A thermally responsive biopolymer for intra-articular drug delivery.
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.
Betre
Helawe
H
Department of Biomedical Engineering, 136 Hudson Hall, Box 90821, Duke University, Durham, NC 27708, USA.
Liu
Wenge
W
Zalutsky
Michael R
MR
Chilkoti
Ashutosh
A
Kraus
Virginia B
VB
Setton
Lori A
LA
D000818:Animals; D001704:Biopolymers / Q000737:chemistry* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004549:Elastin / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D007270:Injections, Intra-Articular; D007553:Isotope Labeling; D007596:Joints / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013696:Temperature
D001704:Biopolymers; D003692:Delayed-Action Preparations; D010455:Peptides; D004549:Elastin