Multi-arm Avidin nano-construct for intra-cartilage delivery of small molecule drugs.

ABSTRACT: Targeted drug delivery to joint tissues like cartilage remains a challenge that has prevented clinical translation of promising osteoarthritis (OA) drugs. Local intra-articular (IA) injections of drugs suffer from rapid clearance from the joint space and slow diffusive transport through the dense, avascular cartilage matrix comprised of negatively charged glycosaminoglycans (GAGs). Here we apply drug carriers that leverage electrostatic interactions with the tissue's high negative fixed charge density (FCD) for delivering small molecule drugs to cartilage cell and matrix sites. We demonstrate that a multi-arm cationic nano-construct of Avidin (mAv) with 28 sites for covalent drug conjugation can rapidly penetrate through the full thickness of cartilage in high concentration and have long i

SUBMITTER: He T 

PROVIDER: S-EPMC7424591 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature