한빛사 논문
Simseok A. Yuk1, Hyungjun Kim1,2, Nader S. Abutaleb3,4, Alexandra M. Dieterly3, Maie S. Taha1,5, Michael D. Tsifansky6, L. Tiffany Lyle3, Mohamed N. Seleem3,4 and Yoon Yeo1,7,*
1Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
2Department of Applied Chemistry, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi, Gyeongbuk 39177, Republic of Korea.
3Department of Comparative Pathobiology, Purdue University, 625 Harrison Street, West Lafayette, IN 47907, USA.
4Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, 1410 Prices Fork Road, Blacksburg, VA 24061, USA.
5Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
6Pediatric Cardiac Critical Care Medicine and Pediatric Pulmonology, Children’s National Medical Center, Michigan Ave NW, Washington, DC 20310, USA.
7Weldon School of Biomedical Engineering, Purdue University, 206 S Martin Jischke Dr., West Lafayette, IN 47907, USA.
*Corresponding author.
Abstract
Systemic therapy of Gram-negative sepsis remains challenging. Polymyxin B (PMB) is well suited for sepsis therapy due to the endotoxin affinity and antibacterial activity. However, the dose-limiting toxicity has limited its systemic use in sepsis patients. For safe systemic use of PMB, we have developed a nanoparticulate system, called D-TZP, which selectively reduces the toxicity to mammalian cells but retains the therapeutic activities of PMB. D-TZP consists of an iron-complexed tannic acid nanocapsule containing a vitamin D core, coated with PMB and a chitosan derivative that controls the interaction of PMB with endotoxin, bacteria, and host cells. D-TZP attenuated the membrane toxicity associated with PMB but retained the ability of PMB to inactivate endotoxin and kill Gram-negative bacteria. Upon intravenous injection, D-TZP protected animals from pre-established endotoxemia and polymicrobial sepsis, showing no systemic toxicities inherent to PMB. These results support D-TZP as a safe and effective systemic intervention of sepsis.
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