Skip to main content
SpringerLink
Log in

Cytotoxicity and Genotoxicity of Solid Lipid Nanoparticles

  • Chapter
  • First Online:
Nanotoxicology

Part of the book series: Nanomedicine and Nanotoxicology ((NANOMED))

Abstract

Solid lipid nanoparticles (SLNs) were the last nanoparticles discovered; however, these particles have received great attention as drug delivery system besides the other one. These particles can be produced by several methods, which include methods without use of organic solvents or with only reagents previously approved by Food and Drug Administration (FDA) through the GRAS rules. Furthermore, the easy scale up of production and particles sterilization led to an increase in the industry interest in these nanostructures. Nowadays, there are some products with SLNs on the market and the tendency is that the number of products with this carrier increases significantly in the next years. For this, studies about their toxicity in vitro and in vivo are increasing. SLN exhibits low or no cyto- and genotoxic effect on different cells that were already studied. The cytotoxicity and genotoxicity depend on the SLN composition, more specifically, of the solid lipid and surfactant used in the preparation. Some solid lipid or surfactant can increase the cyto- or genotoxic effect of SLN indicating that SLN composition plays an important role in the cytotoxic and genotoxic effect of these particles.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

  • Abbasalipurkabir R, Salehzadeh A, Abdullah R (2011a) Delivering tamoxifen within solid lipid nanoparticles. Pharm Technol 36:74–79

    Google Scholar 

  • Abbasalipurkabir R, Salehzadeh A, Abdullah R (2011b) Cytotoxicity effect of solid lipid nanoparticles on human breast câncer cell lines. Biotechnology 10:528–633

    Article  Google Scholar 

  • Allais C, Keller G, Lesieur P et al (2003) X-ray diffraction/calorimetry coupling a tool for polymorphism control. J Therm Anal Calorim 74:723–728

    Article  CAS  Google Scholar 

  • Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13:238–252

    Article  PubMed  CAS  Google Scholar 

  • Barbosa RM, da Silva CMG, Bella TS et al (2013) Cytotoxicity of solid lipid nanoparticles and nanostructured lipid carriers containing the local anesthetic dibucaine designed for topical application. J Phys Conf 429:012035

    Article  Google Scholar 

  • Benford D, Hanley B, Bottrill K (2000) Biomarkers as predictive tools in toxicity-testing. Altern Lab Anim 28:119–131

    Google Scholar 

  • Brioschi A, Zara GP, Calderoni S et al (2008) Cholesterylbutyrate solid lipid nanoparticles as a butyric acid prodrug. Molecules 13:230–254

    Article  PubMed  CAS  Google Scholar 

  • Bunjes H, Steiniger F, Richter W (2007) Visualizing the structure of triglyceride nanoparticles in different crystal modifications. Langmuir 23:4005–4011

    Article  PubMed  CAS  Google Scholar 

  • Buse J, El-Aneed A (2010) Properties, engineering and applications of lipid-based nanoparticle drug-delivery systems: current research and advances. Nanomedicine (Lond) 5:1237–1260

    Article  CAS  Google Scholar 

  • Carbone C, Tomasello B, Ruozi B et al (2012) Preparation and optimization of PIT solid lipid nanoparticles via statistical factorial design. Eur J Med Chem 49:110–117

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Chang X, Du D et al (2006) Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting. J Control Release 110:296–306

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Yuan L, Zhou L et al (2012) Effect of cell-penetrating peptide-coated nanostructured lipid carriers on the oral absorption of tripterine. Int J Nanomed 7:4581–4591

    CAS  Google Scholar 

  • Das S, Chaudhury A (2011) Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech 12:62–76

    Article  PubMed  CAS  Google Scholar 

  • Doktorovova S, Silva AM, Gaivão I et al (2012) Genotoxicity evaluation of cationic solid lipid nanoparticles in Caco-2 cells. In: Proceedings of the ninth central European symposium on pharmaceutical technology, Dubrovnik

    Google Scholar 

  • Durán N, Teixeira Z, Marcato PD (2011) Topical application of nanostructures: solid lipid, polymeric and metallic nanoparticles. In: Guterres SS, Beck R, Polhmann A (eds) Nanocosmetics and nanomedicines: new approaches for skin care. Part II, Chap. 4. Springer, Berlin, pp 69–100

    Chapter  Google Scholar 

  • Ekambaram P, Sathali AAH, Priyanka K (2012) Solid lipid nanoparticles: a review. Sci Rev Chem Commun 2:80–102

    CAS  Google Scholar 

  • Fessi H, Puisieux F, Devissaguet JP et al (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55:R1–R4

    Article  CAS  Google Scholar 

  • Garud A, Singh D, Garud N (2012) Solid lipid nanoparticles (SLN): method, characterization and applications. Int Curr Pharm J 1:384–393

    Article  CAS  Google Scholar 

  • Gasco MR (2007) Lipid nanoparticles: perspectives and challenges. Adv Drug Deliv Rev 59:377–378

    Article  PubMed  CAS  Google Scholar 

  • Hou D, Xie C, Huang K, Zhu C (2003) The production and characteristics of solid lipid nanoparticles (SLNs). Biomaterials 24:1781–1785

    Article  PubMed  CAS  Google Scholar 

  • Hu F-Q, Jiang S-P, Du Y-Z et al (2006) Preparation and characteristics of monostearin nanostructured lipid carriers. Int J Pharm 314:83–89

    Article  PubMed  CAS  Google Scholar 

  • Joshi MD, Müller RH (2009) Lipid nanoparticles for parenteral delivery of actives. Eur J Pharm Biopharm 71:161–172

    Article  PubMed  CAS  Google Scholar 

  • Joshi M, Patravale V (2008) Nanostructure lipid carrier (NLC) based gel of celecoxib. Int J Pharm 346:124–132

    Article  PubMed  CAS  Google Scholar 

  • Khan S (2012) Solid lipid nanoparticles: a review. World J Pharm Sci 1:96–115

    CAS  Google Scholar 

  • Kim HR, Kim IK, Bae KH et al (2008) Cationic solid lipid nanoparticles reconstituted from low density lipoprotein components for delivery of siRNA. Mol Pharm 5:622–631

    Article  PubMed  CAS  Google Scholar 

  • Kristl J, Teskac K, Milek M et al (2008) Surface active stabilizer tyloxapol in colloidal dispersions exerts cytostatic effects and apoptotic dismissal of cells. Toxicol Appl Pharmacol 232:18–25

    Article  Google Scholar 

  • Liu J, Gong T, Fu H et al (2008) Solid lipid nanoparticles for pulmonary delivery of insulin. Int J Pharm 356:333–334

    Article  PubMed  CAS  Google Scholar 

  • Marcato PD (2008) Preparation, characterization and application in drugs and cosmetics of solid lipid nanoparticles. Rev Eletron Fárm 6:1–37

    Google Scholar 

  • Marcato PD, Caverzan J, Rossi-Bergmann B et al (2011) Nanostructured polymer and lipid carriers for sunscreen. Biological effects and skin permeation. J Nanosci Nanotechnol 11:1880–1886

    Article  PubMed  CAS  Google Scholar 

  • Mathur V, Satrawala Y, Rajput MS et al (2010) Solid lipid nanoparticles in cancer therapy. Int J Drug Deliv 2:192–199

    Article  CAS  Google Scholar 

  • Mehnert W, Mader K (2001) Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 47:165–196

    Article  PubMed  CAS  Google Scholar 

  • Meunier V, Bourrie M, Berger Y et al (1995) The human intestinal epithelial cell line Caco-2: pharmacological and pharmacokinetic applications. Cell Biol Toxicol 11:187–194

    Article  PubMed  CAS  Google Scholar 

  • Müller RH, Mehnert W, Lucks JS et al (1995) Solid lipid nanoparticles (SLN): an alternative colloidal carrier system for controlled drug delivery. Eur J Pharm Biopharm 41:62–69

    Google Scholar 

  • Müller RH, Maassen S, Weyhers H et al (1996a) Cytotoxicity of magnetite-loaded polylactide, polylactide/glycolide particles and solid lipid nanoparticles. Int J Pharm 138:85–94

    Article  Google Scholar 

  • Müller RH, Maassen S, Weyhers H et al (1996b) Phagocytic uptake and cytotoxicity of solid lipid nanoparticles (SLN) sterically stabilized with poloxamine 908 and poloxamer 407. J Drug Target 4:161–170

    Article  PubMed  Google Scholar 

  • Müller RH, Rühl D, Runge S et al (1997) Cytotoxicity of solid lipid nanoparticles as a function of the lipid matrix and the surfactant. Pharm Res 14:458–462

    Article  PubMed  Google Scholar 

  • Müller RH, Maëder K, Gohla S (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery: a review of the state of the art. Eur J Pharm Biopharm 50:161–177

    Article  PubMed  Google Scholar 

  • Müller RH, Radtke M, Wissing SA (2002) Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 54:S131–S155

    Article  PubMed  Google Scholar 

  • Müller RH, Petersen RD, Hommoss A et al (2007) Nanostructured lipid carriers (NLC) in cosmetic dermal products. Adv Drug Deliv Rev 59:522–530

    Article  PubMed  Google Scholar 

  • Müller RH, Shegokar R, Cornelia M et al (2011) 20 years of lipid nanoparticles (SLN and NLC): present state of development and industrial applications. Curr Drug Discov Technol 8:207–227

    Article  PubMed  Google Scholar 

  • Nassimi M, Schleh C, Lauenstein HD et al (2009) Low cytotoxicity of solid lipid nanoparticles in in vitro and ex vivo lung models. Inhal Toxicol 21(suppl 1):104–109

    Article  PubMed  CAS  Google Scholar 

  • Nassimi M, Schleh C, Lauenstein HD et al (2010) A toxicological evaluation of inhaled solid lipid nanoparticles used as a potential drug delivery system for the lung. Eur J Pharm Biopharm 75:107–116

    Article  PubMed  CAS  Google Scholar 

  • Pardeike J, Hommoss A, Müller RH (2009) Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm 366:170–184

    Article  PubMed  CAS  Google Scholar 

  • Patel D, Dasgupta S, Dey S et al (2012) Nanostructured lipid carriers (NLC)-based gel for the topical delivery of aceclofenac: preparation, characterization, and in vivo evaluation. Sci Pharm 80:749–764

    Article  PubMed  CAS  Google Scholar 

  • Pedersen N, Hansen S, Heydenreich AV et al (2006) Solid lipid nanoparticles can effectively bind DNA, streptavidin and biotinylated ligands. Eur J Pharm Biopharm 62:155–162

    Article  PubMed  CAS  Google Scholar 

  • Pragati S, Kuldeep S, Ashok S et al (2009) Solid lipoid nanoparticles: a promising drug delivery technology. Int J Pharm Nanotechnol 2:509–516

    CAS  Google Scholar 

  • Puri A, Loomis K, Smith B et al (2009) Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic. Crit Rev Ther Drug Carrier Syst 26:523–580

    Article  PubMed  CAS  Google Scholar 

  • Rawat MK, Jain A, Singh S (2011a) In vivo and cytotoxicity evaluation of repaglinide-loaded binary solid lipid nanoparticles after oral administration to rats. J Pharm Sci 100:2406–2417

    Article  PubMed  CAS  Google Scholar 

  • Rawat MK, Jain A, Singh S (2011b) Studies on binary lipid matrix based solid lipid nanoparticles of repaglinide: in vitro and in vivo evaluation. J Pharm Sci 100:2366–2378

    Article  PubMed  CAS  Google Scholar 

  • Ridolfi DM, Marcato PD, Machado D et al (2011) In vitro cytotoxicity assays of solid lipid nanoparticles in epithelial and dermal cells. J Phys Conf 304:012032

    Article  Google Scholar 

  • Ridolfi M, Marcato PD, Justo GZ et al (2012) Solid lipid nanoparticles coated with chitosan as carrier for topical delivery of tretinoin. Colloids Surf B Biointerfaces 93:36–40

    Article  PubMed  CAS  Google Scholar 

  • Ruktanonchai U, Limpakdee S, Meejoo S et al (2008) The effect of cetyl palmitate crystallinity on physical properties of gamma-oryzanol encapsulated in solid lipid nanoparticles. Nanotechnology 19:095701

    Article  PubMed  Google Scholar 

  • Sanna V, Kirschvink N, Gustin P et al (2003) Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration. AAPS PharmSciTech 5:1–7

    Google Scholar 

  • Schöler N, Zimmermann E, Katzfey U et al (2000) Preserved solid lipid nanoparticles (SLN) at low concentrations do cause neither direct nor indirect cytotoxic effects in peritoneal macrophages. Int J Pharm 196:235–239

    Article  PubMed  Google Scholar 

  • Schöler N, Hahn H, Muller RH et al (2002) Effect of lipid matrix and size of solid lipid nanoparticles (SLN) on the viability and cytokine production of macrophages. Int J Pharm 231:167–176

    Article  PubMed  Google Scholar 

  • Severino P, Andreani T, Macedo AS et al (2012) Current state-of-art and new trends on lipid nanoparticles (SLN and NLC) for oral drug delivery. J Drug Deliv 2012:750891

    Article  PubMed  Google Scholar 

  • Sharma P, Dube B, Sawant K (2011) Development and evaluation of nanostructured lipid carriers of cytarabine for treatment of meningeal leukemia. J Nanosci Nanotechnol 11:6676–6682

    Article  PubMed  CAS  Google Scholar 

  • Silva AH, Filippin-Monteiro FB, Mattei B et al (2012) In vitro biocompatibility of solid lipid nanoparticles. Sci Total Environ 432:382–388

    Article  PubMed  CAS  Google Scholar 

  • Smijs TG, Bouwstra JA (2010) Focus on skin as a possible port of entry for solid nanoparticles and the toxicological impact. J Biomed Nanotechnol 6:469–484

    Article  PubMed  CAS  Google Scholar 

  • Souto EB, Severino P, Santana MHA et al (2011) Solid lipid nanoparticles: classical methods of lab production. Quim Nova 34:1762–1769

    CAS  Google Scholar 

  • Teeranachaideekul V, Boonme P, Souto EB et al (2008a) Influence of oil content on physicochemical properties and skin distribution of Nile red-loaded NLC. J Control Release 128:134–141

    Article  PubMed  CAS  Google Scholar 

  • Teeranachaideekul V, Souto EB, Müller RH et al (2008b) Physicochemical characterization and in vitro release studies of ascorbyl palmitate-loaded semi-solid nanostructured lipid carriers (NLC gels). J Microencapsul 25:111–120

    Article  PubMed  CAS  Google Scholar 

  • Üner M (2006) Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): their benefits as colloidal drug carrier systems. Pharmazie 61:375–386

    PubMed  Google Scholar 

  • Üner M, Radtke M, Wissing AS (2007) Solid lipid nanoparticles and nanostructured lipid carriers. Encyclop Nanosci Nanotechnol 10:43–56

    Google Scholar 

  • Waghmare AS, Grampurohit ND, Gadhave MV et al (2012) Solid lipid nanoparticles: a promising drug delivery system. Int Res J Pharm 3:100–107

    CAS  Google Scholar 

  • Westesen K, Bunjes H, Koch MHJ (1997) Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential. J Control Release 48:223–236

    Article  CAS  Google Scholar 

  • Weyenberg W, Filev P, Van den Plas D et al (2007) Cytotoxicity of submicron emulsions and solid lipid nanoparticles for dermal application. Int J Pharm 337:291–298

    Article  PubMed  CAS  Google Scholar 

  • Weyghers H, Ehlers S, Hahn H et al (2006) Solid lipid nanoparticles (SLN)—effects of lipid composition on in vitro degradation and in vivo toxicity. Pharmazie 61:539–544

    Google Scholar 

  • Wissing SA, Müller RH, Manthel L et al (2004a) Structural characterization of Q10-loaded solid lipid nanoparticles by NMR spectroscopy. Pharm Res 21:400–405

    Article  PubMed  CAS  Google Scholar 

  • Wissing SA, Kayser O, Müller RH (2004b) Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev 56:1257–1272

    Article  PubMed  CAS  Google Scholar 

  • Yuan H, Zhang W, Du YZ et al (2010) Ternary nanoparticles of anionic lipid nanoparticles/protamine/DNA for gene delivery. Int J Pharm 392:224–231

    Article  PubMed  CAS  Google Scholar 

  • Zhang XG, Miao J, Dai YQ et al (2008) Reversal activity of nanostructured lipid carriers loading cytotoxic drug in multi-drug resistant cancer cells. Int J Pharm 361:239–244

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors acknowledge the FAPESP, INOMAT (MCT/CNPq), NanoBioss (MCTI), and Brazilian Network of Nanotoxicology (MCT/CNPq).

Author information

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences of Riberão Preto, Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil

    Priscyla D. Marcato

  2. Biological Chemistry Laboratory, Institute of Chemistry, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil

    Nelson Durán

  3. Center of Natural and Human Sciences, Universidade Federal do ABC – UFABC, Santo André, São Paulo, Brazil

    Nelson Durán

Authors
  1. Priscyla D. Marcato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nelson Durán
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Priscyla D. Marcato .

Editor information

Editors and Affiliations

  1. Institute of Chemistry, Universidade Estadual de Campinas—UNICAMP, Campinas, São Paulo, Brazil

    Nelson Durán

  2. Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Silvia S. Guterres

  3. Institute of Chemistry, Universidade Estadual de Campinas—UNICAMP, Campinas, São Paulo, Brazil

    Oswaldo L. Alves

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Marcato, P.D., Durán, N. (2014). Cytotoxicity and Genotoxicity of Solid Lipid Nanoparticles. In: Durán, N., Guterres, S., Alves, O. (eds) Nanotoxicology. Nanomedicine and Nanotoxicology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8993-1_10

Download citation

Publish with us

Policies and ethics

Search

Navigation