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Mucopenetrating nanocarriers (MP\/NCs) and mucoadhesive nanocarriers (MA\/NCs) were prepared by flash nanoprecipitation employing polystyrene\u2010block\u2010poly(ethylene glycol) and polystyrene\u2010block\u2010poly(<jats:italic>N,N<\/jats:italic>\u2010dimethyl aminoethyl methacrylate), respectively. Their particle distribution in the rat gastrointestinal tract were visualized by fluorescent imaging. Plasma concentrations were monitored after oral administration of CsA\u2010loaded MP\/NCs (MP\/CsA) and MA\/NCs (MA\/CsA) to rats. MP\/NCs and MA\/NCs had a particle size below 200\u00a0nm and <jats:italic>\u03b6<\/jats:italic>\u2010potentials of 4 and 40\u00a0mV, respectively. The results from in vitro experiments demonstrated mucopenetration of MP\/NCs and mucoadhesion of MA\/NCs. Confocal laser scanning microscopic images showed diffusion of MP\/NCs in the gastrointestinal mucus towards epithelial cells and localization of MA\/NCs on the surface of the gastrointestinal mucus layer. In a pH 6.8 solution, rapid and sustained release of CsA were observed for MP\/CsA and MA\/CsA, respectively. After oral dosing (10 mg\u2010CsA\/kg) to rats, amorphous CsA powder exhibited a time to maximum plasma concentration (<jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub>) of 3.4\u00a0h, maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) of 0.12\u00a0\u03bcg\/mL, and bioavailability of 0.7%. Compared with amorphous CsA powder, MP\/CsA shortened <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub> by 1.1 to 2.3\u00a0h and increased the bioavailability by 43\u2010fold to 30.1%, while MA\/CsA prolonged <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub> by 3.4 to 6.8\u00a0h with <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and bioavailability of 0.65\u00a0\u03bcg\/mL and 11.7%, respectively. These pharmacokinetic behaviors would be explained by their diffusion and release properties modulated by polymeric surface modification. The mDDS approach is a promising strategy for the pharmacokinetic control of orally administered CsA.<\/jats:p>","DOI":"10.1002\/bdd.2388","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T08:23:51Z","timestamp":1713774231000},"page":"117-126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetic control of orally dosed cyclosporine A with mucosal drug delivery system"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7781-1731","authenticated-orcid":false,"given":"Kohei","family":"Yamada","sequence":"first","affiliation":[{"name":"Laboratory of Biopharmacy School of Pharmaceutical Sciences University of Shizuoka  Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt D.","family":"Ristroph","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biological Engineering A301 EQUAD Princeton University  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuuki","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmacy School of Pharmaceutical Sciences University of Shizuoka  Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoang D.","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; 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