Poly-beta-amino-ester licofelone conjugates development for osteoarthritis treatment

Area of Science:

• Biomaterials Science
• Pharmacology
• Orthopedics

Background:

• Osteoarthritis (OA) poses a significant health burden, with limited treatment options.
• Current disease-modifying osteoarthritis drugs (DMOADs) face challenges in clinical approval due to poor therapeutic performance.
• The joint environment restricts drug delivery and residence time, hindering DMOAD efficacy.

Purpose of the Study:

• To enhance the delivery of DMOADs into cartilage tissue.
• To improve the uptake and retention time of DMOADs within the joint.
• To investigate the potential of polymer conjugation for improving DMOAD pharmacokinetics.

Main Methods:

• Covalent conjugation of licofelone, a model DMOAD, to poly-beta-amino-ester (PBAE) polymers (A16 and A87).
• Utilizing the hydrolysable, cytocompatible, and cationic properties of PBAEs for drug delivery.
• Quantifying cartilage uptake and retention of licofelone-PBAE conjugates compared to free licofelone.

Main Results:

• Cartilage uptake of licofelone-PBAE conjugates was 18 times higher than free licofelone.
• Tissue retention time of the conjugates was prolonged by 37 times compared to free licofelone.
• Licofelone-PBAE conjugates demonstrated no adverse effects on chondrocyte viability.

Conclusions:

• Cationic PBAE polymers (A87 and A16) effectively increase licofelone concentration within cartilage.
• This polymer conjugation strategy shows promise for enhancing the therapeutic and pharmacokinetic profiles of licofelone and other DMOADs.
• Improved drug delivery may overcome clinical limitations of current DMOADs for osteoarthritis treatment.