Folic acid-decorated and PEGylated PLGA nanoparticles for improving the antitumour activity of 5-fluorouracil.

5-Fluorouracil (5-FU) is a broad spectrum cytotoxic agent being used in chemotherapy of malignancies. However, 5-FU shows a number of limitations like short half-life, non-selective biodistribution, and the development of drug resistances by tumour cells. It was investigated the potential use of folic acid-decorated and PEGylated poly(D,L-lactide-co-glycolide) nanoparticles (FOL-PEG-PLGA NPs) for the targeted delivery of 5-FU to colon and breast cancers. PEG-PLGA and FOL-PEG-PLGA conjugates were synthesized and characterized. NPs of PLGA, PEG-PLGA, and FOL-PEG-PLGA were prepared by nanoprecipitation under optimal formulation conditions. They were found to be haemocompatible, and exhibited negligible cytotoxicity in normal (CCD-18 and MCF-10A) and tumour (HT-29 and MCF-7) human cell lines. 5-FU loading capabilities were also defined, and the NPs exhibited an initial burst drug release followed by a sustained 5-FU release. In vitro cytotoxicity studies in folate-overexpressed HT-29 colon cancer cells and MCF-7 breast cancer cells demonstrated that the half maximal inhibitory concentration (IC50) of 5-FU-loaded FOL-PEG-PLGA NPs was approximately 4-fold less than that of the 5-FU-loaded PLGA NPs (p<0.05). Consequently, FOL-PEG-PLGA NPs could have great potential as a targeted 5-FU delivery system for colon and breast cancer treatment.