Liposomal dexamethasone–diclofenac combinations for local osteoarthritis treatment

Abstract

Conventional chronic and acute treatments for osteoarthritis (OA) are by oral NSAIDs (such as diclofenac) and intra-articular injected glucocorticosteroids (such as dexamethasone). In free form, diclofenac and dexamethasone generate severe adverse effects with risks of toxicity. To reduce these drawbacks, we investigated local injections of liposomal formulations for diclofenac and dexamethasone (each alone, and their combination). Bioadhesive liposomes carrying hyaluronan (HA-BAL) or collagen (COL-BAL) as their surface-anchored ligand were used for the task. Each drug alone or their combination showed high efficiency encapsulations (≥80%) and performance as slow-release depots (half-lives in the range of 1–3 days under the fastest conditions). Employing RIA and immunoblot assay techniques, it was verified that the encapsulated drugs retained their biological activities: inhibitions of Cyclooxygenases enzyme-activity (diclofenac) and of Cyclooxygenases protein-expression (dexamethasone). Using live-animal MRI, a single intra-articular injection of each liposome-drug(s) formulation sufficed to reduce knee joint inflammation in OA rats over a time span of 17 days, HA-BAL better than COL-BAL. The most effective treatment was by the combination of both drugs in HA-BAL, a single dose reducing the inflammation volume down to 12.9% from initial over that time span. We find all three HA-BAL formulations worthy of further studies.