Department of Biomedical Engineering and Chemistry, Boston University, Boston, Massachusetts, United States.
Biomacromolecules. 2012 Feb 13;13(2):406-11. doi: 10.1021/bm201443m. Epub 2012 Feb 1.
A limitation to many polymer-based drug delivery systems is the lack of ability to customize a particular polymer composition for tailoring drug release kinetics to a specific clinical application. In this study, we investigated the structure-property effects of conjugating various hydrophobic biocompatible side chains to poly(glycerol-co-caprolactone) copolymers with the goal of achieving prolonged and controlled release of a chemotherapeutic agent. The choice of side chain significantly affected the resulting polymer properties including thermal transitions, relative crystallinity (ΔH(f)), and hydrophobicity. Drug-loaded films cast from solutions of polymer and 10-hydroxycamptothecin demonstrated prolonged release from four to over seven weeks depending upon side chain structure without initial burst release behavior. Use of the stearic acid-conjugated poly(glycerol-co-caprolactone) films afforded substantial anticancer activity in vitro for at least 50 days when exposed to fresh cultures of A549 human lung cancer cells over 24 h intervals, correlating well with the measured drug release kinetics.
许多基于聚合物的药物输送系统的一个局限性是缺乏为特定的临床应用定制特定聚合物组成的能力，以调整药物释放动力学。在这项研究中，我们研究了将各种疏水性生物相容性侧链接枝到聚（甘油-co-己内酯）共聚物上的结构-性能影响，目的是实现化疗药物的延长和控制释放。侧链的选择显著影响了所得聚合物的性质，包括热转变、相对结晶度（ΔH(f)）和疏水性。从聚合物和 10-羟基喜树碱的溶液浇铸的载药薄膜表现出长达四周至七周以上的延长释放，具体取决于侧链结构，而没有初始突释行为。使用硬脂酸接枝的聚（甘油-co-己内酯）薄膜在暴露于新鲜培养的 A549 人肺癌细胞时，在 24 小时间隔内至少具有 50 天的显著体外抗癌活性，与测量的药物释放动力学非常吻合。
