Polyvinylpyrrolidone-drug conjugate: Synthesis and release mechanism

被引：116

作者：

D'Souza, AJM ^{[1
]}

Schowen, RL ^{[1
]}

Topp, EM ^{[1
]}

机构：

[1] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66047 USA

来源：

JOURNAL OF CONTROLLED RELEASE | 2004年 / 94卷 / 01期

关键词：

polymeric prodrugs; polymer-drug conjugates; intramolecular reaction; controlled release;

D O I：

10.1016/j.jconrel.2003.09.014

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Covalent conjugates of polyvinylpyrrolidone (PVP) with para-nitroaniline (PNA) were synthesized as a model PVP- drug conjugate, and PNA release was evaluated in vitro. Pyrrolidone ring opening with subsequent t-BOC protection of the pyrrolidone nitrogen and reaction with PNA in methylene chloride (CH2Cl2) produced a PVP-PNA conjugate with 3% of the pyrrolidone groups modified. Rates of PNA release from N-deprotected conjugates were twofold greater than those that were N-protected, indicating participation of the pyrrolidone N in release. Additional studies with monomeric analogs supported intramolecular base catalysis rather than lactam formation as the mechanism of this involvement. The approach serves as a prototype for the conjugation of other drugs with primary and secondary amine functional groups with PVP, including peptides and proteins. (C) 2003 Elsevier B.V. All rights reserved.

引用

页码：91 / 100

页数：10

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