Potential use of nanoformulated ascorbyl palmitate as a promising anticancer agent: First comparative assessment between nano and free forms

The aim of the present study is to evaluate, for the first time, the anticancer activity of a stable nanoformulation of ascorbyl palmitate (APnp) and investigate its therapeutic action as well as its mechanism against Ehrlich ascites carcinoma (EAC)-bearing mice in comparison with native AP. AP was loaded into pluronic nanoparticles, fully characterized and then studied as an anticancer agent using EAC model. The APnp were spherical and attained a small size of 220 ± 9 nm and a zetapotential of −41.16 ± 2 mV. The release profile of the AP from the nanoparticles was around 72% within the first 2 h and the rest of the drug amount was released sustainably within 9 days. The results of the present study demonstrated that APnp treatment destroyed tumors with inhibition of proliferation by inhibiting signal transducer and activator of transcription 3 (STAT3) pathway leading to induction of apoptosis and cell cycle arrest at G2/M phase as well as preventing metastasis and invasion. Moreover, APnp significantly elevated antioxidant levels [superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH)], and significantly decreased the levels of oxidative stress biomarkers [malondialdehyde (MDA) and nitric oxide (NO)]. Besides, mitochondrial and nuclear degeneration in cancer cells was demonstrated by an electron microscope to be more severe in the case of using our newly-developed APnp. The present study revealed the superiority of APnp as a potent anticancer agent over free AP via increasing its bioavailability and specificity towards cancer cells.