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A thermally responsive biopolymer for intra-articular drug delivery.

Publication ,  Journal Article
Betre, H; Liu, W; Zalutsky, MR; Chilkoti, A; Kraus, VB; Setton, LA
Published in: J Control Release
October 10, 2006

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.

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Published In

J Control Release

DOI

ISSN

0168-3659

Publication Date

October 10, 2006

Volume

115

Issue

2

Start / End Page

175 / 182

Location

Netherlands

Related Subject Headings

  • Temperature
  • Solubility
  • Rats, Wistar
  • Rats
  • Pharmacology & Pharmacy
  • Peptides
  • Joints
  • Isotope Labeling
  • Injections, Intra-Articular
  • Half-Life
 

Citation

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Betre, H., Liu, W., Zalutsky, M. R., Chilkoti, A., Kraus, V. B., & Setton, L. A. (2006). A thermally responsive biopolymer for intra-articular drug delivery. J Control Release, 115(2), 175–182. https://doi.org/10.1016/j.jconrel.2006.07.022
Betre, Helawe, Wenge Liu, Michael R. Zalutsky, Ashutosh Chilkoti, Virginia B. Kraus, and Lori A. Setton. “A thermally responsive biopolymer for intra-articular drug delivery.J Control Release 115, no. 2 (October 10, 2006): 175–82. https://doi.org/10.1016/j.jconrel.2006.07.022.
Betre H, Liu W, Zalutsky MR, Chilkoti A, Kraus VB, Setton LA. A thermally responsive biopolymer for intra-articular drug delivery. J Control Release. 2006 Oct 10;115(2):175–82.
Betre, Helawe, et al. “A thermally responsive biopolymer for intra-articular drug delivery.J Control Release, vol. 115, no. 2, Oct. 2006, pp. 175–82. Pubmed, doi:10.1016/j.jconrel.2006.07.022.
Betre H, Liu W, Zalutsky MR, Chilkoti A, Kraus VB, Setton LA. A thermally responsive biopolymer for intra-articular drug delivery. J Control Release. 2006 Oct 10;115(2):175–182.
Journal cover image

Published In

J Control Release

DOI

ISSN

0168-3659

Publication Date

October 10, 2006

Volume

115

Issue

2

Start / End Page

175 / 182

Location

Netherlands

Related Subject Headings

  • Temperature
  • Solubility
  • Rats, Wistar
  • Rats
  • Pharmacology & Pharmacy
  • Peptides
  • Joints
  • Isotope Labeling
  • Injections, Intra-Articular
  • Half-Life