Abstract
Intracellular pathogenic bacteria can lead to some of the most life-threatening infections. By evolving a number of ingenious mechanisms, these bacteria have the ability to invade, colonize and survive in the host cells in active or latent forms over prolonged period of time. A variety of nanoparticulate systems have been developed to optimize the delivery of antibiotics. Main advantages of nanoparticulate systems as compared with free drugs are an efficient drug encapsulation, protection from inactivation, targeting infection sites and the possibility to deliver drugs by overcoming cellular barriers. Nevertheless, despite the great progresses in treating intracellular infections using nanoparticulate carriers, some challenges still remain, such as targeting cellular subcompartments with bacteria and delivering synergistic drug combinations. Engineered nanoparticles should allow controlling drug release both inside cells and within the extracellular space before reaching the target cells.
References
- 1 World Health Organization: Global Tuberculosis Report 2014. WHO Press, 1–171 (2014).
- 2 . Bacterial Disease Mechanisms: An Introduction to Cellular Microbiology. Cambridge University Press, NY, USA (2002).
- 3 . Research highlights, tuberculosis on the run. Nat. Med. 13, 911 (2007).
- 4 . Rising Plague: The Global Threat from Deadly Bacteria and Our Dwindling Arsenal to Fight Them. Spellberg Prometheus Books, NY, USA (2009).
- 5 . The phagosome: compartment with a license to kill. Traffic 8, 311–330 (2007).
- 6 . Elie Metchnikoff: father of natural immunity. Eur. J. Immunol. 38, 3257–3264 (2008).
- 7 . Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc. Natl Acad. Sci. USA 97, 8841–8848 (2000).
- 8 . Phagocytosis and comparative innate immunity: learning on the fly. Nat. Rev. Immunol. 8, 131–141 (2008).
- 9 . Phagocytosis and innate immunity. Curr. Opin. Immunol. 14, 13–145 (2002).
- 10 . The cell biology of Listeria monocytogenes infection: the intersection of bacterial pathogenesis and cell-mediated immunity. J. Cell Biol. 158, 409–414 (2002).
- 11 . Drug delivery systems for potential treatment of intracellular bacterial infections. Front. Biosci. (Landmark Ed.) 15, 397–417 (2010).
- 12 . Bacterial avoidance of phagocytosis. Trends Microbiol. 10, 231–237 (2002).
- 13 . Evasion of host cell defense mechanisms by pathogenic bacteria. Curr. Opin. Immunol. 1, 37–44 (2001).
- 14 . Entry and survival of pathogenic mycobacteria in macrophages. Microbes Infect. 3, 249–255 (2001).
- 15 . Phagocytosis of bacterial pathogens: implications in the host response. Semin. Immunol. 13, 381–390 (2001).
- 16 . Manipulation of host-cell pathways by bacterial pathogens. Nature 449, 827–834 (2007).
- 17 . Delivery of antibiotics with polymeric particles. Adv. Drug Deliv. Rev. 78, 63–76 (2014).
- 18 . Present status of nanoparticle research for treatment of tuberculosis. J. Pharm. Pharm. Sci. 14, 100–116 (2011).
- 19 . Best drug treatment for multidrug resistant and extensively drug-resistant tuberculosis. Lancet Infect. Dis. 10, 621–629 (2010).
- 20 . Nanomedicine and experimental tuberculosis: facts, flaws, and future. Nanomedicine 7, 259–272 (2011).
- 21 . Management of tuberculosis in the United States. N. Engl. J. Med. 345, 189–200 (2001).
- 22 . The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages. Trends Cell. Biol. 15, 269–276 (2005).
- 23 Induction of mouse melioidosis with meningitis by CD11b+ phagocytic cells harboring intracellular B. pseudomallei as a Trojan horse. PLoS Negl. Trop. Dis. 7, e2363 (2013).
- 24 . Intra-cellular Staphylococcus aureus: the Trojan horse of recalcitrant chronic rhinosinusitis? Int. Forum Allergy Rhinol. 3, 261–266 (2013).
- 25 . Invasion of the central nervous system by intracellular bacteria. Clin. Microbiol. Rev. 17, 323–347 (2004).
- 26 . Delivery systems to increase the selectivity of antibiotics in phagocytic cells. J. Control. Release 125, 210–227 (2008).
- 27 . Nanomedicines for overcoming biological barriers. Biomed. Pharmacother. 58, 168–172 (2004).
- 28 . Polymeric nanoparticulate system: a potential approach for ocular drug delivery. J. Control. Release 136, 2–13 (2009).
- 29 . Bacterial resistance to antibiotics: the role of biofilms. Prog. Drug Res. 37, 91–105 (1991).
- 30 . Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 9, 34–39 (2001).
- 31 Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. J. Immunol. 186, 6585–6596 (2011).
- 32 . Antibiotics and the resistant microbiome. Curr. Opin. Microbiol. 14, 556–563 (2011).
- 33 . Versatility of aminoglycosides and prospects for their future. Clin. Microbiol. Rev. 16, 430–450 (2003).
- 34 . The aminoglycosides. Med. Clin. North Am. 66, 303–312 (1982).
- 35 . The effect of surface charge on the disposition of liposome-encapsulated gentamicin to the rat liver, brain, lungs and kidneys after intraperitoneal administration. Int. J. Antimicrob. Agents 25, 392–397 (2005).
- 36 . Nanocarriers with gentamicin to treat intracellular pathogens. J. Nanosci. Nanotechnol. 6, 3296–3302 (2006).
- 37 . The importance of efflux pumps in bacterial antibiotic resistance. J. Antimicrob. Chemother. 51, 9–11 (2003).
- 38 . Influence of P-glycoprotein and MRP efflux pump inhibitors on the intracellular activity of azithromycin and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus. J. Antimicrob. Chemother. 51, 1167–1173 (2003).
- 39 . Liposomes and nanoparticles in the treatment of intracellular bacterial infections. Pharm. Res. 8, 1079–1086 (1991).
- 40 . Uptake of ciprofloxacin by human neutrophils. J. Antimicrob. Chemother. 16, 67–73 (1985).
- 41 . Targeted delivery of antibiotics using liposomes and nanoparticles: research and applications. Int. J. Antimicrob. Agents 13, 155–168 (2000).
- 42 . Intracellular distribution and activity of antibiotics. Eur. J. Clin. Microbiol. Infect. Dis. 10, 100–106 (1991).
- 43 . Intracellular pharmacokinetics and localization of antibiotics as predictors of their efficacy against intraphagocytic infections. Scand. J. Infect. Dis. Suppl. 74, 209–217 (1990).
- 44 Cellular accumulation of fluoroquinolones is not predictive of their intracellular activity: studies with gemifloxacin, moxifloxacin and ciprofloxacin in a pharmacokinetic/pharmacodynamic model of uninfected and infected macrophages. Int. J. Antimicrob. Agents 38(3), 249–256 (2011).
- 45 . Intracellular pharmacodynamics of antibiotics. Infect. Dis. Clin. North Am. 17(3), 615–634 (2003).
- 46 Chemical and biological factors in the control of Brucella and brucellosis. Curr. Drug Deliv. 3, 359–365 (2006).
- 47 . Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics. ACS Nano 22, 4279–4287 (2012).
- 48 . Efficacies of liposome encapsulated clarithromycin and ofloxacin against Mycobacterium avium-M. intracellular complex in human macrophages. Antimicrob. Agents Chemother. 38, 523–527 (1994).
- 49 . Overcoming the challenges in administering biopharmaceutical drugs: formulation and delivery strategies. Nat. Rev. Drug Discov. 13, 655–672 (2014).
- 50 . Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem. Soc. Rev. 41, 2971–3010 (2012).
- 51 . Endocytosis and intracellular trafficking as gateways for nanomedicines delivery: opportunities and challenges. Mol. Pharm. 9, 2380–2402 (2012).
- 52 . Nanoparticle–cell interactions: drug delivery implications. Crit. Rev. Ther. Drug Carrier Syst. 25, 485–544 (2008).
- 53 Nanomedicine for intracellular therapy. FEMS Microbiol. Lett. 332, 1–9 (2012).
- 54 . Nanocarriers’ entry into the cell: relevance to drug delivery. Cell. Mol. Life Sci. 66, 2873–2896 (2009).
- 55 . Endocytosis of nanomedicines. J. Control. Release 145, 182–195 (2010).
- 56 . Intracellular delivery: Fundamentals and Applications. Springer, NY, USA (2011).
- 57 The development of site-specific drug delivery nanocarriers based on receptor mediation. J. Control. Release 193, 139–153 (2014).
- 58 . Strategies for the intracellular delivery of nanoparticles. Chem. Soc. Rev. 40(1), 233–245 (2011).
- 59 . Biodegradable long-circulating polymeric nanospheres. Science 263, 1600–1603 (1994).
- 60 . Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog. Lipid Res. 42, 463–478 (2003).
- 61 . Nanoparticles escaping RES and endosome: challenges for siRNA delivery for cancer therapy. J. Nanomater.
doi:10.1155/2011/742895 (2011). - 62 . Virus entry: open sesame. Cell 124, 729–740 (2006).
- 63 . Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 9, 615–627 (2010).
- 64 . Endocytic mechanisms for targeted drug delivery. Adv. Drug Deliv. Rev. 59, 748–758 (2007).
- 65 Intracellular delivery and antibacterial activity of gentamicin encapsulated in pH-sensitive liposomes. Antimicrob. Agents Chemother. 42, 2511–2520 (1998).
- 66 . Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella. J. Antimicrob. Chemother. 68, 2576–2586 (2013).
- 67 . Endocytosis and exocytosis of nanoparticles in mammalian cells. Int. J. Nanomedicine
doi:10.2147/IJN.S26592 (2014) (Epub ahead of print). - 68 . Exocytosis of nanoparticles from cells: role in cellular retention and toxicity. Adv. Colloid Interface Sci. 201–202, 18–29 (2013).
- 69 . Interactions between antimicrobial agents, phagocytic cells and bacteria. Curr. Med. Chem. Anti-Infect. Agents 2, 73–82 (2003).
- 70 . Liposomes and nanoparticles as vehicles for antibiotics. Infection 19(4), S224–S228 (1991).
- 71 . Nanobead-based interventions for the treatment and prevention of tuberculosis. Nat. Rev. Microbiol. 8, 827–834 (2010).
- 72 An isoniazid analogue promotes Mycobacterium tuberculosis-nanoparticle interactions and enhances bacterial killing by macrophages. Antimicrob. Agents Chemother. 56, 2259–2267 (2012).
- 73 . Killing of intraphagocytic Staphylococcus aureus by dihydrostreptomycin entrapped within liposomes. Antimicrob. Agents Chemother. 13, 1049 (1978).
- 74 Efficacy of tetracycline encapsulated O-carboxymethyl chitosan nanoparticles against intracellular infections of Staphylococcus aureus. Int. J. Biol. Macromol. 51, 392–399 (2012).
- 75 Preparation of liposomal vancomycin and intracellular killing of methicillin-resistant Staphylococcus aureus (MRSA). Int. J. Antimicrob. Agents 37, 140–144 (2011).
- 76 . Ciprofloxacin nanoniosomes for targeting intracellular infections: an in vitro evaluation. J. Nanoparticle Res. 15, 1–14 (2013).
- 77 . Intracellular killing of Mycobacterium avium complex by rifapentine and liposome-encapsulated amikacin. J. Infect. Dis. 156, 510–513 (1987).
- 78 . Treatment of disseminated Mycobacterium avium complex infection of beige mice with liposome encapsulated aminoglycosides. J. Infect. Dis. 161, 1262–1268 (1990).
- 79 . The mechanism of enhanced intraphagocytic killing of bacteria by liposomes containing antibiotics. Vet. Immunol. Immunopathol. 24, 135–146 (1990).
- 80 Efficacies of liposome-encapsulated streptomycin and ciprofloxacin against Mycobacterium avium-M. intracellulare complex infections in human peripheral blood monocyte/macrophages. Antimicrob. Agents Chemother. 36, 2808–2815 (1992).
- 81 . Activities of liposome encapsulated azithromycin and rifabutin compared with that of clarithromycin against Mycobacterium avium-intracellulare complex in human macrophages. Int. J. Antimicrob. Agents 4, 281–289 (1994).
- 82 Rifampicinloaded liposomes for the passive targeting to alveolar macrophages: in vitro and in vivo evaluation. J. Liposome Res. 19, 68–76 (2009).
- 83 . Treatment of intracellular Mycobacterium avium complex infection by free and liposome-encapsulated sparfloxacin. Antimicrob. Agents Chemother. 40, 2618–2621 (1996).
- 84 . Formulation and efficacy of liposome encapsulated antibiotics for therapy of intracellular Mycobacterium avium infection. Antimicrob. Agents Chemother. 39, 2104–2111 (1995).
- 85 . Activities of clarithromycin, azithromycin, and ofloxacin in combination with liposomal or unencapsulated granulocyte-macrophage colony-stimulating factor against intramacrophage Mycobacterium avium-Mycobacterium intracellular. J. Infect. Dis. 172, 810–816 (1995).
- 86 . Enhanced intramacrophage activity of resorcinomycin A against Mycobacterium avium–Mycobacterium intracellulare complex after liposome encapsulation. Antimicrob. Agents Chemother. 40, 2545–2549 (1996).
- 87 . Monitoring safety of liposomes containing rifampicin on respiratory cell lines and in vitro efficacy against Mycobacterium bovis in alveolar macrophages. J. Drug Target. 17, 751–762 (2009).
- 88 . Nanoparticles as antituberculosis drugs carriers: effect on activity against Mycobacterium tuberculosis in human monocyte-derived macrophages. J. Nanoparticle Res. 2, 165–171 (2000).
- 89 Encapsulation of moxifloxacin within poly(butyl cyanoacrylate) nanoparticles enhances efficacy against intracellular Mycobacterium tuberculosis. Int. J. Pharm. 345, 154–162 (2007).
- 90 Development of a nanosomal formulation of moxifloxacin based on poly(butyl-2-cyanoacrylate). Pharm. Chem. J 42, 145–149 (2008).
- 91 Targeted intracellular delivery of antituberculosis drugs to Mycobacterium tuberculosis-Infected macrophages via functionalized mesoporous silica nanoparticles. Antimicrob. Agents Chemother. 56(5), 2535–2545 (2012).
- 92 . Efficient drug targeting to rat alveolar macrophages by pulmonary administration of ciprofloxacin incorporated into mannosylated liposomes for treatment of respiratory intracellular parasitic infections. J. Control. Release 127, 50–58 (2008).
- 93 . Respirable PLGA microspheres containing rifampicin for the treatment of tuberculosis: manufacture and characterization. Pharm. Res. 17, 955–961 (2000).
- 94 . Inhalable microparticles containing large payload of anti-tuberculosis drugs. Eur. J. Pharm. Sci. 32, 140–150 (2007).
- 95 . Gelatin nanocarriers as potential vectors for effective management of tuberculosis. Int. J. Pharm. 385, 143–149 (2010).
- 96 . Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolized antitubercular drug carriers for treatment of tuberculosis. J. Antimicrob. Chemother. 54, 761–766 (2004).
- 97 . Poly (DL-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis. J. Antimicrob. Chemother. 52, 981–986 (2003).
- 98 . Inhalable alginate nanoparticles as antitubercular drug carriers against experimental tuberculosis. Int. J. Antimicrob. Agents 26, 298–303 (2005).
- 99 . Preparation and characterization of spray dried inhalable powders containing chitosan nanoparticles for pulmonary delivery of isoniazid. J. Microencapsul. 28, 605–613 (2011).
- 100 Mannosylated gelatin nanoparticles bearing isoniazid for effective management of tuberculosis. J. Drug Target. 19, 219–227 (2011).
- 101 . Antitubercular inhaled therapy: opportunities, progress and challenges. J. Antimicrob. Chemother. 55, 430–435 (2005).
- 102 . Intraphagocytic killing of Salmonella typhimurium by liposome-encapsulated cephalothin. J. Infect. Dis. 148, 563–570 (1983).
- 103 . Liposome-encapsulated cephalothin in the treatment of experimentalmurine salmonellosis. J. Reticuloendothel. Soc. 34, 279–287 (1983).
- 104 . Intracellular visualization of ampicillin-loaded nanoparticles in peritoneal macrophages infected in vitro with Salmonella typhimurium. Pharm. Res. 11, 38–46 (1994).
- 105 . The uptake of ampicillin-loaded nanoparticles by murine macrophages infected with Salmonella typhimurium. J. Antimicrob. Chemother. 33, 509–522 (1994).
- 106 . Intracellular distribution of ampicillin in murine macrophages infected with Salmonella typhimurium and treated with (3H) ampicillin-loaded nanoparticles. Antimicrob. Chemother. 37, 105–115 (1996).
- 107 . Enhanced antibacterial effect of ceftriaxone sodium-loaded chitosan nanoparticles against intracellular Salmonella typhimurium. AAPS PharmSciTech 13, 411–421 (2012).
- 108 Antibacterial efficacy of gentamicin encapsulated in pH-sensitive liposomes against an in vivo Salmonella enterica serovar Typhimurium intracellular infection model. Antimicrob. Agents Chemother. 44, 533–539 (2000).
- 109 In vitro trafficking and efficacy of core-shell nanostructures for treating intracellular Salmonella infections. Antimicrob. Agents Chemother. 53, 3985–3988 (2009).
- 110 . The effect of incorporation of cloxacillin in liposomes on treatment of experimental staphylococcal mastitis in mice. J. Vet. Pharmacol. Ther. 9, 303–309 (1986).
- 111 . Effect of lipid composition on activity of liposome-entrapped ampicillin against intracellular Listeria monocytogenes. Antimicrob. Agents Chemother. 32, 1560–1564 (1988).
- 112 . Effect of nanoparticle-bound ampicillin on the survival of Listeria monocytogenes in mouse peritoneal macrophages. J. Antimicrob. Chemother. 30, 173–179 (1992).
- 113 . Enhanced activity of streptomycin and chloramphenicol against intracellular Escherichia coli in the J774 macrophage cell line mediated by liposome delivery. Antimicrob. Agents Chemother. 24, 742–749 (1983).
- 114 . Enhanced intraphagocytic killing of Brucella abortus in bovine mononuclear cells by liposomes-containing gentamicin. Vet. Immunol. Immunopathol. 8, 171–182 (1985).
- 115 . Treatment of Brucella canis and Brucella abortus in vitro and in vivo by stable plurilamellar vesicle encapsulated aminoglycosides. J. Infect. Dis. 152, 529–535 (1985).
- 116 . Effect of composition and method of preparation of liposomes on their stability and interaction with murine monocytes infected with Brucella abortus. Antimicrob. Agents Chemother. 40, 146–151 (1996).
- 117 Cellular pharmacokinetics and intracellular activity against Listeria monocytogenes and Staphylococcus aureus of chemically modified and nanoencapsulated gentamicin. J. Antimicrob. Chemother. 67, 2158–2164 (2012).
- 118 Block ionomer complexes containing cationic antibiotics to kill intracellular Brucella melitensis in vitro. Polym. Adv. Technol. 23, 1484–1493 (2012).
- 119 . Intracellular killing of Brucella melitensis in human macrophages with microsphere-encapsulated gentamicin. J. Antimicrob. Chemother. 58, 549–556 (2006).
- 120 . Activity of liposomal amphotericin b with prolonged circulation in blood versus those of ambisome and fungizone against intracellular Candida albicans in murine peritoneal macrophages. Antimicrob. Agents Chemother. 42(9), 2437–2439 (1998).
- 121 Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles. Biomaterials 32, 6606–6613 (2011).
- 122 . The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosis. Am. J. Respir. Crit. Care Med. 172, 1487–1490 (2005).
- 123 . Evaluation of ciprofloxacin-loaded Eudragit RS100 or RL100/PLGA nanoparticles. Int. J. Pharm. 314, 72–82 (2006).
- 124 . Pharmacokinetics and in vivo activity of liposome-encapsulated gentamicin. Antimicrob. Agents Chemother. 34, 235–240 (1990).
- 125 . Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection. J. Control. Release 92, 265–273 (2003).
- 126 . Long circulating sterically stabilized liposomes in the treatment of infections. Methods Enzymol. 391, 228–260 (2005).
- 127 . Host factors influencing the preferential localization of sterically stabilized liposomes in Klebsiella pneumoniae-infected rat lung tissue. Pharm. Res. 18, 780–787 (2001).
- 128 . Manipulating cellular transport and immune responses: dynamic interactions between intracellular Salmonella enterica and its host cells. Cell. Microbiol. 8, 728–737 (2006).
- 129 . Successful treatment using gentamicin liposomes of Salmonella Dublin infections in mice. Antimicrob. Agents Chemother. 34, 343–348 (1990).
- 130 . Molecular parameters involved in aminoglycoside nephrotoxicity. J. Toxicol. Environ. Health 44, 263–300 (1995).
- 131 . Chemotherapeutic evaluation of alginate nanoparticle-encapsulated azole antifungal and antitubercular drugs against murine tuberculosis. Nanomedicine 3, 239–243 (2007).
- 132 Targeted drug delivery to enhance efficacy and shorten treatment duration in disseminated Mycobacterium avium infection in mice. J. Antimicrob. Chemother. 60, 1064–1073 (2007).
- 133 . Nanoparticles for drug delivery to the lungs. Trends Biotechnol. 25(12), 563–570 (2007).
- 134 . The chemotherapy of tuberculosis: past, present and future. Int. J. Tuberc. Lung Dis. 16(6), 724–732 (2012).
- 135 . Lipid-based carriers for pulmonary products: preclinical development and case studies in humans. Adv. Drug Deliv. Rev. 75, 53–80 (2014).
- 136 . Nanoparticle formulations in pulmonary drug delivery. Med. Res. Rev. 29(1), 196–212 (2009).
- 137 . Pulmonary drug delivery: a role for polymeric nanoparticles? Curr. Top Med. Chem. 15(4), 386–400 (2015).
- 138 . Enhanced intracellular killing of Staphylococcus aureus by canine monocytes treated with liposomes containing amikacin, gentamicin, kanamycin, and tobramycin. Curr. Microbiol. 6, 373–376 (1981).
- 139 . The use of liposomally-entrapped gentamicin in the treatment of bovine Staphylococcus aureus mastitis. Can. J. Vet. Res. 52, 445–450 (1988).
- 140 . Differential effects of free and liposome encapsulated amikacin on the survival of Mycobacterium avium complex in mouse peritoneal macrophages. Tubercle 71, 215–217 (1990).
- 141 . Activity of free and liposome encapsulated streptomycin against Mycobacterium avium complex (MAC) inside peritoneal macrophages. J. Antimicrob. Chemother. 28, 615–617 (1991).
- 142 . Efficient drug delivery to alveolar macrophages and lung epithelial lining fluid following pulmonary administration of liposomal ciprofloxacin in rats with pneumonia and estimation of its antibacterial effects. Drug Dev. Ind. Pharm. 34, 1090–1096 (2008).
- 143 . Efficacies of cyclodextrin-complexed and liposome-encapsulated clarithromycin against Mycobacterium avium complex infection in human macrophages. Int. J. Pharmaceut. 250, 345–352 (2003).
- 144 . Enhanced killing of methicillin resistant Staphylococcus aureus in human macrophages by liposome-entrapped vancomycin and teicoplanin. Infection 22, 338–342 (1994).
- 145 Evaluation of the efficiency of activity of the liposomal form of isoniazid against different types of mycobacteria in vitro. Probl. Tuberk. Bolezn. Legk. 8, 61–64 (2006).
- 146 In vitro uptake and antimycobacterial activity of liposomal usnic acid formulation. J. Liposome Res. 19, 49–58 (2009).
- 147 . Determination of intracellular (neutrophil and monocyte) concentrations of free and liposome encapsulated ampicillin in sheep. Vet. Med. 51, 51–54 (2006).
- 148 . Liposome-encapsulated ampicillin against Listeria monocytogenes in vivo and in vitro. Infection 16(Suppl. 2), S165–S170 (1988).
- 149 In vivo synergistic interaction of liposome-coencapsulated gentamicin and ceftazidime. J. Pharmacol. Exp. Ther. 298, 369–375 (2001).
- 150 . Attenuation of Pseudomonas aeruginosa virulence factors and biofilms by co-encapsulation of bismuth-ethanedithiol with tobramycin in liposomes. J. Antimicrob. Chemother. 65, 684–693 (2010).
- 151 . Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa. J. Antimicrob. Chemother. 62, 1291–1297 (2008).
- 152 . Nanocarriers for antibiotics: a promising solution to treat intracellular bacterial infections. Int. J. Antimicrob. Agents 43, 485–496 (2014).
- 153 Effectiveness of nanoparticle-bound ampicillin in the treatment of Listeria monocytogenes infection in athymic nude mice. Antimicrob. Agents Chemother. 32(8), 1204–1207 (1988).
- 154 Poly(lactide-co-glycolide)-rifampicin nanoparticles efficiently clear Mycobacterium bovis BCG infection in macrophages and remain membrane-bound in phago-lysosomes. J. Cell. Sci. 126, 3043–3054 (2013).
- 155 Delivery of rifampicin-PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis. J. Control. Release 142, 339–346 (2010).
- 156 Selective delivery of rifampicin incorporated into poly(DL-lactic-co-glycolic) acid microspheres after phagocytotic uptake by alveolar macrophages, and the killing effect against intracellular Mycobacterium bovis Calmette–Guérin. Microbes Infect. 8, 2484–2491 (2006).
- 157 . Treatment of tuberculosis using a combination of sustained-release rifampin-loaded microspheres and oral dosing with isoniazid. Antimicrob. Agents Chemother. 45, 1637–1644 (2001).
- 158 Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin against an in vivo intracellular Salmonella model. Int. J. Nanomedicine 4, 289–297 (2009).
- 159 . Increase in gentamicin uptake by cultured mouse peritoneal macrophages and rat hepatocytes by its binding to polybutylcyanoacrylate nanoparticles. Int. J. Pharm. 164, 21–27 (1998).
- 160 . Effect of liposome-entrapped ampicillin on survival of Listeria monocytogenes in murine peritoneal macrophages. Antimicrob. Agents Chemother. 30, 295–300 (1986).
- 161 . Intracellular targeting of antibiotics by means of biodegradable nanoparticles. J. Control. Release 19, 259–267 (1992).
- 162 . Targeting Brucella melitensis with polymeric nanoparticles containing streptomycin and doxycycline. FEMS Microbiol. Lett 294, 24–31 (2009).
- 163 PAMAM dendrimer-azithromycin conjugate nanodevices for the treatment of Chlamydia trachomatis infections. Nanomedicine 7, 935–944 (2011).
- 164 Poly(amidoamine) dendrimer-erythromycin conjugates for drug delivery to macrophages involved in periprosthetic inflammation. Nanomedicine 7, 284–294 (2011).
- 165 Antibacterial properties of nanoparticles. Trends Biotechnol. 30, 499–511 (2012).
- 166 . “Nanoantibiotics”: a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era. J. Control. Release 156, 128–145 (2011).
- 167 . Antimicrobial applications of nanotechnology: methods and literature. Int. J. Nanomedicine 7, 2767–2781 (2012).
- 168 . Nanotechnology as a therapeutic tool to combat microbial resistance. Adv. Drug Deliv. Rev. 65, 1803–1815 (2013).
- 169 . Silver nanoparticles impede the biofilm formation by Pseudomonas aeruginosa and Staphylococcus epidermidis. Colloids Surf. B Biointerfaces 79, 340–344 (2010).
- 170 . New strategies in the development of antimicrobial coatings: the example of increasing usage of silver and silver nanoparticles. Polymers 3, 340–366 (2011).
- 171 . Antimicrobial surface functionalization of plastic catheters by silver nanoparticle. J. Antimicrob. Chemother. 61, 869–876 (2008).
- 172 . ZnO nanoparticle-coated surfaces inhibit bacterial biofilm formation and increase antibiotic susceptibility. RSC Advances 2, 2314–2321 (2012).
- 173 . Antibiofilm surface functionalization of catheters by magnesium fluoride nanoparticles. Int. J. Nanomedicine 7, 1175–1188 (2012).
- 174 . Silver-coated engineered magnetic nanoparticles are promising for the success in the fight against antibacterial resistance threat. ACS Nano 6, 2656–2664 (2012).
- 175 Inactivation of Pseudomonas aeruginosa PA01 biofilms by hyperthermia using superparamagnetic nanoparticles. J. Microbiol. Methods 84, 41–45 (2011).
- 176 Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria. Int. J. Nanomedicine 8, 3187–3195 (2013).
- 177 . Synergistic antibacterial effects of β-lactam antibiotic combined with silver nanoparticles. Nanotechnology 16, 1912–1917 (2005).
- 178 . Synthesis and effect of silver nanoparticles on the antibacterial activity of different antibiotics against Staphylococcus aureus and Escherichia coli. Nanomedicine 3, 168–171 (2007).
- 179 . Synergistic effect of biogenic silver nanocolloid in combination with antibiotics: a potent therapeutic agent. Int. J. Pharm. Pharm. Sci. 5, 292–295 (2013).
- 180 . Biogenic synthesis of silver nanoparticles and their synergistic effect with antibiotics: a study against gram-positive and gram-negative bacteria. Nanomedicine 6, 103–109 (2010).
- 181 . Therapeutic potential of nanoparticulate systems for macrophage targeting. Biomaterials 26, 7260–7275 (2005).
- 182 . Targeted liposomal drug delivery to monocytes and macrophages. J. Drug Deliv.
doi:10.1155/2011/727241 (2011). - 183 . Design of liposomal aerosols for improved delivery of rifampicin to alveolarmacrophages. Int. J. Pharm. 269, 37–49 (2004).
- 184 . Bacteria-responsive multifunctional nanogel for targeted antibiotic delivery. Adv. Mater. 24, 6175–6180 (2012).
- 185 . Uptake characteristics of liposomes by rat alveolar macrophages: influence of particle size and surface mannose modification. J. Pharm. Pharmacol. 59, 75–80 (2007).
- 186 Nanoconjugated vancomycin. new opportunities for the development of anti-VRSA agents. Nanotechnology 21, 105103 (2010).
- 187 . Nanoparticle approaches against bacterial infections. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 6, 532–547 (2014).
- 188 Bacterial toxin-triggered drug release from gold nanoparticle-stabilized liposomes for the treatment of bacterial infection. J. Am. Chem. Soc. 133, 4132–4139 (2011).
- 189 . Lipase-sensitive polymeric triple-layered nanogel for “on-demand” drug delivery. J. Am. Chem. Soc. 134, 4355–4362 (2012).
- 190 . Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 12, 991–1003 (2013).
- 191 . Bacteria-triggered release of antimicrobial agents. Angew. Chem. Int. Ed. Engl. 53, 439–441 (2014).
- 192 Self-assembled squalenoylated penicillin bioconjugates: an original approach for the treatment of intracellular infections. ACS Nano 6, 3820–3831 (2012).
- 193 . A nano-silver composite based on the ion-exchange response for the intelligent antibacterial applications. Mater. Sci. Eng. C Mater. Biol. Appl. 41, 134–141 (2014).
- 194 Extrapulmonary locations of Mycobacterium tuberculosis DNA during latent infection. J. Infect. Dis. 206, 1194–1205 (2012).
- 195 . Listeria as an enteroinvasive gastrointestinal pathogen. Curr. Top. Microbiol. Immunol. 337, 173–195 (2009).
- 196 Intra-macrophage survival of uropathogenic Escherichia coli: differences between diverse clinical isolates and between mouse and human macrophages. Immunobiology 216, 1164–1171 (2011).
- 197 Leprosy as a model of immunity. Future Microbiol. 9, 43–54 (2014).
- 198 . Bacterial distribution in lung parenchyma early after pulmonary infection with Pseudomonas aeruginosa. Cell Tissue Res. 342, 67–73 (2010).
- 199 . Cell tropism of Salmonella enterica. Int. J. Med. Microbiol. 294, 225–233 (2004).
- 200 . Microbiological aspects of rifapentine. Drugs Today 35, 7–15 (1999).
- 201 . Dormancy in non-sporulating bacteria. FEMS Microbiol. Rev. 10, 271–285 (1993).
- 202 . Drug targeting by polyalkylcyanoacrylate nanoparticles is not efficient against persistent Salmonella. Pharm Res. 15, 544–549 (1998).
- 203 . Cellular uptake, localization and activity of fluoroquinolones in uninfected and infected macrophages. J. Antimicrob. Chemother. 26(Suppl. B), 27–39 (1990).
- 204 . Inhibition of endosomal sequestration of basic anticancer drugs: influence on cytotoxicity and tissue penetration. Br. J. Cancer 94, 863–869 (2006).
- 205 Delivering quantum dot-peptide bioconjugates to the cellular cytosol: escaping from the endolysosomal system. Integr. Biol. (Camb.) 2, 265–277 (2010).
- 206 . in vitro assessment of a novel polyrotaxane-based drug delivery system integrated with a cell-penetrating peptide. J. Control. Release 124, 43–50 (2007).
- 207 . Enhanced folate receptor mediated gene therapy using a novel pH-sensitive lipid formulation. J. Control. Release 64, 27–37 (2000).
- 208 . Cell penetrating peptide-modified pharmaceutical nanocarriers for intracellular drug and gene delivery. Biopolymers 90, 604–610 (2008).