Drug delivery carriers can alter cartilage biomechanics

Abstract

Development of effective osteoarthritis (OA) therapeutics is challenged by difficulties in delivering drug molecules into articular cartilage, owing to the dense nature of cartilage extracellular matrix (ECM) and the fast clearance of drug molecules in the synovial joint ( 1 Bajpayee A.G. Grodzinsky A.J. Cartilage-targeting drug delivery: can electrostatic interactions help?. Nat. Rev. Rheumatol. 2017; 13: 183-193https://doi.org/10.1038/nrrheum.2016.210 Crossref PubMed Scopus (120) Google Scholar ). Cartilage ECM is characterized by a high negative fixed charge density, endowed by the proteoglycan, aggrecan, and its sulfated glycosaminoglycan (sGAG) side chains ( 2 Han L. Grodzinsky A.J. Ortiz C. Nanomechanics of the cartilage extracellular matrix. Annu. Rev. Mater. Res. 2011; 41: 133-168https://doi.org/10.1146/annurev-matsci-062910-100431 Crossref PubMed Scopus (135) Google Scholar ). Building on this knowledge, researchers have developed various cationic drug delivery carriers to promote drug penetration deep into cartilage, targeting chondrocytes throughout the whole tissue depth. A few examples include peptides ( 3 Vedadghavami A. Wagner E.K. Bajpayee A.G. et al. Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues. Acta Biomater. 2019; 93: 258-269https://doi.org/10.1016/j.actbio.2018.12.004 Crossref PubMed Scopus (41) Google Scholar ), proteins ( 4 DiDomenico C.D. Bonassar L.J. The effect of charge and mechanical loading on antibody diffusion through the articular surface of cartilage. J. Biomech. Eng. 2018; 141: 014502https://doi.org/10.1115/1.4041768 Crossref Scopus (4) Google Scholar ), synthetic polymers ( 5 Geiger B.C. Wang S. Hammond P.T. et al. Cartilage-penetrating nanocarriers improve delivery and efficacy of growth factor treatment of osteoarthritis. Sci. Transl. Med. 2018; 10: eaat8800https://doi.org/10.1126/scitranslmed.aat8800 Crossref PubMed Scopus (121) Google Scholar ), and nanoparticles ( 6 Yan H. Duan X. Pham C.T.N. et al. Suppression of NF-κB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury. Proc. Natl. Acad. Sci. USA. 2016; 113: E6199-E6208https://doi.org/10.1073/pnas.1608245113 Crossref PubMed Scopus (79) Google Scholar ). Effects of polycationic drug carriers on the electromechanical and swelling properties of cartilageWarren et al.Biophysical JournalJune 27, 2022In BriefCationic nanocarriers offer a promising solution to challenges in delivering drugs to negatively charged connective tissues, such as to articular cartilage for the treatment of osteoarthritis (OA). However, little is known about the effects that cationic macromolecules may have on the mechanical properties of cartilage at high interstitial concentrations. We utilized arginine-rich cationic peptide carriers (CPCs) with varying net charge (from +8 to +20) to investigate the biophysical mechanisms of nanocarrier-induced alterations to cartilage biomechanical properties. Full-Text PDF