A thermally responsive biopolymer for intra-articular drug delivery.

Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

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 degrees 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.

Full Text

Duke Authors

Cited Authors

  • Betre, H; Liu, W; Zalutsky, MR; Chilkoti, A; Kraus, VB; Setton, LA

Published Date

  • October 10, 2006

Published In

Volume / Issue

  • 115 / 2

Start / End Page

  • 175 - 182

PubMed ID

  • 16959360

International Standard Serial Number (ISSN)

  • 0168-3659

Digital Object Identifier (DOI)

  • 10.1016/j.jconrel.2006.07.022

Language

  • eng

Citation Source

  • PubMed