Ascorbic Palmitate as a Bifunctional Drug and Nanocarrier of Paclitaxel for Synergistic Anti-Tumor Therapy.

Abstract

The in vivo application of ascorbate is currently limited by the very high blood concentrations that are required to achieve therapeutic levels in tumors, which needs to exploit a novel drug platform to improve the pharmacokinetics of vitamin C (Vc) and its antitumoral effects. In this study, ascorbyl palmitate (AP), an amphiphilic molecule, is the palmitate acid ester derivative of ascorbic acid, which can be formed a "bifunctional" nanoparticle in which the AP acts not only as an antitumor drug but also as a nanocarrier for encapsulating hydrophobic antitumor drugs such as paclitaxel (PTX). We developed a bifunctional nanocarrier based on AP, which loaded with PTX for synergistic cancer chemotherapy. The resulting PTX-AP nanoparticles (PTX-APNPs) were spherical and had an average size of 294.2 nm based on dynamic light scattering. The in vitro anti-B16F10 cells test of PTX-APNPs revealed an obvious synergistic effect of AP and PTX, and the PTX-APNPs strongly induced cell apoptosis and production of reactive oxygen species. In addition, PTX-APNPs formulation also effectively suppressed the tumorigenicity of B16F10 cells in female C57BL/6 mice without causing severe toxicity. These results suggest that AP-based nanoparticles formulated with paclitaxel are useful for synergistic chemotherapy.