Bourke Sharon L, Al-Khalili Mohammad, Briggs Tonye, Michniak Bozena B, Kohn Joachim, Poole-Warren Laura A
New Jersey Center for Biomaterials, Department of Chemistry and Chemical Biology, Rutgers University, 610 Taylor Road, Piscataway, NJ, USA.
AAPS PharmSci. 2003 Dec 4;5(4):E33. doi: 10.1208/ps050433.
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.
本研究的目的是开发并评估一种用于伤口愈合应用中生长因子缓释的水凝胶载体。水凝胶通过丙烯酰胺功能化的不可降解聚乙烯醇(PVA)的紫外光交联制备而成。最初使用胰蛋白酶抑制剂(TI)(一种分子量为21000的模型蛋白药物)评估蛋白质渗透性。通过改变凝胶的固体含量和添加亲水性PVA填料来改变TI的渗透性。随着PVA含量从10%增加到20%,蛋白质通量降低,且没有TI透过20%的PVA水凝胶。通过将亲水性PVA填料掺入水凝胶中,实现了模型药物释放的进一步增加。随着填料分子量的增加,TI通量增加。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。释放的蛋白质百分比也会因蛋白质负载浓度的变化而改变。在含有亲水性填料的载体中使用生长因子进行的释放研究表明,血小板衍生生长因子(PDGF-β)持续释放长达3天,而对照组中释放时间不到24小时。与对照组相比,当暴露于负载生长因子的载体时,正常人皮肤成纤维细胞数量增加一倍,证明了体外生物活性。本研究中开发的释放载体采用快速简单的制备方法,并且可以通过改变固体含量、掺入生物相容性亲水性填料以及改变蛋白质负载浓度来调整蛋白质释放。