Kim Jin-Ki, Anderson Joel, Jun Ho-Wook, Repka Michael A, Jo Seongbong
Department of Pharmaceutics, The University of Mississippi, MS 38677, USA.
Mol Pharm. 2009 May-Jun;6(3):978-85. doi: 10.1021/mp900009n.
The aim of this study is to develop a bioresponsive cisplatin (CDDP) delivery system with a self-assembling peptide amphiphile (PA) comprising a cell-adhesive matrix metalloproteinase-2 (MMP-2)-sensitive GTAGLIGQRGDS and a fatty acid. A biomimetic CDDP-PA gel was spontaneously formed upon incubating a mixture of CDDP and the PA for 5 h at 37 degrees C. CDDP-PA gel formation was confirmed by rheological analysis. The structure of self-assembled CDDP-PA nanofibers inside the gel was determined by transmission electron microscopy (TEM). Bioresponsive drug release from the biomimetic gel was demonstrated by in vitro MMP-2-triggered CDDP release. The MMP-2-sensitive CDDP release was dependent on the enzyme concentration in the medium. Enzymatic degradation of the CDDP-PA gel was confirmed by TEM images of the gel degraded in an MMP-2 containing medium. The MMP-2-triggered CDDP release as well as the presentation of RGDS in the gel would potentially provide a spatially and temporally controlled delivery system for targeted anticancer drug delivery.
本研究的目的是开发一种生物响应性顺铂（CDDP）递送系统，该系统具有一种自组装肽两亲物（PA），其包含细胞粘附性基质金属蛋白酶-2（MMP-2）敏感的GTAGLIGQRGDS和一种脂肪酸。将CDDP与PA的混合物在37℃孵育5小时后，自发形成了一种仿生CDDP-PA凝胶。通过流变学分析证实了CDDP-PA凝胶的形成。通过透射电子显微镜（TEM）确定了凝胶内部自组装CDDP-PA纳米纤维的结构。通过体外MMP-2触发的CDDP释放证明了仿生凝胶的生物响应性药物释放。MMP-2敏感的CDDP释放取决于培养基中的酶浓度。通过在含有MMP-2的培养基中降解的凝胶的TEM图像证实了CDDP-PA凝胶的酶促降解。MMP-2触发的CDDP释放以及凝胶中RGDS的呈现可能会为靶向抗癌药物递送提供一种空间和时间上可控的递送系统。
