Novel glucosamine-loaded thermosensitive hydrogels based on poloxamers for osteoarthritis therapy by intra-articular injection

Glucosamine (GlcN) is a common drug used to treat osteoarthritis (OA). To prolong the action time of glucosamine on OA and improve its therapeutic effect, this research explored the potential application of GlcN-loaded thermosensitive hydrogels based on poloxamer 407 and poloxamer 188 for OA therapy by intra-articular injection. The thermosensitive hydrogels were prepared by cold method, and the effects of P407, P188, and GlcN on sol-gel transition temperature (T_sol-gel) were compared. After screening was performed, the optimized formulation showed good temperature sensitivity, and T_sol-gel was approximately 35 °C. In vitro release tests showed that GlcN was slowly released from the thermosensitive hydrogels. After the gels were intra-articularly administered to treat OA in rabbits, the degree of swelling and inflammatory factors were significantly decreased in the hydrogel group compared with those in the OA model group (P < 0.05). Histological results showed that the GlcN-administered group had a good repair effect on damaged cartilage. At the same dose, the effect of the thermosensitive hydrogels was better than that of the aqueous solution. Therefore, GlcN-loaded thermosensitive hydrogels based on poloxamers are promising sustainable delivery systems for OA therapy by intra-articular injection.