Perillyl alcohol in Solid Lipid Nanoparticles (SLN-PA): Cytotoxicity and antitumor potential in sarcoma 180 mice model

Abstract

Cancer is a group of diseases characterized by the uncontrolled growth of cells. These cells invade organs and tissues by extension or direct dissemination and can spread to other regions of the body. Nanomedicine offers many possibilities to prevent the spread of cancer tissue and help cure the disease. In this work, solid lipid nanoparticles (SLN) were used to encapsulate perillyl alcohol (PA), a volatile monoterpene with proven anticancer activity. Encapsulation of PA into SLN (SLN-PA) is expected to promote controlled release, increase PA bioavailability, and impair the volatility of the monoterpene. SLN-PA prepared by high-shear homogenization showed average particle diameter around 254 nm, polydispersity index ~ 0.35, zeta potential ~ -14.7 mV, and encapsulation efficiency 84.6%. Scanning electron microscope analysis revealed a decrease in crystallinity, suggesting the encapsulation of PA in the SLN, confirming the spherical shape and the loading of the monoterpene in the SLN. In vitro cytotoxicity assays against murine fibroblasts (L929) showed that SLN-PA in both treated doses did not induce any cytotoxicity on non-tumoral cells. In vivo antitumor effect of the SLN-PA was evaluated in sarcoma 180-transplanted mice. The in vivo results demonstrated a significant tumor inhibition rate of 51.76 and 54.49% via intraperitoneal application of SLN-PA at doses of 100 and 200 mg/kg/day (p < 0.05), respective when compared to the negative control (dimethyl sulfoxide). Adverse side effects of SLN-PA were not noticed in the liver, the kidney, or spleen tissue. The developed SLN-PA can be considered as a safe approach for site-specific antitumor effect in vivo, reinterpreting new nanoparticles- based cancer therapy.