PH-dependent, extended release and enhanced in vitro efficiency against colon cancer of Tegafur formulated using chitosan-coated poly(ε-caprolactone) nanoparticles

Abstract

Tegafur is used to treat various malignant lesions, including advanced gastric and colorectal cancers. However, its efficacy is limited by its low oral bioavailability, short half-life and serious toxicity. To address these drawbacks, a nanoformulation of poly(ε-caprolactone) nanoparticles coated with chitosan was developed for the delivery of Tegafur. Poly(ε-caprolactone) particles were prepared by an interfacial polymer disposition method, while surface functionalization with chitosan followed a coacervation procedure. Transmission electron microscopy and elemental analyses, and electrokinetics of the particles demonstrated that such core/shell nanostructure was obtained. Compared to unmodified particles, chitosan-coated nanoparticles demonstrated a substantially increased stability at both 4 and 25 °C over 30 days. Particles showed an encapsulation efficiency of ≈64% and a pH-dependent behavior in which complete Tegafur release was extended over 168, 48 or 24 h at pH 7.4 (blood), 6.5 (extracellular microenvironment of tumors) or 5.5 (endosomes/lysosomes of tumor cells), respectively. Based on hemocompatibility and cell viability tests, chitosan-coated nanoparticles exhibited satisfactory biocompatibility and safety for drug delivery. Furthermore, Tegafur-loaded chitosan-decorated particles demonstrated enhanced anticancer efficiency, with half maximal inhibitory concentration values in HT-29 and T-84 cells of ≈ 4-fold and ≈3.5-fold less than that of the free drug and drug-loaded unmodified nanoparticles, respectively. In vivo studies are needed to fully assess their efficacy and safety.