The problem: Osteoarthritis (OA) is ignited by the transformation of chondrocytes from cartilage-producing (homeostatic or anabolic state) to cartilage-degrading (catabolic state) cells. Thus, agents able to reestablish chondrocyte homeostasis by blocking the expression of catabolic state promoters in chondrocytes are in principle promising anti-OA drugs. Nevertheless, it is difficult to deliver drugs to chondrocytes, as they reside in the cartilage extracellular matrix (ECM), which is avascular, water-filled and has a mesh size of ~ 60 nm. Because of the cartilage ECM’s lack of vascularity, the intra-articular (IA) route is preferred to enable drug access to chondrocytes. However, the development of IA-injected OA drugs has been hampered by the rapid clearance of small molecules out of the synovial cavity through its loose lining, and the poor penetration of large molecules through the cartilage ECM. Thus, strategies to enhance penetration of OA drugs into the cartilage are needed.
The solution: Nanodrugs are obtained by loading known drugs into/onto nanotechnology-derived particles (nanoparticles) and have the potential to improve the bioavailability and final fate of therapeutically relevant molecules. Our group developed polyethylene glycol (PEG)-modified carbon nanotubes (PEG-CNTs) and investigated their use in medicine. PEG-CNTs are biocompatible and, due to their elongated shape, display a favorable trafficking profile in healthy and pathologic tissues. We recently demonstrated that PEG-CNTs can deliver model cargo into both healthy and OA chondrocytes in vivo (ACS Nano 2014). Additionally, we found that PEG-CNTs can be degraded by neutrophils (Nanoscale 2014), and thus they offer potential as a biodegradable delivery system. These results shed the light on the use of our PEG-CNTs as an IA-injectable system to deliver drugs into OA chondrocytes and reestablish cartilage homeostasis. Currently we are focused on optimizing our PEG-CNTs to improve their ability to deliver inhibitors of cartilage catabolic state promoters into chondrocytes in OA mouse models.
Additional on-going projects: Our lab is also: