title: Nanotechnology as a therapeutic tool to combat microbial resistance.
abstract: Use of nanoparticles is among the most promising strategies to overcome microbial drug resistance. This review article consists of three parts. The first part discusses the epidemiology of microbial drug resistance. The second part describes mechanisms of drug resistance used by microbes. The third part explains how nanoparticles can overcome this resistance, including the following: Nitric oxide-releasing nanoparticles (NO NPs), chitosan-containing nanoparticles (chitosan NPs), and metal-containing nanoparticles all use multiple mechanisms simultaneously to combat microbes, thereby making development of resistance to these nanoparticles unlikely. Packaging multiple antimicrobial agents within the same nanoparticle also makes development of resistance unlikely. Nanoparticles can overcome existing drug resistance mechanisms, including decreased uptake and increased efflux of drug from the microbial cell, biofilm formation, and intracellular bacteria. Finally, nanoparticles can target antimicrobial agents to the site of infection, so that higher doses of drug are given at the infected site, thereby overcoming resistance.
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Electronic address: robert.pelgrift@med.einstein.yu.edu.
authors.forename: Robert Y
authors.initials: RY
authors.lastname: Pelgrift
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Friedman
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D004337:Drug Carriers / Q000737:chemistry*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers
keywords: .OH; Ag; Ag NP; Al(2)O(3) NP; Antibacterial; Antibiotic; Antimicrobial; Au; Au NP; Au NP-AMP; Au@Van NP; Bi NP; Biofilm; CFU; Chitosan; Cu; CuO NP; Drug resistant; EPS; Erm; Fe(3)O(4); GSH; GSNO; H(2)O(2); HBV; HIV 1; Hepatitis B virus; LPS; LTP NP; MBC; MDR; MFS; MIC; MIC90; MPS; MRAB; MRSA; MSSA; Mg; MgO NP; MgX(2) NP; N(2)O(3); NDM-1; NO NP; NO NP/GSH; NO(2); NOS; NP; Nanoparticle; New Delhi metallo beta-lactamase 1; Nitric oxide; O(2); OONO; PABA; PBP; PPNG; PVA; QAC; RND; RNOS; ROS; RSNO; S-nitrosoglutathione; S-nitrosothiol; SCC; SMR; SPION; Silver; TA genes; TFC; Ti; TiO(2) NP; TiO(2)–Ag NP; VRE; VRSA; VatD; Zn; ZnO NP; aluminum oxide-containing nanoparticle; bismuth-containing nanoparticle; chitosan NP; chitosan-containing nanoparticle; chitosan–Ag NP; chitosan–alginate NP; chitosan–alginate nanoparticle; colony forming unit; copper; copper oxide-containing nanoparticle; dinitrogen trioxide; erythromycin resistance methylase; extracellular polymeric substance; glutathione; gold; gold-containing nanoparticle; gold-containing nanoparticle capped with vancomycin; gold-containing nanoparticle with ampicillin bound to its surface; human immunodeficiency virus type 1; hydrogen peroxide; hydroxyl radical; l-tyrosine polyphosphate nanoparticle; lipopolysaccharide; magnesium; magnesium halogen-containing nanoparticle; magnesium oxide-containing nanoparticle; magnetite; major facilitator superfamily; methicillin-resistant Staphylococcus aureus; methicillin-sensitive Staphylococcus aureus; minimum bactericidal concentration; minimum inhibitory concentration; mixture of hydrogel/glass composite NO NPs with glutathione (GSH) in aqueous solution; mononuclear phagocyte system; multidrug resistant; multidrug-resistant Acinetobacter baumannii; nanoparticle; nanoparticle containing zero-valent Bi; nanoparticles containing both TiO(2) and Ag; nitric oxide synthetase; nitric oxide-releasing nanoparticle; nitrogen dioxide; para-aminobenzoic acid; penicillin binding protein; penicillin-resistant Neisseria gonorrhoeae; peroxynitrite; polyvinyl alcohol; quaternary ammonium compound; reactive nitrogen oxide intermediates; reactive oxygen species; resistance nodulation cell division family; silver; silver carbene complex; silver-containing nanoparticle; silver-containing nanoparticle which also contains chitosan; small multidrug resistance family; superoxide; superparamagnetic iron oxide NP; thin film composite; titanium; titanium dioxide-containing nanoparticle; toxin–antitoxin genes; vancomycin-resistant Enterococcus; vancomycin-resistant Staphylococcus aureus; virginiamycin acetyltransferase; zero-valent Bi NP; zinc; zinc oxide-containing nanoparticle