title: Intra-articular fate of degradable poly(ethyleneglycol)-hydrogel microspheres as carriers for sustained drug delivery.
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.
authors: Occlugel, Archimed, 12 rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors: Laurent
authors: L
authors: Bédouet
authors: Florentina
authors: F
authors: Pascale
authors: Laurence
authors: L
authors: Moine
authors: Michel
authors: M
authors: Wassef
authors: Saïda H
authors: SH
authors: Ghegediban
authors: Van-Nga
authors: VN
authors: Nguyen
authors: Michel
authors: M
authors: Bonneau
authors: Denis
authors: D
authors: Labarre
authors: Alexandre
authors: A
authors: Laurent
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007261:Infusions, Intra-Arterial; D008863:Microspheres; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012756:Sheep; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols
keywords: DDD-MS; DDS; Drug delivery; Hydrogel; IA; IA-DDS; Intra-articular; Microspheres; Osteoarthritis; degradable drug delivery system; drug delivery system; intra-articular; intra-articular drug delivery system