Improving breast cancer therapy using doxorubicin loaded solid lipid nanoparticles: Synthesis of a novel arginine-glycine-aspartic tripeptide conjugated, pH sensitive lipid and evaluation of the nanomedicine in vitro and in vivo

Abstract

Breast cancer is the leading cause of cancer mortality in women worldwide. To overcome the toxic side effects and multidrug resistance (MDR) during doxorubicin (DOX) chemotherapy, an arginine-glycine-aspartic (RGD) tripeptide modified, pH-sensitive solid lipid nanoparticles (SLNs) is employed in this study. In this study, a RGD conjugated, pH sensitive lipid was synthesized using glycerin monostearate (GMS) and adipic acid dihydrazide (HZ) as lipid materials and named RGD-HZ-GMS. RGD-HZ-GMS was applied to encapsulate DOX to construct a RGD modified, DOX loaded SLNs (RGD-DOX-SLNs). To evaluate the anticancer effect of RGD-DOX-SLNs, breast cancer cell line (MCF-7 cells) and DOX resistant cell line (MCF-7/ADR cells) were used. in vivo tumor suspension and toxicity effects were evaluated on mice bearing MCF-7/ADR cells breast cancer model. RGD-DOX-SLNs had a uniformly spherical shape. The mean particle size and zeta potential of the RGD-DOX-SLNs was 96.3 nm and 35.6 mV, respectively. RGD-DOX-SLNs showed 5.58 fold higher area under the plasma concentration - time curve (AUC) compared with DOX solution. Terminal half life (T_1/2) and peak concentration (C_max) of RGD-DOX-SLNs was 10.85 h and 39.12 ± 2.71 L/kg/h. in vitro and in vivo antitumor results indicate that RGD-DOX-SLNs might be a promising novel lipid carrier which could improve breast cancer therapy.

Keywords: Arginine-glycine-aspartic tripeptide; Breast cancer; Doxorubicin; Solid lipid nanoparticles; pH sensitive.