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Antimicrobial Agents and Chemotherapy, October 2009, p. 4270-4274, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00815-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Silica-Antibiotic Hybrid Nanoparticles for Targeting Intracellular Pathogens {triangledown}

Mohamed N. Seleem,1,4 Prabhakaran Munusamy,2 Ashish Ranjan,3 Hamzeh Alqublan,4 Gary Pickrell,2 and Nammalwar Sriranganathan4*

Institute for Critical Technology and Applied Science,1 Department of Materials Science and Engineering,2 Department of Large Animal Science, Virginia-Maryland Regional College of Veterinary Medicine,3 Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia4

Received 17 June 2009/ Returned for modification 12 July 2009/ Accepted 3 August 2009

We investigated the capability of biodegradable silica xerogel as a novel carrier of antibiotic and the efficacy of treatment compared to that with the same dose of free drug against murine salmonellosis. The drug molecules (31%) entrapped in the sol-gel matrix remained in biologically active form, and the bactericidal effect was retained upon drug release. The in vitro drug release profiles of the gentamicin from the xerogel and that from the xerogel-polyethylene glycol (PEG) were distinctly different at pH 7.4. A delayed release of gentamicin was observed from the silica xerogel network (57% in 33 h), and with the addition of 2% PEG, the release rate reached 90% in 33 h. Administration of two doses of the silica xerogel significantly reduced the Salmonella enterica serovar Typhimurium load in the spleens and livers of infected AJ 646 mice. The silica xerogel and xerogel-PEG achieved a 0.45-log and a 0.41-log reduction in the spleens, respectively, while for the free drug there was no reduction. On the other hand, silica xerogel and xerogel-PEG achieved statistically significant 1.13-log and 1.15-log reductions in the livers, respectively, while for the free drug the reduction was a nonsignificant value of 0.07 log. This new approach, which utilizes a room-temperature synthetic route for incorporating therapeutic drugs into the silica matrix, should improve the capability for targeting intracellular pathogens.

* Corresponding author. Mailing address: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 1410 Prices Fork Rd., Blacksburg, VA 24061. Phone: (540) 231-7171. Fax: (540) 231-3426. E-mail: nathans{at}vt.edu

{triangledown} Published ahead of print on 10 August 2009.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4270-4274, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00815-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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