{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:50:42Z","timestamp":1792270242527,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nigerian Institute of Medical Research","award":["NIMR-PRDG-0003-18-01"],"award-info":[{"award-number":["NIMR-PRDG-0003-18-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>The challenges encountered with conventional microbicide gels has necessitated the quest for alternative options. This study aimed to formulate and evaluate a bigel and thermosensitive gel, designed to combat the challenges of leakage and short-residence time in the vagina. Ionic-gelation technique was used to formulate maraviroc and tenofovir microspheres. The microspheres were incorporated into a thermosensitive gel and bigel, then evaluated. Enzyme degradation assay was used to assess the effect of the acid phosphatase enzyme on the release profile of maraviroc and tenofovir microspheres. HIV efficacy and cytotoxicity of the microspheres were assessed using HIV-1-BaL virus strain and HeLa cell lines, respectively. Maraviroc and tenofovir release kinetics followed zero-order and Higuchi model kinetics. However, under the influence of the enzyme, maraviroc release was governed by first-order model, while tenofovir followed a super case II transport-mechanism. The altered mode of release and drug transport mechanism suggests a triggered release. The assay of the microspheres suspension on the HeLa cells did not show signs of cytotoxicity. The thermosensitive gel and bigel elicited a progressive decline in HIV infectivity, until at concentrations of 1 \u03bcg\/mL and 0.1 \u03bcg\/mL, respectively. The candidate vaginal gels have the potential for a triggered release by the acid phosphatase enzyme present in the seminal fluid, thus, serving as a strategic point to prevent HIV transmission.<\/jats:p>","DOI":"10.3390\/gels8010015","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Enzyme Responsive Vaginal Microbicide Gels Containing Maraviroc and Tenofovir Microspheres Designed for Acid Phosphatase-Triggered Release for Pre-Exposure Prophylaxis of HIV-1: A Comparative Analysis of a Bigel and Thermosensitive Gel"],"prefix":"10.3390","volume":"8","author":[{"given":"Sabdat Ozichu","family":"Ekama","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, Surulere, Lagos P.M.B 12003, Nigeria"},{"name":"Nigerian Institute of Medical Research, 6 Edmund Crescent, Yaba, Lagos P.M.B 12003, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8819-1937","authenticated-orcid":false,"given":"Margaret O.","family":"Ilomuanya","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, Surulere, Lagos P.M.B 12003, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chukwuemeka Paul","family":"Azubuike","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, Surulere, Lagos P.M.B 12003, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3693-1096","authenticated-orcid":false,"given":"James Babatunde","family":"Ayorinde","sequence":"additional","affiliation":[{"name":"Nigerian Institute of Medical Research, 6 Edmund Crescent, Yaba, Lagos P.M.B 12003, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0688-3898","authenticated-orcid":false,"given":"Oliver Chukwujekwu","family":"Ezechi","sequence":"additional","affiliation":[{"name":"Nigerian Institute of Medical Research, 6 Edmund Crescent, Yaba, Lagos P.M.B 12003, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia Ihuoma","family":"Igwilo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, Surulere, Lagos P.M.B 12003, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babatunde Lawal","family":"Salako","sequence":"additional","affiliation":[{"name":"Nigerian Institute of Medical Research, 6 Edmund Crescent, Yaba, Lagos P.M.B 12003, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-med-090518-093731","article-title":"Topical Microbicides in HIV Prevention: State of the Promise","volume":"71","author":"Baeten","year":"2020","journal-title":"Annu. Rev. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ijid.2019.08.004","article-title":"HIV-1 Heterosexual Transmission and Association with Sexually Transmitted Infections in the Era of Treatment as Prevention","volume":"87","author":"Melo","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chan, S.S., Chappel, A.R., Maddox, K.E.J., Hoover, K.W., Huang, Y.-L.A., Zhu, W., Cohen, S.M., Klein, P.W., and De Lew, N. (2020). Pre-Exposure Prophylaxis for Preventing Acquisition of HIV: A Cross-Sectional Study of Patients, Prescribers, Uptake, and Spending in the United States, 2015\u20132016. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003072"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2174\/157016212799304625","article-title":"Non-Specific Microbicide Product Development: Then and Now","volume":"10","author":"Romano","year":"2012","journal-title":"Curr. HIV Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.antiviral.2012.09.015","article-title":"Development and Evaluation of a Thermosensitive Vaginal Gel Containing raltegravir + efavirenz Loaded Nanoparticles for HIV Prophylaxis","volume":"96","author":"Date","year":"2012","journal-title":"Antivir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41565-021-00866-8","article-title":"Nanotechnology Approaches for Global Infectious Diseases","volume":"16","author":"Kirtane","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3109\/21691401.2013.856016","article-title":"Stimuli-Sensitive Systems\u2014An Emerging Delivery System for Drugs","volume":"43","author":"Bhardwaj","year":"2015","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7090545\u201310","DOI":"10.1155\/2019\/7090545","article-title":"Prostatic Acid Phosphatase (PAP) Predicts Prostate Cancer Progress in a Population-Based Study: The Renewal of PAP?","volume":"2019","author":"Xu","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sakurada, K., Watanabe, K., and Akutsu, T. (2020). Current Methods for Body Fluid Identification Related to Sexual Crime: Focusing on Saliva, Semen, and Vaginal Fluid. Diagnostics, 10.","DOI":"10.3390\/diagnostics10090693"},{"key":"ref_10","first-page":"5447","article-title":"Maraviroc: A Review of Its Use in HIV Infection and Beyond","volume":"9","author":"Woolard","year":"2015","journal-title":"DDDT"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Karava, A., Lazaridou, M., Nanaki, S., Michailidou, G., Christodoulou, E., Kostoglou, M., Iatrou, H., and Bikiaris, D.N. (2020). Chitosan Derivatives with Mucoadhesive and Antimicrobial Properties for Simultaneous Nanoencapsulation and Extended Ocular Release Formulations of Dexamethasone and Chloramphenicol Drugs. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12060594"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.jsps.2019.08.001","article-title":"Thermo-Sensitive Hydrogels for Delivering Biotherapeutic Molecules: A Review","volume":"27","author":"Huang","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mart\u00edn-Illana, A., Notario-P\u00e9rez, F., Cazorla-Luna, R., Ruiz-Caro, R., and Veiga, M.D. (2019). Smart Freeze-Dried Bigels for the Prevention of the Sexual Transmission of HIV by Accelerating the Vaginal Release of Tenofovir During Intercourse. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11050232"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s43094-019-0015-8","article-title":"Development and Evaluation of Mucoadhesive Bigel Containing Tenofovir and Maraviroc for HIV Prophylaxis","volume":"6","author":"Ilomuanya","year":"2020","journal-title":"Futur. J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/j.ijbiomac.2014.10.038","article-title":"Kinetic Models for the Release of the Anticancer Drug Doxorubicin from Biodegradable polylactide\/Metal Oxide-Based Hybrids","volume":"72","author":"Mhlanga","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jconrel.2019.07.004","article-title":"Enzyme Responsive Drug Delivery Systems in Cancer Treatment","volume":"308","author":"Shahriari","year":"2019","journal-title":"J. Control Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1021\/acs.est.7b04553","article-title":"Phosphatase-Mediated Hydrolysis of Linear Polyphosphates","volume":"52","author":"Huang","year":"2018","journal-title":"Environ. Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11095-017-2302-4","article-title":"Hyaluronidase Enzyme-Responsive Targeted Nanoparticles for Effective Delivery of 5-Fluorouracil in Colon Cancer","volume":"35","author":"Jiang","year":"2018","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4103\/0974-8490.199774","article-title":"The Influence of Pluronic F68 and F127 Nanocarrier on Physicochemical Properties, in Vitro Release, and Antiproliferative Activity of Thymoquinone Drug","volume":"9","author":"Kaus","year":"2017","journal-title":"Pharmacogn. Res."},{"key":"ref_20","first-page":"2517","article-title":"Optimization and Evaluation of a Thermoresponsive Ophthalmic in Situ Gel Containing Curcumin-Loaded Albumin Nanoparticles","volume":"9","author":"Lou","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Russo, E., and Villa, C. (2019). Poloxamer Hydrogels for Biomedical Applications. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120671"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1093\/jac\/dks173","article-title":"Reformulated Tenofovir Gel for Use as a Dual Compartment Microbicide","volume":"67","author":"Dezzutti","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6221","DOI":"10.2147\/IJN.S140934","article-title":"Ketoprofen-Loaded Polymer Carriers in Bigel Formulation: An Approach to Enhancing Drug Photostability in Topical Application Forms","volume":"12","author":"Andonova","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S1473-3099(08)70254-8","article-title":"Vaginal Microbicides and the Prevention of HIV Transmission","volume":"8","author":"Cutler","year":"2008","journal-title":"Lancet Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.2147\/DDDT.S133170","article-title":"Historical Development of Vaginal Microbicides to Prevent Sexual Transmission of HIV in Women: From past Failures to Future Hopes","volume":"11","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_26","first-page":"46","article-title":"Organogels, Hydrogels and Bigels as Transdermal Delivery Systems for Dilti-Azem Hydrochloride","volume":"8","author":"Ibrahim","year":"2013","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1742-6405-7-22","article-title":"Safety and Anti-HIV Assessments of Natural Vaginal Cleansing Products in an Established Topical Microbi-Cides in Vitro Testing Algorithm","volume":"7","author":"Snyder","year":"2010","journal-title":"AIDS Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.antiviral.2012.12.019","article-title":"Spray Drying Tenofovir Loaded Mucoadhesive and PH-Sensitive Microspheres Intended for HIV Prevention","volume":"97","author":"Zhang","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1128\/AAC.00450-16","article-title":"Topical Tenofovir Disoproxil Fumarate Nanoparticles Prevent HIV-1 Vaginal Transmission in a Humanized Mouse Model","volume":"60","author":"Destache","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2147\/HIV.S291065","article-title":"Mucoadhesive Microspheres of Maraviroc and Tenofovir Designed for Pre-Exposure Prophylaxis of HIV-1: An in Vitro Assessment of the Effect on Vaginal Lactic Acid Bacteria Microflora","volume":"13","author":"Ekama","year":"2021","journal-title":"HIV\/AIDS Res. Palliat. Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1208\/s12248-013-9546-7","article-title":"Hyaluronidase-Sensitive Nanoparticle Templates for Triggered Release of HIV\/AIDS Microbicide In Vitro","volume":"16","author":"Agrahari","year":"2013","journal-title":"AAPS J."},{"key":"ref_32","first-page":"1","article-title":"Application of Mathematical Models in Drug Release Kinetics of Carbidopa and Levodopa ER Tablets","volume":"6","author":"Gouda","year":"2017","journal-title":"J. Develop. Drugs"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1166\/jbn.2015.1942","article-title":"Thermosensitive Gel Containing Cellulose Acetate Phthalate-Efavirenz Combination Nanoparticles for Prevention of HIV-1 Infection","volume":"11","author":"Date","year":"2015","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1080\/03639045.2018.1464021","article-title":"Development of Hydrogels, Oleogels, and Bigels as Local Drug Delivery Systems for Periodontitis","volume":"44","author":"Hamed","year":"2018","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s43094-019-0015-8","article-title":"Development of Trigger Sensitive Hyaluronic acid\/Palm Oil-Based Organogel for in Vitro Release of HIV\/AIDS Microbicides Using Artificial Neural Networks","volume":"6","author":"Ilomuanya","year":"2020","journal-title":"Futur. J. Pharm. Sci."}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/8\/1\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:53:15Z","timestamp":1760169195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/8\/1\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,24]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["gels8010015"],"URL":"https:\/\/doi.org\/10.3390\/gels8010015","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,24]]}}}