{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:37:43Z","timestamp":1788478663343,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CONACyT Mexico Postdoctoral Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Hydrogels (HDs) offer a promising platform for localized and sustained drug delivery. In this study, carboxymethyl chitosan (CMC)\u2014based hydrogels were crosslinked with genipin and evaluated for the controlled release and tissue retention of suramin, a polyanionic drug with anti-inflammatory and antifibrotic properties. The influence of crosslinking density (1%, 3%, and 5%) on drug release, permeation kinetics, and retention was investigated using in vitro synthetic membranes and reconstructed human epithelial tissue models. The 1% genipin HD exhibited the highest cumulative release and drug retention (48.8 \u00b1 6.8 \u03bcg\/cm2 in synthetic membranes; 24.06 \u00b1 7.33 \u03bcg\/cm2 in epithelial models), along with a sustained release profile governed by first-order and Fickian diffusion kinetics. Notably, the 1% crosslinked formulation also demonstrated enhanced transmembrane flux (&gt;140 \u03bcg\/cm2\/h after six hours), suggesting that lower crosslinking density favors both diffusional mobility and depot functionality. In contrast, free suramin solution displayed limited tissue interaction and minimal permeation, highlighting the role of the hydrogel matrix in regulating local bioavailability. These findings demonstrate that CMC\u2013genipin HD can closely modulate drug delivery kinetics through crosslinking density, offering a biocompatible strategy for localized treatment of ulcerated epithelial conditions such as oral mucositis or chronic wounds. Diffusion models included a synthetic multilayer membrane (Strat-M\u00ae) and a reconstructed human epidermis (EpiDerm\u2122) to simulate skin-like barrier properties.<\/jats:p>","DOI":"10.3390\/gels11050312","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:38:37Z","timestamp":1745390317000},"page":"312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evaluation of Carboxymethyl Chitosan\u2013Genipin Hydrogels as Reservoir Systems for Suramin Delivery in Epithelial Tissues"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4988-9192","authenticated-orcid":false,"given":"David","family":"Encinas-Basurto","sequence":"first","affiliation":[{"name":"Nanotechnology Program, Department of Physics, Universidad de Sonora, Hermosillo 83000, Sonora, Mexico"},{"name":"Skaggs Pharmaceutical Sciences Center, The University of Arizona R. Ken Coit College of Pharmacy, 1703 E Mabel St., Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3252-8262","authenticated-orcid":false,"given":"Victor H.","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Skaggs Pharmaceutical Sciences Center, The University of Arizona R. Ken Coit College of Pharmacy, 1703 E Mabel St., Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick G.","family":"Schnellmann","sequence":"additional","affiliation":[{"name":"Skaggs Pharmaceutical Sciences Center, The University of Arizona R. Ken Coit College of Pharmacy, 1703 E Mabel St., Tucson, AZ 85721, USA"},{"name":"Department of Medicine, The University of Arizona College of Medicine, 501 N Campbell Ave., Tucson, AZ 85724, USA"},{"name":"BIO5 Institute, The University of Arizona, 1657 E Helen St., Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3993-9210","authenticated-orcid":false,"given":"Heidi M.","family":"Mansour","sequence":"additional","affiliation":[{"name":"Skaggs Pharmaceutical Sciences Center, The University of Arizona R. Ken Coit College of Pharmacy, 1703 E Mabel St., Tucson, AZ 85721, USA"},{"name":"Department of Medicine, The University of Arizona College of Medicine, 501 N Campbell Ave., Tucson, AZ 85724, USA"},{"name":"BIO5 Institute, The University of Arizona, 1657 E Helen St., Tucson, AZ 85719, USA"},{"name":"Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Raffetto, J.D., Ligi, D., Maniscalco, R., Khalil, R.A., and Mannello, F. (2020). Why venous leg ulcers have difficulty healing: Overview on pathophysiology, clinical consequences, and treatment. J. Clin. Med., 10.","DOI":"10.3390\/jcm10010029"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhao, R., Liang, H., Clarke, E., Jackson, C., and Xue, M. (2016). Inflammation in chronic wounds. Int. 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