Delivery of rifampicin-chitin nanoparticles into the intracellular compartment of polymorphonuclear leukocytes

Polymorphonuclear leukocytes (PMNs) provide the primary host defence against invading pathogens by producing reactive oxygen species (ROS) and microbicidal products. However, few pathogens can survive for a prolonged period of time within the PMNs. Additionally their intracellular lifestyle within the PMNs protect themselves from the additional lethal action of host immune systems such as antibodies and complements. Antibiotic delivery into the intracellular compartments of PMNs is a major challenge in the field of infectious diseases. In order to deliver antibiotics within the PMNs and for the better treatment of intracellular bacterial infections we synthesized rifampicin (RIF) loaded amorphous chitin nanoparticles (RIF-ACNPs) of 350 ± 50 nm in diameter. RIF-ACNPs nanoparticles are found to be non-hemolytic and non-toxic against a variety of host cells. The release of rifampicin from the prepared nanoparticles was ∼60% in 24 h, followed by a sustained pattern till 72 h. The RIF-ACNPs nanoparticles showed 5-6 fold enhanced delivery of RIF into the intracellular compartments of PMNs. The RIF-ACNPs showed anti-microbial activity against Escherichia coli, Staphylococcus aureus and a variety of other bacteria. In summary, our results suggest that RIF-ACNPs could be used to treat a variety of intracellular bacterial infections.