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Novel norcantharidin-loaded liver targeting chitosan nanoparticles to enhance intestinal absorption

Authors Bei YY, Chen XY, Liu Y, Xu JY, Wang WJ, Gu ZL, Xing KL, Zhu AJ, Chen WL, Shi LS, Wang Q, Zhang XN, Zhang Q

Received 15 January 2012

Accepted for publication 3 February 2012

Published 3 April 2012 Volume 2012:7 Pages 1819—1827

DOI https://doi.org/10.2147/IJN.S29958

Review by Single-blind

Peer reviewer comments 3

Yong-yan Bei1, Xiao-yan Chen1, Yang Liu1, Jing-yu Xu1, Wen-juan Wang1, Zong-lin Gu1, Kong-lang Xing1, Ai-jun Zhu1, Wei-liang Chen1, Lin-seng Shi1, Qin Wang1, Xue-nong Zhang1, Qiang Zhang2
1College of Pharmaceutical Science, Soochow University, Suzhou, 2Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, People's Republic of China

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.

Keywords: P-glycoprotein, absorption enhancers

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