ArtinM Grafted Phospholipid Nanoparticles for Enhancing Antibiotic Cellular Uptake Against Intracellular Infection

An antimicrobial delivery in the form of surface-modified lectin of lipid nanoparticles was proposed to improve cellular accumulation. ArtinM, an active toll-like receptor 2 (TLR2) agonist lectin isolated from cempedak (Arthocarpus integrifolia) seeds, was selected to induce cellular engulfment of nanoparticles within infected host cells.

Lipid nanoparticles were prepared using the emulsification technique before electrostatic adsorption of artinM. The formula comprising of rifampicin, soy phospholipid, and polysorbate 80 was optimized by Box-Behnken design to produce the desired particle size, entrapment efficiency, and drug loading. The optimum formula was characterized for morphology, in vitro release, and cellular transport.

Soy phospholipid showed a profound effect on controlling drug loading and entrapment efficiency. Owing to its surface activity, polysorbate 80 contributed significantly to reduce particle size; however, a higher ratio to lipid concentration resulted in a decrease of rifampicin encapsulation. The adsorption of artinM on the surface of nanoparticles was accomplished by electrostatic binding at pH 4, where this process maintained the stability of encapsulated rifampicin. A high proportion of artinM adsorbed on the surface of the nanoparticles shown by haemagglutination assay, zeta potential measurement, and transmission electron microscopy imaging. Cellular uptake revealed by confocal microscopy showed the success in transporting Nile-red labelled nanoparticles across fibroblast cells.

The delivery system of nanoparticles bearing artinM becomes a potential platform technology for antibiotic targeting in the treatment of life-threatening chronic diseases caused by intracellular infections.