Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
J Am Chem Soc. 2012 May 9;134(18):7978-82. doi: 10.1021/ja301710z. Epub 2012 Apr 30.
Asymmetric bifunctional silyl ether (ABS) prodrugs of chemotherapeutics were synthesized and incorporated within 200 nm × 200 nm particles. ABS prodrugs of gemcitabine were selected as model compounds because of the difficulty to encapsulate a water-soluble drug within a hydrogel. The resulting drug delivery systems were degraded under acidic conditions and were found to release only the parent or active drug. Furthermore, changing the steric bulk of the alkyl substituents on the silicon atom could regulate the rate of drug release and, therefore, the intracellular toxicity of the gemcitabine-loaded particles. This yielded a family of novel nanoparticles that could be tuned to release drug over the course of hours, days, or months.
合成了具有不对称双功能硅醚（ABS）的化疗药物前药，并将其包裹在 200nm×200nm 的颗粒内。选择吉西他滨的 ABS 前药作为模型化合物，是因为将水溶性药物包裹在水凝胶内具有一定的难度。所得药物递送系统在酸性条件下降解，且仅释放母体药物或活性药物。此外，改变硅原子上烷基取代基的空间位阻可以调节药物释放速率，从而调节载有吉西他滨的颗粒的细胞内毒性。这得到了一系列新型纳米颗粒，其可以在数小时、数天或数月的时间内释放药物。
