Papers Published

  1. Betre, Helawe and Liu, Wenge and Zalutsky, Michael R. and Chilkoti, Ashutosh and Kraus, Virginia B. and Setton, Lori A., A thermally responsive biopolymer for intra-articular drug delivery, Journal of Controlled Release, vol. 115 no. 2 (2006), pp. 175 - 182 [022] .
    (last updated on 2007/04/10)

    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 °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. © 2006 Elsevier B.V. All rights reserved.

    Keywords:
    Controlled drug delivery;Pharmacokinetics;Polypeptides;Phase transitions;Joints (anatomy);Diseases;