Assessing the Dual Drug 9-hydroxymethyl Noscapine and Telmisartan-loaded Stearic Acid Nanoparticles against (H1299) non-small cell lung cancer and its mechanistic interaction with Bovine Serum Albumin

Abstract

Solid lipid nanoparticles are appealing to the scientific community owing to their expedient and versatile nature as systems for drug delivery and therefore are being used to treat variety of illnesses. With parallel line of thought, herein, we have reported the synthesis, characterisation of dual drug stearic acid loaded solid lipid nanoparticles and screened their efficacy in non-small cell lung cancer. The desired nanoparticle namely 9-CH2OH Nos-Tel-SLNs was prepared using solvent diffusion method. TEM and AFM images revealed that the nanoparticles have spherical formwith a mean size of 36.6 nm. The zeta potential and hydrodynamic size of the nanostructures was found to be -36.23 mV and ~ 406.8 nm, respectively. From RP-HPLC, the noscapine and telmisartan loaded in the nanoparticles were found to be 1.86 % and 1.97 % respectively. Additionally, we have probed into the interaction of BSA with the synthesized nanocomposite using UV-Vis, Fluorescence and CD spectroscopic techniques along with computational techniques namely molecular docking, molecular dynamic simulations and MM-PBSA/GBSA calculations. From the fluorescence quenching of BSA upon interaction with the SLNs, we deduced that aa stable ground-state complex between 9-CH2OH Nos-Tel-SLN and BSA were formed. Similarly, in-silico evaluation indicated formation of a stable dual drug complex with BSA with telmisartan being more compatible to bind to the protein. To assess further, we also evaluated the anticancer property of 9-CH2OH noscapine, Telmisartan and 9-CH2OH Nos-Tel-SLN against H1299 lung cancer cell line using MTT assay and the calculated IC50 of 9-CH2OH Nos-Tel-SLN was 186 µg/mL. Overall, based on the promising results in this research; such SLNs could be a promising drug delivery tool and can be crucial in the conversion of potent anticancer drugs to marketed anticancer drugs in near future.