LAUSR

Arginine decorated nanocarriers exhibited intravacuolar targeting capability which was utilized to deliver antibiotics into the intracellular niche of pathogens like Salmonella and Mycobacterium. The arginine based nanocarrier system (Arg-MSN) was developed on a mesoporous silica nanoparticle (MSN) template by conjugating L-arginine to protamine and pectin coated MSN by using a layer-by-layer coating approach. The synthesized nanocarriers were characterized using microscopy, FTIR spectroscopy, and zeta potential analyses. Lower cytotoxicity and hemolysis was observed for Arg-MSN nanocarrier compared to bare MSN template. Ciprofloxacin, a fluoroquinolone antibiotic was entrapped in Arg-MSN which showed gradual release of ciprofloxacin over a period of 24 h. In vitro experiments in Salmonella infected macrophages and epithelial cells exhibited two-fold higher antibacterial activity with ciprofloxacin-loaded Arg-MSN (Cip Arg-MSN) compared to free ciprofloxacin. The increased antibacterial activity of Cip Arg-MSN is believed to result from co-localization of Arg-MSN with the intravacuolar Salmonella and localized delivery of the antibiotic. We also observe an increase in reactive nitrogen species upon Arg-MSN treatment in the infected cells. In vivo bacterial burden and morbidity studies exhibited nearly ten-fold lower Salmonella burden in the infected organs such as spleen, liver and MLN (mesenteric lymph nodes). Similar survival rates were observed at a lower dosage of Cip Arg-MSN over free ciprofloxacin. The coordinated effect of improved antibiotic delivery, intracellular targeting and production of reactive nitrogen species was found to result in enhanced antibacterial activity. The developed Arg-MSN system is expected to be an attractive carrier system for delivery of antibiotics for clearing intravacuolar infections.