1-monooleoyl-rac-glycerol and Osteoarthritis

This study aimed to evaluate glycerol monooleate (GMO) as a carrier to develop viscoelastic and injectable sustained-release drug delivery systems. The potential pro- and antioxidant activity of the developed hydrolipidic gels were evaluated by measuring the production of ROS by polymorphonuclear leukocytes (PMNs). In addition, the biocompatibility and effectiveness of two selected gel candidates were evaluated in vivo by evaluating the benefit of a single intraarticular injection of these new treatments in a model of osteoarthritis in rabbits. The in vitro study demonstrated that the carrier F1 did not have a pro-oxidative effect and even protected PMNs against natural auto-activation, regardless of the incorporation of either clonidine chlorhydrate or betamethasone dipropionate. The in vivo study demonstrated that F1 and F1-BDP induced a loss of cartilage quality in comparison to the control and reference groups but that the lesions of cartilage observed were generally mild, with not much full-depth erosion. Moreover, no exacerbating inflammation was observed when considering the synovial membranes and the PGE2 and CRP levels. These results seemed to demonstrate that the sustained-release formulation based on GMO could be well-tolerated after intraarticular injection. Moreover, it could have the potential to prevent inflammatory conditions while sustaining drug activity locally over weeks.

Topics: Animals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Gels; Glycerides; Horses; Injections; Injections, Intra-Articular; Osteoarthritis; Rabbits

Osteoarthritis is characterized by slow degenerative processes in the articular cartilage within synovial joints. It could be interesting to develop a sustained-release formulation that could be effective on both pain/inflammation and restoration of mechanical integrity of the joint. Recently, an injectable system based on glycerol monooleate (GMO), containing clonidine as a model hydrophilic analgesic/anti-inflammatory drug and hyaluronic acid as a viscoelastic scaffold, showed promising potential as a biodegradable and biocompatible preparation to sustain the drug activity. However, drug release from the system is relatively fast (complete within 1 week) and the underlying drug release mechanisms not fully understood. The aims of this study were: (i) to significantly improve this type of local controlled drug delivery system by further sustaining clonidine release, and (ii) to elucidate the underlying mass transport mechanisms. The addition of FDA-approved inactive ingredients such as sodium oleate or purified soybean oil was found to be highly effective. The release rate could be substantially reduced (e.g., 50% release after 10 days), due to the increased hydrophobicity of the systems, resulting in slower and reduced water uptake and reduced drug mobility. Interestingly, Fick's second law of diffusion could be used to quantitatively describe drug release.

Topics: Analgesics; Clonidine; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Excipients; Gels; Glycerides; Hyaluronic Acid; Hydrophobic and Hydrophilic Interactions; Injections, Intra-Articular; Oleic Acid; Osteoarthritis; Soybean Oil; Time Factors; Viscosupplements