Cartilage-Penetrating Nanocarrier-Drug Conjugate for Disease-Modifying Intervention in Post-Traumatic Osteoarthritis
Abstract
Post traumatic osteoarthritis (PTOA) is a debilitating disease that causes the breakdown of cartilage in articulating joints when triggered by an injury to the cartilage. It is a condition that represents 12 percent of all osteoarthritis (OA) cases, and it has a significant impact on soldiers and civilians who suffer from extensive pain and gradual degradative loss of joint function. There have been a number of attempts to create a biologic disease-modifying osteoarthritis drug (DMOAD) to either stop OA progression or reverse the disease entirely, but these drug candidates have failed in clinical trials due to poor delivery to cartilage and lowered access to cartilage matrix producing cells, which are critical for regeneration and recovery in cartilage. In order to achieve clinical success, the drug delivery challenges that caused the proposed drugs to fail must be resolved. Our labs demonstrated that biologic drugs can be directly conjugated to a positively charged, multivalent dendrimer nanocarrier that has been modified with biocompatible polymeric groups to yield a nanocarrier for biologic proteins without loss of bioactivity. The nanocarrier is successful in addressing the drug delivery challenges that caused OA biologic drugs to fail in clinical trials. These dendrimer-drug conjugates have been shown to create a tenfold increase in joint residence time compared to the free drug, from about 3 days to 30 days, and we have shown promising cartilage regeneration results in rat studies. This PRMRP grant will move this technology toward clinical translation by improving the procedure of attaching proteins to polymeric nanocarriers and investigating the best biologic for therapeutic efficacy using tissue regeneration as a primary and pain as a secondary endpoint.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1191165
Entities
People
- Paula T. Hammond
Organizations
- Massachusetts Institute of Technology