title: Comparison of Simple Eudragit Microparticles Loaded with Prednisolone and Eudragit-Coated Chitosan-Succinyl-Prednisolone Conjugate Microparticles: Part II. In Vivo Evaluation of Efficacy, Toxicity, and Biodisposition Characteristics.
abstract: We previously prepared and evaluated simple Eudragit S100 microparticles loaded with prednisolone (ES-MP) and Eudragit S100-coated chitosan-succinyl-prednisolone conjugate microparticles (Ch-MP/ES) in vitro. In this work, the effectiveness, toxic side effects (5 mg prednisolone (PD) eq/kg × 3 d, 10 mg PD eq/kg × 3 d), and pharmacokinetic characteristics (5 mg PD eq/kg) were examined using rats with colitis induced through 2,4,6-trinitrobenzenesulfonic acid. ES-MP did not change the efficacy or toxic side effects of PD, and this was attributed to incomplete delivery to the target site and prolonged systemic drug absorption by ES-MP. On the other hand, Ch-MP/ES promoted the efficacy of PD and ameliorated its toxic side effects due to better delivery to the target site, very slow drug release and the strong suppression of drug absorption. Only Ch-MP/ES, which markedly changed drug release characteristics, improved the in vivo features of PD.
authors.affiliation: Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. onishi@hoshi.ac.jp.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Onishi
authors.affiliation: Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. onsh-hrk@ezweb.ne.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kikuchi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D048271:Chitosan; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy; D016503:Drug Delivery Systems; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011109:Polymethacrylic Acids; D011239:Prednisolone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D051381:Rats; D013386:Succinates; D014018:Tissue Distribution
chemical_list: D011109:Polymethacrylic Acids; D013386:Succinates; C038300:methylmethacrylate-methacrylic acid copolymer; D048271:Chitosan; D011239:Prednisolone
keywords: 2,4,6-trinitrobenzenesulfonic acid-induced; Eudragit S100-coated chitosan-succinyl-prednisolone conjugate microparticle; efficacy; pharmacokinetic characteristics; simple Eudragit S100 microparticle; toxicity