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Some skin conditions may be due to genetic and lifestyle factors and immune\u2010mediated factors. The current skin disease treatment can include oral medication, topical cream, or ointments. Nanotechnology is revolutionizing the drug delivery systems, increasing the time life of active therapeutic compounds and improving the treatment efficiency. This work hypothesizes that varying the surface properties of chitosan nanoparticles (Ch\u2010NPs) can modulate their diffusion through dermal tissue. Thus, Ch\u2010NPs were synthesized, and their surface was modified with polyethylene glycol, oxalic acid, and linoleic acid for transdermal therapy. The different Ch\u2010NPs were labeled with a fluorophore, and the dermal diffusion was measured on human skin by histological preparations and fluorescent microscopy. The surface properties of nanoparticles were shown to play an essential role in skin diffusion rate. Surface modification with a lipophilic moiety such as linoleic fatty acid showed a diffusion rate of 7.23\u2009mm<jats:sup>2<\/jats:sup>\/h in human full\u2010thickness abdominal flap, which is 2.7 times faster nanoparticle diffusion through dermal tissue when compared with the unmodified Ch\u2010NPs (2.92\u2009mm<jats:sup>2<\/jats:sup>\/h). The positive (zeta potential +27.5\u2009mV) or negative (zeta potential \u22122.2\u2009mV) surface charge does not affect the chitosan nanoparticle diffusion. Polyethylene glycol surface modification slightly improved the nanoparticle diffusion rate (3.63\u2009mm<jats:sup>2<\/jats:sup>\/h). Thus, modulating the nanoparticle surface properties can control the skin diffusion rate. The implications of this finding on dermic drug delivery are discussed.<\/jats:p>","DOI":"10.1002\/bip.70006","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T11:59:36Z","timestamp":1739793576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of Surface Properties of Chitosan\u2010Based Nanoparticles in the Skin\u2010Diffusion Rate"],"prefix":"10.1002","volume":"116","author":[{"given":"Luciana","family":"Ram\u00edrez","sequence":"first","affiliation":[{"name":"School of Medicine, Centro de Estudios Universidad Xochicalco  Ensenada Baja California Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Corral","sequence":"additional","affiliation":[{"name":"School of Medicine, Centro de Estudios Universidad Xochicalco  Ensenada Baja California 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