A Novel Nanoemulsion Formula for an Improved Delivery of a Thalidomide Analogue to Triple-Negative Breast Cancer; Synthesis, Formulation, Characterization and Molecular Studies

Background: Thalidomide (THD) and its analogues were recently reported as a promising treatment for different types of solid tumors due to their antiangiogenic effect.

Methods: In this work, we synthesized a novel THD analogue (TA), and its chemistry was confirmed with different techniques such as IR, mass spectroscopy, elemental analysis as well as H and C NMR. To increase solubility and anticancer efficacy, a new oil in water (O/W) nanoemulsion (NE) was used in the formulation of the analogue. The novel formula's surface charge, size, stability, FTIR, FE-TEM, in vitro drug release and physical characteristics were investigated. Furthermore, molecular docking studies were conducted to predict the possible binding modes and molecular interactions behind the inhibitory activities of the THD and TA.

Results: TA showed a significant cytotoxic activity with IC ranging from 0.326 to 43.26 µmol/mL when evaluated against cancerous cells such as MCF-7, HepG2, Caco-2, LNCaP and RKO cell lines. The loaded analogue showed more potential cytotoxicity against MDA-MB-231 and MCF-7-ADR cell lines with IC values of 0.0293 and 0.0208 nmol/mL, respectively. Moreover, flow cytometry of cell cycle analysis and apoptosis were performed showing a suppression in the expression levels of TGF-β, MCL-1, VEGF, TNF-α, STAT3 and IL-6 in the MDA-MB-231 cell line.

Conclusion: The novel NE formula dramatically reduced the anticancer dosage of TA from micromolar efficiency to nanomolar efficiency. This indicates that the synthesized analogue exhibited high potency in the NE formulation and proved its efficacy against triple-negative breast cancer cell line.