Skip to main content

Advertisement

SpringerLink
Log in

Nano-fats for bugs: the benefits of lipid nanoparticles for antimicrobial therapy

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Bacterial infections are an imminent global healthcare threat evolving from rapidly advancing bacterial defence mechanisms that antibiotics fail to overcome. Antibiotics have been designed for systemic administration to target planktonic bacteria, leading to difficulties in reaching the site of localized bacterial infection and an inability to overcome the biological, chemical and physical barriers of bacteria, including biofilms, intracellular infections and antimicrobial resistance. The amphiphilic, biomimetic and antimicrobial properties of lipids provide a promising toolbox to innovate and advance antimicrobial therapies, overcoming the barriers presented by bacteria in order to directly and effectively treat recalcitrant infections. Nanoparticulate lipid-based drug delivery systems can enhance antibiotic permeation through the chemical and physical barriers of bacterial infections, as well as fuse with bacterial cell membranes, release antibiotics in response to bacteria and act synergistically with loaded antibiotics to enhance the total antimicrobial efficacy. This review explores the barriers presented by bacterial infections that pose bio-pharmaceutical challenges to antibiotics and how different structural and functional mechanisms of lipids can enhance antimicrobial therapies. Different nanoparticulate lipid-based systems are presented as valuable drug delivery systems to advance the efficacy of antibiotics, including liposomes, liquid crystalline nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers and lipid nanocarriers. In summary, liquid crystalline nanoparticles are emerging with the greatest potential for clinical applications and commercial success as an “all-rounder” advanced lipid-based antimicrobial therapy that overcomes the multiple biological, chemical and physical barriers of bacteria.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. WHO. The top 10 causes of death. 2018.

  2. Wolf DM, et al. Memory in microbes: quantifying history-dependent behavior in a bacterium. PLoS One. 2008;3(2):e1700.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Beceiro A, Tomás M, Bou G. Antimicrobial resistance and virulence: a successful or deleterious association in the bacterial world? Clin Microbiol Rev. 2013;26(2):185–230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ciofu O, et al. Antibiotic treatment of biofilm infections. APMIS. 2017;125(4):304–19.

    Article  PubMed  Google Scholar 

  5. Thakur A, Mikkelsen H, Jungersen G. Intracellular pathogens: host immunity and microbial persistence strategies. J Immunol Res. 2019. 

  6. Forier K, et al. Lipid and polymer nanoparticles for drug delivery to bacterial biofilms. J Control Release. 2014;190:607–23.

    Article  CAS  PubMed  Google Scholar 

  7. Canaparo R, et al. Recent Developments in Antibacterial Therapy: Focus on stimuli-responsive drug-delivery systems and therapeutic nanoparticles. Molecules. 2019;24(10)

  8. Dua K, et al. Whether a novel drug delivery system can overcome the problem of biofilms in respiratory diseases? Drug Deliv Transl Res. 2017;7(1):179–87.

    Article  CAS  PubMed  Google Scholar 

  9. Lee NY, Ko WC, Hsueh PR. Nanoparticles in the Treatment of infections caused by multidrug-resistant Organisms. Front Pharmacol. 2019;0(1153).

  10. Bongers S, et al. Intracellular penetration and effects of antibiotics on Staphylococcus aureus inside human neutrophils: a comprehensive review. Antibiotics. 2019;8(2):54.

    Article  CAS  PubMed Central  Google Scholar 

  11. Baptista PV, et al. Nano-Strategies to Fight Multidrug Resistant Bacteria—“A Battle of the Titans”. Frontiers in Microbiology. 2018;9(1441).

  12. Umerska A, et al. Synergistic interactions between antimicrobial peptides derived from plectasin and lipid nanocapsules containing monolaurin as a cosurfactant against Staphylococcus aureus. Int J Nanomed. 2017;12:5687–99.

    Article  CAS  Google Scholar 

  13. Desbois AP, Smith VJ. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential. Appl Microbiol Biotechnol. 2010;85(6):1629–42.

    Article  CAS  PubMed  Google Scholar 

  14. Flemming HC, et al. Biofilms: an emergent form of bacterial life. 2016;14: p. 563.

  15. Mansour SC, et al. Bacterial abscess formation is controlled by the stringent stress response and can be targeted therapeutically. EBioMedicine. 2016;12:219–26.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Costerton JW, et al. Microbial biofilms. Annu Rev Microbiol. 1995;49:711–45.

    Article  CAS  PubMed  Google Scholar 

  17. Brauner A, et al. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat Rev Micro. 2016;14(5):320–30.

    Article  CAS  Google Scholar 

  18. Silva VO, et al. Biofilm formation on biotic and abiotic surfaces in the presence of antimicrobials by Escherichia coli Isolates from cases of bovine mastitis. Appl Environ Microbiol. 2014;80(19):6136–45.

    Article  PubMed  PubMed Central  Google Scholar 

  19. World Health Organisation: Geneva. 2017.

  20. Davies JC. Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence. Paediatr Respir Rev. 2002;3(2):128–34.

    Article  PubMed  Google Scholar 

  21. de la Fuente-Nunez C, et al. D-enantiomeric peptides that eradicate wild-type and multidrug-resistant biofilms and protect against lethal Pseudomonas aeruginosa infections. Chem Biol. 2015;22(2):196–205.

    Article  PubMed  PubMed Central  Google Scholar 

  22. de la Fuente-Núñez C, et al. Broad-spectrum anti-biofilm peptide that targets a cellular stress response. PLoS Pathog. 2014;10(5):e1004152.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Pletzer D, Hancock REW. Antibiofilm peptides: potential as broad-spectrum agents. J Bacteriol. 2016;198(19):2572–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. van Delden C, et al. Stringent response activates quorum sensing and modulates cell density-dependent gene expression Pseudomonas aeruginosa. J Bacteriol. 2001;183(18):5376.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pesci EC, et al. Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa. J Bacteriol. 1997;179(10):3127–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Papenfort K, Bassler BL. Quorum sensing signal-response systems in Gram-negative bacteria. Nat Rev Microbiol. 2016;14(9):576–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Miller MB, Bassler BL. Quorum sensing in bacteria. Annu Rev Microbiol. 2001;55:165–99.

    Article  CAS  PubMed  Google Scholar 

  28. Ferrand J, Ferrero RL. Recognition of extracellular bacteria by NLRs and its role in the development of adaptive immunity. Front immunol. 2013;4:344–344.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Fraunholz M, Sinha B. Intracellular Staphylococcus aureus: live-in and let die. Front Cell Infec Microbiol. 2012;2:43.

    Article  Google Scholar 

  30. Löffler B, et al. Staphylococcus aureus persistence in non-professional phagocytes. Int J Med Microbiol. 2014;304(2):170–6.

    Article  PubMed  Google Scholar 

  31. Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis. 2008;197(8):1079–81.

    Article  PubMed  Google Scholar 

  32. Santajit S, Indrawattana N. Mechanisms of antimicrobial resistance in ESKAPE pathogens. Biomed Res Int. 2016;2016:2475067.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Munita JM, Arias CA. Mechanisms of Antibiotic Resistance. Microbiology Spectrum. 2016;4(2): p. https://doi.org/10.1128/microbiolspec.VMBF-0016-2015.

  34. Blair JMA, et al. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2015;13(1):42–51.

    Article  CAS  PubMed  Google Scholar 

  35. O’Neill J. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations, in the review on antimicrobial resistance. 2014; p. 1–16.

  36. Thambavita D, et al. Biowaiver monograph for immediate-release solid oral dosage forms: amoxicillin trihydrate. J Pharm Sci. 2017;106(10):2930–45.

    Article  CAS  PubMed  Google Scholar 

  37. Jafari Ozumchelouei E, et al. Physicochemical properties of antibiotics: a review with an emphasis on detection in the aquatic environment. Water Environ Res. 2020;92(2):177–88.

    Article  CAS  PubMed  Google Scholar 

  38. delMoral-Sanchez JM, et al. Classification of WHO essential oral medicines for children applying a provisional pediatric biopharmaceutics classification system. Pharmaceutics. 2019;11(11).

  39. Hancock REW, Bell A, Uptakeinto Gram-Negative Bacteria. A. Berlin. Heidelberg: Springer, Berlin Heidelberg; 1989.

    Google Scholar 

  40. Graef F, Gordon S, Lehr CM. Anti-infectives in drug delivery—overcoming the gram-negative bacterial cell envelope. In: Stadler M, Dersch P, editors. How to overcome the antibiotic crisis : Facts, challenges, technologies and future perspectives. Cham: Springer International Publishing; 2016. p. 475–96.

    Chapter  Google Scholar 

  41. Nakae T. Outer-membrane permeability of bacteria. CRC Crit Rev Microbiol. 1986;13(1):1–62.

    Article  CAS  Google Scholar 

  42. Dever LA, Dermody TS. Mechanisms of bacterial resistance to antibiotics. Arch Intern Med. 1991;151(5):886–95.

    Article  CAS  PubMed  Google Scholar 

  43. Pagès JM, James CE, Winterhalter M. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol. 2008;6(12):893–903.

    Article  PubMed  Google Scholar 

  44. Cowan T. Biofilms and their management: from concept to clinical reality. J Wound Care. 2011;20(5): p. 220, 222–6.

  45. Lewis R. The rise of antibiotic-resistant infections. FDA consumer magazine. 1995;29(1).

  46. Hastedt JE, et al. Scope and relevance of a pulmonary biopharmaceutical classification system AAPS/FDA/USP Workshop March 16–17th, 2015 in Baltimore, MD. AAPS Open. 2016;2(1):1.

    Article  Google Scholar 

  47. Shah VP, et al. A science based approach to topical drug classification system (TCS). Int J Pharm. 2015;491(1):21–5.

    Article  CAS  PubMed  Google Scholar 

  48. Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med. 2010;363(23):2233–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Tseng BS, et al. The extracellular matrix protects Pseudomonas aeruginosa biofilms by limiting the penetration of tobramycin. Environ Microbiol. 2013;15(10):2865–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Alipour M, Suntres ZE, Omri A. Importance of DNase and alginate lyase for enhancing free and liposome encapsulated aminoglycoside activity against Pseudomonas aeruginosa. J Antimicrob Chemother. 2009;64(2):317–25.

    Article  CAS  PubMed  Google Scholar 

  51. Justo JA, Bookstaver B. Antibiotic lock therapy: review of technique and logistical challenges. Infection and Drug Resistance. 2014;7:343–63.

    PubMed  PubMed Central  Google Scholar 

  52. Singh R, et al. Penetration of antibiotics through Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Antimicrob Chemother. 2010;65(9):1955–8.

    Article  CAS  PubMed  Google Scholar 

  53. Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol. 2010;8(9):623–33.

    Article  CAS  PubMed  Google Scholar 

  54. Tanford C. The hydrophobic effect: formation of micelles and biological membranes 2d ed. 1980: J. Wiley.

  55. Hyde ST. Identification of lyotropic liquid crystalline mesophases. Handbook of Applied Surface and Colloid Chemistry. 2001;2:299–332.

    Google Scholar 

  56. Cronan Jr, JE, Gelmann EP. Physical properties of membrane lipids: biological relevance and regulation. Bacteriol Rev. 1975;39(3): p. 232.

  57. Small DM. A classification of biologic lipids based upon their interaction in aqueous systems. J Am Oil Chem Soc. 1968;45(3):108.

    Article  CAS  PubMed  Google Scholar 

  58. Israelachvili JN, Mitchell DJ, Ninham BW. Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers. J Chem Soc Faraday Trans 2. 1976;72(0): p. 1525–1568.

  59. Israelachvili JN, Mitchell DJ, Ninham BW. Theory of self-assembly of lipid bilayers and vesicles. Biochim Biophys Acta Biomembr. 1977;470(2): p. 185–201.

  60. Khalil RA, Al-hakam AZ. Theoretical estimation of the critical packing parameter of amphiphilic self-assembled aggregates. App Surf Sci. 2014;318: p. 85–89.

  61. Tan A, et al. Self-assembled nanostructured lipid systems: is there a link between structure and cytotoxicity? Adv Sci. 2019;6(3):1801223.

    Article  Google Scholar 

  62. Dong Y-D, et al. Impurities in commercial phytantriol significantly alter its lyotropic liquid-crystalline phase behavior. Langmuir. 2008;24(13):6998–7003.

    Article  CAS  PubMed  Google Scholar 

  63. Dong Y-D, et al. Bulk and dispersed aqueous phase behavior of phytantriol: effect of vitamin E acetate and F127 polymer on liquid crystal nanostructure. Langmuir. 2006;22(23):9512–8.

    Article  CAS  PubMed  Google Scholar 

  64. Du JD, et al. A novel approach to enhance the mucoadhesion of lipid drug nanocarriers for improved drug delivery to the buccal mucosa. Int J Pharm. 2014;471(1–2):358–65.

    Article  CAS  PubMed  Google Scholar 

  65. Kaasgaard T, Drummond CJ. Ordered 2-D and 3-D nanostructured amphiphile self-assembly materials stable in excess solvent. Phys Chem Chem Phys. 2006;8(43):4957–75.

    Article  CAS  PubMed  Google Scholar 

  66. Bulbake U, et al. Liposomal formulations in clinical use: an updated review. Pharmaceutics. 2017;9(2):12.

    Article  PubMed Central  Google Scholar 

  67. Sharma A, Sharma US. Liposomes in drug delivery: progress and limitations. Int J Pharm. 1997;154(2):123–40.

    Article  CAS  Google Scholar 

  68. Rizwan SB, et al. Bicontinuous cubic liquid crystals as sustained delivery systems for peptides and proteins. Expert Opin Drug Deliv. 2010;7(10):1133–44.

    Article  CAS  PubMed  Google Scholar 

  69. Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Research in Pharmaceutical Sciences. 2018;13(4):288–303.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009;71(4):349–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Naseri N, Valizadeh H, Zakeri-Milani P. Solid lipid nanoparticles and nanostructured lipid carriers: structure. Preparation and Application Advance Pharmaceutical Bulletin. 2015;5(3):305–13.

    CAS  Google Scholar 

  72. Joyce P, et al. Solidification to improve the biopharmaceutical performance of SEDDS: opportunities and challenges. Adv Drug Deliv Rev. 2019;142:102–17.

    Article  CAS  PubMed  Google Scholar 

  73. Dening TJ, et al. Novel nanostructured solid materials for modulating oral drug delivery from solid-state lipid-based drug delivery systems. AAPS J. 2016;18(1):23–40.

    Article  CAS  PubMed  Google Scholar 

  74. Chakraborty S, et al. Lipid–an emerging platform for oral delivery of drugs with poor bioavailability. Eur J Pharm Biopharm. 2009;73(1):1–15.

    Article  CAS  PubMed  Google Scholar 

  75. Williams HD, et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev. 2013;65(1):315–499.

    Article  PubMed  Google Scholar 

  76. Thomas N, Rades T, Müllertz A. Recent developments in oral lipid-based drug delivery. J Drug Delivery Sci Technol. 2013;23(4):375–82.

    Article  CAS  Google Scholar 

  77. Islan GA, et al. Smart lipid nanoparticles containing levofloxacin and DNase for lung delivery. Design and Characterization Colloids Surf B. 2016;143:168–76.

    Article  CAS  Google Scholar 

  78. Phan TNQ, Shahzadi I, Bernkop-Schnürch A. Hydrophobic ion-pairs and lipid-based nanocarrier systems: the perfect match for delivery of BCS class 3 drugs. J Control Release. 2019;304:146–55.

    Article  CAS  PubMed  Google Scholar 

  79. Zhang Q, et al. Antimicrobial lipids in nano-carriers for antibacterial delivery. J Drug Target. 2020;28(3):271–81.

    Article  CAS  PubMed  Google Scholar 

  80. Eleraky NE, et al. Nanomedicine fight against antibacterial resistance: an overview of the recent pharmaceutical innovations. Pharmaceutics. 2020;12(2):142.

    Article  CAS  PubMed Central  Google Scholar 

  81. Wang DY, et al. Lipid-based antimicrobial delivery-systems for the treatment of bacterial infections. Front Chem. 2020;7:872–872.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Natan M, Banin E. From Nano to Micro: using nanotechnology to combat microorganisms and their multidrug resistance. FEMS Microbiol Rev. 2017;41(3):302–22.

    Article  CAS  PubMed  Google Scholar 

  83. Koo H, et al. Targeting microbial biofilms: current and prospective therapeutic strategies. Nat Rev Microbiol. 2017.

  84. Thormar H. Antibacterial effects of lipids: Historical review (1881 to 1960), in lipids and essential oils as antimicrobial agents. p. 25–45.

  85. Brogden NK, et al. The emerging role of peptides and lipids as antimicrobial epidermal barriers and modulators of local inflammation. Skin Pharmacol Physiol. 2012;25(4):167–81.

    Article  CAS  PubMed  Google Scholar 

  86. Glassman HN. Surface active agents and their application in bacteriology. Bacteriol Rev. 1948;12(2):105–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Fischer CL. Antimicrobial Activity of Host-Derived Lipids Antibiotics. 2020;9(2):75.

    CAS  Google Scholar 

  88. Kabara JJ, Vrable R, Lie Ken Jie MSF. Antimicrobial lipids: Natural and synthetic fatty acids and monoglycerides. Lipids. 1977;12(9): p. 753–759.

  89. Umerska A, et al. Antibacterial action of lipid nanocapsules containing fatty acids or monoglycerides as co-surfactants. Eur J Pharm Biopharm. 2016;108:100–10.

    Article  CAS  PubMed  Google Scholar 

  90. Schlievert PM, Peterson ML. Glycerol monolaurate antibacterial activity in broth and biofilm cultures. PLoS One. 2012;7(7):e40350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Mueller EA, Schlievert PM. Non-aqueous glycerol monolaurate gel exhibits antibacterial and anti-biofilm activity against Gram-positive and Gram-negative pathogens. PLoS One. 2015;10(3):e0120280.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Science, H.L. Pipeline: Human Health Initiatives. 2017;[20 April 2020]. Available from: http://www.hennepinlifesciences.com/human/.

  93. Thomas ND, Richter K, Prestidge CA. Antimicrobial compositions and methods of use. Filed 2018, issued 2019.

  94. Chanda W, et al. Combined effect of linolenic acid and tobramycin on Pseudomonas aeruginosa biofilm formation and quorum sensing. Exp Ther Med. 2017;14(5):4328–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Obonyo M, et al. Antibacterial activities of liposomal linolenic acids against antibiotic-resistant Helicobacter pylori. Mol Pharm. 2012;9(9):2677–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Huang C-M, et al. Eradication of drug resistant Staphylococcus aureus by liposomal oleic acids. Biomaterials. 2011;32(1):214–21.

    Article  CAS  PubMed  Google Scholar 

  97. Chanda W, et al. Effectiveness of omega-3 polyunsaturated fatty acids against microbial pathogens. J Zhejiang Univ Sci B. 2018;19(4):253–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Mendrok-Edinger C, Mongiat SRT, Schlifke-Poschalko A. Use of Phytantriol as an Antimicrobial Agent, DSM, Editor. 2017.

  99. Kossena GA, et al. A novel cubic phase of medium chain lipid origin for the delivery of poorly water soluble drugs. J Control Release. 2004;99(2):217–29.

    Article  CAS  PubMed  Google Scholar 

  100. Ahmed A, et al. Current concepts in combination antibiotic therapy for critically ill patients. Indian Journal of Critical Care Medicine. 2014;18(5):310–4.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Coates ARM, et al. Antibiotic combination therapy against resistant bacterial infections: synergy, rejuvenation and resistance reduction. Expert Rev Anti-Infect Ther. 2020;18(1):5–15.

    Article  CAS  PubMed  Google Scholar 

  102. Sueke H, et al. An in vitro investigation of synergy or antagonism between antimicrobial combinations against isolates from bacterial keratitis. Invest Ophthalmol Vis Sci. 2010;51(8):4151–5.

    Article  PubMed  Google Scholar 

  103. Håkansson J, et al. Characterization of the in vitro, ex vivo, and in vivo Efficacy of the Antimicrobial Peptide DPK-060 Used for Topical Treatment. Front Cell Infect Microbiol. 2019;9(174).

  104. Nafee N, et al. Antibiotic-free nanotherapeutics: ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors. J Control Release. 2014;192:131–40.

    Article  CAS  PubMed  Google Scholar 

  105. Nicolosi D, et al. Nanotechnology approaches for antibacterial drug delivery: preparation and microbiological evaluation of fusogenic liposomes carrying fusidic acid. Int J Antimicrob Agents. 2015;45(6):622–6.

    Article  CAS  PubMed  Google Scholar 

  106. Ducat E, et al. Cellular uptake of liposomes monitored by confocal microscopy and flow cytometry. J Drug Delivery Sci Technol. 2011;21(6):469–77.

    Article  CAS  Google Scholar 

  107. Ellens H, Bentz J, Szoka FC. Fusion of phosphatidylethanolamine-containing liposomes and mechanism of L.alpha.-HII phase transition. Biochemistry. 1986;25(14): p. 4141–4147.

  108. Jahn R, Lang T, Südhof TC. Membrane fusion. Cell. 2003;112(4):519–33.

    Article  CAS  PubMed  Google Scholar 

  109. Zhang C, et al. Antibiotic-derived lipid nanoparticles to treat intracellular Staphylococcus aureus. ACS Appl Bio-Mater. 2019;2(3):1270–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Couvreur P, Fattal E, Andremont A. Liposomes and nanoparticles in the treatment of intracellular bacterial infections. Pharm Res. 1991;8(9):1079–86.

    Article  CAS  PubMed  Google Scholar 

  111. Shirley M. Amikacin liposome inhalation suspension: a review in Mycobacterium avium complex lung disease. Drugs. 2019;79(5):555–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Sachetelli S, et al. Demonstration of a fusion mechanism between a fluid bactericidal liposomal formulation and bacterial cells. Biochem Biophys Acta. 2000;1463(2):254–66.

    Article  CAS  PubMed  Google Scholar 

  113. Jacqueline Lagace CB. Sébastien Clement-Major, Low rigidity liposomal antibacterial composition, and U.D. Montreal, Editors. 1994: World.

  114. Beaulac C, et al. Eradication of mucoid Pseudomonas aeruginosa with fluid liposome-encapsulated tobramycin in an animal model of chronic pulmonary infection. Antimicrob Agents Chemother. 1996;40(3):665–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Omri A, et al. Pulmonary retention of free and liposome-encapsulated tobramycin after intratracheal administration in uninfected rats and rats infected with Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1994;38(5):1090–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. AG, AP. Cystic Fibrosis - Orphan drug designation for innovative treatment against lung infections by Axentis Pharma AG. 2009.

  117. Barriga HMG, Holme MN, Stevens MM. Cubosomes; the next generation of smart lipid nanoparticles? Angewandte Chemie. 0(ja).

  118. Hinton TM, et al. Bicontinuous cubic phase nanoparticle lipid chemistry affects toxicity in cultured cells. Toxicol Res. 2014;3(1):11–22.

    Article  CAS  Google Scholar 

  119. Dyett BP, et al. Fusion dynamics of cubosome nanocarriers with model cell membranes. Nat Commun. 2019;10(1):4492.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Shen H-H, et al. The influence of dipalmitoyl phosphatidylserine on phase behaviour of and cellular response to lyotropic liquid crystalline dispersions. Biomaterials. 2010;31(36):9473–81.

    Article  CAS  PubMed  Google Scholar 

  121. Seddon J. Inverse cubic phases of membrane-lipids, and their relevance to the static and dynamic structure of biomembranes. Acta Pharm. 1992;42(4):255–62.

    CAS  Google Scholar 

  122. Larsson K. Cubic lipid-water phases: structures and biomembrane aspects. J Phys Chem. 1989;93(21):7304–14.

    Article  CAS  Google Scholar 

  123. Dong Y-D, et al. Adsorption of nonlamellar nanostructured liquid-crystalline particles to biorelevant surfaces for improved delivery of bioactive compounds. ACS Appl Mater Interfaces. 2011;3(5):1771–80.

    Article  CAS  PubMed  Google Scholar 

  124. Rattanapak T, et al. Comparative study of liposomes, transfersomes, ethosomes and cubosomes for transcutaneous immunisation: characterisation and in vitro skin penetration. J Pharm Pharmacol. 2012;64(11):1560–9.

    Article  CAS  PubMed  Google Scholar 

  125. Boge L, et al. Peptide-loaded cubosomes functioning as an antimicrobial unit against Escherichia coli. ACS Appl Mater Interfaces. 2019;11(24):21314–22.

    Article  CAS  PubMed  Google Scholar 

  126. Tran N, et al. Non-lamellar lyotropic liquid crystalline nanoparticles enhance the antibacterial effects of rifampicin against Staphylococcus aureus. J Colloid Interface Sci. 2018;519:107–18.

    Article  CAS  PubMed  Google Scholar 

  127. Transport of nanoparticles and tobramycin-loaded liposomes in Burkholderia cepacia complex biofilms. PLoS One. 2013;8(11): p. no pagination.

  128. Yang M, et al. Biodegradable nanoparticles composed entirely of safe materials that rapidly penetrate human mucus. Angew Chem Int Ed Engl. 2011;50(11):2597–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Beaulac C, Sachetelli S, Lagace J. In-vitro bactericidal efficacy of sub-MIC concentrations of liposome-encapsulated antibiotic against gram-negative and gram-positive bacteria. J Antimicrob Chemother. 1998;41(1):35–41.

    Article  CAS  PubMed  Google Scholar 

  130. Meers P, et al. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother. 2008;61(4):859–68.

    Article  CAS  PubMed  Google Scholar 

  131. Dong D, et al. Distribution and inhibition of liposomes on Staphylococcus aureus and Pseudomonas aeruginosa biofilm. PLoS One. 2015;10(6):e0131806.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Messiaen AS, et al. Transport of nanoparticles and tobramycin-loaded liposomes in Burkholderia cepacia complex biofilms. PLoS One. 2013;8(11):e79220.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Carlson TL, Lock JY, Carrier RL. Engineering the mucus barrier. Annu Rev Biomed Eng. 2018;20:197–220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Torge A, et al. Ciprofloxacin-loaded lipid-core nanocapsules as mucus penetrating drug delivery system intended for the treatment of bacterial infections in cystic fibrosis. Int J Pharm. 2017;527.

  135. Swoboda JG, et al. Wall teichoic acid function, biosynthesis, and inhibition. Chem Bio Chem. 2010;11(1):35–45.

    Article  CAS  PubMed  Google Scholar 

  136. Silhavy TJ, Kahne D, Walker S. The bacterial cell envelope. Cold Spring Harbor Perspect Biol. 2010;2(5):a000414–a000414.

    Article  Google Scholar 

  137. Hancock REW, Sahl H-G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotech. 2006;24(12):1551–7.

    Article  CAS  Google Scholar 

  138. Germoni LA, Bremer PJ, Lamont IL. The effect of alginate lyase on the gentamicin resistance of Pseudomonas aeruginosa in mucoid biofilms. J Gen Microbiol. 2016;121(1):126–35.

    CAS  Google Scholar 

  139. Halwani M, et al. Bactericidal efficacy of liposomal aminoglycosides against Burkholderia cenocepacia. J Antimicrob Chemother. 2007;60(4):760–9.

    Article  CAS  PubMed  Google Scholar 

  140. Liu Q, et al. Sensitivity of nanostructure in charged cubosomes to phase changes triggered by ionic species in solution. Langmuir. 2013;29(46):14265–73.

    Article  CAS  PubMed  Google Scholar 

  141. Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomed. 2012;7:5577–91.

    Article  Google Scholar 

  142. Lunov O, et al. Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line. ACS Nano. 2011;5(3):1657–69.

    Article  CAS  PubMed  Google Scholar 

  143. Boehm F. Nanomedical device and systems design: challenges, possibilities, visions. 2016: CRC Press.

  144. Vyas SP, et al. Design of liposomal aerosols for improved delivery of rifampicin to alveolar macrophages. Int J Pharm. 2004;269(1):37–49.

    Article  CAS  PubMed  Google Scholar 

  145. Zanin M, et al. The interaction between respiratory pathogens and mucus. Cell Host Microbe. 2016;19(2):159–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Yu T, et al. Biodegradable mucus-penetrating nanoparticles composed of diblock copolymers of polyethylene glycol and poly(lactic-co-glycolic acid). Drug Deliv Transl Res. 2012;2(2):124–8.

    Article  CAS  Google Scholar 

  147. Mucoadhesive buccal drug delivery system. Review article. Int J Curr Pharm Res. 2017;9(4):1–4.

    Article  Google Scholar 

  148. Schneider CS, et al. Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation. Sci Adv. 2017;3(4):e1601556.

    Article  PubMed  PubMed Central  Google Scholar 

  149. Spicer PT, et al. Novel process for producing cubic liquid crystalline nanoparticles (cubosomes). Langmuir. 2001;17(19):5748–56.

    Article  CAS  Google Scholar 

  150. Nafee N, et al. Mucus-penetrating solid lipid nanoparticles for the treatment of cystic fibrosis: proof of concept, challenges and pitfalls. Eur J Pharm Biopharm. 2018;124:125–37.

    Article  CAS  PubMed  Google Scholar 

  151. Kirchner S, et al. Use of artificial sputum medium to test antibiotic efficacy against Pseudomonas aeruginosa in conditions more relevant to the cystic fibrosis lung. J Visualized Exp. 2012;64:e3857.

    Google Scholar 

  152. Huck BC, et al. Macro- and microrheological properties of mucus surrogates in comparison to native intestinal and pulmonary mucus. Biomacromol. 2019;20(9):3504–12.

    Article  CAS  Google Scholar 

  153. Moreno-Sastre M, et al. Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis. Int J Pharm. 2016;498(1):263–73.

    Article  CAS  PubMed  Google Scholar 

  154. Nielsen LS, Schubert L, Hansen J. Bioadhesive drug delivery systems: I. Characterisation of mucoadhesive properties of systems based on glyceryl mono-oleate and glyceryl monolinoleate. Eur J Pharm Sci. 1998;6(3): p. 231–239.

  155. Nguyen TH, et al. Nanostructured reverse hexagonal liquid crystals sustain plasma concentrations for a poorly water-soluble drug after oral administration. Drug Deliv Transl Res. 2011;1(6):429–38.

    Article  CAS  PubMed  Google Scholar 

  156. Swarnakar NK, et al. Enhanced oromucosal delivery of progesterone via hexosomes. Pharm Res. 2007;24(12):2223–30.

    Article  CAS  PubMed  Google Scholar 

  157. Popov A, Enlow EM. and H. Particles, compositions and methods for ophthalmic and/or other applications: Chen; 2018.

    Google Scholar 

  158. Torchilin VP. Passive and active drug targeting: Drug delivery to tumors as an example, in drug delivery, M. Schäfer-Korting, Editor. 2010, Springer Berlin Heidelberg: Berlin, Heidelberg. p. 3–53.

  159. Albanese A, Tang PS, Chan WC. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng. 2012;14:1–16.

    Article  CAS  PubMed  Google Scholar 

  160. Yu J, et al. Advances in bioresponsive closed-loop drug delivery systems. Int J Pharm. 2018;544(2):350–7.

    Article  CAS  PubMed  Google Scholar 

  161. Waters V, Ratjen F. Inhaled liposomal amikacin. Expert Rev Respir Med. 2014;8(4):401–9.

    Article  CAS  PubMed  Google Scholar 

  162. Rudkin JK, et al. Bacterial toxins: offensive, defensive, or something else altogether? PLoS Pathog. 2017;13(9):e1006452.

    Article  PubMed  PubMed Central  Google Scholar 

  163. Shorrock SM, Kun S, Peura R. The exploration of tissue pH in wounds and its relationship to bacterial contamination. Master Degree Thesis. 2000: p. 20–24.

  164. Dinarello CA. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res. 2004;10(4):201–22.

    CAS  PubMed  Google Scholar 

  165. Actor JK. 11 - Basic Bacteriology. In: Actor JK, editor. Elsevier’s Integrated Review Immunology and Microbiology (Second Edition). Philadelphia: W.B. Saunders; 2012. p. 93–103.

    Chapter  Google Scholar 

  166. Cavaillon J-M. Exotoxins and endotoxins: inducers of inflammatory cytokines. Toxicon. 2018;149:45–53.

    Article  CAS  PubMed  Google Scholar 

  167. Schmiel DH, Miller VL. Bacterial phospholipases and pathogenesis. Microbes Infect. 1999;1(13):1103–12.

    Article  CAS  PubMed  Google Scholar 

  168. Jaeger KE, et al. Bacterial lipases. FEMS Microbiol Rev. 1994;15(1):29–63.

    Article  CAS  PubMed  Google Scholar 

  169. Coll Ferrer MC, et al. Designing nanogel carriers for antibacterial applications. Acta Biomater. 2014;10(5):2105–11.

    Article  CAS  PubMed  Google Scholar 

  170. Pornpattananangkul D, et al. Bacterial toxin-triggered drug release from gold nanoparticle-stabilized liposomes for the treatment of bacterial infection. J Am Chem Soc. 2011;133(11):4132–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Yang S, et al. Bacteria-targeting nanoparticles with microenvironment-responsive antibiotic release to eliminate intracellular Staphylococcus aureus and associated infection. ACS Appl Mater Interfaces. 2018;10(17):14299–311.

    Article  CAS  PubMed  Google Scholar 

  172. Thorn CR, et al. Pseudomonas infection responsive liquid crystals for glycoside hydrolase and antibiotic combination. ACS Applied Bio Mat. 2018;1(2):281–8.

    Article  CAS  Google Scholar 

  173. Thorn CR, et al. Bacterial lipase triggers the release of antibiotics from digestible liquid crystal nanoparticles. J Control Release. 2020;319:168–82.

    Article  CAS  PubMed  Google Scholar 

  174. Thamphiwatana S, et al. Phospholipase A2-responsive antibiotic delivery via nanoparticle-stabilized liposomes for the treatment of bacterial infection. J Mater Chem B. 2014;2(46):8201–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Jadhav M, et al. Novel lipids with three C18-fatty acid chains and an amino acid head group for pH-responsive and sustained antibiotic delivery. Chem Phys Lipids. 2018;212:12–25.

    Article  CAS  PubMed  Google Scholar 

  176. Ahmed S, et al. Identifying the interaction of vancomycin with novel pH-responsive lipids as antibacterial biomaterials via accelerated molecular dynamics and binding free energy calculations. Cell Biochem Biophys. 2018;76(1–2):147–59.

    Article  CAS  PubMed  Google Scholar 

  177. Kalhapure RS, et al. Enhancing targeted antibiotic therapy via pH responsive solid lipid nanoparticles from an acid cleavable lipid. Nanomedicine. 2017;13(6):2067–77.

    Article  CAS  PubMed  Google Scholar 

  178. Negrini R, et al. pH-responsive lyotropic liquid crystals and their potential therapeutic role in cancer treatment. Chem Commun (Camb). 2015;51(30):6671–4.

    Article  CAS  Google Scholar 

  179. Bisset NB, Boyd BJ, Dong YD. Tailoring liquid crystalline lipid nanomaterials for controlled release of macromolecules. Int J Pharm Res. 2015;495(1):241–8.

    CAS  Google Scholar 

  180. Negrini R, Mezzenga R. pH-responsive lyotropic liquid crystals for controlled drug delivery. Langmuir. 2011;27(9):5296–303.

    Article  CAS  PubMed  Google Scholar 

  181. Bender J, Flieger A. Lipases as pathogenicity factors of bacterial pathogens of humans, in handbook of hydrocarbon and lipid microbiology, Timmis KN, Editor. 2010. Springer Berlin Heidelberg: Berlin, Heidelberg. p. 3241–3258.

  182. Reis P, et al. Lipases at interfaces: a review. Adv Colloid Interface Sci. 2009;147–148:237–50.

    Article  PubMed  Google Scholar 

  183. Alford JA, Pierce DA, Suggs FG. Activity of microbial lipases on natural fats and synthetic triglycerides. J Lipid Res. 1964;5(3):390–4.

    Article  CAS  PubMed  Google Scholar 

  184. Hong L, et al. Understanding the mechanism of enzyme-induced formation of lyotropic liquid crystalline nanoparticles. Langmuir. 2015;31(24):6933–41.

    Article  CAS  PubMed  Google Scholar 

  185. Pham AC, et al. In vivo formation of cubic phase in situ after oral administration of cubic phase precursor formulation provides long duration gastric retention and absorption for poorly water-soluble drugs. Mol Pharm. 2016;13(1):280–6.

    Article  CAS  PubMed  Google Scholar 

  186. Parmentier J, et al. Exploring the fate of liposomes in the intestine by dynamic in vitro lipolysis. Int J Pharm. 2012;437(1):253–63.

    Article  CAS  PubMed  Google Scholar 

  187. Drummond CJ, Fong C. Surfactant self-assembly objects as novel drug delivery vehicles. Curr Opin Colloid Interface Sci. 1999;4(6):449–56.

    Article  CAS  Google Scholar 

  188. Bhakdi S, Tranum-Jensen J. Alpha-toxin of Staphylococcus aureus. Microbiol Rev. 1991;55(4):733–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Wardenburg JB, Schneewind O. Vaccine protection against Staphylococcus aureus pneumonia. J Exp Med. 2008;205(2):287–94.

    Article  CAS  PubMed Central  Google Scholar 

  190. Jones EM, Cochrane CA, Percival SL. The effect of pH on the extracellular matrix and biofilms. Advance in Wound Care. 2015;4(7):431–9.

    Article  Google Scholar 

  191. Foulston L, et al. The extracellular matrix of Staphylococcus aureus biofilms comprises cytoplasmic proteins that associate with the cell surface in response to decreasing pH. MBio. 2014;5(5):e01667-e1714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Percival SL, et al. The effects of pH on wound healing, biofilms, and antimicrobial efficacy. Wound Repair Regen. 2014;22(2):174–86.

    Article  PubMed  Google Scholar 

  193. Garrard W, Lascelles J. Regulation of Staphylococcus aureus lactate dehydrogenase. J Bacteriol. 1968;95(1):152–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Ferreira MT, et al. Effect of oxygen on glucose metabolism: utilization of lactate in Staphylococcus aureus as revealed by in vivo NMR studies. PLoS One. 2013;8(3):e58277–e58277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Torres IM, et al. Acidosis increases the susceptibility of respiratory epithelial cells to Pseudomonas aeruginosa-induced cytotoxicity. Am J Physiol Lung Cell Mol Physiol. 2017;313(1): p. L126-L137.

  196. Welbourn C, et al. Pathophysiology of ischaemia reperfusion injury: central role of the neutrophil. Br J Surg. 1991;78(6):651–5.

    Article  CAS  PubMed  Google Scholar 

  197. Simmen HP, et al. Analysis of pH, pO2 and pCO2 in drainage fluid allows for rapid detection of infectious complications during the follow-up period after abdominal surgery. Infection. 1994;22(6):386–9.

    Article  CAS  PubMed  Google Scholar 

  198. Irwin NJ, et al. Infection-responsive drug delivery from urinary biomaterials controlled by a novel kinetic and thermodynamic approach. Pharm Res. 2013;30(3):857–65.

    Article  CAS  PubMed  Google Scholar 

  199. McCoy CP, et al. An infection-responsive approach to reduce bacterial adhesion in urinary biomaterials. Mol Pharm. 2016;13(8):2817–22.

    Article  CAS  PubMed  Google Scholar 

  200. Radovic-Moreno AF, et al. Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics. ACS Nano. 2012;6(5):4279–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Albayaty Y, et al. pH-Responsive copolymer micelles to enhance itraconazole efficacy against Candida albicans biofilms. J Mater Chemi B. 2020;8.

  202. Boge L, et al. Lipid-based liquid crystals as carriers for antimicrobial peptides: phase behavior and antimicrobial effect. Langmuir. 2016;32(17):4217–28.

    Article  CAS  PubMed  Google Scholar 

  203. Zhang J, et al. Amikacin liposome inhalation suspension (ALIS) penetrates non-tuberculous mycobacterial biofilms and enhances amikacin uptake into macrophages. Front Microbiol. 2018;9:915–915.

    Article  PubMed  PubMed Central  Google Scholar 

  204. Alhariri M, et al. Efficacy of neutral and negatively charged liposome-loaded gentamicin on planktonic bacteria and biofilm communities. Int J Nanomed. 2017;12:6949–61.

    Article  CAS  Google Scholar 

  205. Cipolla D, Blanchard J, Gonda I. Development of liposomal ciprofloxacin to treat lung infections. Pharmaceutics. 2016;8(1):6.

    Article  PubMed Central  Google Scholar 

  206. Serisier D, et al. Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial. Thorax. 2013;68:812–7.

    Article  PubMed  Google Scholar 

  207. Haworth CS, et al. Inhaled liposomal ciprofloxacin in patients with non-cystic fibrosis bronchiectasis and chronic lung infection with Pseudomonas aeruginosa (ORBIT-3 and ORBIT-4): two phase 3, randomised controlled trials. Lancet Respir Med. 2019;7(3):213–26.

    Article  CAS  PubMed  Google Scholar 

  208. Sarkar S, Heise MT. Mouse models as resources for studying infectious diseases. Clin Ther. 2019;41(10):1912–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Lavelle GM, et al. Animal models of cystic fibrosis pathology: phenotypic parallels and divergences. Biomed Res Int. 2016;2016:5258727.

    Article  PubMed  PubMed Central  Google Scholar 

  210. Artzy-Schnirman A, Lehr CM, Sznitman J. Advancing human in vitro pulmonary disease models in preclinical research: opportunities for lung-on-chips. Expert Opin Drug Deliv. 2020;p. 1–5.

  211. Scriboni AB, et al. Fusogenic Liposomes Increase the Antimicrobial Activity of Vancomycin Against Staphylococcus aureus Biofilm. Front Pharmacol. 2019;10(1401).

Download references

Acknowledgement

This research is supported by the Australian Government and the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology. CRT is supported by the Australian Government Research Training Program and the Australian Government Endeavour Postgraduate Leadership Award. NT is supported by a Mid-Career Fellowship from the Hospital Research Foundation.

Author information

Authors and Affiliations

  1. Clinical and Health Science, University of South Australia, City East Campus, Adelaide, SA, 5000, Australia

    Chelsea R. Thorn, Nicky Thomas & Clive A. Prestidge

  2. The Basil Hetzel Institute for Translational Health Research, Woodville, SA, 5011, Australia

    Chelsea R. Thorn & Nicky Thomas

  3. ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, University of South Australia, SA, 5000, Adelaide, Australia

    Chelsea R. Thorn, Nicky Thomas, Ben J. Boyd & Clive A. Prestidge

  4. Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Pde, Parkville, VIC, 3052, Australia

    Ben J. Boyd

Authors
  1. Chelsea R. Thorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicky Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ben J. Boyd
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Clive A. Prestidge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clive A. Prestidge.

Ethics declarations

Ethics approval

No ethics approval was required for this work.

Research involving human participants and/or Animals

No animal or human studies were carried out by the authors for this article.

Conflict of interest

The other authors declare no conflict of interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thorn, C.R., Thomas, N., Boyd, B.J. et al. Nano-fats for bugs: the benefits of lipid nanoparticles for antimicrobial therapy. Drug Deliv. and Transl. Res. 11, 1598–1624 (2021). https://doi.org/10.1007/s13346-021-00921-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-021-00921-w

Keywords

Search

Navigation