Büyükköroğlu Gülay, Şenel Behiye, Başaran Ebru, Yenilmez Evrim, Yazan Yasemin
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
Eur J Pharm Biopharm. 2016 Dec;109:174-183. doi: 10.1016/j.ejpb.2016.10.017. Epub 2016 Oct 25.
Cervical cancer is one of the most life threatening types of cancer among women and is generally resistant to chemotherapy. The objective of this study was to prepare a vaginal suppository containing a chemotherapeutic agent and a genetic material that can be applied locally for cervical cancer. Paclitaxel was selected as the chemotherapeutic agent and siRNA which inhibits BCL-2 oncogene was selected as the genetic material. Bcl-2 siRNA, paclitaxel and paclitaxel/Bcl-2 siRNA combination were incorporated into solid lipid nanoparticles (SLNs) and were dispersed separately in vaginal suppositories prepared with PEG 6000. Physicochemical properties of SLNs, their cytotoxicities on HeLa cell lines and also the effect of SLNs on the total protein amount of the cells were examined followed by the investigation of release rates of the active materials from the SLNs prepared. Average diameters of all SLNs prepared were below 180nm with a positive zeta potential value between +22.20 and +48.16mV at the pH range of 4.2 and 7.4. The release of Bcl-2 siRNA from SLNs incorporated Bcl-2 siRNA and the release of paclitaxel (PTX) from PTX incorporated SLNs were completed within 12h and 36h. SLNs incorporating Bcl-2 siRNA and paclitaxel/Bcl-2 siRNA were found to be more toxic when compared to paclitaxel incorporated SLN and placebo SLN. The disintegration of the vaginal suppositories as well as the release of the SLNs was completed within 2 h. This study indicates that vaginal suppository containing SLNs can bring the advantages of the simultaneous delivery of paclitaxel and siRNA via vaginal route with no help from professionals.
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。本研究的目的是制备一种含有化疗药物和遗传物质的阴道栓剂，可局部应用于宫颈癌治疗。选择紫杉醇作为化疗药物，选择抑制BCL-2癌基因的小干扰RNA（siRNA）作为遗传物质。将Bcl-2 siRNA、紫杉醇以及紫杉醇/Bcl-2 siRNA组合物包封于固体脂质纳米粒（SLNs）中，并分别分散于用聚乙二醇6000制备的阴道栓剂中。检测了SLNs的理化性质、其对HeLa细胞系的细胞毒性以及SLNs对细胞总蛋白量的影响，随后研究了所制备的SLNs中活性物质的释放速率。所制备的所有SLNs的平均直径均低于180nm，在pH值为4.2至7.4的范围内，zeta电位正值在+22.20至+48.16mV之间。包封有Bcl-2 siRNA的SLNs中Bcl-2 siRNA的释放以及包封有紫杉醇（PTX）的SLNs中紫杉醇的释放分别在12小时和36小时内完成。与包封有紫杉醇的SLN和空白SLN相比，包封有Bcl-2 siRNA和紫杉醇/Bcl-2 siRNA的SLNs毒性更强。阴道栓剂的崩解以及SLNs的释放均在2小时内完成。本研究表明，含有SLNs的阴道栓剂可在无需专业人员协助的情况下，通过阴道途径同时递送紫杉醇和siRNA，带来诸多优势。
