Preclinical Study of the Efficacy and Safety of Chondroitin Sulfate

Chondroitin sulfate is used for osteoarthritis combination therapy. It should be taken into account that the structure and properties of polysaccharides included in chondroitin sulfate, as well as the raw materials used for its production, have a significant effect on its absorption, bioavailability, and, as a consequence, on the safety and efficacy of orally administered products.

The aim of the study was to assess toxic properties, local irritant effect, immunotoxicity, basic pharmacokinetic parameters, and therapeutic efficacy of the new Chondroitin sulfate product (produced by Federal State Unitary Enterprise “Moscow Endocrine Plant”, Russia) as compared to Structum (produced by “Pierre Fabre Medicament Production”, France).

Materials and methods: White Giant rabbits were used in the experiments. Toxicity, immunotoxicity and local irritation effects of the products were assessed following daily oral administration at the dose of 168 mg/kg (about 6 Maximum Recommended Therapeutic Doses) to male and female rabbits for 28 days. The follow-up period was 14 days. The pharmacokinetic study included blood sampling on days 1‒2 of the experiment, complete blood count and blood chemistry tests were performed on days 28 and 43. After killing the animals, pathomorphological and histological examinations were performed on their organs and tissues. Therapeutic efficacy was studied in an osteoarthritis model made by cruciate ligament transaction in rabbits. The animals received therapy at doses of 16.8 mg/kg, 33.6 mg/kg, and 67.2 mg/kg for 56 days starting from day 8 after the pathology induction.

Results: the medicines had no toxic, local irritant, or immunotoxic effect. The NOAEL was established at 168 mg/kg. The study demonstrated the comparability of the pharmacokinetic profiles of the studied products following single oral administration. The maximum concentration of the active ingredient (C_max = 79 ± 6 μg/mL—Chondroitin sulfate; C_max = 71 ± 4 μg/mL— Structum) in blood plasma was observed within 3–4 hours after administration. A decrease in the severity of cartilage structural damage was observed for the doses of 33.6 mg/kg and 67.2 mg/kg. The results of quantitative determination of sulfated glycosaminoglicans in the proteoglycans of the cartilage articular surface in the animals with osteoarthritis demonstrated an increase in the level of sulfated glycosaminoglicans in the groups treated with the maximum doses of the studied products, as compared to the other groups.

Conclusions: the obtained data confirm that the test product has a favourable safety profile, and therapeutic (chondroprotective) effect. All the tested properties of Chondroitin sulfate were comparable to those of Structum.

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