Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella

Gnanadhas, Divya Prakash and Ben Thomas, Midhun and Elango, Monalisha and Raichur, Ashok M and Chakravortty, Dipshikha (2013) Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella. In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 68 (11). pp. 2576-2586.

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Abstract

Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

Item Type:	Journal Article
Publication:	JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Publisher:	OXFORD UNIV PRESS
Additional Information:	Copy right of this article belongs to the OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
Keywords:	intravacuolar pathogens; typhoid; layer-by-layer (LbL); polyelectrolyte capsules; ciprofloxacin/ceftriaxone/gentamicin
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Mechanical Sciences > Aerospace Engineering(Formerly Aeronautical Engineering) Division of Mechanical Sciences > Materials Engineering (formerly Metallurgy)
Date Deposited:	14 Aug 2015 04:43
Last Modified:	14 Aug 2015 04:43
URI:	http://eprints.iisc.ac.in/id/eprint/52096

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