Retention of peptide-based vesicles in murine knee joints after intra-articular injection

While intra-articular injections continue to be utilized in the remediation of osteoarthritis, the efficacy of such treatment regimens continues to be plagued by the rapid clearance of drug therapeutics from the joint space, independent of whether the therapeutic is a macromolecule or a small-molecule pharmaceutical. Nanoparticle drug delivery vehicles have emerged as potential candidates to enhance the retention of therapeutics within the joint, with a wide variety of formulations that utilize retention strategies such as electrostatic interactions, collagen-type II binding domains, and passive targeting based on the physical size of the particles. However, despite these advances, significant issues regarding carrier and drug retention within the joint remain, so we sought to explore a novel nanoparticle retention scheme based on the integration of collagen peptides. In this work, we demonstrate the successful synthesis and fluorophore labeling of elastin-b-collagen peptide nanovesicles (ECnV). We further demonstrate the matrix/tissue retention and survivability of these ECnVs after novel tissue clearing processes that aid observation and detection of the nanovesicles in vitro. We also demonstrate the retention of these ECnVs in vivo and show successful localization of the ECnVs within murine knee joints. This study represents the first demonstration of the retention of elastin-b-collagen peptide-derived nanovesicles within joints, and suggests their potential for enhancing intra-articular treatment approaches for osteoarthritis.