title: Novel norcantharidin-loaded liver targeting chitosan nanoparticles to enhance intestinal absorption.
abstract: In this paper, two novel liver-targeting nanoparticles, norcantharidin-loaded chitosan nanoparticles (NCTD-CS-NPs) and norcantharidin-associated galactosylated chitosan nanoparticles (NCTD-GC-NPs), were prepared using ionic cross-linkage. The physical properties, particle size, encapsulation efficiency, and drug release characteristics of the nanoparticles were investigated in vitro. To investigate the intestinal absorption mechanisms of the two preparations, a series of experiments was carried out, including in situ circulation method, in vitro everted gut sacs, and Ussing chamber perfusion technique. The absorption rate constants (Ka) of NCTD at different segments were found to be duodenum > jejunum > ileum > colon. The concentration had no distinctive effect on absorption kinetics, suggesting that drug absorption is not dose-dependent. The transport of NCTD was found to be inhibited by P-glycoprotein (P-gp) inhibitor, indicating that NCTD might be the substrate of P-gp. The order of the absorption enhancer effects were as follows: low molecular weight chitosan (CS-8kDa) > high molecular weight chitosan (CS-30kDa) > Poloxamer > sodium dodecyl sulfate (SDS) > sodium deoxycholate (SDCh). The results indicate that the chitosan nanoparticles can improve intestinal absorption of NCTD.
authors.affiliation: College of Pharmaceutical Science, Soochow University, Suzhou, People’s Republic of China.
authors.forename: Yong-yan
authors.initials: YY
authors.lastname: Bei
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jing-yu
authors.initials: JY
authors.lastname: Xu
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: Wang
authors.forename: Zong-lin
authors.initials: ZL
authors.lastname: Gu
authors.forename: Kong-lang
authors.initials: KL
authors.lastname: Xing
authors.forename: Ai-jun
authors.initials: AJ
authors.lastname: Zhu
authors.forename: Wei-liang
authors.initials: WL
authors.lastname: Chen
authors.forename: Lin-seng
authors.initials: LS
authors.lastname: Shi
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Xue-nong
authors.initials: XN
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004337:Drug Carriers; C069741:norcantharidin; D048271:Chitosan