Biodegradable block copolymers for delivery of proteins and water-insoluble drugs
Biodegradable block copolymers for delivery of proteins and water-insoluble drugs
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DOI：
10.1016/s0168-3659(01)00276-0
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发表时间：
2001-05-14
影响因子：
10.8
通讯作者：
Weitman, S
中科院分区：
文献类型：
--
作者：
Zentner, GM;Rathi, R;Weitman, S
介绍了几种药物从新型ABA型生物可降解热凝胶Regel(R)中释放的情况，包括蛋白质和常规分子。这些是可生物降解、生物相容的聚合物，具有反向热凝胶性。有机溶剂不用于合成、提纯或配制这些聚合物。Regel(R)的独特特性取决于以下两个关键特性：(1)Regel(R)是一种在凝胶转变温度以下的水溶、可生物降解的聚合物；(2)Regel(R)一旦注入就会形成不溶于水的凝胶。这与疏水键合凝胶状态是一致的，在这种状态下，所有相互作用都是物理的，没有共价交联。随着溶胶-凝胶转变，粘度增加了大约4个数量级。该凝胶形成了一个控释药库，释放时间从1周到6周不等。Regel(R)的S固有的增溶能力(400倍至2000倍)和稳定难溶和敏感药物，包括蛋白质，是一个实质性的好处。该凝胶对紫杉醇的释放提供了良好的控制约50天。直接瘤内注射Regel(R)/紫杉醇(OncoGel(TM))导致紫杉醇从注射SIRE中缓慢清除，在任何器官中的分布最少。在OncoGel(TM)剂量低10倍的情况下，观察到与最大耐受全身剂量相当的疗效。讨论了蛋白质释放(PGH、G-CSF、胰岛素、rHbsAg)和聚合物生物相容性的数据。(C)2001年，爱思唯尔科学公司出版。
Release of several drugs from new ABA-type biodegradable thermal gels, ReGel(R), including proteins and conventional molecules, are presented. These are biodegradable, biocompatible polymers that demonstrate reverse thermal gelation properties. Organic solvents are not used in the synthesis, purification, or formulation of these polymers. The unique characteristics of ReGel(R) hinge on the following two key properties: (1) ReGel(R) is a water soluble, biodegradable polymer at temperatures below the gel transition temperature; (2) ReGel(R) forms a water-insoluble gel once injected. This is consistent with a hydrophobically bonded gel state where all interactions are physical, with no covalent crosslinking. An increase in viscosity of approximately 4 orders of magnitude accompanies the sol-gel transition. The gel forms a controlled release drug depot with delivery times ranging from 1 to 6 weeks. ReGel(R)'s inherent ability to solubilize (400 to >2000-fold) and stabilize poorly soluble and sensitive drugs, including proteins is a substantial benefit. The gel provided excellent control of the release of paclitaxel for approximately 50 days. Direct intratumoral injection of ReGel(R)/paclitaxel (OncoGel(TM)) results in a slow clearance of paclitaxel from the injection sire with minimal distribution into any organ. Efficacies equivalent to maximum tolerated systemic dosing were observed at OncoGel(TM) doses that were 10-fold lower. Data on protein release (pGH, G-CSF, insulin, rHbsAg) and polymer biocompatibility are discussed. (C) 2001 Published by Elsevier Science B.V.