Intra-articular fate of degradable poly(ethyleneglycol)-hydrogel microspheres as carriers for sustained drug delivery |
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Authors: | Laurent Bé douet,Florentina Pascale,Laurence Moine,Michel Wassef,Saï da H. Ghegediban,Van-Nga Nguyen,Michel Bonneau,Denis Labarre,Alexandre Laurent |
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Affiliation: | 1. Occlugel, Archimed, 12 rue Charles de Gaulle, 78350 Jouy en Josas, France;2. AP-HP and INRA, Center for Research of Interventional Imaging (CR2i), 78352 Jouy en Josas, France;3. Université Paris Sud, UMR CNRS 8612, IFR 141-ITFM, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France;4. AP-HP Hôpital Lariboisière, Department of Pathology, University of Paris 7 – Denis Diderot, Faculty of Medicine, 2 rue Ambroise Paré, 75010 Paris, France;5. AP-HP Hôpital Lariboisière, Department of Interventional Neuroradiology, 2 rue Ambroise Paré, 75475 Paris, France |
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Abstract: | A novel degradable microsphere (MS) for intra-articular drug delivery, composed of a polyethylene glycol (PEG) core containing degradable regions made of short poly-(lactic-co-glycolic acid) (PLGA) sequences – named PEG-hydrogel MS – was injected into the cavity of sheep shoulder joint, and compared to non-degradable MS devoid of hydrolysable crosslinker in terms of location, degradation and inflammation. One week after intra-articular injection both groups of MS were localized beneath the synovial lining of the synovial fringes located at bottom of the shoulder joint, while a fraction of particles remained in synovial fluid. Histological analyses made one and 4 weeks after intra-articular injection showed cell proliferation around the non-degradable MS entrapped within the synovium. By contrast, degradable PEG-hydrogel MS were surrounded by few cells. The degradation of degradable PEG-hydrogel MS within the synovium was slow and was not fully complete after four weeks. Our findings indicate that the tissue entrapment of MS below the synovial lining was independent of the material degradability, while degradable PEG-hydrogel MS are less inflammatory than the non-degradable one. Degradable PEG-hydrogel MS offer several advantages over the non-degradable MS as carriers for a sustained drug delivery in synovial tissue according to the low intensity of inflammatory reaction triggered in synovium. |
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Keywords: | IA, intra-articular DDS, drug delivery system DDD-MS, degradable drug delivery system IA-DDS, intra-articular drug delivery system |
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