Journal
JOURNAL OF CONTROLLED RELEASE
Volume 115, Issue 2, Pages 175-182Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2006.07.022
Keywords
intra-articular; osteoarthritis; drug delivery; sustained release; drug carriers; thermogelling; thermally responsive; elastin-like polypeptide
Funding
- NIAMS NIH HHS [AR047442] Funding Source: Medline
- NIBIB NIH HHS [EB002263] Funding Source: Medline
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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 ostcoarthritis and other arthritides. (c) 2006 Elsevier B.V. All rights reserved.
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