Lignin and Pluronic-based nanomicelles as promising amiodarone nanocarriers: Synthesis, physical characterization, biological, and in silico evaluations

Abstract

Lignin, a major component of herbaceous plants, is one of the most abundant natural poly-mers that has lipophilic character and antipathogenic properties. Another biocompatible polymer is Pluronic F127, that can cross the blood brain barrier (BBB). Herein, novel drug delivery nanosystems based on oil-in-water microemulsions made of these two biocompatible polymers were developed to load amiodarone (AM), a cationic amphipathic drug used for treating cardiac arrhythmia that displays antifungal and antibacterial properties. The use of drug delivery nanocarriers enhances the solubilization and controlled release of this medication, thus reducing its therapeutic dosage and associated side effects. The morphology, size and surface charge of the nanomiceles was characterized via scanning and transmission electron microscopy (SEM and TEM), dynamic light scattering (DLS) and zeta potential measurements, respectively, which demonstrated their spherical shape, with an average diameter of 27 nm and a zeta potential of −25 mV. Very high entrapment efficiencies were attained for both types of nanomicelles (79.1% and 83.1% for lignin and F127, respectively). Furthermore, both types of AM-loaded nanomicelles exhibited a slower release profile compared to the free drug. Cytotoxicity assay with morphological examination of NIH/3T3 fibroblast cells confirmed a reduction in drug toxicity upon loading onto the nanocarriers. Blood cultures in a chocolate agar medium corroborated that the antibacterial properties of AM are preserved after nanomicelle encapsulation. The interactions of AM with F127 and lignin monomers were investigated via quantum mechanical computations, which revealed the formation of strong hydrogen bonds, the most intense being between AM and lignin. Overall, these novel formulations exhibit great potential for the sustained and targeted AM delivery.