{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:49:05Z","timestamp":1788994145424,"version":"build-2803163510"},"reference-count":28,"publisher":"Georg Thieme Verlag KG","issue":"03\/04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic retinopathy, the most common microvascular complication of diabetes\n                    mellitus, is the leading cause of vision impairment worldwide. Flavonoids with\n                    antioxidant properties have been shown to slow its progression. Myricetin, a\n                    flavonoid polyphenolic compound, possesses antioxidant properties, but its\n                    clinical use in ocular delivery is limited by poor aqueous solubility,\n                    stability, and bioavailability. Recently, in situ gels have gained interest as\n                    ocular drug delivery vehicles due to their ease of installation and sustained\n                    drug release. This study aimed to develop a myricetin-loaded thermoresponsive in\n                    situ nanoemulgel to enhance its efficacy in treating diabetic retinopathy.\n                    Nanoemulsions were developed via aqueous phase titration using Sefsol 218 as the\n                    oil phase, Kolliphore RH40 as the surfactant, and PEG 400 as the co-surfactant.\n                    Physicochemical evaluations identified formulation batch ISG17, consisting of\n                    10% oil phase, 30% Smix (1:2), and 60% distilled water, as the\n                    optimal formulation. The developed in situ nanoemulgel showed significant\n                    enhancement in corneal permeation and retention, which was further confirmed by\n                    fluorescence microscopy. Ocular tolerability was demonstrated through corneal\n                    hydration tests and histopathology investigations. The antioxidant potential of\n                    the myricetin-loaded nanoemulgel was assessed using the DPPH assay. Myricetin\n                    was found to be an efficient antioxidant, as indicated by its IC50\n                    values compared to ascorbic acid. The MTT cell viability assay results showed\n                    that the developed formulation effectively inhibits the proliferation of Y79\n                    retinoblastoma cells, demonstrating comparable efficacy to the standard marketed\n                    preparation Avastin (Bevacizumab injection). In conclusion, the nanoemulsion\n                    formulation containing a thermoresponsive polymer for in situ gelling presents a\n                    promising drug delivery system, offering superior therapeutic efficacy and\n                    better patient compliance for the treatment of diabetic retinopathy.<\/jats:p>","DOI":"10.1055\/a-2517-4967","type":"journal-article","created":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T01:45:32Z","timestamp":1738979132000},"page":"100-113","source":"Crossref","is-referenced-by-count":4,"title":["In situ Forming Nanoemulgel for Diabetic Retinopathy:\n                    Development, characterization, and in vitro efficacy\n                    assessment"],"prefix":"10.1055","volume":"75","author":[{"given":"Soumya","family":"Singh","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Integral University, Lucknow, India"},{"name":"Institute of Pharmaceutical Sciences, University of Lucknow, Lucknow,\n                    India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poonam","family":"Kushwaha","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Integral University, Lucknow, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujeet","family":"Gupta","sequence":"additional","affiliation":[{"name":"J. S. Singh Institute of Pharmacy, Sitapur, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"ref2","doi-asserted-by":"crossref","first-page":"103835","DOI":"10.1016\/j.jddst.2022.103835","article-title":"Development of surface modified nanoparticles of curcumin for topical treatment\n                    of diabetic retinopathy: in vitro, ex vivo and in vivo investigation","volume":"76","author":"U D Laddha","year":"2022","journal-title":"Journal of Drug Delivery Science and Technology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1007\/s00125-009-1548-8","article-title":"Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early\n                    stages of diabetic retinopathy","volume":"52","author":"M Garcia-Ram\u00edrez","year":"2009","journal-title":"Diabetologia"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1175660","DOI":"10.3389\/fnut.2023.1175660","article-title":"Therapeutic potential of multifunctional myricetin for treatment of type 2\n                    diabetes mellitus","volume":"10","author":"N Niisato","year":"2023","journal-title":"Frontiers in Nutrition"},{"key":"ref5","first-page":"87","article-title":"Antioxidant activity of polyphenolic myricetin in vitro cell-free and cell-based\n                    systems","volume":"5","author":"A Barzegar","year":"2016","journal-title":"Molecular biology research communications"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.3390\/nu12103169","article-title":"The benefits of flavonoids in diabetic retinopathy","volume":"12","author":"A L Matos","year":"2020","journal-title":"Nutrients"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.bcp.2014.09.022","article-title":"Myricetin inhibits advanced glycation end product (AGE)-induced migration of\n                    retinal pericytes through phosphorylation of ERK1\/2, FAK-1, and paxillin in\n                    vitro and in vivo","volume":"93","author":"Y S Kim","year":"2015","journal-title":"Biochemical Pharmacology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2021\/6612063","article-title":"Nanotechnology in the treatment of diabetic complications: a comprehensive\n                    narrative review","volume":"2021","author":"Y He","year":"2021","journal-title":"Journal of Diabetes Research"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"100045","DOI":"10.1016\/j.fhfh.2021.100045","article-title":"Fabrication of nanoemulsion-based in situ gel using moxifloxacin hydrochloride\n                    as model drug for the treatment of conjunctivitis","volume":"1","author":"B G Prajapati","year":"2021","journal-title":"Food Hydrocolloids for Health"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"576","DOI":"10.3109\/10837450.2015.1026607","article-title":"Thermosensitive in situ nanogel as ophthalmic delivery system of curcumin:\n                    development, characterization, in vitro permeation and in vivo pharmacokinetic\n                    studies","volume":"21","author":"R Liu","year":"2016","journal-title":"Pharmaceutical development and technology"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.3390\/molecules23061363","article-title":"Localized in situ nanoemulgel drug delivery system of quercetin for\n                    periodontitis: development and computational simulations","volume":"23","author":"G C Aithal","year":"2018","journal-title":"Molecules"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ijbiomac.2020.02.097","article-title":"Polysaccharide as renewable responsive biopolymer for in situ gel in the\n                    delivery of drug through ocular route","volume":"150","author":"A Chowhan","year":"2020","journal-title":"International journal of biological macromolecules"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/j.drudis.2019.05.036","article-title":"Poloxamer-based in situ gelling thermoresponsive systems for ocular drug\n                    delivery applications","volume":"24","author":"K A Soliman","year":"2019","journal-title":"Drug Discovery Today"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajps.2018.04.008","article-title":"Research progress of in-situ gelling ophthalmic drug delivery system","volume":"14","author":"Y Wu","year":"2019","journal-title":"Asian journal of pharmaceutical sciences"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.colsurfb.2009.11.021","article-title":"Study of surfactant combinations and development of a novel nanoemulsion for\n                    minimising variations in bioavailability of ezetimibe","volume":"76","author":"V Bali","year":"2010","journal-title":"Colloids and Surfaces B: Biointerfaces"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3109\/10717544.2014.907842","article-title":"Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the\n                    treatment of periodontitis","volume":"23","author":"M Srivastava","year":"2016","journal-title":"Drug delivery"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"780","DOI":"10.3109\/03639045.2012.707203","article-title":"Design and development of a novel pH triggered nanoemulsified in-situ ophthalmic\n                    gel of fluconazole: ex-vivo transcorneal permeation, corneal toxicity and\n                    irritation testing","volume":"39","author":"M K Pathak","year":"2013","journal-title":"Drug Development and Industrial Pharmacy"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s13346-019-00697-0","article-title":"Design, optimisation and evaluation of in situ gelling nanoemulsion formulations\n                    of brinzolamide","volume":"10","author":"H Bhalerao","year":"2020","journal-title":"Drug Delivery and Translational Research"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ejps.2017.04.013","article-title":"Nanoemulsion-based electrolyte triggered in situ gel for ocular delivery of\n                    acetazolamide","volume":"104","author":"N Morsi","year":"2017","journal-title":"European journal of pharmaceutical sciences"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"320","DOI":"10.54085\/ap.2022.11.1.33","article-title":"Development and evaluation of thermoresponsive in situ nanoemulgel of myricetin\n                    for diabetic retinopathy","volume":"11","author":"S Singh","year":"2022","journal-title":"Ann Phytomed"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"764","DOI":"10.3389\/fbioe.2020.00764.","article-title":"An in-situ gelling system based on methylcellulose and tranilast solid\n                    nanoparticles enhances ocular residence time and drug absorption into the cornea\n                    and conjunctiva","volume":"8","author":"N Nagai","year":"2020","journal-title":"Front Bioeng Biotechnol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/10837450.2017.1413658","article-title":"Enhanced ocular bioavailability of fluconazole from niosomal gels and\n                    microemulsions: Formulation, optimization, and in vitro\u2013in vivo evaluation","volume":"24","author":"O A Soliman","year":"2019","journal-title":"Pharmaceutical Development and Technology"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"215","DOI":"10.4236\/jbnb.2020.114014","article-title":"Synthesis and characterization of Citrus limonum essential oil based\n                    nanoemulsion and its enhanced antioxidant activity with stability for\n                    transdermal application","volume":"11","author":"H Kaur","year":"2020","journal-title":"Journal of Biomaterials and Nanobiotechnology"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"88401","DOI":"10.18632\/oncotarget.19365","article-title":"Mechanism study of isoflavones as an anti-retinoblastoma progression agent","volume":"8","author":"Q Wu","year":"2017","journal-title":"Oncotarget"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0014-4835(89)90021-3","article-title":"Y-79 retinoblastoma cells: isolation and characterization of clonal\n                    lineages","volume":"48","author":"M A Campbell","year":"1989","journal-title":"Experimental eye research"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3390\/nu8020090","article-title":"Myricetin: A dietary molecule with diverse biological activities","volume":"8","author":"D K Semwal","year":"2016","journal-title":"Nutrients"},{"key":"ref30","first-page":"638","article-title":"In vitro and in vivo evaluation of in situ gelling systems for\n                    sustained topical ophthalmic delivery: state of the art and beyond. Drug\n                    discovery today","volume":"22","author":"P L Destruel","year":"2017"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2174\/1872211309666150724101227","article-title":"In Situ Gelling Ophthalmic Drug Delivery System: An Overview and Its\n                    Applications","volume":"9","author":"R Sheshala","year":"2015","journal-title":"Recent Patents on Drug Delivery & Formulation"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3746\/pnf.2018.23.4.341","article-title":"Isolation and identification of myricitrin, an antioxidant flavonoid, from\n                        daebong persimmon peel","volume":"23","author":"I W Hwang","year":"2018","journal-title":"Preventive nutrition and food science"}],"container-title":["Drug Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2517-4967.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T22:44:55Z","timestamp":1744152295000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2517-4967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,7]]},"references-count":28,"journal-issue":{"issue":"03\/04","published-online":{"date-parts":[[2025,4,8]]},"published-print":{"date-parts":[[2025,4]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2517-4967","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2194-9379","2194-9387"],"issn-type":[{"value":"2194-9379","type":"print"},{"value":"2194-9387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,7]]}}}