Development of arginine based nanocarriers for targeting and treatment of intracellular Salmonella. Issue 12 (20th January 2017)

• Record Type: Journal Article
• Authors: Mudakavi, Rajeev J.; Vanamali, Surya; Chakravortty, Dipshikha; Raichur, Ashok M.
• Is Part Of: RSC advances. Volume 7:Issue 12(2017)
• Page Start: 7022
• Page End: 7032
• Publication Date: 2017-01-20
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6ra27868j
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Arginine decorated nanocarriers exhibited intravacuolar targeting capability which was utilized to deliver antibiotics and reactive NO into the intracellular niche of pathogens like Salmonella and Mycobacterium . Abstract : 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 conjugatingl -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.