title: A novel biocompatible hyaluronic acid-chitosan hybrid hydrogel for osteoarthrosis therapy.
abstract: A conventional therapy for the treatment of osteoarthrosis is intra-articular injection of hyaluronic acid, which requires repeated, frequent injections. To extend the viscosupplementation effect of hyaluronic acid, we propose to associate it with another biopolymer in the form of a hybrid hydrogel. Chitosan was chosen because of its structural similarity to synovial glycosaminoglycans, its anti-inflammatory effects and its ability to promote cartilage growth. To avoid polyelectrolyte aggregation and obtain transparent, homogeneous gels, chitosan was reacetylated to a 50% degree, and different salts and formulation buffers were investigated. The biocompatibility of the hybrid gels was tested in vitro on human arthrosic synoviocytes, and in vivo assessments were made 1 week after subcutaneous injection in rats and 1 month after intra-articular injection in rabbits. Hyaluronic acid-chitosan polyelectrolyte complexes were prevented by cationic complexation of the negative charges of hyaluronic acid. The different salts tested were found to alter the viscosity and thermal degradation of the gels. Good biocompatibility was observed in rats, although the calcium-containing formulation induced calcium deposits after 1 week. The sodium chloride formulation was further tested in rabbits and did not show acute clinical signs of pain or inflammation. Hybrid HA-Cs hydrogels may be a valuable alternative viscosupplementation agent.
authors: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland.
authors: S
authors: S
authors: Kaderli
authors: UPSP ICE 2011.03.101, University of Lyon, VetAgro Sup, Campus Vétérinaire de Lyon 69280 Marcy l'Etoile, Lyon, France.
authors: C
authors: C
authors: Boulocher
authors: UPSP ICE 2011.03.101, University of Lyon, VetAgro Sup, Campus Vétérinaire de Lyon 69280 Marcy l'Etoile, Lyon, France.
authors: E
authors: E
authors: Pillet
authors: UPSP ICE 2011.03.101, University of Lyon, VetAgro Sup, Campus Vétérinaire de Lyon 69280 Marcy l'Etoile, Lyon, France.
authors: D
authors: D
authors: Watrelot-Virieux
authors: Division of Clinical Pathology, Geneva University Hospital, Rue Michel-Servet 1, 1211 Geneva, Switzerland.
authors: A L
authors: AL
authors: Rougemont
authors: UPSP ICE 2011.03.101, University of Lyon, VetAgro Sup, Campus Vétérinaire de Lyon 69280 Marcy l'Etoile, Lyon, France.
authors: T
authors: T
authors: Roger
authors: UPSP ICE 2011.03.101, University of Lyon, VetAgro Sup, Campus Vétérinaire de Lyon 69280 Marcy l'Etoile, Lyon, France.
authors: E
authors: E
authors: Viguier
authors: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland.
authors: R
authors: R
authors: Gurny
authors: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland.
authors: L
authors: L
authors: Scapozza
authors: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland. Electronic address: olivier.jordan@unige.ch.
authors: O
authors: O
authors: Jordan
mesh_terms: D000368:Aged; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry*; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007270:Injections, Intra-Articular; D007279:Injections, Subcutaneous; D008297:Male; D008970:Molecular Weight; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014783:Viscosity
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D006820:Hyaluronic Acid; D048271:Chitosan
keywords: Biocompatibility; Biopolymers; Chitosan; Chitosan (PubChem CID: 21896651); Hyaluronic acid; Hyaluronic acid (PubChem CID: 453617); Hybrid hydrogel; Viscosupplementation