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.

Novel semi-interpenetrating hydrogel networks with enhanced mechanical properties and thermoresponsive engineered drug delivery, designed as bioactive endotracheal tube biomaterials

“…Poly(HEMA) was prepared by free radical polymerisation, as previously described by the authors [1,27,28]. Briefly, the required masses of monomer, initiator (AIBN 1% w/w), metronidazole (1% w/w, as a model drug) and crosslinker (EGDMA, 1% w/w) were mixed by stirring, then injected between two glass plates separated by silicone tubing spacer and release liner and heated at 90°C for one hour.…”

“…The resultant properties of the hydrogels are dependent on several key parameters including the hydrophilicity of the polymer chains and the degree of cross-linking [1]. Hydrogels may be produced from a wide range of materials (both natural and synthetic) and may be synthesised to offer a wide range of properties that are relevant to drug delivery and medical device design [2].…”

“…For example, hydrogel-coated catheters have been loaded with antimicrobial agents, their subsequent release being associated with reduced medical device related infection [1,8].…”

“…Drug release from hydrogels is dependent on the physicochemical properties of the drug and the hydrogel and, in addition, the degree of cross-linking [1]. However, in many cases, the release kinetics are inappropriate for the desired application.…”

“…delamination, fracture upon the application of normal stresses, may occur. The mechanical properties of hydrogels may be improved by copolymerisation [19], improving crosslink density [1,24] and using composites, however, whilst incremental improvements have been reported, these strategies are associated with associated disadvantages including modification of the equilibrium water content and adverse modification of drug release profiles. P(NIPAA) hydrogels have been previously reported to possess poor mechanical properties, which have in turn limited their thermoresponsive properties and their potential clinical applications [19,25].…”