PREPARATION AND IN VITRO CHARACTERIZATION OF e-VINIFERINE AND VINCRISTINE SULFATE LOADED PLGA-b-PEG NANOPARTICLES

Yüksel ÖĞÜNÇ1, Müzeyyen DEMİREL2, Arzu YAKAR3, Zerrin İNCESU1

1 Anadolu University, Faculty of Pharmacy, Department of Biochemistry

2 Anadolu University, Faculty of Pharmacy , Department of Pharmaceutical Technology

3 Afyon Kocatepe University, Faculty of Engineering, Department of Chemical Enginering

Cancer research is moving towards developing the right strategies for inhibition of tumor formation, diagnosis and treatment. Nowadays, the studies of drug-loaded nanoparticles to a targeted area are increasing as well as often used conventional anticancer drug. During the cancer treatment, the drug should remain in the bloodstream until it reaches the target tissue and with the controlled release in the target tissues is to kill cancer cells without affecting normal cells. Thereby, providing effective treatment with minimal side effects.

For many years, vincristine sulfate used to treat cancer is isolated from the plant named “Vinca Rosea”. In case, e-viniferine isolated from “Vitis Vinifera” is a resveratrol derivative. Previous studies have been shown that the e-viniferine with combined use of vincristine sulfate had a synergic effect on HepG2 cells. The purpose of this study, the formulation of PLGA-b-PEG nanoparticles loaded with combination of e-viniferine and vincristine sulfate in order to reduce side effects of the high dose. It is predicted that using a lower dose of this formulation on HepG2 cells could be more effective as compared to free forms of the drugs.

PLGA-b-PEG nanoparticles formulation was prepared by the nanoprecipitation method as a aqueous suspension. Prepared nanoparticles formulation has shown a homogeneous distribution with 123.13 ± 9.35 nm particle size (PS) and 0.294 ± 0.069 polydispersity index (PDI). Zeta potential (ZP) of the formulation was determined as -28.83 ± 1.49 mV (mean ± SE). Atomic force microscope (AFM) was performed for morphological examination. The result showed that the nanoparticles were spherical in shape and had a smooth surface property. According to HPLC analysis, the formulation of e-viniferine and vincristine sulfate concentrations were 104.1 ± 11.7 µg.mL-1 and 30.2 ± 0.7 µg.mL-1; loading rate were approximately 4.4 ± 0.4 % and 1.5 ± 0.1 % respectively (mean ± SE) (n=3). PS, PDI and ZP values didn't change at all in the reconstitution of the lyophilized formulation. In addition, cellular uptake studies showed that coumarine 6 labeled formulation was uptake in HepG2 cells within 2 hours about 20 %.

As a result, combine e-viniferin and vincristine sulfate were loaded successfully to PLGA-b-PEG nanoparticles by nanoprecipitation method. Investigation of anticancer effect of this formulation on HepG2 cells and normal hepatocyte cells is considered in a future study.

This study was financed by Anadolu University Scientific Research Project Foundation (No:1406S313).