Supramolecular assemblies based on Polymeric Cyclodextrin, Hyaluronic acid and Diclofenac as antiinflammatory nanodrug

Osteoarthritis (OA) is a very common degenerative joint disease in old age, caused by an abnormal alteration of tissue metabolism that leads to a continuous and progressive inflammatory state in situ. The covalent conjugate between diclofenac (DCF) and hyaluronic acid (HA) was developed for intraarticular injection (IA) in patients with osteoarthritis of the knee required to reduce the number of administrations and prolong the therapeutic effect at the target site. Phase III clinical trial in Japan.1 For this reason we decided to use injectable therapeutic polymers capable of locally fighting inflammation to obtain nano-sized drug delivery systems for the treatment of OA. As part of our ongoing research we have developed a new anti-inflammatory nanotherapy based on the ternary supramolecular assembly of poly-β-amino-cyclodextrin (PolyCD) and hyaluronic acid (HA) loaded with the non-steroidal anti-inflammatory drug diclofenac (DCF). Our goal is to obtain biodegradable, biocompatible and non-immunogenic nanosystems constructed with polymeric cyclodextrins2,3 that combine the properties of biomaterials. The decoration of PolyCD with HA aims to minimize the local toxicity of cationic nanosystems. The nanoassemblies were prepared by hydrating an organic DCF film with an aqueous solution of PolyCD/ HA. The interaction between DCF and the polymer matrix (PolyCD/ HA) in the DCF/ PolyCD/ HA complex was investigated using complementary techniques such as UV/ Vis spectroscopy, Dynamic Light Scattering (DLS), -potential and 1H NMR. The stability of the assembly and the DCF release kinetics have been studied in media that mimic physiological conditions to ensure control over time and efficacy. Biological experiments in in vitro and in vivo OA models are underway to highlight the therapeutic efficacy of DCF/ PolyCD/ HA.