Davis, Mollie Sussman. Sustained release local anesthetics and encapsulated mesenchymal stromal cells for the treatment of osteoarthritis. Retrieved from https://doi.org/doi:10.7282/t3-n4c4-se38
DescriptionOsteoarthritis (OA) is an age-related disease characterized by degeneration of articular cartilage due to imbalances between synthesis and destruction in the cartilage. Due to the complexity of the disease, there is no cure for OA, and treatments focus on the two main symptoms of OA, pain and inflammation. The goal of our work is to create a multi-modal therapy to target pain and inflammation in OA utilizing sustained release local anesthetics (LA) and encapsulated mesenchymal stromal cells (eMSC)s. Our engineered bupivacaine liposomal construct enabled LA release for up to four days while maintaining MSC and eMSC viability. Moreover, it promoted a less inflammatory environment by increasing PGE2 secretions. Through computational modeling, higher dose liposomal constructs were analyzed and tested in vitro, significantly increasing the starting concentration while maintaining eMSC viability and anti-inflammatory function. The liposomal construct was tested on chondrocytes and all LA starting doses maintained chondrocyte viability while slightly decreasing inflammatory cytokine secretions and increasing proteoglycan deposition. To target OA, we aimed to develop a sustained release system that released clinically relevant doses of drug for 35+ days. We developed sustained release poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) which release 70% of the LA within 35 days. Encapsulating the NP in an alginate construct reduced percent release to 16% of the LA within 35 days. The NP construct maintained chondrocyte viability at clinically relevant doses while maintaining cytokine secretions and increasing proteoglycan deposition. Moreover, the LA concentrations from the NP construct enable co-administration with eMSC allowing for a complete multi-modal therapy to treat OA pain and inflammation.