Quality-by-design-based microemulsion of disulfiram for repurposing in melanoma and breast cancer therapy
Abstract
Aim: The current study aims to develop and optimize microemulsions (ME) through Quality-by-Design (QbD) approach to improve the aqueous solubility and dissolution of poorly water-soluble drug disulfiram (DSF) for repurposing in melanoma and breast cancer therapy.
Materials & methods: The ME was formulated using Cinnamon oil & Tween® 80, statistically optimized using a D-optimal mixture design-based QbD approach to develop the best ME with low vesicular size (Zavg) and polydispersity index (PDI).
Results: The DSF-loaded optimized stable ME showed enhanced dissolution, in-vitro cytotoxicity and improved cellular uptake in B16F10 and MCF-7 cell lines compared with their unformulated free DSF.
Conclusion: Our investigations suggested the potential of the statistically designed DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.
Article Highlights
Formulation & development
- The ME of the poorly water-soluble drug DSF was made with Cinnamon oil, Tween® 80, and water. The selection of suitable oil and surfactant was made using a solubility study.
- The influence of the ME composition on the extent of the monophasic isotropic region was explored with the use of pseudo-ternary phase diagrams through the water titration method.
Response surface analysis & optimization of microemulsion
- Statistical analysis and optimization were carried out using the D-optimal mixture design-based QbD approach to obtain the optimized ME with low Zavg and PDI.
Characterizations of microemulsion
- The ME was found to have very low viscosity and was transparent, without any sign of precipitation or phase separation.
- The RI and %T reflected the isotropic and transparency of the optimized ME.
- The robustness to dilution and conductivity measurements represented the o/w type emulsion.
- The DLS results displayed the globules with nanometric hydrodynamic size, and the ZP value reflected the existence of a negative charge on the surface of the globules.
- The morphological analysis through HRTEM further showed the existence of spherical globules with nanometric size in accordance with DLS results.
- The optimized ME reflected excellent accelerated and kinetic stability. The ATR-FTIR results demonstrated the retention of the important peaks of DSF in the ME, reflecting the compatibility of DSF with the formulation excipients.
- The developed ME significantly enhanced (p < 0.05) the dissolution of poorly water-soluble drug DSF, which is ascribed to its nanometric globule size, improved effective surface area and solubility.
Anticancer activity evaluation
- The optimized ME showed significantly (p < 0.05) enhanced cytotoxicity and cellular uptake against melanoma (B16F10) and breast cancer (MCF-7) cell lines, which is ascribed to the nano size, improved solubility and partitioning into the cellular region.
- In addition, the pure DSF and optimized ME demonstrated no cytotoxicity to healthy noncancerous kidney cells (HEK293), reflecting its safety toward normal cells and selected cytotoxicity against cancerous cells.
- Our research suggested the potential of the DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.
Read more here
Mohapatra, D., Senapati, P. C., Senapati, S., Pandey, V., Dubey, P. K., Singh, S., & Sahu, A. N. (2024). Quality-by-design-based microemulsion of disulfiram for repurposing in melanoma and breast cancer therapy. Therapeutic Delivery, 1–24. https://doi.org/10.1080/20415990.2024.2363136
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