Enhanced in vitro cytotoxicity and anti-tumor activity of vorinostat-loaded pluronic micelles with prolonged release and reduced hepatic and renal toxicities.

Autor: Mohamed EA; Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: elhamelsaid@yahoo.com., Abu Hashim II; Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., Yusif RM; Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41411, Saudi Arabia., Suddek GM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., Shaaban AAA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., Badria FAE; Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2017 Jan 01; Vol. 96, pp. 232-242. Date of Electronic Publication: 2016 Sep 22.
DOI: 10.1016/j.ejps.2016.09.029
Abstrakt: Vorinostat is the first histone deacetylase inhibitor approved by US FDA for use in cancer therapy. However, its limited aqueous solubility, low permeability, and suboptimal pharmacokinetics hinder its delivery. Thus, in this study, micelles of vorinostat with each of pluronic F68 (PF68) and pluronic F127 (PF127) were developed and optimized based on drug loading and entrapment. The optimized micelles were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), zeta analyzer, and electron transmission microscopy. Their in vitro release, stability, in vitro cytotoxicity against HepG2, Caco-2, and MCF-7 cell lines, and finally, in vivo antitumor activity in mice bearing Ehrlich Ascites Carcinoma (EAC) were assessed. The highest entrapment efficiency was 99.09±2.16% and 94.19±2.37% for micelles of 1:50 drug to polymer ratio with each of PF127 and PF68, respectively. These micelles were nearly spherical with nanoscopic mean diameters of 72.61±10.66nm for PF68 and 91.88±10.70nm for PF127 with narrow size distribution. The micelles provided prolonged release at phosphate buffer saline pH7.4 up to 24h for PF68 and 72h for PF127. Potentiation of in vitro cytotoxicity of vorinostat was more pronounced with PF127 micelles particularly against MCF-7 cells. Compared with free vorinostat, the micelles with PF127 were more effective in inhibiting tumor growth as well as exhibiting significantly (p<0.05) diminished hepatic and renal toxicities. In conclusion, 1:50 vorinostat-PF127 micelles may facilitate i.v. formulations and can be suggested as a promising stable and safe nanoparticulate delivery system with prolonged release and potentiated cytotoxicity.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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