Long-Term Efficacy Following Intra-articular Injection of Carboxymethyl-chitosan, a New Product Class for Knee Osteoarthritis: Results from an Observational Study in Germany.

INTRODUCTION: Evaluate the real-world efficacy of a single intra-articular injection of carboxymethyl-chitosan (CM-chitosan), a new product class for knee osteoarthritis (OA). METHODS: This post-marketing study included adult patients with knee OA, who received a single injection of 60 mg CM-chitosan (currently marketed as KioMedinevsone) according to the instructions for use. Follow-up was performed at weeks 1, 12, 24, and 36. Efficacy was evaluated using a Visual Analog Scale (VAS) score for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS), Patient's Global Assessment (PGA), and overall patient satisfaction. RESULTS: Forty-nine patients were included in the study. VAS pain score significantly decreased from a median of 49.0 mm at baseline to 24.0 mm at week 1 and to 18 mm at week 36. Pain improvement was stable since at week 36; 91.8% of patients confirmed pain reduction. All KOOS subscales (symptoms, pain, activities of daily living, sports and recreational activities, quality of life) improved significantly compared to baseline at all time points. KOOS pain improved progressively from a median of 58.3% at baseline (mean 56.2 ± 18.8%) to 86.1% (mean 74.1 ± 24%) at week 36 compared to baseline. Overall, more than 70% of patients reported a condition gain (PGA), matching well with the more than 75% of patients being satisfied with the treatment. At 6 months, 72.7% of the patients could be classified as responder according to the OMERACT-OARSI proposed set of responder criteria. CONCLUSION: CM-chitosan showed a rapid onset of pain relief after 1 week and with a duration of 9 months. In a real-world setting, treatment with CM-chitosan would appear to be a potentially effective option to reduce pain and improve physical function and global condition in patients with knee OA, opening new perspectives in patients who are considered as refractory to current symptomatic therapies and where the unmet need is high. TRIAL REGISTRATION NUMBER: NCT04757051 (ClinicalTrials.gov).

Non-clinical assessment of lubrication and free radical scavenging of an innovative non-animal carboxymethyl chitosan biomaterial for viscosupplementation: An in-vitro and ex-vivo study.

OBJECTIVE: Lubrication and free radical scavenging are key features of biomaterials used for viscosupplementation (VS) of joints affected by osteoarthritis (OA). The objective of this study was to describe the non-clinical performance characterization of KiOmedine® CM-Chitosan, a non-animal carboxymethyl chitosan, in order to assess its intended action in VS and to compare it to existing viscosupplements based on crosslinked hyaluronan (HA) formulations. METHOD: The lubrication capacity of the tested viscosupplements (VS) was evaluated in-vitro and ex-vivo. In-vitro, the coefficient of friction (COF) was measured using a novel tribological system. Meanwhile, an ex-vivo biomechanical model in ovine hindlimbs was developed to assess the recovery of join mobility after an intra-articular (IA) injection. Free radical scavenging capacity of HA and KiOmedine® CM-Chitosan formulations was evaluated using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. RESULTS: In the in-vitro tribological model, KiOmedine® CM-Chitosan showed high lubrication capacity with a significant COF reduction than crosslinked HA formulations. In the ex-vivo model, the lubrication effect of KiOmedine® CM-Chitosan following an IA injection in the injured knee was proven again by a COF reduction. The recovery of joint motion was optimal with an IA injection of 3 ml of KiOmedine® CM-Chitosan, which was significantly better than the crosslinked HA formulation at the same volume. In the in-vitro TEAC assay, KiOmedine® CM-Chitosan showed a significantly higher free radical scavenging capacity than HA formulations. CONCLUSION: Overall, the results provide a first insight into the mechanism of action in terms of lubrication and free radical scavenging for the use of KiOmedine® CM-Chitosan as a VS treatment of OA. KiOmedine® CM-Chitosan demonstrated a higher capacity to scavenge free radicals, and it showed a higher recovery of mobility after a knee lesion than crosslinked HA formulations. This difference could be explained by the difference in chemical structure between KiOmedine® CM-Chitosan and HA and their formulations.

Block copolymers of the type poly(caprolactone)-b-poly(ethylene oxide) for the preparation and stabilization of nanoemulsions.

Block copolymers poly(caprolactone)-block-poly(ethylene oxide) are promising non-ionic macromolecular surfactants for the stabilization of emulsions because they display a stronger adsorption and provide an increased long-term stability. But such amphiphilic copolymers should also allow the fabrication of the suspensions according to the emulsification process used. An evaluation of such block copolymers was done regarding the nanoprecipitation and the miniemulsion polymerization processes that both afford aqueous suspensions of nanoparticles. Both the fabrication and the long-term stability were investigated. It was found that the emulsification by means of the nanoprecipitation process was successful when the amphiphilic block copolymer was added into the organic phase. The studies on the structure-activity relationships have shown that a minimum length of the poly(ethylene oxide) block was necessary in order to ensure both the long-term colloidal stability of the suspensions and the instantaneous stability during the preparation process. The length of the hydrophobic block was a parameter of less relevance, but a minimum length was required for the copolymers to be soluble in the organic phase. The miniemulsion polymerization process using block copolymer emulsifiers could be adapted to the incorporation of large loads of vitamin E acetate used as a hydrophobe stabilizer.