Assessing dual drug 9-hydroxymethyl noscapine and telmisartan-loaded stearic acid nanoparticles against (H1299) non-small cell lung cancer and their 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 a variety of illnesses. With parallel line of thought, herein, we have reported the synthesis and characterisation of dual drug stearic acid-loaded solid lipid nanoparticles and screened their efficacy in non-small cell lung cancer. The desired nanoparticles, namely 9-CH₂OH Nos-Tel-SLNs, were prepared using the solvent diffusion method. TEM and AFM images revealed that the nanoparticles have spherical form with a mean size of 36.6 nm. The nanostructures' zeta potential and hydrodynamic size were 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-visible, 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 a stable ground-state complex between 9-CH₂OH Nos-Tel-SLN and BSA was formed. Similarly, in silico evaluation indicated formation of a stable dual drug complex with BSA with telmisartan being more compatible for binding 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⁻¹. 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 potential anticancer drugs to marketed anticancer drugs in the near future.