Abstract

Killing intracellular pathogens is often hampered by poor antibiotic penetration. A nanoparticle formula with surface properties similar to microbial particles can be advantageous as a carrier for intracellular delivery of antimicrobial agents. Surface-modified lipid nanoparticles with chitosan conjugated acemannan—an acetylated polymannose of aloe gel isolate—have been proposed to deliver rifampicin intracellularly. Chitosan-acemannan (COS-ACE) conjugate was bound electrostatically to rifampicin-loaded nanostructured lipid carrier (NLC) to form COS-ACE lipid nanoparticles. The nanoparticles showed a diameter size of around 300 nm at a low polydispersity index, and positive zeta potential of 1.66±1.39 mV. Transmission electron microscope and confocal images showed that the COS-ACE lipid nanoparticles were spherical in shape with NLC in the center surrounded by COS-ACE conjugate. Rifampicin was highly entrapped within lipid nanoparticles and released from the particles at pH 5 at higher rate compared to pH 7.4. The lyophilized nanoparticles were stable at the storage temperature of 4 °C and 25 °C, in terms of the content and particle size. Furthermore, the COS-ACE lipid nanoparticles was non-toxic against Vero and BALB/c 3T3 cells and increased intracellular accumulation of lipid soluble antibiotic, suggesting its functionality in intracellular targeting.

Key words: intracellular infection, lipid nanoparticles, acemannan-chitosan conjugate, rifampicin