Vaginal Suppositories with siRNA and Paclitaxel-Incorporated Solid Lipid Nanoparticles for Cervical Cancer: Preparation and In Vitro Evaluation

Methods Mol Biol. 2019:1974:303-328. doi: 10.1007/978-1-4939-9220-1_22.

Abstract

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.

Keywords: Bcl-2 siRNA; Cationic SLN; Paclitaxel; Vaginal suppository.

MeSH terms

  • Drug Delivery Systems / methods*
  • Female
  • HeLa Cells
  • Humans
  • Lipids / chemistry
  • Lipids / pharmacology
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / pharmacology
  • Suppositories / chemistry
  • Suppositories / therapeutic use
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*

Substances

  • BCL2 protein, human
  • Lipids
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Suppositories
  • Paclitaxel