{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:55:44Z","timestamp":1792155344303,"version":"4.4.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T00:00:00Z","timestamp":1541980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>(1) Background: Fluconazole, used orally for vaginal candidiasis, has reported gastrointestinal side effects. Therefore, researchers directed towards the drug vaginal delivery. However, vaginal delivery is limited by poor retention and leakage. Thus, this work aimed at exploring chitosan\/anion polyelectrolyte complex (PEC) for the formulation of fluconazole vaginal inserts with controlled release and appreciable mucoadhesion. (2) Methods: PECs were prepared and assessed for interactions. Fluconazole PEC based vaginal inserts were prepared by lyophilization using mannitol. 3151 factorial design was applied to investigate the effect of the anion type and Chitosan\/anion ratio on the inserts mucoadhesion and release properties. The optimized insert [based on 5:5 chitosan: anionic polymer (sodium alginate)] release was modulated by the release retardant; Compritol\u00ae 888. The selected formulation was subjected to microbiological and histological evaluation. (3) Results: Fluconazole inserts showed satisfactory drug content, acceptable friability percentages and highest swelling indices at six hours. Statistical analysis showed significant effect of the studied factors on detachment force and release properties. Microbiological assays revealed significantly higher antifungal activity of inserts compared to fluconazole solution. Reduced inflammatory cells were confirmed by histological evaluation. (4) Conclusion: CH\/Alg based vaginal insert could be a promising platform for vaginal delivery of antifungal drugs used for vaginal candidiasis treatment.<\/jats:p>","DOI":"10.3390\/pharmaceutics10040227","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T02:42:41Z","timestamp":1542163361000},"page":"227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Optimized Chitosan\/Anion Polyelectrolyte Complex Based Inserts for Vaginal Delivery of Fluconazole: In Vitro\/In Vivo Evaluation"],"prefix":"10.3390","volume":"10","author":[{"given":"Bayan","family":"Darwesh","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9067-8565","authenticated-orcid":false,"given":"Hibah M.","family":"Aldawsari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa M.","family":"Badr-Eldin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1128\/CMR.00076-09","article-title":"Candida infections of the genitourinary tract","volume":"23","author":"Achkar","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1128\/AAC.01151-09","article-title":"Glycerol monolaurate inhibits Candida and Gardnerella vaginalis in vitro and in vivo but not Lactobacillus","volume":"54","author":"Strandberg","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_3","first-page":"23","article-title":"Development of a curcumin bioadhesive monolithic tablet for treatment of vaginal candidiasis","volume":"15","author":"Hani","year":"2016","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/BF03259125","article-title":"Erratum to Fluconazole: An update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients","volume":"51","author":"Goa","year":"1996","journal-title":"Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"174","DOI":"10.2174\/156720109787846252","article-title":"Formulation and evaluation of lecithin organogel for topical delivery of fluconazole","volume":"6","author":"Jadhav","year":"2009","journal-title":"Curr. Drug Deliv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jsps.2017.12.016","article-title":"Role of chitosan on controlling the characteristics and antifungal activity of bioadhesive fluconazole vaginal tablets","volume":"26","author":"Fitaihi","year":"2018","journal-title":"Saudi Pharm. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ijpharm.2008.08.021","article-title":"Microemulsion based vaginal gel of fluconazole: Formulation, in vitro and in vivo evaluation","volume":"365","author":"Bachhav","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.colsurfb.2014.01.011","article-title":"Formulation and in vitro evaluation of coconut oil-core cationic nanocapsules intended for vaginal delivery of clotrimazole","volume":"116","author":"Santos","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.3390\/md8041305","article-title":"Chitosan based polyelectrolyte complexes as potential carrier materials in drug delivery systems","volume":"8","author":"Hamman","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Xu, Q., Wu, Y.-X., Jia, Q., Qing, H.-J., Nie, F., and Zhou, Y.-J. (2016, January 27\u201329). Synthesis and photochromic properties of spiropyran-graft-chitosan biopolymers. Proceedings of the 2016 International Conference on Advanced Materials and Energy Sustainability (AMES2016), Wuhan, China.","DOI":"10.1142\/9789813220393_0002"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3390\/polym7030552","article-title":"Chitosan: Gels and interfacial properties","volume":"7","author":"Strand","year":"2015","journal-title":"Polymers"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"481","DOI":"10.4103\/0250-474X.58165","article-title":"Polyelectrolyte complexes: A review of their applicability in drug delivery technology","volume":"71","author":"Lankalapalli","year":"2009","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ejpb.2010.04.013","article-title":"Freeze-dried chitosan\/pectin nasal inserts for antipsychotic drug delivery","volume":"75","author":"Luppi","year":"2010","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.3109\/10717544.2016.1160458","article-title":"Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration","volume":"23","author":"Ibrahim","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_15","first-page":"585","article-title":"Preparation and characterisation of fluconazole vaginal films for the treatment of vaginal candidiasis","volume":"75","author":"Kumar","year":"2013","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.carbpol.2012.08.074","article-title":"Chitosan\/alginate complexes for vaginal delivery of chlorhexidine digluconate","volume":"91","author":"Abruzzo","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1081\/AL-100106841","article-title":"Quantitative Determination of Fluconazole in Capsules and IV Solutions by UV Spectrophotometric Methods","volume":"34","year":"2001","journal-title":"Anal. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ijpharm.2014.12.008","article-title":"Vaginal inserts based on chitosan and carboxymethylcellulose complexes for local delivery of chlorhexidine: Preparation, characterization and antimicrobial activity","volume":"478","author":"Bigucci","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/2008-2231-20-67","article-title":"Development and characterization of chitosan-polycarbophil interpolyelectrolyte complex-based 5-fluorouracil formulations for buccal, vaginal and rectal application","volume":"20","author":"Pendekal","year":"2012","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/S1984-82502010000100002","article-title":"Mucoadhesive drug delivery systems","volume":"46","author":"Carvalho","year":"2010","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ijpharm.2007.08.042","article-title":"A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: Design, in vitro and \u2018in vivo\u2019evaluation","volume":"350","author":"Wang","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijpharm.2012.04.001","article-title":"Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil","volume":"431","author":"Villar","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_23","first-page":"217","article-title":"Kinetic modeling on drug release from controlled drug delivery systems","volume":"67","author":"Dash","year":"2010","journal-title":"Acta Pol. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.17077\/2154-4751.1246","article-title":"Importance of the physical exam and in-office tests in the evaluation of vulvovaginal irritation","volume":"4","author":"Christensen","year":"2014","journal-title":"Proc. Obstet. Gynecol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1086\/510431","article-title":"New consensus guidelines from the Clinical and Laboratory Standards Institute for antimicrobial susceptibility testing of infrequently isolated or fastidious bacteria","volume":"44","author":"Jorgensen","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","first-page":"109","article-title":"Formulation and evaluation of gel containing fluconazole-antifungal agent","volume":"3","author":"Basha","year":"2011","journal-title":"Int. J. Drug Dev. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.micpath.2010.02.010","article-title":"Outcome of experimental rat vaginitis by Candida albicans isolates with different karyotypes","volume":"49","author":"Tavanti","year":"2010","journal-title":"Microb. Pathog."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1111\/j.2042-7158.2011.01315.x","article-title":"In-situ gel formulations of econazole nitrate: Preparation and in-vitro and in-vivo evaluation","volume":"63","author":"Baloglu","year":"2011","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1081\/PDT-120015052","article-title":"Solid-state characterization of fluconazole","volume":"7","author":"Alkhamis","year":"2002","journal-title":"Pharm. Dev. Technol."},{"key":"ref_30","first-page":"769","article-title":"Lyophilized chitosan\/xanthan polyelectrolyte complex based mucoadhesive inserts for nasal delivery of promethazine hydrochloride","volume":"13","author":"Dehghan","year":"2014","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1081\/DDC-120003853","article-title":"Alginate in drug delivery systems","volume":"28","author":"Karlsen","year":"2002","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1093\/jaoac\/93.1.108","article-title":"Development and validation of a stability-indicating assay method for simultaneous determination of perindopril and indapamide in combined dosage form by reversed-phase high-performance liquid chromatography","volume":"93","author":"Jogia","year":"2010","journal-title":"J. AOAC Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1211\/jpp.61.02.0003","article-title":"Novel mucoadhesive nasal inserts based on chitosan\/hyaluronate polyelectrolyte complexes for peptide and protein delivery","volume":"61","author":"Luppi","year":"2009","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijpharm.2005.10.044","article-title":"On the use of the Weibull function for the discernment of drug release mechanisms","volume":"309","author":"Papadopoulou","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_35","first-page":"3486384","article-title":"Influence of Hydrophilic Polymers on the Factor in Weibull Equation Applied to the Release Kinetics of a Biologically Active Complex of Aesculus hippocastanum","volume":"2017","author":"Sowa","year":"2017","journal-title":"Int. J. Polym. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ejpb.2008.11.005","article-title":"Modulating pH-independent release from coated pellets: Effect of coating composition on solubilization processes and drug release","volume":"72","author":"Ensslin","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1208\/s12249-010-9534-5","article-title":"Formulation and in vitro evaluation of xanthan gum or carbopol 934-based mucoadhesive patches, loaded with nicotine","volume":"12","author":"Obaidat","year":"2011","journal-title":"AAPS PharmSciTech"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1208\/s12249-014-0243-3","article-title":"Lyophilized sustained release mucoadhesive chitosan sponges for buccal buspirone hydrochloride delivery: Formulation and in vitro evaluation","volume":"16","author":"Kassem","year":"2015","journal-title":"AAPS PharmSciTech"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.ejpb.2008.01.011","article-title":"Design and in vitro\/in vivo evaluation of novel nicorandil extended release matrix tablets based on hydrophilic interpolymer complexes and a hydrophobic waxy polymer","volume":"69","author":"Abdelbary","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1163\/138577209X12486896623418","article-title":"Chitosan: A new versatile bio-polymer for various applications","volume":"12","author":"Sahoo","year":"2009","journal-title":"Des. Monomers Polym."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/10\/4\/227\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:29:11Z","timestamp":1760196551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/10\/4\/227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,12]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["pharmaceutics10040227"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics10040227","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,12]]}}}