title: Cartilage-targeting drug delivery: can electrostatic interactions help?
abstract: Current intra-articular drug delivery methods do not guarantee sufficient drug penetration into cartilage tissue to reach cell and matrix targets at the concentrations necessary to elicit the desired biological response. Here, we provide our perspective on the utilization of charge-charge (electrostatic) interactions to enhance drug penetration and transport into cartilage, and to enable sustained binding of drugs within the tissue's highly negatively charged extracellular matrix. By coupling drugs to positively charged nanocarriers that have optimal size and charge, cartilage can be converted from a drug barrier into a drug reservoir for sustained intra-tissue delivery. Alternatively, a wide variety of drugs themselves can be made cartilage-penetrating by functionalizing them with specialized positively charged protein domains. Finally, we emphasize that appropriate animal models, with cartilage thickness similar to that of humans, must be used for the study of drug transport and retention in cartilage.
authors.affiliation: Department of Bioengineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Ambika G
authors.initials: AG
authors.lastname: Bajpayee
authors.affiliation: Departments of Biological Engineering, Mechanical Engineering, and Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, Massachusetts 02139, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007270:Injections, Intra-Articular / Q000379:methods; D010003:Osteoarthritis / Q000188:drug therapy; D055672:Static Electricity
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers