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Papers Published

1. Betre, H; Liu, W; Zalutsky, MR; Chilkoti, A; Kraus, VB; Setton, LA, A thermally responsive biopolymer for intra-articular drug delivery., J Control Release, vol. 115 no. 2 (October, 2006), pp. 175-182 [16959360], [doi] .
   (last updated on 2025/04/17)

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