A thermally responsive biopolymer for intra-articular drug delivery
- 作者：Helawe Betre ; Wenge Liu ; Michael R. Zalutsky ; Ashutosh Chilkoti ; Virginia B. Kraus and Lori A. Setton
- 关键词：Intra-articular ; Osteoarthritis ; Drug delivery ; Sustained release ; Drug carriers ; Thermogelling ; Thermally responsive ; Elastin-like polypeptide
- 刊名：Journal of Controlled Release
- 出版年：2006
- 期刊代码：25_01683659
- 类别：pha
- 出版时间：10 October 2006
- 卷：115
- 期：2
- 页码：175-182
- 文件大小：639 K
摘要
Intra-articular drug delivery is the preferred standard for targeting pharmacologic treatment directly to joints to reduce undesirable side effects associated with systemic drug delivery. In this study, a biologically based drug delivery vehicle was designed for intra-articular drug delivery using elastin-like polypeptides (ELPs), a biopolymer composed of repeating pentapeptides that undergo a phase transition to form aggregates above their transition temperature. The ELP drug delivery vehicle was designed to aggregate upon intra-articular injection at 37 °C, and form a drug ‘depot’ that could slowly disaggregate and be cleared from the joint space over time. We evaluated the in vivo biodistribution and joint half-life of radiolabeled ELPs, with and without the ability to aggregate, at physiological temperatures encountered after intra-articular injection in a rat knee. Biodistribution studies revealed that the aggregating ELP had a 25-fold longer half-life in the injected joint than a similar molecular weight protein that remained soluble and did not aggregate. These results suggest that the intra-articular joint delivery of ELP-based fusion proteins may be a viable strategy for the prolonged release of disease-modifying protein drugs for osteoarthritis and other arthritides.