Leveraging Electrostatic Interactions for Drug Delivery to the Joint

Arthritis is a debilitating joint disease with a high economic burden and prevalence. There are many challenges delivering therapeutics to the joint, including low bioavailability when administered systemically and low joint retention after intra-articular injection. Therefore, drug delivery systems such as nanoparticles, liposomes, dendrimers, and carrier proteins have been utilized to overcome some of these limitations. To enhance joint tissue localization and retention, there are opportunities to leverage electrostatic interactions between drug carriers and various tissues and cells. These opportunities, as they pertain to specific joint tissues, are explored in this review. Further, the impact that electrostatic interactions has on various drug delivery parameters, such as the formation of a protein corona, the uptake and cytotoxicity, and the biodistribution of the drug delivery systems, is discussed. Lastly, this review summarizes key findings from studies that have investigated the use of electrostatic interactions to increase targeting of specific joint tissues and limitations in preclinical investigations are identified. As more novel targets are discovered in treating arthritis, there will be a continued need to localize therapeutics to specific tissues for greater therapeutic outcomes and hence attention must be paid in designing the drug delivery systems.