Hyaluronic acid hydrogel added with ibuprofen-lysine for the local treatment of chondral lesions in the knee: in vitro and in vivo investigations

The effect of hyaluronan-based hydrogel with a cross-linking degree of 50% (i.e., the amount of carboxylate groups involved in the cross-lining reaction) (Hyal 50%), loaded with an anti-inflammatory drug (ibuprofen-lysine) for local administration in the osteoarthritic knee was evaluated. The kinetic of drug release from Hyal 50% hydrogel was performed in vitro by a continuous flow system. The release was studied at three different rates (0.375, 0.073, and 0.005 mL/s), and for the slowest one a period of 8 days was necessary to receive the complete release of the drug. A chondral defect was caused in the right femoral medial condyle of 24 rabbits. Twelve animals were treated with Hyal 50%+ibuprofen-lysine and 12 with Hyal 50% by percutaneous injection. The treatments were repeated every 10 days, for three or five times. At 30 and 50 days, no significant differences were observed between the groups (mean score at 30 days: 4.4+/-0.6 in Hyal 50%-treated group and 5.1+/-0.7 in Hyal 50% +Ibuprofen-lysine-treated group; mean score at 50 days: 6.9+/-0.6 in Hyal 50%-treated group and 7.1+/-0.6 in Hyal 50%+ Ibuprofen-lysine-treated group). A significant difference was observed in bone mineral density of the total tibia of rabbits treated by Hyal 50% + Ibuprofen-lysine in comparison with those treated only by Hyal 50%. The positive effects of Hyal 50% on chondral lesions were maintained in the presence of ibuprofen-lysine with the adjunctive effect of an increased limb usage, most likely due to less pain and discomfort.