title: Characterization of crosslinking effects on the physicochemical and drug diffusional properties of cationic hydrogels designed as bioactive urological biomaterials.
abstract: This study examined the effects of concentration and type of crosslinker (tetraethyleneglycol diacrylate, TEGDA; diethyleneglycol dimethacrylate, DEGDMA; and polyethyleneglycol dimethacrylate, PEGDMA) on the mechanical and drug diffusional properties of hydrogels that had been selected as candidate coatings for bioactive medical devices. Hydrogels (dimethylaminoethylmethacrylate-co-vinylpyrrolidone; 1:1) were prepared by free radical polymerization and characterized using tensile analysis, dynamic contact angle analysis and analysis of swelling at pH 6.0. The release of fusidic acid and chlorhexidine was evaluated using buffered medium at pH 6.0 and, in addition, using dissolution medium that had been buffered to pH 9 in the presence and absence of elevated concentrations of calcium, representative of urinary encrustation. Crosslinker concentration, but not type, affected the advancing and receding contact angles. Conversely, both crosslinker type and concentration affected the mechanical and swelling properties of the hydrogels. Maximum swelling and elongation at break were associated with the PEGDMA-crosslinked hydrogels whereas TEGDA-crosslinked hydrogels exhibited the maximum ultimate tensile strength and Young's modulus. Drug release from all systems occurred by diffusion. The mass of chlorhexidine and fusidic acid released was dependent on crosslinker type and concentration, with hydrogels crosslinked with PEGDMA offering the greatest mass of drug released at each sampling period. The mass of fusidic acid but not chlorhexidine released at pH 9.0 in a calcium augmented medium was lower than that released in the same medium devoid of elevated calcium, due to the formation of the poorly soluble calcium salt. In conclusion, this study has uniquely examined the effects of crosslinker type and concentration on physicochemical and drug release properties essential to the clinical and non-clinical performance of bioactive hydrogels for medical device application.
authors.affiliation: Medical Devices Unit, School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. d.jones@qub.ac.uk
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Andrews
authors.forename: Sean P
authors.initials: SP
authors.lastname: Gorman
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002710:Chlorhexidine / Q000493:pharmacokinetics / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004864:Equipment and Supplies; D005260:Female; D005672:Fusidic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D009570:Nitriles / Q000737:chemistry; D019904:Polymethyl Methacrylate / Q000737:chemistry; D013997:Time Factors; D014546:Urinary Catheterization / Q000295:instrumentation
chemical_list: D000890:Anti-Infective Agents; D020099:Coated Materials, Biocompatible; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D009570:Nitriles; D005672:Fusidic Acid; D019904:Polymethyl Methacrylate; C004526:azobis(isobutyronitrile); D002710:Chlorhexidine