Polymeric Cyclodextrins for Intra-Articular Therapy: Novel Nanoassemblies fighting Localized Inflammation in Osteoarthritis

Currently, osteoarthritis (OA), a degenerative pathological disorder of the joints caused by abnormal alteration of tissue metabolism and characterized by a continuous and localized inflammation, is affecting about 50% of the aging population. Therefore, it is deemed necessary to formulate novel therapeutics for intra-articular (IA) injection to locally treat OA inflammation. As part of our research on drug delivery systems, with the aim to reduce the number of administrations and to increase the therapeutic effect at the target site, here we propose novel anti-inflammatory supramolecular ternary assemblies based on poly-β-amino-cyclodextrin (PolyCD)1,2 and hyaluronic acid loaded with the nonsteroidal anti-inflammatory drug diclofenac (DCF). These nanoassemblies were prepared by hydration of an organic film of DCF with an aqueous solution of PolyCD/HA. Decoration of PolyCD with HA aims to minimize the local toxicity of cationic nanosystems and to increase the visco supplementation in the arthritic joint. The interaction between drug and polymer matrix (PolyCD/HA) in the DCF/PolyCD/HA complex was studied using complementary techniques such as UV/Vis, Dynamic Light Scattering (DLS), ζ-potential, 1H NMR and ROESY. The assembly stability and release kinetics of DCF were studied in biologically relevant media mimicking physiological conditions to ensure efficacy and controlled release over time. In addition, preliminary biological studies carried out in in vitro models of OA confirmed promising effects of the designed nanoassemblies in OA treatment.