Büyükköroğlu Gülay, Şenel Behiye, Yenilmez Evrim
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey.
Methods Mol Biol. 2019;1974:303-328. doi: 10.1007/978-1-4939-9220-1_22.
The objective of this study is to prepare vaginal suppository containing chemotherapeutic agent and genetic material that can be applied locally for cervical cancer. Cervical cancer is one of the most life-threatening types of cancer among women and is generally resistant to chemotherapy. Paclitaxel has been selected as chemotherapeutic agent, and siRNA that inhibits the Bcl-2 oncogene has been selected as the genetic material for simultaneous vaginal delivery. For this purpose, three different solid lipid nanoparticles (SLNs) were prepared that include Bcl-2 siRNA and paclitaxel and paclitaxel/Bcl-2 siRNA combination separately, and these SLN formulations were dispersed in vaginal suppositories prepared with PEG 6000. First, the physicochemical properties of SLNs, their cytotoxicities on HeLa cell lines, and the transfection ability of siRNA-incorporated SLN on the cells have been examined. Afterward, the release of SLNs from the three different vaginal suppositories prepared has been determined via horizontal diffusion chamber system. The loaded amount to the SLNs and release amount from suppositories of paclitaxel have been determined via HPLC, whereas stability, loading, and release amount of siRNA has been determined via gel retardation system and UV spectrophotometer.
本研究的目的是制备含有化疗药物和遗传物质的阴道栓剂，用于宫颈癌的局部治疗。宫颈癌是女性中最具生命威胁的癌症类型之一，通常对化疗耐药。已选择紫杉醇作为化疗药物，并选择抑制Bcl-2癌基因的小干扰RNA（siRNA）作为同时经阴道递送的遗传物质。为此，制备了三种不同的固体脂质纳米粒（SLN），分别包含Bcl-2 siRNA和紫杉醇以及紫杉醇/Bcl-2 siRNA组合，并且将这些SLN制剂分散在由聚乙二醇6000制备的阴道栓剂中。首先，研究了SLN的物理化学性质、它们对HeLa细胞系的细胞毒性以及掺入siRNA的SLN对细胞的转染能力。随后，通过水平扩散室系统测定了所制备的三种不同阴道栓剂中SLN的释放情况。通过高效液相色谱法测定了紫杉醇在SLN中的负载量以及从栓剂中的释放量，而通过凝胶阻滞系统和紫外分光光度计测定了siRNA的稳定性、负载量和释放量。
