Preparation and in vitro evaluation of vaginal formulations including siRNA and paclitaxel-loaded SLNs for cervical cancer


BÜYÜKKÖROĞLU G., ŞENEL B., BAŞARAN E., Yenilmez E., Yazan Y.

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, cilt.109, ss.174-183, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 109
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1016/j.ejpb.2016.10.017
  • Dergi Adı: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.174-183
  • Anahtar Kelimeler: Bcl-2 siRNA, Paclitaxel, Cationic SLN, Vaginal suppository, SOLID LIPID NANOPARTICLES, DRUG-DELIVERY, RNA INTERFERENCE, DNA DELIVERY, CATIONIC LIPIDS, GENE DELIVERY, CO-DELIVERY, POLYMERS, THERAPY, SYSTEMS
  • Anadolu Üniversitesi Adresli: Evet

Özet

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/Bc1-2 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 180 nm with a positive zeta potential value between +22.20 and +48.16 mV 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 12 h and 36 h. SLNs incorporating Bc1-2 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.