Development and characterization of Brigatinib loaded solid lipid nanoparticles: In-vitro cytotoxicity against human
Mohammed Muqtader Ahmed1, Farhat Fatima1, Md Khalid Anwer1
1Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj-11942, Saudi Arabia.
Abstract:
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.
Insights
Brigatinib (BG) loaded solid lipid nanoparticles (SLNs) were developed for non-small cell lung cancer. Optimized BG-SLNs demonstrated enhanced cytotoxicity against lung cancer cells compared to BG alone.
Area of Science:
- Pharmaceutical Nanotechnology
- Cancer Therapeutics
- Drug Delivery Systems
Background:
- Brigatinib (BG) is a tyrosine kinase inhibitor used as an antineoplastic agent.
- Cancer cells' multiplication can be blocked by inhibiting abnormal protein activity.
- Solid lipid nanoparticles (SLNs) offer a promising platform for drug delivery.
Purpose of the Study:
- To develop and characterize brigatinib (BG)-loaded solid lipid nanoparticles (SLNs).
- To evaluate the in vitro cytotoxicity of BG-loaded SLNs against lung cancer cell lines.
- To optimize SLN formulation using a 3^2 factorial design.
Main Methods:
- SLNs were prepared using the solvent emulsification technique with stearic acid and soya-lecithin.
- A 3^2 factorial design was employed to optimize particle size, PDI, zeta potential, entrapment efficiency (EE), and drug loading (DL).
- Characterization included DSC, FTIR, NMR, SEM, in vitro release studies, and MTT assay.
Main Results:
- Developed nano-sized SLNs (176-787 nm) with good monodispersity (PDI 0.19-0.5) and stability (zeta potential +1.78 to -15.4 mV).
- Achieved high entrapment efficiency (61.31-87.87%) and drug loading (3.35-31.01%).
- Optimized BG-SLNs (BS5) exhibited sustained release and superior cytotoxicity against A549 lung cancer cells compared to BG suspension.
Conclusions:
- BG-loaded SLNs were successfully developed and characterized.
- The optimized BG-SLN formulation (BS5) demonstrated enhanced anti-cancer efficacy.
- BG-loaded SLNs represent a viable strategy for non-small cell lung cancer treatment.
