Dasatinib Cube-O-Needle hybrid system for effective and safe site-specific treatment for triple-negative breast cancer
摘要
The goal of the existing investigation was to design a Dasatinib (DAS) Cube-O-Needle (Cubosome-MNs hybrid system) for triple-negative breast cancer (TNBC) to improve potency and reduce side effects. In Cube-O-Needle, the Cubosome was formulated at an optimal ratio of Glyceryl monooleate (GMO), Poloxamer 407 (PLX), Soya lecithin (SL), Soluplus, and Tween 80. Hyaluronic acid (HA) was used to target DAS to TNBC cells. A risk assessment was conducted to recognize key variables. The amounts of GMO, PLX, and SL have been tailored using a Box-Behnken Design (BBD) to attain the anticipated DAS release, particle size, and zeta potential. The MTT assay was performed to evaluate the potency of DAS and its cubosomes (CUB). Cube-O-Needle was designed by infusing CUB into a microneedle patch (MNs). PMVE/MA was used to improve the mechanical characteristics and distinct needle shape. Cube-O-Needle was evaluated using various parameters. DSC, FTIR, and XRD revealed new H-bond formation and a conversion from the crystalline to the amorphous state, indicating increased solubility. The amounts of GMO, SL, and PLX were identified as significant in the FMEA analysis, and the remaining CUB were further optimized and confirmed using BBD. Optimal CUB exhibited a size of 167.2 nm, a zeta potential of − 36.5 mV, an entrapment efficiency of 79.31%, and 90% DAS release up to 12 h. The newer DAS was found to be effective against TNBC, with IC50 values of 29.68 ± 0.18 and 4.514 ± 0.10 in CUB. PMVE/MA was chosen for its mechanical strength and rapid dissolution rate. Optimized CUBs were infused into MN patches to form Cube-O-Needle, which controls DAS release for 24 h. The hybrid system Cube-O-Needle demonstrated excellent site specificity and high potency. MNs can overcome transdermal barriers, whereas CUB can release DAS for up to 24 h. DAS was effective in treating TNBC, and its CUB demonstrated greater therapeutic efficacy.