Skip to main content

Advertisement

SpringerLink
Log in

Strategies to overcome the barrier: use of nanoparticles as carriers and modulators of barrier properties

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The blood–brain barrier (BBB) protects the brain from toxic substances within the bloodstream and keeps the brain’s homeostasis stable. On the other hand, it also represents the main obstacle in the treatment of many CNS diseases. Among different techniques, nanoparticles have emerged as promising tools to enhance brain drug delivery of therapeutic molecules. For successful drug delivery, nanoparticles may either modulate BBB integrity or exploit transport systems present on the endothelium. In this review, we present two different nanoparticles to enhance brain drug delivery. Poly(butyl cyanoacrylate) nanoparticles were shown to induce a reversible disruption of the BBB in vitro which may be exploited by simultaneous injection of the drug in question. By coating the poly(butyl cyanoacrylate) nanoparticles with, e.g., ApoE, it is also possible to circumvent the BBB via the LDL-receptor. Another example of the use of receptor-mediated endocytosis to enhance brain uptake of nanoparticles are poly(ethylene glycol)-coated Fe3O4 nanoparticles which are covalently attached to lactoferrin. These nanoparticles have been shown to facilitate the transport via the lactoferrin receptor, and so could then be used for magnetic resonance imaging.

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

Similar content being viewed by others

References

  • Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7:41–53

    Article  PubMed  CAS  Google Scholar 

  • Alam MI, Beg S, Samad A, Baboota S, Kohli K, Ali J, Ahuja A, Akbar M (2010) Strategy for effective brain drug delivery. Eur J Pharm Sci 40:385–403

    Article  PubMed  CAS  Google Scholar 

  • Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J (1997) Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm Res 14:325–328

    Article  PubMed  CAS  Google Scholar 

  • Ambruosi A, Gelperina S, Khalansky A, Tanski S, Theisen A, Kreuter J (2006) Influence of surfactants, polymer and doxorubicin loading on the anti-tumour effect of poly(butyl cyanoacrylate) nanoparticles in a rat glioma model. J Microencapsul 23:582–592

    Article  PubMed  CAS  Google Scholar 

  • Andrieux K, Couvreur P (2009) Polyalkylcyanoacrylate nanoparticles for delivery of drugs across the blood-brain barrier. Wiley Interdiscip Rev Nanomedicine Nanobiotechnol 1:463–474

    Article  CAS  Google Scholar 

  • Beduneau A, Saulnier P, Benoit J-P (2007) Active targeting of brain tumors using nanocarriers. Biomaterials 28:4947–4967

    Article  PubMed  CAS  Google Scholar 

  • Begley DJ (2004) Delivery of therapeutic agents to the central nervous system: the problems and the possibilities. Pharmacol Ther 104:29–45

    Article  PubMed  CAS  Google Scholar 

  • Bootz A, Russ T, Gores F, Karas M, Kreuter J (2005) Molecular weights of poly(butyl cyanoacrylate) nanoparticles determined by mass spectrometry and size exclusion chromatography. Eur J Pharm Biopharm 60:391–399

    Article  PubMed  CAS  Google Scholar 

  • Brun E, Carrière M, Mabondzo A (2012) In vitro evidence of dysregulation of blood-brain barrier function after acute and repeated/long-term exposure to TiO2 nanoparticles. Biomaterials 33:886–896

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Yokel RA, Henning B, Toborek M (2008) Manufactured aluminium oxide nanoparticles decrease expression of tight junction proteins in brain vasculature. J Neuroimmune Pharmacol 3:286–295

    Google Scholar 

  • Chrai SS, Murani R, Ahmad I (2001) Liposomes: a review, part one: manufacturing issues. BioPharm Int Appl Techn Biopharm Dev 14:10–14

    CAS  Google Scholar 

  • Cornford EM, Young D, Paxton JW, Finlay GJ, Wilson WR, Pardridge WM (1992) Melphalan penetration of the blood-brain barrier via the neutral amino acid transporter in tumor-bearing brain. Cancer Res 52:138–143

    PubMed  CAS  Google Scholar 

  • Cramer S, Rempe R, Galla HJ (2012) Exploiting the properties of biomolecules for brain targeting of nanoparticulate systems. Curr Med Chem 19:3163–3187

    Article  PubMed  CAS  Google Scholar 

  • Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Ann Rev Biochem 78:857–902

    Article  PubMed  CAS  Google Scholar 

  • Dohgu S, Banks WA (2008) Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by the p38 mitogen-activated protein kinase pathway. Exp Neurol 210:740–749

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Eavarone DA, Yu X, Bellamkonda RV (2000) Targeted drug delivery to C6 glioma by transferrin-coupled liposomes. J Biomed Mater Res 51:10–14

    Article  PubMed  CAS  Google Scholar 

  • Eisenblatter T, Galla HJ (2002) A new multidrug resistance protein at the blood-brain barrier. Biochem Biophys Res Commun 293:1273–1278

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Garcia E, Gil S, Andrieux K, Desmaele D, Nicolas V, Taran F, Georgin D, Andreux JP, Roux F, Couvreur P (2005) A relevant in vitro rat model for the evaluation of blood-brain barrier translocation of nanoparticles. Cell Mol Life Sci 62:1400–1408

    Article  PubMed Central  PubMed  Google Scholar 

  • Gessner A, Olbrich C, Schroder W, Kayser O, Muller RH (2001) The role of plasma proteins in brain targeting: species dependent protein adsorption patterns on brain-specific lipid drug conjugate (LDC) nanoparticles. Int J Pharm 214:87–91

    Article  PubMed  CAS  Google Scholar 

  • Gil ES, Wu L, Xu L, Lowe TL (2012) β-Cyclodextrin-poly(β-Amino Ester) nanoparticles for sustained drug delivery across the blood-brain barrier. Biomacromolecules 13:3533–3541

    Article  PubMed  CAS  Google Scholar 

  • Gojova A, Guo B, Kota RS, Rutledge JC, Kennedy IM, Barakat AI (2007) Induction of inflammation in vascular endothelial cells by metal oxide nanoparticles: effect of particle composition. Environ Health Perspect 115:403–409

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hall WA (1991) Transferrin receptor on glioblastoma multiforme. J Neurosurg 74:313–314

    PubMed  CAS  Google Scholar 

  • Halmos T, Santarromana M, Antonakis K, Scherman D (1996) Synthesis of glucose-chlorambucil derivatives and their recognition by the human GLUT1 glucose transporter. Eur J Pharmacol 318:477–484

    Article  PubMed  CAS  Google Scholar 

  • Hu K, Li J, Shen Y, Lu W, Gao X, Zhang Q, Jiang X (2009) Lactoferrin-conjugated PEG-PLA nanoparticles with improved brain delivery: in vitro and in vivo evaluations. J Control Release 134:55–61

    Article  PubMed  CAS  Google Scholar 

  • Huang RQ, Ke WL, Qu YH, Zhu JH, Pei YY, Jiang C (2007) Characterization of lactoferrin receptor in brain endothelial capillary cells and mouse brain. J Biomed Sci 14:121–128

    Article  PubMed  CAS  Google Scholar 

  • Huynh NT, Passirani C, Saulnier P, Benoit JP (2009) Lipid nanocapsules: a new platform for nanomedicine. Int J Pharm 379:201–209

    Article  PubMed  CAS  Google Scholar 

  • Ivanov AI (2008) Exocytosis and endocytosis. Humana, Totowa

    Book  Google Scholar 

  • Jefferies WA, Brandon MR, Hunt SV, Williams AF, Gatter KC, Mason DY (1984) Transferrin receptor on endothelium of brain capillaries. Nature 312:162–163

    Article  PubMed  CAS  Google Scholar 

  • Jenning V, Thünemann AF, Gohla SH (2000) Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids. Int J Pharm 199:167–177

    Article  PubMed  CAS  Google Scholar 

  • Jia Q, Zeng J, Qiao R, Jing L, Peng L, Gu F, Gao M (2011) Gelification: an effective measure for achieving differently sized biocompatible Fe3O4 nanocrystals through a single preparation recipe. J Am Chem Soc 133:19512–19523

    Article  PubMed  CAS  Google Scholar 

  • Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162

    Article  PubMed  CAS  Google Scholar 

  • Kennedy IM, Wilson D, Barakat AI (2009) Uptake and inflammatory effects of nanoparticles in a human vascular endothelial cell line. Res Rep Health Eff Inst 3–32

  • Kratzer I, Wernig K, Panzenboeck U, Bernhart E, Reicher H, Wronski R, Windisch M, Hammer A, Malle E, Zimmer A, Sattler W (2007) Apolipoprotein A-I coating of protamine-oligonucleotide nanoparticles increases particle uptake and transcytosis in an in vitro model of the blood-brain barrier. J Control Release 117:301–311

    Article  PubMed  CAS  Google Scholar 

  • Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch-Brandt C, Alyautdin R (2002) Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier. J Drug Target 10:317–325

    Article  PubMed  CAS  Google Scholar 

  • Kreuter J, Ramge P, Petrov V, Hamm S, Gelperina SE, Engelhardt B, Alyautdin R, von Briesen H, Begley DJ (2003) Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles. Pharm Res 20:409–416

    Article  PubMed  CAS  Google Scholar 

  • Kreuter J, Hekmatara T, Dreis S, Vogel T, Gelperina S, Langer K (2007) Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain. J Control Release 118:54–58

    Article  PubMed  CAS  Google Scholar 

  • Kumagai AK, Eisenberg JB, Pardridge WM (1987) Absorptive-mediated endocytosis of cationized albumin and a beta-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood-brain barrier transport. J Biol Chem 262:15214–15219

    PubMed  CAS  Google Scholar 

  • Laske DW, Youle RJ, Oldfield EH (1997) Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med 3:1362–1368

    Article  PubMed  CAS  Google Scholar 

  • Lemmen J, Tozakidis IEP, Galla H-J (2013) Pregnane X receptor upregulates ABC-transporter Abcg2 and Abcb1 at the blood-brain barrier. Brain Res 1491:1–13

    Article  PubMed  CAS  Google Scholar 

  • Lenaerts V, Couvreur P, Christiaens-Leyh D, Joiris E, Roland M, Rollman B, Speiser P (1984) Degradation of poly (isobutyl cyanoacrylate) nanoparticles. Biomaterials 5:65–68

    Article  PubMed  CAS  Google Scholar 

  • Levin VA (1980) Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J Med Chem 23:682–684

    Article  PubMed  CAS  Google Scholar 

  • Liu L-b, Xue Y-x, Liu Y-h, Wang Y-b (2008) Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton. J Neurosci Res 86:1153–1168

    Article  PubMed  CAS  Google Scholar 

  • Liu S, Jia B, Qiao R, Yang Z, Yu Z, Liu Z, Liu K, Shi J, Ouyang H, Wang F, Gao M (2009) A novel type of dual-modality molecular probe for MR and nuclear imaging of tumor: preparation, characterization and in vivo application. Mol Pharm 6:1074–1082

    Article  PubMed  CAS  Google Scholar 

  • Lockman PR, Mumper RJ, Khan MA, Allen DD (2002) Nanoparticle technology for drug delivery across the blood-brain barrier. Drug Dev Ind Pharm 28:1–13

    Article  PubMed  CAS  Google Scholar 

  • Lockman PR, Koziara J, Roder KE, Paulson J, Abbruscato TJ, Mumper RJ, Allen DD (2003) In vivo and in vitro assessment of baseline blood-brain barrier parameters in the presence of novel nanoparticles. Pharm Res 20:705–713

    Article  PubMed  CAS  Google Scholar 

  • Lossinsky AS, Vorbrodt AW, Wisniewski HM (1995) Scanning and transmission electron microscopic studies of microvascular pathology in the osmotically impaired blood-brain barrier. J Neurocytol 24:795–806

    Article  PubMed  CAS  Google Scholar 

  • Markoutsa E, Papadia K, Clemente C, Flores O, Antimisiaris SG (2012) Anti-Aβ-MAb and dually decorated nanoliposomes: effect of Aβ1-42 peptides on interaction with hCMEC/D3 cells. Eur J Pharm Biopharm 81:49–56

    Article  PubMed  CAS  Google Scholar 

  • Marquet F, Tung Y-S, Teichert T, Ferrera VP, Konofagou EE (2011) Noninvasive, transient and selective blood-brain barrier opening in non-human primates in vivo. PLoS ONE 6:e22598

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Martel CL, Mackic JB, Matsubara E, Governale S, Miguel C, Miao W, McComb JG, Frangione B, Ghiso J, Zlokovic BV (1997) Isoform-specific effects of apolipoproteins E2, E3, and E4 on cerebral capillary sequestration and blood-brain barrier transport of circulating Alzheimer’s amyloid beta. J Neurochem 69:1995–2004

    Article  PubMed  CAS  Google Scholar 

  • Michaelis K, Hoffmann MM, Dreis S, Herbert E, Alyautdin RN, Michaelis M, Kreuter J, Langer K (2006) Covalent linkage of apolipoprotein e to albumin nanoparticles strongly enhances drug transport into the brain. J Pharmacol Exp Ther 317:1246–1253

    Article  PubMed  CAS  Google Scholar 

  • Miller DW, Keller BT, Borchardt RT (1994) Identification and distribution of insulin receptors on cultured bovine brain microvessel endothelial cells: possible function in insulin processing in the blood-brain barrier. J Cell Physiol 161:333–341

    Article  PubMed  CAS  Google Scholar 

  • Mulik RS, Monkkonen J, Juvonen RO, Mahadik KR, Paradkar AR (2010) ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model. Mol Pharm 7:815–825

    Article  PubMed  CAS  Google Scholar 

  • Muller RH, Lherm C, Herbort J, Couvreur P (1990) In vitro model for the degradation of alkylcyanoacrylate nanoparticles. Biomaterials 11:590–595

    Article  PubMed  CAS  Google Scholar 

  • Oerlemans C, Bult W, Bos M, Storm G, Nijsen J, Hennink W (2010) Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res 27:2569–2589

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Olivier J-C, Fenart L, Chauvet R, Pariat C, Cecchelli R, Couet W (1999) Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity. Pharm Res 16:1836–1842

    Article  PubMed  CAS  Google Scholar 

  • Pang Z, Lu W, Gao H, Hu K, Chen J, Zhang C, Gao X, Jiang X, Zhu C (2008) Preparation and brain delivery property of biodegradable polymersomes conjugated with OX26. J Control Release 128:120–127

    Article  PubMed  CAS  Google Scholar 

  • Patel M, Souto EB, Singh KK (2013) Advances in brain drug targeting and delivery: limitations and challenges of solid lipid nanoparticles. Expert Opin Drug Deliv 10:889–905

    Article  PubMed  CAS  Google Scholar 

  • Petri B, Bootz A, Khalansky A, Hekmatara T, Muller R, Uhl R, Kreuter J, Gelperina S (2007) Chemotherapy of brain tumour using doxorubicin bound to surfactant-coated poly(butyl cyanoacrylate) nanoparticles: revisiting the role of surfactants. J Control Release 117:51–58

    Article  PubMed  CAS  Google Scholar 

  • Provias J, Jeynes B (2011) Correlation analysis of capillary APOE, VEGF and eNOS expression in Alzheimer brains. Curr Alzheim Res 8:197–202

    Article  CAS  Google Scholar 

  • Qiao R, Jia Q, Hüwel S, Xia R, Liu T, Gao F, Galla H-J, Gao M (2012) Receptor-mediated delivery of magnetic nanoparticles across the blood-brain barrier. ACS Nano 6:3304–3310

    Article  PubMed  CAS  Google Scholar 

  • Ramge P, Unger RE, Oltrogge JB, Zenker D, Begley D, Kreuter J, Von Briesen H (2000) Polysorbate-80 coating enhances uptake of polybutylcyanoacrylate (PBCA)-nanoparticles by human and bovine primary brain capillary endothelial cells. Eur J Neurosci 12:1931–1940

    Article  PubMed  CAS  Google Scholar 

  • Rempe R (2012) Untersuchungen zum Transfer von Nanopartikeln über in vitro-Modelle der cerebralen Schrankensysteme. PhD thesis, University of Münster, Department of Biochemistry

  • Rempe R, Cramer S, Hüwel S, Galla H-J (2011) Transport of Poly(n-butylcyano-acrylate) nanoparticles across the blood-brain barrier in vitro and their influence on barrier integrity. Biochem Biophys Res Commun 406:64–69

    Article  PubMed  CAS  Google Scholar 

  • Saupe A, Rades T (2006) Solid lipid nanoparticles. In: Mozafari MR (ed) Nanocarrier technologies. Springer, Netherlands, pp 41–50

    Chapter  Google Scholar 

  • Scherer D, Robinson JR, Kreuter J (1994) Influence of enzymes on the stability of polybutylcyanoacrylate nanoparticles. Int J Pharm 101:165–168

    Article  CAS  Google Scholar 

  • Sharma HS, Hussain S, Schlager J, Ali SF, Sharma A (2010) Influence of nanoparticles on blood-brain barrier permeability and brain edema formation in rats. Acta Neurochir Suppl 106:359–364

    Article  PubMed  Google Scholar 

  • Talukder MJ, Takeuchi T, Harada E (2003) Receptor-mediated transport of lactoferrin into the cerebrospinal fluid via plasma in young calves. J Vet Med Sci 65:957–964

    Article  PubMed  CAS  Google Scholar 

  • Trickler WJ, Lantz SM, Murdock RC, Schrand AM, Robinson BL, Newport GD, Schlager JJ, Oldenburg SJ, Paule MG, Slikker W Jr, Hussain SM, Ali SF (2010) Silver nanoparticle induced blood-brain barrier inflammation and increased permeability in primary rat brain microvessel endothelial cells. Toxicol Sci 118:160–170

    Google Scholar 

  • Trickler WJ, Lantz SM, Murdock RC, Schrand AM, Robinson BL, Newport GD, Schlager JJ, Oldenburg SJ, Paule MG, Slikker W Jr, Hussain SM, Ali SF (2011) Brain microvessel endothelial cells responses to gold nanoparticles: In vitro pro-inflammatory mediators and permeability. Nanotoxicology 5:479–492

    Google Scholar 

  • van de Waterbeemd H, Camenisch G, Folkers G, Chretien JR, Raevsky OA (1998) Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J Drug Target 6:151–165

    Article  PubMed  Google Scholar 

  • Vauthier C, Dubernet C, Fattal E, Pinto-Alphandary H, Couvreur P (2003) Poly(alkylcyanoacrylates) as biodegradable materials for biomedical applications. Adv Drug Deliv Rev 55:519–548

    Article  PubMed  CAS  Google Scholar 

  • Vezin WR, Florence AT (1980) In vitro heterogeneous degradation of poly(n-alkyl alpha-cyanoacrylates). J Biomed Mater Res 14:93–106

    Article  PubMed  CAS  Google Scholar 

  • Wagner S, Kufleitner J, Zensi A, Dadparvar M, Wien S, Bungert J, Vogel T, Worek F, Kreuter J, von Briesen H (2010) Nanoparticulate transport of oximes over an in vitro blood-brain barrier model. PLoS ONE 5:e14213

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Weigel PH, Oka JA (1981) Temperature dependence of endocytosis mediated by the asialoglycoprotein receptor in isolated rat hepatocytes. Evidence for two potentially rate-limiting steps. J Biol Chem 256:2615–2617

    PubMed  CAS  Google Scholar 

  • Williams DL, Dawson PA, Newman TC, Rudel LL (1985) Apolipoprotein E synthesis in peripheral tissues of nonhuman primates. J Biol Chem 260:2444–2451

    PubMed  CAS  Google Scholar 

  • Winkler K, Scharnagl H, Tisljar U, Hoschutzky H, Friedrich I, Hoffmann MM, Huttinger M, Wieland H, Marz W (1999) Competition of Abeta amyloid peptide and apolipoprotein E for receptor-mediated endocytosis. J Lipid Res 40:447–455

    PubMed  CAS  Google Scholar 

  • Witt KA, Gillespie TJ, Huber JD, Egleton RD, Davis TP (2001) Peptide drug modifications to enhance bioavailability and blood-brain barrier permeability. Peptides 22:2329–2343

    Article  PubMed  CAS  Google Scholar 

  • Yang XX, Chen JH, Guo D (2005) Study of biocompatibility of polybutylcyanoacrylate nanoparticles. Di Yi Jun Yi Da Xue Xue Bao 25:1261–1263

    PubMed  CAS  Google Scholar 

  • Zensi A, Begley D, Pontikis C, Legros C, Mihoreanu L, Büchel C, Kreuter J (2010) Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain. J Drug Target 18:842–848

    Article  PubMed  CAS  Google Scholar 

  • Zhu MT, Wang B, Wang Y, Yuan L, Wang HJ, Wang M, Ouyang H, Chai ZF, Feng WY, Zhao YL (2011) Endothelial dysfunction and inflammation induced by iron oxide nanoparticle exposure: risk factors for early atherosclerosis. Toxicol Lett 203:162–171

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Münster, Wilhelm-Klemm-Straße 2, 48149, Muenster, Germany

    Ralf Rempe, Sandra Cramer & Hans-Joachim Galla

  2. Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing, 100190, China

    Ruirui Qiao

Authors
  1. Ralf Rempe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandra Cramer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruirui Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hans-Joachim Galla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hans-Joachim Galla.

Additional information

Ralf Rempe and Sandra Cramer contributed equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rempe, R., Cramer, S., Qiao, R. et al. Strategies to overcome the barrier: use of nanoparticles as carriers and modulators of barrier properties. Cell Tissue Res 355, 717–726 (2014). https://doi.org/10.1007/s00441-014-1819-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-014-1819-7

Keywords

Search

Navigation