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作为生物活性泌尿外科生物材料设计的阳离子水凝胶交联对其物理化学和药物扩散特性影响的表征

Characterization of crosslinking effects on the physicochemical and drug diffusional properties of cationic hydrogels designed as bioactive urological biomaterials.

作者信息

Jones David S, Andrews Gavin P, Gorman Sean P

机构信息

Medical Devices Unit, School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.

出版信息

J Pharm Pharmacol. 2005 Oct;57(10):1251-59. doi: 10.1211/jpp.57.10.0003.

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.

摘要

本研究考察了交联剂(四甘醇二丙烯酸酯,TEGDA;二甘醇二甲基丙烯酸酯,DEGDMA;聚乙二醇二甲基丙烯酸酯,PEGDMA)的浓度和类型对已被选为生物活性医疗器械候选涂层的水凝胶的力学性能和药物扩散性能的影响。通过自由基聚合制备水凝胶(甲基丙烯酸二甲氨基乙酯 - 共 - 乙烯基吡咯烷酮;1:1),并使用拉伸分析、动态接触角分析以及在pH 6.0下的溶胀分析对其进行表征。使用pH 6.0的缓冲介质评估夫西地酸和氯己定的释放情况,此外,还使用了在存在和不存在高浓度钙(代表尿路结石)的情况下缓冲至pH 9的溶出介质进行评估。交联剂浓度而非类型影响前进接触角和后退接触角。相反,交联剂类型和浓度均影响水凝胶的力学性能和溶胀性能。最大溶胀率和断裂伸长率与PEGDMA交联的水凝胶相关,而TEGDA交联的水凝胶表现出最大的极限拉伸强度和杨氏模量。所有体系中的药物释放均通过扩散发生。氯己定和夫西地酸的释放量取决于交联剂类型和浓度,在每个采样期,PEGDMA交联的水凝胶释放的药物量最大。由于形成了难溶性钙盐,在钙增强介质中pH 9.0时释放的夫西地酸量低于在相同无高钙介质中释放的量。总之,本研究独特地考察了交联剂类型和浓度对生物活性水凝胶在医疗器械应用中的临床和非临床性能所必需的物理化学和药物释放性能的影响。

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