Nanoscaled devices have great potential for
drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of
5-fluorouracil (5-FU)-entrapped
poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the
lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double
emulsion method, and their
biological evaluation was done in
glioma (U87MG) and breast
adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of
5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of
5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free
drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by
acridine orange/
ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free
5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free
5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate
drug concentrations is more favorable than regular administration of higher concentration of the
drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as
controlled release formulation to multiplex the
therapeutic effect of
cancer chemotherapy.