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| Publications [#87736] of Virginia B Kraus
Papers Published
- H Betre, W Liu, MR Zalutsky, A Chilkoti, VB Kraus, LA Setton, A thermally responsive biopolymer for intra-articular drug delivery.,
Journal of controlled release : official journal of the Controlled Release Society, Netherlands, vol. 115 no. 2
(October, 2006),
pp. 175-82, ISSN 0168-3659
(last updated on 2007/11/29)
Abstract:
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.
Keywords:
Animals • Biopolymers • Delayed-Action Preparations • Drug Delivery Systems* • Elastin • Female • Half-Life • Injections, Intra-Articular* • Isotope Labeling • Joints • Peptides • Rats • Rats, Wistar • Solubility • Temperature • chemical synthesis • chemistry • chemistry* • metabolism • pharmacokinetics
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