title: Novel thermosensitive chitosan hydrogels: in vivo evaluation.
abstract: Chitosan is an attractive biopolymer for the preparation of hydrogels. Its unique combination of biocompatibility, biodegradability, bioadhesivity, and tissue-promoting abilities allows pharmaceutical applications. We investigated novel thermosensitive hydrogels based on chitosan homogeneously reacetylated to a deacetylation degree of about 50%, combined with selected polyols or polyoses such as trehalose, a nontoxic polysaccharide. The latter, a gel-inducing and lyoprotective agent enabled the formulation to be lyophilized and rehydrated without affecting the thermosensitive behavior. This made possible long-term storage and promoted its use in a clinical setup. The thermally induced sol-gel transition allowed injectability and in situ setting. Rheological characterization revealed that storage moduli could be increased by one decade by increasing the chitosan concentration from 1.4 to 2.2% (w/w). Evaluation in vivo provided evidence of in situ implant formation in subcutaneous tissue of Sprague-Dawley rats and permanence for up to 3 months. Histopathological analysis demonstrated a mild, chronic, inflammatory reaction that disappeared with the complete absorption of the gel implant over a few months period. Such in situ forming hydrogels could be advantageous for specific applications in drug delivery and tissue engineering.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Emilie
authors.initials: E
authors.lastname: Patois
authors.forename: Suzanne
authors.initials: S
authors.lastname: Osorio-da Cruz
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Tille
authors.forename: Beat
authors.initials: B
authors.lastname: Walpoth
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
authors.forename: Olivier
authors.initials: O
authors.lastname: Jordan
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D055119:Elastic Modulus; D005612:Freeze Drying; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000276:immunology / Q000648:ultrastructure; D013696:Temperature; D014199:Trehalose
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D048271:Chitosan; D014199:Trehalose