한빛사 논문
Marwa G. Elnaggara,b, Kunyu Jianga,c, Hassan E. Eldesoukyd, Yihua Peia, Jinho Parka, Simseok A. Yuka, Fanfei Menga, Alexandra M. Dieterlyd, Haroon T. Mohammadd, Youssef A. Hegazyd, Hesham M. Tawfeekb, Aly A. Abdel-Rahmanb, Ahmed E. Aboutalebb, Mohamed M. Seleemd,e, Yoon Yeoa,f,*
aDepartment of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA
bDepartment of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt
cDepartment of Pharmaceutics, School of Pharmacy, China Medical University, 77 Puhe Road Shenyang, Liaoning, 110122, China
dDepartment of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA
ePurdue Institute of Inflammation, Immunology and Infectious Disease, West Lafayette, IN, 47907, USA
fWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, 47907, USA
*Corresponding author
Abstract
Bacterial pathogens residing in host macrophages in intracellular infections are hard to eradicate because traditional antibiotics do not readily enter the cells or get eliminated via efflux pumps. To overcome this challenge, we developed a new particle formulation with a size amenable to selective macrophage uptake, loaded with two antibacterial agents - pexiganan and silver (Ag) nanoparticles. Here, pexiganan was loaded in 600 nm poly(lactic-co-glycolic acid) (PLGA) particles (NP), and the particle surface was modified with an iron-tannic acid supramolecular complex (pTA) that help attach Ag nanoparticles. PLGA particles coated with Ag (NP-pTA-Ag) were taken up by macrophages but not by non-phagocytic cells, such as fibroblasts, reducing non-specific toxicity associated with Ag nanoparticles. NP-pTA-Ag loaded with pexiganan (Pex@NP-pTA-Ag) showed more potent antibacterial activity against various intracellular pathogens than NP-pTA-Ag or Pex@NP (pexiganan-loaded NP with no Ag), suggesting a collaborative function between pexiganan and Ag nanoparticles. Mouse whole-body imaging demonstrated that, upon intravenous injection, NP-pTA-Ag quickly accumulated in the liver and spleen, where intracellular bacteria tend to reside. These results support that Pex@NP-pTA-Ag is a promising strategy for the treatment of intracellular bacterial infection.
Keywords : Intracellular infection; Pexiganan; Silver nanoparticles; Macrophages; Intracellular drug delivery
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