Optimization of Capecitabine-Loaded Niosomes Using Factorial Design: An Approach for Enhanced Drug Release and Cytotoxicity in Breast Cancer

Capecitabine, an oral prodrug of 5-fluorouracil, is increasingly being loaded into various drug delivery system to enhance its bioavailability and cytotoxicity. This study aimed to prepare and evaluate capecitabine-loaded niosomes as a drug delivery system for breast cancer treatment. The niosomes were prepared by thin film hydration method using Span 60 and cholesterol. Optimization was done using 3² factorial design with the responses of particle size and entrapment efficiency. Scanning electron microscopy (SEM) was used to observe the morphology. Fourier transform infrared spectroscopy (FTIR) and ultraviolet (UV) spectrophotometry were used to confirm the nature of the interactions. The optimized batch was further assessed for percent cumulative drug release, nature of crystallinity using the X-ray diffraction method, and drug excipient compatibility using FTIR and Differential Scanning Calorimetry (DSC). The optimized batch (F8) exhibited a particle size of 118 nm, a zeta potential of 24.1 mV, an entrapment efficiency of 93%, and a polydispersibility index (PDI) of 0.25. The cumulative drug release in a pH of 6.8 indicated that 86.46 ± 0.45% of the drug was released in 24 h. Cytotoxicity testing using MTT assay on MCF-7 breast cancer cell lines showed that the capecitabine niosomes were 2.6 times more cytotoxic than the pure drug. The study demonstrates that capecitabine-niosomes significantly enhanced the anticancer activity of capecitabine, suggesting a promising approach for breast cancer treatment.

Graphical Abstract