Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for osteoarthritis (OA) prevention or inhibition of the disease development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic performances in clinical trials. The joint environment has played a role in this process by limiting the amount of drug effectively delivered as well as the time that the drug stays within the joint space. The current study aimed to improve the delivery of the DMOADs into cartilage tissue by increasing uptake and retention time of the DMOADs within the tissue. Licofelone was used a model DMOAD due to its significant therapeutic effect against OA progression as shown in the recent phase III clinical trial. For this purpose licofelone was covalently conjugated to the two different A16 and A87 poly-beta-amino-ester (PBAEs) polymers taking advantage of their hydrolysable, cytocompatible, and cationic nature. We have shown cartilage uptake of the licofelone–PBAE conjugates increased 18 times and retention in tissues was prolonged by 37 times compared to the equivalent dose of the free licofelone. Additionally, these licofelone conjugates showed no detrimental effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 PBAE polymers increased the amount of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of this drug and other DMOADs clinically.