This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Sakuma, S. Articles by Kopecek, J. Search for Related Content Social Bookmarking                         What's this?

N-(2-Hydroxypropyl)methacrylamide Copolymer-9-Aminocamptothecin Conjugate: Colon-Specific Drug Delivery in Rats

Zheng-Rong Lu

Barbara Pecharová

Department of Pharmaceutics and Pharmaceutical Chemistry, Salt Lake City, Utah 84112, USA

Pavla Kopeková

Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA

Jindich Kopeek

Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, USAjindrich.kopecek{at}m.cc.utah.edu

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugate containing 9-aminocamptothecin (9-AC) boundvia a spacer containing an aromatic azo bond and leucylalanine (P-Azo-Leu-Ala-9-AC) was synthesized. The in vivo pharmacokinetic profile after oral administration was examined in rats and comparedto free 9-AC. The aromatic azo bond of P-Azo-Leu-Ala-9-AC was stable in stomach and small intestine; the delivery of a large amount of intact conjugate to the colon was achieved. In the colon, the azoreductase activity first cleaved the azo bond followed by peptidase catalyzed cleavage of the leucylalanyl drug derivative resulting in the release of free 9-AC. However, the release rate from the conjugate was not fast enough to achieve high colon concentrations of free 9-AC. The results of the study suggest design features for the second generation of conjugates, including the use of a side-chain with a higher cleavage rate in the colon, combined with the incorporation of bioadhesion technology, to increase colon transit time.

Key Words: HPMA copolymer • anticancer agents • bioconjugates • camptothecin • colon-specific drug delivery

Journal of Bioactive and Compatible Polymers, Vol. 17, No. 5, 305-319 (2002)
DOI: 10.1177/0883911502017005557


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?