs) based on Tween 80 (T) or Poloxamer 188 (P). Moreover, ITZ was loaded into biopolymer-coated DLs to augment its ocular availability. ITZ-loaded DLs were coated with hyaluronic acid (HA-DLs), chitosan (CS-DLs), or a layer-by-layer coating (CS\/HA-DLs). These formulations were further laden into pH-sensitive in situ gels to provide a hybrid system to intensify their ocular adhesion properties. The prepared DLs were successfully prepared with vesicle sizes in nonorange (&lt;200 nm). The zeta potential values of DLS were negative before coating and shifted to high negativity with HA coating and positivity with CS and CS\/HA bilayer coating. These variations of zeta potential indicate successful CS and HA coatings. The optimized A high EE% was achieved with DLs-T: 89% (CS\/HA-DLs-T), 86% (CS-DLs-T), 85% (HA-DLs-T), and 79% (HA-DLs-T). Therefore, DLs-T were incorporated into in situ gels, displaying optimal gelling capacity and viscosity. The release rate of ITZ from the coated DLs-laden in situ gels was slower than that observed with the uncoated DLs-gel. CS\/HA-DLs-T laden-in situ gels showed the highest ex vivo transcorneal permeability and antifungal efficacy. These data suggest that the layer-by-layer-CS\/HA-DLs-T presents a hopeful strategy for the ocular delivery of ITZ, offering a promising approach for managing ocular fungal infections.<\/jats:p>","DOI":"10.3390\/gels11010019","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:34:19Z","timestamp":1735630459000},"page":"19","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Layer-by-Layer Biopolymer-Coated Deformable Liposomes\u2013In Situ Gel: A Hybrid Strategy for Enhanced Ocular Delivery of Itraconazole: In Vitro and In Vivo Appraisal"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1814-0215","authenticated-orcid":false,"given":"Mohamed M.","family":"Badran","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Nanobiotechnology Research Unit, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areej","family":"Alsubaie","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mounir M. Salem","family":"Bekhit","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah H.","family":"Alomrani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Nanobiotechnology Research Unit, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0181-6330","authenticated-orcid":false,"given":"Aliyah","family":"Almomen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Irimia, T., Dinu-P\u00eervu, C.-E., Ghica, M.V., Lupuleasa, D., Muntean, D.-L., Udeanu, D.I., and Popa, L. (2018). Chitosan-Based In Situ Gels for Ocular Delivery of Therapeutics: A State-of-the-Art Review. Mar. Drugs, 16.","DOI":"10.3390\/md16100373"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1124\/jpet.119.256933","article-title":"Ocular Drug Delivery: Present Innovations and Future Challenges","volume":"370","author":"Gote","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100794","DOI":"10.1016\/j.colcom.2024.100794","article-title":"Nanoparticle-Based Drug Delivery Systems: An Updated Strategy for Treating Fungal Keratitis","volume":"61","author":"Guo","year":"2024","journal-title":"Colloid Interface Sci. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Gonz\u00e1lez, N., Rodr\u00edguez-Lagunas, M.J., Calpena-Campmany, A.C., Bozal-de Febrer, N., Halbaut-Bellowa, L., Mallandrich, M., and Clares-Naveros, B. (2023). Caspofungin-Loaded Formulations for Treating Ocular Infections Caused by Candida spp.. Gels, 9.","DOI":"10.3390\/gels9040348"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1080\/17458080.2013.822108","article-title":"Preparation and Evaluation of Chitosan\u2013Itraconazole Co-Precipitated Nanosuspension for Ocular Delivery","volume":"10","author":"Ahuja","year":"2015","journal-title":"J. Exp. Nanosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s10792-012-9696-0","article-title":"Intraocular Penetration of Itraconazole in Patient with Fungal Endophthalmitis","volume":"33","author":"Mochizuki","year":"2013","journal-title":"Int. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Badran, M.M., Alomrani, A.H., Almomen, A., Bin Jardan, Y.A., and Abou El Ela, A.E.S. (2022). Novel Metoprolol-Loaded Chitosan-Coated Deformable Liposomes in Thermosensitive In Situ Gels for the Management of Glaucoma: A Repurposing Approach. Gels, 8.","DOI":"10.3390\/gels8100635"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.3390\/neurolint15040083","article-title":"Remdesivir-Loaded Nanoliposomes Stabilized by Chitosan\/Hyaluronic Acid Film with a Potential Application in the Treatment of Coronavirus Infection","volume":"15","author":"Milkova","year":"2023","journal-title":"Neurol. Int."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Badran, M.M., Alouny, N.N., Aldosari, B.N., Alhusaini, A.M., and Abou El Ela, A.E.S. (2022). Transdermal Glipizide Delivery System Based on Chitosan-Coated Deformable Liposomes: Development, Ex Vivo, and In Vivo Studies. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14040826"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, C., Wang, J., Wu, H., Fan, W., Li, S., Wei, D., Song, Z., and Tao, Y. (2024). Hydrogel-Based Therapy for Age-Related Macular Degeneration: Current Innovations, Impediments, and Future Perspectives. Gels, 10.","DOI":"10.3390\/gels10030158"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"118006","DOI":"10.1016\/j.carbpol.2021.118006","article-title":"Hyaluronic Acid in Ocular Drug Delivery","volume":"264","author":"Zhang","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103045","DOI":"10.1016\/j.jddst.2021.103045","article-title":"How Liposomes Pave the Way for Ocular Drug Delivery after Topical Administration","volume":"67","author":"Tasharrofi","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, T.-J., Rethi, L., Ku, M.-Y., Nguyen, H.T., and Chuang, A.E.-Y. (2024). A Review on Revolutionizing Ophthalmic Therapy: Unveiling the Potential of Chitosan, Hyaluronic Acid, Cellulose, Cyclodextrin, and Poloxamer in Eye Disease Treatments. Int. J. Biol. Macromol., 273.","DOI":"10.1016\/j.ijbiomac.2024.132700"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1007\/s11814-013-0110-z","article-title":"Proliposomes of Lisinopril Dihydrate for Transdermal Delivery: Formulation Aspects and Evaluation","volume":"30","author":"Bandari","year":"2013","journal-title":"Korean J. Chem. Eng."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104057","DOI":"10.1016\/j.jddst.2022.104057","article-title":"Bile Salt Stabilized Nanovesicles as a Promising Drug Delivery Technology: A General Overview and Future Perspectives","volume":"79","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ijpharm.2010.06.034","article-title":"Role of Edge Activators and Surface Charge in Developing Ultradeformable Vesicles with Enhanced Skin Delivery","volume":"397","author":"Awad","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Koty\u0144ska, J., and Naumowicz, M. (2024). Monitoring Changes in the Zeta Potential and the Surface Charge of Human Glioblastoma Cells and Phosphatidylcholine Liposomes Induced by Curcumin as a Function of pH. Chem.-Biol. Interact., 402.","DOI":"10.1016\/j.cbi.2024.111215"},{"key":"ref_18","first-page":"2379","article-title":"Functionalization of Nanostructured Surfaces: From the Impact on Morphological Control during Synthesis to the Effect on Colloidal Dispersion","volume":"39","author":"Sampaio","year":"2024","journal-title":"J. Mater. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1517\/17425247.2013.860130","article-title":"Nanovesicular Carriers as Alternative Drug Delivery Systems: Ethosomes in Focus","volume":"11","author":"Mbah","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8767","DOI":"10.2147\/IJN.S261932","article-title":"The Impact of Surfactant Composition and Surface Charge of Niosomes on the Oral Absorption of Repaglinide as a BCS II Model Drug","volume":"15","author":"Yaghoobian","year":"2020","journal-title":"IJN"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1208\/s12249-012-9904-2","article-title":"Evaluation of Meloxicam-Loaded Cationic Transfersomes as Transdermal Drug Delivery Carriers","volume":"14","author":"Duangjit","year":"2013","journal-title":"AAPS PharmSciTech"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Toopkanloo, S.P., Tan, T.B., Abas, F., Alharthi, F.A., Nehdi, I.A., and Tan, C.P. (2020). Impact of Quercetin Encapsulation with Added Phytosterols on Bilayer Membrane and Photothermal-Alteration of Novel Mixed Soy Lecithin-Based Liposome. Nanomaterials, 10.","DOI":"10.3390\/nano10122432"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5982","DOI":"10.1021\/acsanm.3c05884","article-title":"Lecithin\/Cholesterol\/Tween 80 Liposomes for Co-Encapsulation of Vitamin C and Xanthoxylin","volume":"7","author":"Wang","year":"2024","journal-title":"ACS Appl. Nano Mater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"200","DOI":"10.2174\/1872208311206030200","article-title":"Poloxamer 188 (P188) as a Membrane Resealing Reagent in Biomedical Applications","volume":"6","author":"Moloughney","year":"2012","journal-title":"BIOT"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Islam, N., Irfan, M., Khan, S.-U.-D., Syed, H.K., Iqbal, M.S., Khan, I.U., Mahdy, A., Raafat, M., Hossain, M.A., and Inam, S. (2021). Poloxamer-188 and d-\u03b1-Tocopheryl Polyethylene Glycol Succinate (TPGS-1000) Mixed Micelles Integrated Orodispersible Sublingual Films to Improve Oral Bioavailability of Ebastine; In Vitro and In Vivo Characterization. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010054"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.xphs.2022.09.019","article-title":"Micelle Formation and Phase Separation of Poloxamer 188 and Preservative Molecules in Aqueous Solutions Studied by Small Angle X-Ray Scattering","volume":"112","author":"Ford","year":"2023","journal-title":"J. Pharm. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jconrel.2016.03.012","article-title":"Hyaluronic Acid-Coated Liposomes for Targeted Delivery of Paclitaxel, in-Vitro Characterization and in-Vivo Evaluation","volume":"229","author":"Ravar","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.jsps.2019.02.008","article-title":"The Use of Chitosan-Coated Flexible Liposomes as a Remarkable Carrier to Enhance the Antitumor Efficacy of 5-Fluorouracil against Colorectal Cancer","volume":"27","author":"Alomrani","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"488","DOI":"10.2174\/1567201820666230504115446","article-title":"A Mini-Review on New Developments in Nanocarriers and Polymers forOphthalmic Drug Delivery Strategies","volume":"21","author":"Sharma","year":"2024","journal-title":"Curr. Drug Deliv."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rahbar, N., Darvish, S., Farrahi, F., and Kouchak, M. (2024). Chitosan\/Carbomer Nanoparticles- Laden in Situ Gel for Improved Ocular Delivery of Timolol: In Vitro, in Vivo, and Ex Vivo Study. Drug Deliv. Transl. Res.","DOI":"10.1007\/s13346-024-01663-1"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"416","DOI":"10.35333\/jrp.2020.164","article-title":"Development and Evaluation of a pH Triggered in Situ Ocular Gel of Brimonidine Tartrate","volume":"24","author":"Karuppaiah","year":"2020","journal-title":"JRP"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jconrel.2024.05.031","article-title":"In Situ Gelling Systems for Ocular Drug Delivery","volume":"371","author":"Ahmed","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"124508","DOI":"10.1016\/j.ijpharm.2024.124508","article-title":"Augmented Ocular Uptake and Anti-Inflammatory Efficacy of Decorated Genistein-Loaded NLCs Incorporated in in Situ Gel","volume":"662","author":"Elmanawy","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"47","DOI":"10.5497\/wjp.v2.i2.47","article-title":"Ocular Drug Delivery Systems: An Overview","volume":"2","author":"Patel","year":"2013","journal-title":"WJP"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1080\/03639045.2017.1386196","article-title":"Dorzolamide Nanoliposome as a Long Action Ophthalmic Delivery System in Open Angle Glaucoma and Ocular Hypertension Patients","volume":"44","author":"Kouchak","year":"2018","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.ajps.2019.09.003","article-title":"A Stepwise Optimization Strategy to Formulate in Situ Gelling Formulations Comprising Fluconazole-Hydroxypropyl-Beta-Cyclodextrin Complex Loaded Niosomal Vesicles and Eudragit Nanoparticles for Enhanced Antifungal Activity and Prolonged Ocular Delivery","volume":"15","author":"Elmotasem","year":"2020","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.colsurfb.2016.01.014","article-title":"Hyaluronic Acid-Coated Niosomes Facilitate Tacrolimus Ocular Delivery: Mucoadhesion, Precorneal Retention, Aqueous Humor Pharmacokinetics, and Transcorneal Permeability","volume":"141","author":"Zeng","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mansour, M., Elmowafy, E., and Gad, H.A. (2021). Intranasal versus Intraperitoneal Myrj 59-Stabilized Cubosomes: A Potential Armamentarium of Effective Anti-Diabetic Therapy. Colloids Surf. B Biointerfaces, 199.","DOI":"10.1016\/j.colsurfb.2020.111534"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1080\/02652048.2017.1321048","article-title":"Nanodispersion-Loaded Mucoadhesive Polymeric Inserts for Prolonged Treatment of Post-Operative Ocular Inflammation","volume":"34","author":"Morsi","year":"2017","journal-title":"J. Microencapsul."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.colsurfb.2015.03.018","article-title":"Improved Stability and Skin Permeability of Sodium Hyaluronate-Chitosan Multilayered Liposomes by Layer-by-Layer Electrostatic Deposition for Quercetin Delivery","volume":"129","author":"Jeon","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.biomaterials.2007.11.012","article-title":"Protein Release Kinetics for Core\u2013Shell Hybrid Nanoparticles Based on the Layer-by-Layer Assembly of Alginate and Chitosan on Liposomes","volume":"29","author":"Haidar","year":"2008","journal-title":"Biomaterials"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"124741","DOI":"10.1016\/j.ijpharm.2024.124741","article-title":"A One-Platform Comparison Study of Brinzolamide-Loaded Liposomes, Niosomes, Transfersomes, and Transniosomes for Better Management of Glaucoma","volume":"666","author":"Srivastava","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"39603","DOI":"10.1021\/acsami.9b13851","article-title":"Overcoming the Anatomical and Physiological Barriers in Topical Eye Surface Medication Using a Peptide-Decorated Polymeric Micelle","volume":"11","author":"Lin","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, X., Wu, J., Lin, X., Wu, X., Yu, X., Wang, B., and Xu, W. (2022). Tacrolimus Loaded Cationic Liposomes for Dry Eye Treatment. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.838168"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.mimet.2019.01.020","article-title":"Antifungal Efficacy of Itraconazole Loaded PLGA-Nanoparticles Stabilized by Vitamin-E TPGS: In Vitro and Ex Vivo Studies","volume":"161","author":"Alhowyan","year":"2019","journal-title":"J. Microbiol. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gamil, Y., Hamed, M.G., Elsayed, M., Essawy, A., Medhat, S., Zayed, S.O., and Ismail, R.M. (2024). The Anti-Fungal Effect of Miconazole and Miconazole-Loaded Chitosan Nanoparticles Gels in Diabetic Patients with Oral Candidiasis-Randomized Control Clinical Trial and Microbiological Analysis. BMC Oral Health, 24.","DOI":"10.1186\/s12903-024-03952-0"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"31575","DOI":"10.1021\/acsomega.3c01988","article-title":"Superficial Dermatophytosis across the World\u2019s Populations: Potential Benefits from Nanocarrier-Based Therapies and Rising Challenges","volume":"8","author":"Keshwania","year":"2023","journal-title":"ACS Omega"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zamboulis, A., Nanaki, S., Michailidou, G., Koumentakou, I., Lazaridou, M., Ainali, N.M., Xanthopoulou, E., and Bikiaris, D.N. (2020). Chitosan and Its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments. Polymers, 12.","DOI":"10.3390\/polym12071519"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2478\/acph-2014-0013","article-title":"Evaluation of Chitosan Based Vaginal Bioadhesive Gel Formulations for Antifungal Drugs","volume":"64","author":"Karavana","year":"2014","journal-title":"Acta Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.ajps.2015.02.001","article-title":"Design and Development of Novel Bioadhesive Niosomal Formulation for the Transcorneal Delivery of Anti-Infective Agent: In-Vitro and Ex-Vivo Investigations","volume":"10","author":"Zubairu","year":"2015","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Valachov\u00e1, K., and \u0160olt\u00e9s, L. (2021). Versatile Use of Chitosan and Hyaluronan in Medicine. Molecules, 26.","DOI":"10.3390\/molecules26041195"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Shah, H., Madni, A., Rahim, M.A., Jan, N., Khan, A., Khan, S., Jabar, A., and Ali, A. (2021). Fabrication, in Vitro and Ex Vivo Evaluation of Proliposomes and Liposomal Derived Gel for Enhanced Solubility and Permeability of Diacerein. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0258141"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1038\/aps.2010.98","article-title":"Novel Vehicle Based on Cubosomes for Ophthalmic Delivery of Flurbiprofen with Low Irritancy and High Bioavailability","volume":"31","author":"Han","year":"2010","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s13346-022-01217-3","article-title":"Formulation of Tizanidine Hydrochloride\u2013Loaded Provesicular System for Improved Oral Delivery and Therapeutic Activity Employing a 23 Full Factorial Design","volume":"13","author":"Mohsen","year":"2023","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Riaz, M., Zaman, M., Hameed, H., Sarwar, H.S., Khan, M.A., Irfan, A., Shazly, G.A., Paiva-Santos, A.C., and Jardan, Y.A.B. (2023). Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol\u2013Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study. Gels, 9.","DOI":"10.3390\/gels9100817"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"654","DOI":"10.5530\/ijper.53.4.127","article-title":"Formulation and Characterization of pH Induced in Situ Gels Containing Sulfacetamide Sodium for Ocular Drug Delivery: A Combination of Carbopol\u00ae\/HPMC Polymer","volume":"53","author":"Sheshala","year":"2019","journal-title":"IJPER"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Alsaidan, O.A., Zafar, A., Yasir, M., Alzarea, S.I., Alqinyah, M., and Khalid, M. (2022). Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study. Gels, 8.","DOI":"10.3390\/gels8110687"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1111\/jphp.13106","article-title":"Vancomycin-Loaded Niosomes Integrated within pH-Sensitive in-Situ Forming Gel for Treatment of Ocular Infections While Minimizing Drug Irritation","volume":"71","author":"Allam","year":"2019","journal-title":"J. Pharm. 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