Formulation and development of smart pH responsive mesoporous silica nanoparticles for breast cancer targeted delivery of anastrozole: In vitro and in vivo characterizations

Abstract

Abstract In the present study, pH responsive, breast cancer targeted mesoporous silica nanoparticles (MSNs) have been developed as a carrier with a view to overcome problems such as non-selectivity, low cellular uptake and side effects associated with traditional chemotherapeutic drugs and improve their therapeutic efficacy. MCM-41 type of MSNs was synthesized using modified Stober's process and further modified by first reacting with (3-aminopropyl)triethoxysilane (APTES) and then succinic anhydride (SA) in order to obtain carboxylic acid functionalized MSN-COOH. Anastrozole was loaded into the MSNs and then capped with chitosan-folate conjugate. The MSNs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, small angle x-ray scattering (SAXS), nitrogen adsorption/desorption analysis, differential scanning calorimetry (DSC), HPLC and UV-visible spectroscopy. In vitro release studies confirmed triggered drug release from these nanoparticles under acidic (pH 5.5) environment. Hemolysis study proved that the formulation was safe for intravenous administration. The formulation exhibited 1.5 folds higher cytotoxicity as compared to free drug indicating its improved therapeutic potency. The in-vivo anticancer activity of formulations was studied against Ehrlich Ascites Carcinoma (EAC) induced breast cancer in Balb C mice in which these nanoparticles showed superior anticancer activity. Excellent tumor suppressing activity was demonstrated by these nanoparticles against EAC induced breast cancer model.