Preparation and biological evaluation of novel 5-Fluorouracil and Carmofur loaded polyethylene glycol / rosin ester nanocarriers as potential anticancer agents and ceramidase inhibitors

Abstract

With advancing trends on the applications of nanotechnology to pharmacology, it has been drawn considerable attention towards the development of drug loaded nanocarriers with high performance in drug delivery systems. Herein, novel carmofur (CAR) and 5-fluorouracil (5FU) loaded PEG/rosin-pentaerythritol-ester (RPE) based nanocariers were developed as smart drug delivery systems in cancer therapy. Surface and chemical characterizations of the PEG/RPE-NPs were determined by different techniques such as STEM, DLS, UV–visible, and FTIR. The computer-aided STEM results were utilized for a data analytical characterization using an artificial intelligent approach. Results showed that the nanoformulations had a spherical shape and uniform distributions in the range of 108–204 nm. The cumulative releases (%) were calculated in a different medium (pH:1.2, pH:7.4). In-vitro experimental results showed that 5FU-NPs and CAR-NPs were highly cytotoxic on MCF-7 and MDA-MB-231 breast cancer cells, whereas they had no significant cytotoxicity on normal HUVEC cells. Furthermore, ASAH1, S1P, Bcl-2 expression levels were decreased with CAR-NPs and 5FU-NPs. The novelty of this study was to evaluate in vitro antitumor efficacy and cytotoxicity of the prepared 5FU-NPs and CAR-NPs on MCF-7 and MDA-MB-231 breast cancer cell lines. Consequently, the biological and pharmacological evaluations of nanocarriers showed that they were promising nanomaterials for drug delivery systems in clinical applications.