Popat KUMBHAR, Vıshvajıt KHADE, Varsha KHADAKE, Pradnya MARALE, Arehallı MANJAPPA, Sameer NADAF, Vıjay KUMBAR, Durgacharan BHAGWAT, John DİSOUZA

Ifosfamide-Loaded Cubosomes: An Approach to Potentiate Cytotoxicity against MDA-MB-231 Breast Cancer Cells

Background: Ifosfamide (IFS) is proved efficacious against breast cancer, an enormously diagnosed cancer across the globe. However, the clinical efficacy of IFS is limited owing to its hydrophilicity, less stability, and dose-dependent toxicities. Therefore, the primary goal of the present research was to develop IFS-loaded cubosomes with improved anticancer efficacy and reduced dose-dependent toxicities. Methods: The IFS-cubosomes were optimized using a 32 factorial design based on IFS content and zeta potential. The optimized cubosomal dispersion was further assessed for particle size, in vitro IFS release, haemolysis, cytotoxicity, cellular uptake and physical stability. Results: The optimized IFS-cubosomal dispersion exhibited maximum IFS content (89.75±4.3%) and better zeta potential value (-40.0±1.6 mV), and size in nanometer. Moreover, IFS-cubosomes retarded IFS release (about 91 %) after 12 h than plain IFS solution (>99 % within 2 h). The IFS-cubosomes displayed lower haemolysis (3.7±0.79%) towards human RBCs. Besides, the in vitro cytotoxicity of IFS-cubosomes was noticed to be substantially higher (IC50: 0.64±0.08 µM) than plain IFS solution (IC50: 1.46±0.21 µM) against multi-drug resistant (MDR) breast cancer (MDA-MB-231) cells. DAPI staining revealed death of IFS-cubosomes treated cells mainly by apoptosis. The cubosomes showed increased uptake by cancer cells. Furthermore, IFS-cubosomes were found to be more stable at refrigeration temperature than at room temperature. Conclusion: Thus, IFS-cubosomes could be a novel avenue in the treatment of breast cancer with improved anticancer efficacy and reduced toxicity. However, further in vivo investigations are desired to validate these claims.

Keywords:

Breast cancer, ifosfamide, cubosomes, haemolysis, cytotoxicity, cellular uptake,

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