Abstract
•Development of brigatinib loaded solid lipid nanoparticles by 32 factorial design.•Physicochemical characterization was inclusive of NMR and cytotoxicity studies.•Optimized formulation showed sustained drug release for an extended time.•The Brigatinib exhibit efficacy in reduced dose with potential cytotoxicity against the lung cell lines.
Brigatinib (BG) is a tyrosine kinase receptor inhibitor act as an antineoplastic agent by blocking the action of an abnormal protein that causes cancer cells to multiply. In the current study, nine formulae of BG loaded solid lipid nanoparticles (SLNs) were developed using 32 factorial design. SLNs were prepared by the solvent emulsification technique using stearic acid as lipid and soya- lecithin as a surfactant, both of these act as independent variables, whereas Particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE) and drug loading (DL) were selected as responses. The particle size was found to be in the nano range (176−787 nm), fairly monodisperse (PDI indices 0.19−0.5), interparticle electrical stability was supported by zeta-potential (+1.78 mV to -15.4 mV), whereas EE and DL were in the range of (61.31–87.87 %) (3.35–31.01 %), respectively. Differential scanning calorimetry (DSC) thermograms indicated the amorphous state of BG in the SLN. Fourier transform infrared spectroscopy (FTIR) spectrums confirm non-interaction between drug and polymer while nuclear magnetic resonance (NMR) spectroscopy study revealed BG incorporation in the SLN. A scanning electron microscope (SEM) image exhibit a spherical shape of SLN. The in-vitro release profile demonstrates a sustained release pattern for the selected BS5 SLNs. MTT assay was performed on the optimized SLNs (BS5) and the results are indicative that BG loaded SLN (BS5) showed better cytotoxicity against A349 lung cell lines while compared to BG suspension and blank SLN. Thus, BG loaded SLNs can find Its better place in the non-small cell lung cancer treatment.