Antibacterial nanotruffles for treatment of intracellular bacterial infection

Marwa G Elnaggar; Kunyu Jiang; Hassan E Eldesouky; Yihua Pei; Jinho Park; Simseok A Yuk; Fanfei Meng; Alexandra M Dieterly; Haroon T Mohammad; Youssef A Hegazy; Hesham M Tawfeek; Aly A Abdel-Rahman; Ahmed E Aboutaleb; Mohamed N Seleem; Yoon Yeo

doi:10.1016/j.biomaterials.2020.120344

Antibacterial nanotruffles for treatment of intracellular bacterial infection

Biomaterials. 2020 Dec:262:120344. doi: 10.1016/j.biomaterials.2020.120344. Epub 2020 Aug 29.

Authors

Affiliations

¹ Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA; Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
² Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA; Department of Pharmaceutics, School of Pharmacy, China Medical University, 77 Puhe Road Shenyang, Liaoning, 110122, China.
³ Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA.
⁴ Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA.
⁵ Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
⁶ Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA; Purdue Institute of Inflammation, Immunology and Infectious Disease, West Lafayette, IN, 47907, USA.
⁷ Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, 47907, USA. Electronic address: [email protected].

PMID: 32905902
DOI: 10.1016/j.biomaterials.2020.120344

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 drug delivery; Intracellular infection; Macrophages; Pexiganan; Silver nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Bacterial Infections*
Macrophages
Metal Nanoparticles*
Mice
Nanoparticles*
Silver

Substances

Anti-Bacterial Agents
Silver