title: Preparation and in vitro evaluation of vaginal formulations including siRNA and paclitaxel-loaded SLNs for cervical cancer.
abstract: 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.
authors: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey. Electronic address: gbuyukko@anadolu.edu.tr.
authors: Gülay
authors: G
authors: Büyükköroğlu
authors: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
authors: Behiye
authors: B
authors: Şenel
authors: Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
authors: Ebru
authors: E
authors: Başaran
authors: Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
authors: Evrim
authors: E
authors: Yenilmez
authors: Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
authors: Yasemin
authors: Y
authors: Yazan
mesh_terms: D000282:Administration, Intravaginal; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003124:Colorimetry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D012997:Solvents; D013488:Suppositories / Q000737:chemistry; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C000595707:BCL2 protein, human; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D012997:Solvents; D013488:Suppositories; D017239:Paclitaxel
keywords: Bcl-2 siRNA; Cationic SLN; Dichloromethane (PubChem CID: 6344); N-[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammonium chloride (PubChem CID: 123922); Paclitaxel; Paclitaxel (PubChem CID: 36314); Sorbitane trioleate (PubChem SID: 24888385); Vaginal suppository