Antibacterial nanotruffles for treatment of intracellular bacterial infection

被引:44
作者
Elnaggar, Marwa G. [1 ,2 ]
Jiang, Kunyu [1 ,3 ]
Eldesouky, Hassan E. [4 ]
Pei, Yihua [1 ]
Park, Jinho [1 ]
Yuk, Simseok A. [1 ]
Meng, Fanfei [1 ]
Dieterly, Alexandra M. [4 ]
Mohammad, Haroon T. [4 ]
Hegazy, Youssef A. [4 ]
Tawfeek, Hesham M. [2 ]
Abdel-Rahman, Aly A. [2 ]
Aboutaleb, Ahmed E. [2 ]
Seleem, Mohamed N. [4 ,5 ]
Yeo, Yoon [1 ,6 ]
机构
[1] Purdue Univ, Dept Ind & Phys Pharm, 575 Stadium Mall Dr, W Lafayette, IN 47907 USA
[2] Assiut Univ, Fac Pharm, Dept Ind Pharm, Assiut 71526, Egypt
[3] China Med Univ, Sch Pharm, Dept Pharmaceut, 77 Puhe Rd, Shenyang 110122, Liaoning, Peoples R China
[4] Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA
[5] Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA
[6] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA
基金
美国国家科学基金会;
关键词
Intracellular infection; Pexiganan; Silver nanoparticles; Macrophages; Intracellular drug delivery; SILVER NANOPARTICLES; CELLULAR UPTAKE; PARTICLE-SIZE; LOCALIZATION; MACROPHAGES; DISSOLUTION; PEXIGANAN; TOXICITY; DELIVERY; LIFE;
D O I
10.1016/j.biomaterials.2020.120344
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
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页数:13
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