Enhanced in vitro cytotoxicity and anti-tumor activity of vorinostat-loaded pluronic micelles with prolonged release and reduced hepatic and renal toxicities
| Autor: | Ghada M. Suddek, Rehab Mohammad Yusif, Farid A. Badria, Irhan Ibrahim Abu Hashim, Ahmed A. Shaaban, Elham Abdelmonem Mohamed |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.drug_class Pharmaceutical Science Antineoplastic Agents Poloxamer 02 engineering and technology Pharmacology Hydroxamic Acids Kidney Micelle Ehrlich ascites carcinoma Mice 03 medical and health sciences Pharmacokinetics In vivo medicine Animals Humans Carcinoma Ehrlich Tumor Cytotoxicity Vorinostat Micelles Drug Carriers Cytotoxins Chemistry Histone deacetylase inhibitor Hep G2 Cells 021001 nanoscience & nanotechnology 030104 developmental biology Liver Delayed-Action Preparations MCF-7 Cells Female Caco-2 Cells 0210 nano-technology medicine.drug |
| Zdroj: | European Journal of Pharmaceutical Sciences. 96:232-242 |
| ISSN: | 0928-0987 |
| DOI: | 10.1016/j.ejps.2016.09.029 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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