Skip to main content
SpringerLink
Log in

Nanotoxicity of Lipid-Based Nanomedicines

  • Chapter
  • First Online:
Book cover Nanomaterials: Ecotoxicity, Safety, and Public Perception

Abstract

The impact of lipid-based nanomedicines on living beings widely differs from that caused by non-intentional exposition of metallic, metallic oxides, or carbon-based inhaled nanomaterials. The scarce data gathered on nanotoxicity of lipid-based nanomedicines is mostly related to intravenous and inhalation routes. This last is also the most important non-intentional exposition route. Intravenous nanomedicines mostly consist of antitumoral and antimycotic agents, both responsible for the induction of potentially lethal acute hypersensitivity reactions. Their nanotoxicity is explained according to different mechanisms. The so called double hit theory states that the clinical symptoms arise from the sum of the complement activation (Complement Activation Related Pseudo Allergy, CARPA effect), where the anaphylatoxins C3a, C4a and C5a induce the release of allergomedins by mast cells, and from the direct activation by nanomedicines binding to pattern recognizing receptors on macrophages ; activation of bradykinin receptors B1 and B2 may contribute to the clinical picture. The rapid phagocytic response hypothesis instead, states that the complement activation would not be responsible for the clinical symptoms, whereas the hypersensitivity reaction occur by direct activation of IgG opsonized nanomedicines , of receptors expressed mostly in pulmonary intravascular macrophages (PIM). Activated PIMs thus, would release platelet activating factor (PAF), a highly active and very short-lived molecule, a mast cells activator responsible for the potentially lethal toxic effects. The nanotoxicity of inhaled liposomes , developed to treat bronchiectasis caused by bacterial infections on the other hand, was preclinically observed in rodents (species of unknown value as reliable predictors of the effects of inhaled medicines in humans), while in dogs was reported as transient, lymph node reactions (perivascular/peribronchiolar lymphoid cell infiltration) that are not readily reversible and lymphoid findings associated with foamy macrophages. In early clinical phase, the nanotoxicity manifested after repeated administrations along months, as higher airway reactogenicity, higher rates of treatment-related adverse events and higher rates of discontinuations due to adverse events. In case of liposomal amikacin—a per se irritant drug—, the nanotoxicity was related to the presence of free antibiotic; in case of liposomal ciprofloxacin, it was manifested as dyspnea, bronchospasm, hemoptysis, cough, taste disorders. Not surprisingly, the nanotoxicity of nanomedicines has not been properly anticipated by preclinical studies. More accurate disease models for example based on artificial three-dimensional human cell organs, may aid preclinical studies to acquire higher significance.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alsaleh NB, Brown JM (2018) Immune responses to engineered nanomaterials: current understanding and challenges. Curr Opin Toxicol 10:8–14

    Article  PubMed  Google Scholar 

  • Altube MJ, Cutro A, Bakas L, Morilla MJ, Disalvo EA, Romero EL (2017) Nebulizing novel multifunctional nanovesicles: the impact of macrophage-targeted-pH-sensitive archaeosomes on pulmonary surfactant. J Mater Chem B 5:8083–8095

    Article  CAS  PubMed  Google Scholar 

  • Bakand S, Hayes A, Dechsakulthorn F (2012) Nanoparticles: a review of particle toxicology following inhalation exposure. Inhal Toxicol 24(2):125–135

    Article  CAS  PubMed  Google Scholar 

  • Beck-Broichsitter M, Ruppert C, Schmehl T, Günther A, Seeger W (2014) Biophysical inhibition of synthetic vs. naturally-derived pulmonary surfactant preparations by polymeric nanoparticles. Biochim Biophys Acta-Biomembr 1838(1):474–481

    Article  CAS  Google Scholar 

  • Bermudez LE, Blanchard JD, Hauck L, Gonda I (2015) Treatment of Mycobacterium avium subsphominissuis (MAH) lung infection with liposome-encapsulated ciprofloxacin resulted in significant decrease in bacterial load in the lung. Am J Respir Crit Care Med 191:A6293

    Google Scholar 

  • Bertrand N, Leroux J-C (2012) The journey of a drug-carrier in the body: an anatomo-physiological perspective. J Control Rel 161:152–163

    Article  CAS  Google Scholar 

  • Bilton D, Pressler T, Fajac I, Clancy JP, Sands D, Minic P, Cipolli M, LaRosa M, Galeva I, Sole A, Staab D, Dupont L, Goss CH, Hamblett N, Quittner A, Ramsey B, Gupta R, Konstan M (2013) Phase 3 efficacy and safety data from randomized, multicenter study of liposomal amikacin for inhalation (Arikace) compared with TOBI in cystic fibrosis patients with chronic infection due to Pseudomonas aeruginosa. North American Cystic Fibrosis Conference; Salt Lake City, Utah. Pediatr Pulmonol 36:290

    Google Scholar 

  • Bobo D, Robinson KJ, Islam J, Thurecht KJ, Corrie SR (2016) Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date. Pharm Res 33(10):2373–2387

    Article  CAS  PubMed  Google Scholar 

  • Borm P, Cassee FR, Oberdörster G (2015) Lung particle overload: old school—new insights? Part Fibre Toxicol 12:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Cabriales S, Bresnahan J, Testa D, Espina BM, Scadden DT, Ross M, Gill PS (1998) Extravasation of liposomal daunorubicin in patients with AIDS-associated Kaposi’s sarcoma: a report of four cases. Oncol Nurs Forum 25:67–70

    CAS  PubMed  Google Scholar 

  • Caster JM, Patel AN, Zhang T, Wang A (2017) Investigational nanomedicines in 2016: a review of nanotherapeutics currently undergoing clinical trials. Wiley Interdiscip Rev Nanomed Nanobiotechnol 9(1)

    Google Scholar 

  • Cedervall T, Lynch I, Lindman S, Berggard T, Thulin E, Nilsson H, Dawson KA, Linse S (2007) Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc Natl Acad Sci USA 104:2050–2055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chambers E, Mitragotri S (2004) Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes. J Control Release 100:111–119

    Article  CAS  PubMed  Google Scholar 

  • Champion JA, Mitragotri S (2006) Role of target geometry in phagocytosis. Proc Natl Acad Sci USA 103(13):4930–4934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen F, Wang G, Griffin JI, Brenneman B, Banda NK, Holers VM, Backos DS, Wu L, Moghimi SM, Simberg D (2017) Complement proteins bind to nanoparticle protein corona and undergo dynamic exchange in vivo. Nat Nanotechnol 12:387–393

    Article  CAS  PubMed  Google Scholar 

  • Chhoden T, Clausen PA, Larsen ST, Nørgaard AW, Lauritsen FR (2015) Interactions between nanoparticles and lung surfactant investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 29(11):1080–1086

    Article  CAS  PubMed  Google Scholar 

  • Chinoy MR, Fisher AB, Shuman H (1994) Confocal imaging of time-dependent internalization and localization of NBD-PC in intact rat lungs. Am J Physiol 266(6 Pt 1):L713–L721

    Article  CAS  Google Scholar 

  • Churg A, Brauer M, del Carmen Avila-Casado M, Fortoul TI, Wright JL (2003) Chronic exposure to high levels of particulate air pollution and small airway remodeling. Environ Health Perspect 111:714–718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Churg A, Wright JL (2002) Airway wall remodelling induced by occupational mineral dusts and air pollutant particles. Chest 122:306–309

    Article  Google Scholar 

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

    Article  PubMed Central  Google Scholar 

  • Cipolla D, Gonda I, Chan H-K (2013) Liposomal Formulations for Inhalation. Ther Deliv 4:1047–1072

    Article  CAS  PubMed  Google Scholar 

  • Cipolla D, Shekunov B, Blanchard J, Hickey A (2014) Lipid-based carriers for pulmonary products: preclinical development and case studies in humans. Adv Drug Del Rev 75:53–80

    Article  CAS  Google Scholar 

  • Commission Recommendation of 18 October 2011 on the definition of nanomaterial. http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:275:0038:0040

  • Committee on Hazardous Substances, BAuA (2015) Assessment Criterion (Reference Value) for Granular Biopersistent Particles Without Known Significant Specific Toxicity (Nanoscaled GBP) (Respirable Dust) Generated From Manufactured Ultrafine Particles. http://www.baua.de/en/Topics-from-A-to-Z/Hazardous-Substances/TRGS/pdf/ 910/nanoscaled-GBP.pdf

  • Conley J, Yang H, Wilson T, Blasetti K, Di Ninno V, Schnell G, Wong JP (1997) Aerosol delivery of liposome-encapsulated ciprofloxacin: aerosol characterization and efficacy against Francisella tularensis infection in mice. Antimicrob Agents Chemother 41(6):1288–1292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coppo R, Amore A (2000) Importance of the bradykinin-nitric oxide synthase system in the hypersensitivity reactions of chronic haemodialysis patients. Nephrol Dial Transpl 15:1288–1290

    Article  CAS  Google Scholar 

  • Crommelin DJA, Shah VP, Klebovich I, McNeil SE, Weinstein V, Flühmann B, Mühlebach S, de Vlieger JS (2015) The similarity question for biological and non-biological complex drugs. Eur J Pharm Sci 76:10–17

    Article  CAS  PubMed  Google Scholar 

  • Dankovic D, Kuempel E, Wheeler M (2007) An approach to risk assessment for TiO2. Inhal Toxicol 19:205–212

    Article  CAS  PubMed  Google Scholar 

  • Davis BK, Wen H, Ting JP (2011) The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol 29:707–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng ZJ, Liang M, Monteiro M, Toth I, Minchin RF (2011) Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. Nat Nanotechnol 6:39–44

    Article  CAS  PubMed  Google Scholar 

  • Docter D, Westmeier D, Markiewicz M, Stolte S, Knauer SK, Stauber RH (2015) The nanoparticle biomolecule corona: lessons learned—challenge accepted? Chem Soc Rev 44:6094–6121

    Article  CAS  PubMed  Google Scholar 

  • Donaldson K, Tran L, Jimenez LA, Duffin R, Newby DE, Mills N, MacNee W, Stone V (2005) Combustion-derived nanoparticles: a review of their toxicology following inhalation exposures. Part Fibre Toxicol 2:10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Donaldson K, Schinwald A, Murphy F, Cho WS, Duffin R, Tran L, Poland C (2013) The biologically effective dose in inhalation nanotoxicology. Acc Chem Res 46(3):723–732

    Article  CAS  PubMed  Google Scholar 

  • Duffin R, Tran CL, Clouter A, Brown DM, Macnee W, Stone V, Donaldson K (2002) The Importance of surface area and specific reactivity in the acute pulmonary inflammatory response to particles. Ann Occup Hyg 46:242–245

    Google Scholar 

  • Dushianthan A, Cusack R, Goss V, Postle AD, Grocott MPW (2012) Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome–where do we go from here? Crit Care 16:238–248

    Article  PubMed  PubMed Central  Google Scholar 

  • EMA. Withdrawal assessment report EMA/493973/2016

    Google Scholar 

  • EU Scientific Committee Recommendation on the definition of a nanomaterial (2011/696/EU). http://ec.europa.eu/environment/chemicals/nanotech/faq/definition_en.htm

  • European Science Foundation (2005) Nanomedicine, an ESF–European Medical Research Councils (EMRC) forward look report

    Google Scholar 

  • European Technology Platform on Nanomedicine, Nanotechnology for Health, Vision paper and basis for a strategic research agenda for nanomedicine, EC Publication Office, September 2005

    Google Scholar 

  • European Union 004-EN-N (2010) Scientific Committee on Emerging and Newly Identified Health Risks. Scientific Basis for the Definition of the Term “nanomaterial”; BN 978-92-79-12757-1; https://doi.org/10.2772/39703 ND-AS-09

  • European Food Safety Agency (EFSA), EU Regulation No. 1169/2011. European Commission 2011

    Google Scholar 

  • Fadeel B (2012) Clear and present danger? Engineered nanoparticles and the immune system. Swiss Med Wkly 142:w13609

    PubMed  Google Scholar 

  • Fan Q, Wang YE, Zhao X, Loo JS, Zuo YY (2011) Adverse biophysical effects of hydroxyapatite nanoparticles on natural pulmonary surfactant. ACS Nano 5(8):6410–6416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farhangrazi ZS, Moghimi SM (2016) Materials etiquette and complement responses. Curr Bionanotechnol 2:6–10

    Article  Google Scholar 

  • FDA for patients. https://www.fda.gov/ForPatients/Approvals/Drugs/ucm405622.htm

  • FDA (2014) Considering whether an FDA-regulated product involves the application of nanotechnology Guidance for Industry. http://www.fda.gov/RegulatoryInformation/Guidances/ucm257698.htm

  • Frohlich E (2012) The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine 7:5577–5591

    Article  PubMed  PubMed Central  Google Scholar 

  • Ganguly P, Breen A, Pillai SC (2018) Toxicity of nanomaterials: exposure, pathways, assessment and recent advances. ACS Biomater Sci Eng. https://doi.org/10.1021/acsbiomaterials.8b00068

    Article  CAS  Google Scholar 

  • Ge C, Du J, Zhao L, Wang L, Liu Y, Li D, Yang Y, Zhou R, Zhao Y, Chai Z, Chen C (2011) Binding of blood proteins to carbon nanotubes reduces cytotoxicity. Proc Natl Acad Sci USA 108:16968–16973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gebel T, Foth H, Damm G, Freyberger A, Kramer P-J, Lilienblum W, Röhl C, Schupp T, Weiss C, Wollin C-M, Georg J (2014) Manufactured nanomaterials: categorization and approaches to hazard assessment Hengstler. Arch Toxicol 88:2191–2211

    Article  CAS  PubMed  Google Scholar 

  • Gehr P, Bachofen M, Weibel ER (1978) The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir Physiol 32:121–140

    Article  CAS  PubMed  Google Scholar 

  • Geiser M (2010) Update on macrophage clearance of inhaled micro- and nanoparticles. J Aerosol Med Pulm Drug Deliv 23:207–217

    Article  CAS  PubMed  Google Scholar 

  • Griffin JI, Wang G, Smith WJ, Vu VP, Scheinman R, Stitch D, Moldovan R, Moghimi SM, Simberg D (2017) Revealing dynamics of accumulation of systemically injected liposomes in the skin by intravital microscopy. ASC Nano 11(11):11584. https://doi.org/10.1021/acsnano.7b06524

    Article  CAS  Google Scholar 

  • Granular biopersitent. http://nano.dguv.de/en/news/news-detail-english/new-baua-report-on-granular-biopersistent-particles-gbp-at-workplaces

  • Hamad I, Al-Hanbali O, Hunter AC, Rutt KJ, Andresen TL, Moghimi SM (2010) Distinct polymer architecture mediates switching of complement activation pathways at the nanosphere-serum interface: implications for stealth nanoparticle engineering. ACS Nano 4:6629–6638

    Article  CAS  PubMed  Google Scholar 

  • Hamad I, Hunter AC, Szebeni J, Moghimi SM (2008) Poly(ethylene glycol)s generate complement activation products in human serum through increased alternative pathway turnover and a MASP-2-dependent process. Mol Immunol 46:225–232

    Article  CAS  PubMed  Google Scholar 

  • Hamad I, Hunter AC, Moghimi SM (2013) Complement monitoring of Pluronic 127 gel and micelles: suppression of copolymer-mediated complement activation by elevated serum levels of HDL, LDL, and apolipoproteins A1 and B-100. J Control Release 170:167–174

    Article  CAS  PubMed  Google Scholar 

  • Harishchandra RK, Saleem M, Galla H-J (2010) Nanoparticle interaction with model lung surfactant monolayers. J R Soc Interface 7(Suppl 1):S15–S26

    CAS  PubMed  Google Scholar 

  • Hayes AJ, Bakand S (2014) Toxicological perspectives of inhaled therapeutics and nanoparticles. Expert Opin Drug Metab Toxicol 10(7):933–947

    Article  CAS  PubMed  Google Scholar 

  • Heyder J, Gebhart J, Rudolf G, Schiller CF, Stahlhofen W (1986) Deposition of particles in the human respiratory tract in the size range 0.005–15 μm. J Aerosol Sci 17:811–825

    Article  Google Scholar 

  • Hinds WC (1999) Uniform particle motion. In: Aerosol technology: properties, behavior and measurement of airborne particles, 2nd edn, p. 53–55

    Google Scholar 

  • Holers VM (2014) Complement and its receptors: new insights into human disease. Annu Rev Immunol 32:433–459

    Article  CAS  PubMed  Google Scholar 

  • Hu W, Peng C, Lv M, Li X, Zhang Y, Chen N, Fan C, Huang Q (2011) Protein corona-mediated mitigation of cytotoxicity of graphene oxide. ACS Nano 5:3693–3700

    Article  CAS  PubMed  Google Scholar 

  • Insmed Company website. Accessed on 24 July 2018

    Google Scholar 

  • ISO/TS 80004-1:2015 (2015) Nanotechnology—Vocabulary—Part 1: core terms. International Organization for Standardization: Geneva, Switzerland

    Google Scholar 

  • ISO/TS 80004-2:2015 Nanotechnologies—Vocabulary—Part 2: nano-objects

    Google Scholar 

  • Jeevanandam J, Barhoum A, Chan YS, Dufresne A, Danquah MK (2018) Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations. Beilstein J Nanotechnol 9:1050–1074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones CV, Williams TM, Walker KA, Dickinson H, Sakkal S, Rumballe BA, Little MH, Jenkin G, Ricardo SD (2013) M2 macrophage polarisation is associated with alveolar formation during postnatal lung development. Respir Res 14:41

    Article  PubMed  PubMed Central  Google Scholar 

  • Krafft MP (2015) Overcoming inactivation of the lung surfactant by serum proteins: a potential role for fluorocarbons? Soft Matter 11:5982–5994

    Article  CAS  PubMed  Google Scholar 

  • Kreyling WG, Semmler-Behnke M, Seitz J, Scymczak W, Wenk A, Mayer P, Takenaka S, Oberdörster G (2009) Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs. Inhal Toxicol 21(Sl):55–60

    Article  CAS  PubMed  Google Scholar 

  • Kuempel ED, Attfield MD, Stayner LT, Castranova V (2014) Human and animal evidence supports lower occupational exposure limits for poorly-soluble respirable particles: letter to the Editor re: ‘Low-toxicity dusts: current exposure guidelines are not sufficiently protective’ by Cherrie, Brosseau, Hay and Donaldson. Ann Occup Hyg 58(9):1205–1208

    PubMed  Google Scholar 

  • Lachmann B, Robertson B. Vogel J (1980) In vivo lung lavage as an experimental model of the respiratory distress syndrome. Acta Anaesth Scand 24:231–236

    Article  CAS  PubMed  Google Scholar 

  • Lazarou J, Pomeranz BH, Corey PN (1998) JAMA. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies 15;279(15):1200–1205

    Article  CAS  PubMed  Google Scholar 

  • Lesniak A, Fenaroli F, Monopoli MP, Aberg C, Dawson KA, Salvati A (2012) Effects of the presence or absence of a protein corona on silica nanoparticle uptake and impact on cells. ACS Nano 6:5845–5857

    Article  CAS  PubMed  Google Scholar 

  • Li N, Xia T, Nel AE (2008) The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 44:1689–1699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Rodriguez E, Pérez-Gil J (2014) Structure-function relationships in pulmonary surfactant membranes: from biophysics to therapy. Biochim Biophys Acta-Biomembr 1838(6):1568–1585

    Article  CAS  Google Scholar 

  • Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson KA (2008) Nanoparticlesize and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci USA 105:14265–14270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MAK Commission (2014) The MAK-collection part I, MAK value documentations 2014. In: Deutsche (ed) Forschungsgemeinschaft. The MAK collection for occupational health and safety. Wiley-VCH Verlag GmbH & Co, KGaA, p. 320

    Google Scholar 

  • Mallick S, Choi JS (2014) Liposomes: versatile and biocompatible nanovesicles for efficient biomolecules delivery. J Nanosci Nanotechnol 14(1):755–765

    Article  CAS  PubMed  Google Scholar 

  • Mansour HM, Rhee YS, Wu X (2009) Nanomedicine in pulmonary delivery. Int J Nanomedicine 4:299–319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin TR, Frevert CW (2005) Innate immunity in the lungs. Proc Am Thorac Soc 2:403–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martini WZ, Chinkes DL, Barrow RE, Murphey ED, Wolfe RR (1999) Lung surfactant kinetics in conscious pigs. Am J Physiol 277(1 Pt 1):E187–E195

    CAS  PubMed  Google Scholar 

  • Moghimi M, Hunter C, Dadswell CM, Savay S, Alving C, Szebeni J (2004) Causative factors behind poloxamer 188 (Pluronic F68, Flocor trade mark)-induced complement activation in human sera; A protective role against poloxamer mediated complement activation by elevated serum lipoprotein levels. Biochim Biophys Acta 1689:103–113

    Article  CAS  PubMed  Google Scholar 

  • Moghimi SM (2018) Nanomedicine safety in preclinical and clinical development: focus on idiosyncratic injection/infusion reactions. Drug Discov Today 23(5):1034–1042

    Article  CAS  PubMed  Google Scholar 

  • Moghimi SM, Andersen AJ, Hashem SH, Lettiero B, Ahmadvand D, Hunter AC, Andresen TL, Hamad I, Szebeni J (2010) Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: the challenges ahead. J Control Release 146:175–181

    Article  CAS  PubMed  Google Scholar 

  • Moghimi SM, Hamad I, Andresen TL, Jørgensen K, Szebeni J (2006) Methylation of the phosphate oxygen moiety of phospholipid-methoxy(polyethylene glycol) conjugate prevents PEGylated liposome-mediated complement activation and anaphylatoxin production. FASEB J 20:2591–2593

    Article  CAS  PubMed  Google Scholar 

  • Moghimi SM, Andersen AJ, Ahmadvand D, Wibroe PP, Andresen TL, Hunter AC (2011) Material properties in complement activation. Adv Drug Deliv Rev 63:1000–1007

    Article  CAS  PubMed  Google Scholar 

  • Moghimi SM, Wibroe PP, Helvig SY, Farhangrazi ZS, Hunter AC (2012) Genomic perspectives in inter-individual adverse responses following nanomedicine administration: the way forward. Adv Drug Deliver Rev 64:1385–1393

    Article  CAS  Google Scholar 

  • Money-Kyrle JF, Bates F, Ready J, Gazzard BG, Phillips RH, Boag FC (1993) Liposomal daunorubicin in advanced Kaposi’s sarcoma: a phase II study. Clin Oncol (R Coll Radiol) 5:367–371

    Article  CAS  Google Scholar 

  • Monopoli MP, Bombelli FB, Dawson KA (2011) Nanobiotechnology: nanoparticle coronas take shape. Nat Nanotechnol 6:11–12

    Article  CAS  PubMed  Google Scholar 

  • Morawska L, Hofmann W, Hitchins-Loveday J, Swanson C, Mengersen K (2005) Experimental study of the deposition of combustion aerosols in the human respiratory tract. J Aerosol Sci 36:939–957

    Article  CAS  Google Scholar 

  • Morrow PE (1988) Possible mechanisms to explain dust overloading of the lungs. Fundam Appl Toxicol 10(3):369–384

    Article  CAS  PubMed  Google Scholar 

  • Nanomedicine 2020 (May 2013) Contribution of nanomedicine to horizon 2020. ETP Nanomedicine—NANOMED2020

    Google Scholar 

  • Napierska D, Thomassen LC, Rabolli V, Lison D, Gonzalez L, Kirsch-Volders M, Martens JA, Hoet PH (2009) Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small 5:846–853

    Article  CAS  PubMed  Google Scholar 

  • Neville M, Liu S, Artis C, Dadey E, Gupta R (2009) Functionality of foamy alveolar macrophages after inhalation of aerosolized liposomal Amikacin (ArikaceTM). Pediatr Pulmonol 44:109–212

    Article  Google Scholar 

  • NIH Roadmap for Medical Research (2008) http://pubs.niaaa.nih.gov/publications/arh311/12-13.pdf

  • Nel AE, Mädler L, Velegol D, Xia T, Hoek Van, Somasundaran S, Klaessig F, Castranova V, Thompson M (2009) Understanding biophysicochemical interactions at the nano–bio interface. Nat Mater 8:543–557

    Article  CAS  PubMed  Google Scholar 

  • O’Donnell A, Swarnakar R, Yashina L, Nikolova P, Marinov R, Waghray P (2009) A placebo-controlled study of liposomal amikacin for inhalation (ARIKACE™) nebulized once-daily in the treatment of bronchiectasis patients with chronic Pseudomonas aeruginosa lung infection. Eur Respir J 34(Suppl. 53):1361

    Google Scholar 

  • Oberdörster G (2010) Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. J Intern Med 267:89–105

    Article  PubMed  CAS  Google Scholar 

  • Oberdörster G, Ferin J, Morrow PE (1992) Volumetric loading of alveolar macrophages (AM): a possible basis for diminished AM-mediated particle clearance. Exp Lung Res 18(1):87–104

    Article  PubMed  Google Scholar 

  • Oberdorster G, Kane AB, Klaper RD, Hurt RH (2013) Nanotoxicology. In: Klaassen CD (ed) Casarett and Doull’s toxicology-the basic science of poisons. McGraw Hill, New York, NY, USA, pp. 1189–1229

    Google Scholar 

  • Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H (2005) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • O’Dwyer PJ, Weiss R (1984) Hypersensitivity reactions induced by etoposide. Cancer Treat Rep 68:959–961

    PubMed  Google Scholar 

  • Olivier KN, Maas-Moreno R, Whatley M, Cheng KT, Lee J-H, Fiorentino C, Shaffer R, Macdonald S, Gupta R, Corcoran TE, Malinin VS, Eagle G, Perkins W, Paik C, Chen C (2016) Airway deposition and retention of liposomal amikacin for inhalation in patients with pulmonary nontuberculous mycobacterial disease. Am J Respir Crit Care Med 193:A3732

    Google Scholar 

  • OSHA Occupational safety and health administration. Safety and health tips: nanotechnology http://www.osha.gov/dsg/nanotechnology/nanotechnology.html

  • Padmore T, Stark C, Turkevich LA, Champion JA (2017) Quantitative analysis of the role of fiber length on phagocytosis and inflammatory response by alveolar macrophages. Biochim Biophys Acta 1861(2):58–67

    Article  CAS  Google Scholar 

  • Patton JS, Byron PR (2007) Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov 6:67–74

    Article  CAS  PubMed  Google Scholar 

  • Pauluhn J (2011) Poorly soluble particulates: searching for a unifying denominator of nanoparticles and fine particles for DNEL estimation. Toxicology 279(1–3):176–188

    Article  CAS  PubMed  Google Scholar 

  • Pauluhn J (2014) Repeated inhalation exposure of rats to an anionic high molecular weight polymer aerosol: application of prediction models to better understand pulmonary effects and modes of action. Exp Toxicol Pathol 66(5–6):243–256

    Article  CAS  PubMed  Google Scholar 

  • Pedersen MB, Zhou X, Larsen EK, Sørensen US, Kjems J, Nygaard JV, Nyengaard JR, Meyer RL, Boesen T, Vorup-Jensen T (2010) Curvature of synthetic and natural surfaces is an important target feature in classical pathway complement activation. J Immunol 184:1931–1945

    Article  CAS  PubMed  Google Scholar 

  • Pelaz B, Charron G, Pfeiffer C, Zhao Y, de la Fuente JM, Liang XJ, Parak WJ, Del Pino P (2013) Interfacing engineered nanoparticles with biological systems: anticipating adverse nano-bio interactions. Small 9:1573–1584

    Article  CAS  PubMed  Google Scholar 

  • Pérez de la Ossa DH (2014) Quality aspects of nano-based medicines. In: SME Workshop: Focus on quality for medicines containing chemical entities. London, 4 April 2014

    Google Scholar 

  • Peters A, von Klot S, Heier M, Trentinaglia I, Hormann A, Wichmann HE, Löwel H (2004) Exposure to traffic and the onset of myocardial infarction. N Engl J Med 351:1721–1730

    Article  CAS  PubMed  Google Scholar 

  • Piantadosi CA, Schwartz DA (2004) The acute respiratory distress syndrome. Ann Intern Med 141:460–470

    Article  PubMed  Google Scholar 

  • Possmayer F (2004) Physicochemical aspects of pulmonary surfactant. In: Polin RA, Fox WW, Abman SH (eds) Fetal and neonatal physiology. WB. Saunders Company, Philadelphia, pp 1014–1034

    Chapter  Google Scholar 

  • Rabolli V, Badissi AA, Devosse R, Uwambayinema F, Yakoub Y, Palmai-Pallag M, Lebrun A, De Gussem V, Couillin I, Ryffel B, Marbaix E, Lison D, Huaux F (2014) The alarmin IL-1alpha is a master cytokine in acute lung inflammation induced by silica micro- and nanoparticles. Part Fibre Toxicol 11:69

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ramachandran G, Howard J, Maynard A, Philbert M (2012) Handling worker and third-party exposures to nanotherapeutics during clinical trials. J Law Med Ethics 40:856–864

    Article  PubMed  Google Scholar 

  • Rinderknecht A, Oberdörster G, de Mesy Bentley K et al (2009) Serum protein coated gold nanoparticles in the perfused human term placenta. Toxicologist 108

    Google Scholar 

  • Ring J, Messmer K (1977) Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet 1:466–469

    Article  Google Scholar 

  • Ring J, Grosber M, Mohrenschlager M, Brockow K (2010) Anaphylaxis: acute treatment and management. Chem Immunol Allergy 95:201–210

    Google Scholar 

  • Robertson B (1984) Pathology and pathophysiology of neonatal surfactant deficiency (“respiratory distress syndrome”, “hyaline membrane disease”). In: Robertson B, Van Golde LMG, Batenburg JJ (eds) Pulmonary surfactant. Elsevier Science Publishers, Amsterdam, pp 383–418

    Google Scholar 

  • Roller M, Pott F (2006) Lung tumor risk estimates from rat studies with not specifically toxic granular dusts. Ann N Y Acad Sci 1076:266–280

    Article  CAS  PubMed  Google Scholar 

  • Roller J, Laschke MW, Tschernig T, Schramm R, Veith NT, Thorlacius H, Menger MD (2011) How to detect a dwarf: in vivo imaging of nanoparticles in the lung. Nanomedicine 7(6):753–762

    Article  CAS  PubMed  Google Scholar 

  • Roller M (2003) Dose-response relationships of granular bio-durable dusts in rat lungs: does a cancer threshold exist? Eur J Oncol 8(4):277–293

    Google Scholar 

  • Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC (1993) Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol 20:1–15

    CAS  PubMed  Google Scholar 

  • Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LDN (2005) Incidence and outcomes of acute lung injury. Engl J Med 353:11685–11693

    Article  Google Scholar 

  • Rubins JB (2003) Alveolar macrophages—wielding the double-edged sword of inflammation. Am J Respir Crit Care Med 167:103–104

    Article  PubMed  Google Scholar 

  • Rugonyi S, Biswas SC, Hall SB (2008) The biophysical function of pulmonary surfactant. Respir Physiol Neurobiol 163(1):244–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schleh C, Hohlfeld JM (2009) Interaction of nanoparticles with the pulmonary surfactant system. Inhalation Toxicol 21(sup1):97–103

    Article  CAS  Google Scholar 

  • Schmid O, Stoeger T (2016) Surface area is the biologically most effective dosemetric for acute nanoparticle toxicity in the lung. J Aerosol Sci 99:133–143

    Article  CAS  Google Scholar 

  • Schneberger D, Aharonson-Raz K, Singh B (2012) Pulmonary intravascular macrophages and lung health: what are we missing? Am J Physiol Lung Cell Mol Physiol 302:L498–L503

    Article  CAS  PubMed  Google Scholar 

  • Schurch S (1982) Surface tension at low lung volumes: dependence on time and alveolar size. Respir Physiol 48:339–355

    Article  CAS  PubMed  Google Scholar 

  • Sculier JP, Coune A, Brassinne C, Laduron C, Atassi G, Ruysschaert JM, Fruhling J (1986) Intravenous infusion of high doses of liposomes containing NSC251635, a water-insoluble cytostatic agent. A pilot study with pharmacokinetic data. J Clin Oncol 4:789–797

    Article  CAS  PubMed  Google Scholar 

  • Sharifi S, Behzadi S, Laurent S, Laird Forrest M, Stroeve M, Mahmoud M (2012) Toxicity of nanomaterials. Chem Soc Rev 41:2323–2343

    Article  CAS  PubMed  Google Scholar 

  • Shi C, Zhang X, Chen Z, Robinson MK, Simon DI (2001) Leukocyte integrin Mac-1 recruits Toll/interleukin-1 receptor superfamily signalling intermediates to modulate NF-κB activity. Circ Res 89:859–865

    Article  CAS  PubMed  Google Scholar 

  • Simard JC, Vallieres F, de Liz R, Lavastre V, Girard D (2015) Silver nanoparticles induce degradation of the endoplasmic reticulum stress sensor activating transcription factor-6 leading to activation of the NLRP-3 inflammasome. J Biol Chem 290(9):5926–5939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith T (2018) Clinical team leader division of anti-infective products. FDA Opening Remarks

    Google Scholar 

  • Strait MD (2002) Pathways of anaphylaxis in the mice. J Allergy Clin Immunol 109:658–668

    Article  CAS  PubMed  Google Scholar 

  • Szebeni J, Muggia F, Gabizon A, Barenholz Y (2011) Activation of complement by therapeutic liposomes and other lipid excipient-based therapeutic products: prediction and prevention. Adv Drug Deliv Rev 63:1020–1030

    Article  CAS  PubMed  Google Scholar 

  • Szebeni J (2018) Mechanism of nanoparticle-induced hypersensitivity in pigs: complement or not complement? Drug Discov Today 23(3):487–492

    Article  CAS  PubMed  Google Scholar 

  • Szebeni J, Alving CR, Savay S, Barenholz Y, Priev A, Danino D, Talmon Y (2001) Formation of complement-activating particles in aqueous solutions of Taxol: possible role in hypersensitivity reactions. Int Immunopharm 1:721–735

    Article  CAS  Google Scholar 

  • Szebeni J, Muggia FM, Alving CR (1998) Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study. J Natl Cancer Inst 90:300–330

    Article  CAS  PubMed  Google Scholar 

  • Szebeni J, Fontana JL, Wassef NM, Mongan PD, Morse DS, Dobbins DE, Stahl GL, Bünger R, Alving CR (1999) Hemodynamic changes induced by liposomes and liposome-encapsulated hemoglobin in pigs: a model of pseudollargic cardiopulmonary reactions to liposomes. Role of complement and inhibition by soluble CR1 and anti-C5a antibody. Circulation 99:2302–2309

    Article  CAS  PubMed  Google Scholar 

  • Szebeni J, Fishbane S, Hedenus M, Howaldt S, Locatelli F, Patni S, Rampton D, Weiss G, Folkersen J (2015) Hypersensitivity to intravenous iron: classification, terminology, mechanisms and management. Br J Pharmacol 172:5025–5036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Technical fact sheet—Nanomaterials, November 2017

    Google Scholar 

  • Tenzer S, Docter D, Kuharev J, Musyanovych A, Fetz V, Hecht R, Schlenk F, Fischer D, Kiouptsi K, Reinhardt C, Landfester K, Schild H, Maskos M, Knauer SK, Stauber RH (2013) Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat Nanotechnol 8:772–781

    Article  CAS  PubMed  Google Scholar 

  • Vance ME, Kuiken T, Vejerano EP, McGinnis SP, Hochella MF Jr, Rejeski D, Hull MS (2015) Nanotechnology in the real world: redeveloping the nanomaterial consumer products inventory. Beilstein J Nanotechnol 6:1769–1780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ventola C, Lee MS (2017) Progress in nanomedicine: approved and investigational nanodrugs. P&T 42:742–755

    Google Scholar 

  • Verresen L, Fink E, Lemke HD, Vanrenterghem Y (1994) Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN69 membranes. Kidney Int 45:1497–1503

    Article  CAS  PubMed  Google Scholar 

  • Vogler EA (2012) Protein adsorption in three dimensions. Biomaterials 33:1201–1237

    Article  CAS  PubMed  Google Scholar 

  • Vroman L (1962) Effect of absorbed proteins on the wettability of hydrophilic and hydrophobic solids. Nature 196:476–477

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Li J, Pan J, Jiang X, Ji Y, Li Y, Qu Y, Zhao Y, Wu X, Chen C (2013a) Revealing the binding structure of the protein corona on gold nanorods using synchrotron radiation-based techniques: understanding the reduced damage in cell membranes. J Am Chem Soc 135:17359–17368

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Podila R, Shannahan JH, Rao AM, Brown JM (2013b) Intravenously delivered graphene nanosheets and multiwalled carbon nanotubes induce site-specific Th2 inflammatory responses via the IL-33/ST2 axis. Int J Nanomedicine 8:1733–1748

    PubMed  PubMed Central  Google Scholar 

  • Warner AE (1996) Pulmonary intravascular macrophages. Role in acute lung injury. Clin Chest Med 17:125–135

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER (1963) Morphometry of the Human Lung; Springer: New York, NY, USA

    Chapter  Google Scholar 

  • Weissig V, Pettinger TK, Murdock N (2014) Nanopharmaceuticals (part 1): products on the market. Int J Nanomed 9:4357–4373

    Article  CAS  Google Scholar 

  • Wibro PP, Anselmo AC, Nilsson PH, Sarode A, Gupta V, Urbanics R, Szebeni J, Hunter AC, Mitragotri S, Mollnes TE, Moghimi SM (2017) Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes. Nat Nanotechnol 12:589–590

    Google Scholar 

  • Wibroe PP, Ahmadvand D, Oghabian MA, Yaghmur A, Moghimi SM (2016) An integrated assessment of morphology, size, and complement activation of the PEGylated liposomal doxorubicin products Doxil®, Caelyx®, DOXOrubicin, and SinaDoxosome. J Control Release 221:1–8

    Article  CAS  PubMed  Google Scholar 

  • Wolfram J, Yang Y, Shen J, Moten A, Chen C, Shen H, Ferrari M, Zhao Y (2014) The nano-plasma interface: implications of the protein corona. Colloids Sur B Biointerfaces 124:17–24

    Article  CAS  Google Scholar 

  • Wright JR (2005) Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5:58–68

    Article  CAS  PubMed  Google Scholar 

  • Zhu M, Nie G, Meng H, Xia T, Nel A, Zhao Y (2013) Physicochemical properties determine nanomaterial cellular uptake, transport, and fate. Acc Chem Res 46:622–631

    Article  CAS  PubMed  Google Scholar 

  • Zuo G, Kang SG, Xiu P, Zhao Y, Zhou R (2013) Interactions between proteins and carbon-based nanoparticles: exploring the origin of nanotoxicity at the molecular level. Small 9:1546–1556

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Science and Technology, Nanomedicines Research and Development Center, Quilmes National University, Buenos Aires, Argentina

    Maria Jose Morilla & Eder Lilia Romero

Authors
  1. Maria Jose Morilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eder Lilia Romero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eder Lilia Romero .

Editor information

Editors and Affiliations

  1. Department of Biotechnology, Sant Gadge Baba Amravati University, Amravati, Maharashtra, India

    Mahendra Rai

  2. International Centre for Ecological Engineering, Department of Ecological Studies, University of Kalyani, Kalyani, Nadia, West Bengal, India

    Jayanta Kumar Biswas

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Morilla, M.J., Romero, E.L. (2018). Nanotoxicity of Lipid-Based Nanomedicines. In: Rai, M., Biswas, J. (eds) Nanomaterials: Ecotoxicity, Safety, and Public Perception. Springer, Cham. https://doi.org/10.1007/978-3-030-05144-0_8

Download citation

Publish with us

Policies and ethics

Search

Navigation