Development and evaluation in vitro and in vivo of injectable hydrolipidic gels with sustained-release properties for the management of articular pathologies such as 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.
Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Campus de la Plaine, BC B-1050 Brussels, Belgium.
Jonathan
J
Réeff
Bone and Cartilage Research Unit (B.C.R.U.), Arthropôle Liège, University of Liège, Liège, Belgium.
Frederic
F
Oprenyeszk
Center for Oxygen, Research and Development, Chemical Institute B6a, Sart Tilman, Liège, Belgium.
Thierry
T
Franck
Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Campus de la Plaine, BC B-1050 Brussels, Belgium.
Jonathan
J
Goole
Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Campus de la Plaine, BC B-1050 Brussels, Belgium.
Carine
C
De Vriese
Center for Oxygen, Research and Development, Chemical Institute B6a, Sart Tilman, Liège, Belgium.
Didier
D
Serteyn
Bone and Cartilage Research Unit (B.C.R.U.), Arthropôle Liège, University of Liège, Liège, Belgium.
Yves
Y
Henrotin
Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Campus de la Plaine, BC B-1050 Brussels, Belgium. Electronic address: kamighi@ulb.ac.be.
Karim
K
Amighi
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry; D006736:Horses; D007267:Injections / Q000379:methods; D007270:Injections, Intra-Articular / Q000379:methods; D010003:Osteoarthritis / Q000188:drug therapy*; D011817:Rabbits
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D005989:Glycerides; C005953:monoolein
Drug delivery systems; Glycerol monooleate; Intraarticular; Osteoarthritis; ROS; Rabbit