Poly (ɛ-Caprolactone) Nanoparticles with pH-Responsive Behavior Improved the In Vitro Antitumor Activity of Methotrexate.

A promising approach to achieve a more efficient antitumor therapy is the conjugation of the active molecule to a nanostructured delivery system. Therefore, the main objective of this research was to prepare nanoparticles (NPs), with the polymer poly (ε-caprolactone) (PCL), as a carrier for the antitumor drug methotrexate (MTX). A pH-responsive behavior was obtained through conjugation of the amino acid-based amphiphile, 77KL, to the NP matrix. The NPs showed mean hydrodynamic diameter and drug entrapment efficiency of 178.5 nm and 20.52%, respectively. Owing to its pH-sensitivity, the PCL-NPs showed membrane-lytic behavior upon reducing the pH value of surrounding media to 5.4, which is characteristic of the endosomal compartments. The in vitro antitumor assays demonstrated that MTX-loaded PCL-NPs have higher antiproliferative activity than free drug in MCF-7 cells and, to a lesser extent, in HepG2 cells. This same behavior was also achieved at mildly acidic conditions, characteristic of the tumor microenvironment. Altogether, the results evidenced the pH-responsive properties of the designed NPs, as well as the higher in vitro cytotoxicity compared to free MTX, representing thus a promising alternative for the antitumor therapy.