Preactivated-thiolated polyacrylic acid/1-vinyl pyrrolidone nanoparticles as nicotine carriers for smoking cessation

Abstract

This study aimed to develop nicotine-loaded mucoadhesive preactivated-thiolated polymeric nanoparticles (PNPs) for smoking cessation. 2-Mercaptonicotinic acid (2MNA) was coupled as dithionicotinic acid dimer and used in the preactivation of thiolated polyacrylic acid/vinyl pyrrolidone PNPs (thiolated AA/VP PNPs). Preactivated-thiolated AA/VP PNPs were synthesized through surfactant-free emulsion polymerization and coupling reactions. The structural attributes of the preactivated-thiolated AA/VP PNPs were characterized using Fourier-transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. The particle size and zeta potential were evaluated by dynamic light scattering evaluation. The morphology of the preactivated-thiolated AA/VP PNPs was examined using scanning electron microscopy. In addition, the mucoadhesive properties, drug loading and release, and biocompatibility of the preactivated-thiolated AA/VP PNPs were assessed. The spherical preactivated-thiolated AA/VP PNPs were successfully synthesized with a particle size of 410.3 ± 7.4 nm and a negative surface charge. The preactivated-thiolated AA/VP PNPs exhibited superior mucoadhesive properties compared with the thiolated AA/VP PNPs. Drug loading by PNP to a nicotine ratio of 1 : 1 provided desirable loading capacity and % loading efficiency of 285.7 ± 36.7 μg mg⁻¹ and 57.1 ± 7.4%, respectively. More than 50% of the nicotine contained in the PNPs was rapidly released in the first hour, followed by a sustained release for up to 12 h. Moreover, the synthesized PNPs were non-toxic to human gingival cells. Therefore, the preactivated-thiolated AA/VP PNPs may be a candidate carrier of nicotine for smoking cessation.