Iman Akbarzadeh1,2, Anita Saremi Poor3, Soheila Yaghmaei2, Dariush Norouzian1, Hassan Noorbazargan4, Samaneh Saffar5, Reza Ahangari Cohan1, Haleh Bakhshandeh1. 1. Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran. 2. Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran. 3. Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. 4. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5. Core Facility Center, Pasteur Institute of Iran, Tehran, Iran.
Abstract
OBJECTIVE: The objective of this study was to use nano-niosomal formulations to deliver simvastatin as a poor-water soluble drug into breast cancer cells. SIGNIFICANCE: Our study focused on the problem associated with poor water-soluble drugs which have significant biological activity in vivo. METHODS: Different niosomal formulations of simvastatin were prepared and characterized in terms of morphology, size, encapsulation efficiency (EE), and release kinetic. Antiproliferative activity and the mechanism were assessed by quantitative real-time PCR and flow cytometry. Moreover, confocal microscopy was employed to analyze the cell uptake of simvastatin loaded niosomes to the cancerous cells. RESULTS: Size, polydispersity index (PDI), and EE of the best formulation were obtained as 164.8 nm, 0.232, and 97%, respectively. The formulated simvastatin had a spherical shape and showed a slow release profile of the drug after 72 h. Stability data elucidated an increase in mean diameter and PDI which was lower for 4 °C than 25 °C. Confocal microscopy showed the localization of drug loaded niosomes in the cancer cells. The MTT assay revealed both free drug and drug loaded niosomes exhibited a dose-dependent cytotoxicity against breast cancer cells (MDA-MB-231 cells). Flow cytometry and qPCR analysis revealed drug loaded niosomes exert their cytotoxicity on cancerous cells via regulation of apoptotic and anti-apoptotic genes. CONCLUSION: The prepared niosomal simvastatin showed good physicochemical and biological properties than free drug. Our study suggests that niosomal delivery could be considered as a promising strategy for the delivery of poor water-soluble drugs to cancer cells.
OBJECTIVE: The objective of this study was to use nano-niosomal formulations to deliver simvastatin as a poor-water soluble drug into breast cancer cells. SIGNIFICANCE: Our study focused on the problem associated with poor water-soluble drugs which have significant biological activity in vivo. METHODS: Different niosomal formulations of simvastatin were prepared and characterized in terms of morphology, size, encapsulation efficiency (EE), and release kinetic. Antiproliferative activity and the mechanism were assessed by quantitative real-time PCR and flow cytometry. Moreover, confocal microscopy was employed to analyze the cell uptake of simvastatin loaded niosomes to the cancerous cells. RESULTS: Size, polydispersity index (PDI), and EE of the best formulation were obtained as 164.8 nm, 0.232, and 97%, respectively. The formulated simvastatin had a spherical shape and showed a slow release profile of the drug after 72 h. Stability data elucidated an increase in mean diameter and PDI which was lower for 4 °C than 25 °C. Confocal microscopy showed the localization of drug loaded niosomes in the cancer cells. The MTT assay revealed both free drug and drug loaded niosomes exhibited a dose-dependent cytotoxicity against breast cancer cells (MDA-MB-231 cells). Flow cytometry and qPCR analysis revealed drug loaded niosomes exert their cytotoxicity on cancerous cells via regulation of apoptotic and anti-apoptotic genes. CONCLUSION: The prepared niosomal simvastatin showed good physicochemical and biological properties than free drug. Our study suggests that niosomal delivery could be considered as a promising strategy for the delivery of poor water-soluble drugs to cancer cells.
Entities:
Keywords:
Breast cancer; drug delivery; niosome; simvastatin; solubility
Authors: Shaimaa M Badr-Eldin; Hibah M Aldawsari; Nabil A Alhakamy; Usama A Fahmy; Osama A A Ahmed; Thikryat Neamatallah; Singkome Tima; Raghad H Almaghrabi; Fayda M Alkudsi; Asmaa A Alamoudi; Amjad A Alzahrani; Sabna Kotta; Omar D Al-Hejaili Journal: Pharmaceutics Date: 2022-05-09 Impact factor: 6.525