Formulation of 5-fluorouracil loaded chitosan-based nanoparticles and evaluation of its cytotoxic effects against MCF-7 human breast cancer cells

Abstract

Breast cancer remains a major global health issue with a high mortality rate. In breast cancer treatment, chemotherapeutic drugs have a toxic effect on both cancerous and healthy cells which can lead to severe adverse effects and chemoresistance. Chitosan-based nanoparticles (NPs) have been reported to improve cellular drug delivery, thereby remediating the chemoresistance of anticancer drugs. The purpose of this research was to formulate 5-fluorouracil (5-FU) loaded chitosan nanoparticles. 5-FU nanoparticles were synthesized using ionic gelation technique which is based on the ionic interaction of positively charged chitosan and negatively charged tripolyphosphate that serves as a cross linker. The formulated nanoparticles were evaluated using UV spectrophotometer, Fourier-transform infrared spectroscopy, X-ray diffraction, Scanning Electron Microscopy. The cytotoxicity study was done using MTT assays. FTIR analysis revealed complete drug encapsulation of the nanoparticles via intermolecular interactions. The result of the XRD analysis showed that the drug was crystalline in the nanoparticle distribution. The SEM analysis confirmed the spherical morphology and structure. The synthesized nanoparticles had a mean particle size of 218.62 nm, zeta potential values of ≤+32.18 mV, Pdi values ranging from 0.14–0.29 and encapsulation efficiency results of ≤37.54%. The drug release mechanism was via Fickian diffusion. MTT analysis showed a time-dependent cytotoxic effect of 5-FU nanoparticles on breast cancer (MCF-7) cell lines after 72 h. This study confirmed that formulation of 5-FU into nanoparticles is a promising approach for sustained release and site-specific anticancer drug delivery which can potentially minimize the systemic side effects and improve treatment outcomes in cancer patients.