A photo-crosslinked poly(vinyl alcohol) hydrogel growth factor release vehicle for wound healing applications.

AAPS PharmSci Pub Date : 2003-12-04 DOI:10.1208/ps050433
Sharon L Bourke, Mohammad Al-Khalili, Tonye Briggs, Bozena B Michniak, Joachim Kohn, Laura A Poole-Warren
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Abstract

The objective of this study was to develop and evaluate a hydrogel vehicle for sustained release of growth factors for wound healing applications. Hydrogels were fabricated using ultraviolet photo-crosslinking of acrylamide-functionalized nondegradable poly(vinyl alcohol) (PVA). Protein permeability was initially assessed using trypsin inhibitor (TI), a 21 000 MW model protein drug. TI permeability was altered by changing the solids content of the gel and by adding hydrophilic PVA fillers. As the PVA content increased from 10% to 20%, protein flux decreased, with no TI permeating through 20% PVA hydrogels. Further increase in model drug release was achieved by incorporating hydrophilic PVA fillers into the hydrogel. As filler molecular weight increased, TI flux increased. The mechanism for this is most likely an alteration in protein/gel interactions and transient variations in water content. The percent protein released was also altered by varying protein loading concentration. Release studies conducted using growth factor in vehicles with hydrophilic filler showed sustained release of platelet-derived growth factor (PDGF-beta,beta) for up to 3 days compared with less than 24 hours in the controls. In vitro bioactivity was demonstrated by doubling of normal human dermal fibroblast numbers when exposed to growth factor-loaded vehicle compared to control. The release vehicle developed in this study uses a rapid and simple fabrication method, and protein release can be tailored by modifying solid content, incorporating biocompatible hydrophilic fillers, and varying protein loading concentration.

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用于伤口愈合的光交联聚乙烯醇水凝胶生长因子释放载体。
本研究旨在开发和评估一种用于伤口愈合的生长因子持续释放的水凝胶载体。水凝胶是通过紫外线光交联丙烯酰胺功能化的不可降解聚乙烯醇(PVA)制成的。蛋白质渗透性最初使用胰蛋白酶抑制剂(TI)(一种 21 000 MW 的蛋白质模型药物)进行评估。通过改变凝胶的固体含量和添加亲水性 PVA 填充物来改变 TI 的渗透性。随着 PVA 含量从 10% 增加到 20%,蛋白质通量下降,20% 的 PVA 水凝胶中没有 TI 渗透。通过在水凝胶中加入亲水性 PVA 填充剂,进一步增加了模型药物释放量。随着填料分子量的增加,TI 通量也随之增加。其机制很可能是蛋白质/凝胶相互作用的改变和含水量的瞬时变化。蛋白质释放的百分比也会随着蛋白质负载浓度的变化而改变。使用亲水性填充物载体中的生长因子进行的释放研究表明,血小板衍生生长因子(PDGF-beta,beta)的持续释放时间长达 3 天,而对照组的释放时间不到 24 小时。体外生物活性的证明是,与对照组相比,正常人真皮成纤维细胞暴露于含有生长因子的载体时,其数量增加了一倍。本研究中开发的释放载体采用了快速、简单的制造方法,可通过改变固体含量、加入生物相容性亲水填料和改变蛋白质负载浓度来定制蛋白质释放。
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