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Preparation and properties of nanoscale containers for biomedical application in drug delivery: preliminary studies with kynurenic acid

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

The main purpose of this study was to facilitate the delivery of kynurenic acid (KYNA) across the blood–brain barrier (BBB) by applying micelles as nanoscale containers. Non-ionic amphiphilic molecules were used for preparation of spherical micelles for delivery of kynurenic acid in aqueous solution in physiological condition. It was established that Triton X 100 and Lutensol AP 20 non-ionic surfactants are able to produce stable nanocontainers for delivery of kynurenic acid molecules. The incorporation of KYNA molecules was investigated by dynamic light scattering and the size of micelles were calculated between 5 and 10 nm in 150 mM NaCl and pH 7.5–7.6 solutions. Encapsulated kynurenic acid showed a significantly higher blood–brain barrier permeability compared with non-encapsulated kynurenic acid. The in vivo experiments showed that the encapsulated kynurenic acid is able to display effects within the central nervous system, even after its peripheral administration.

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References

  • Aswal VK, De S, Goyal PS, Bhattacharya S, Heenan RK (1999) Micellar structures of dimeric surfactants with phosphate head groups and wettable spacers: a small-angle neutron scattering study. Phys Rev E 59:3116–3122

    Article  CAS  Google Scholar 

  • Dill KA, Koppel DE, Cantor RS, Dill JD, Bendedouch D, Chen SH (1984) Molecular conformations in surfactant micelles. Nature 309:42–45

    Article  CAS  Google Scholar 

  • Evans DF, Wennerström H (1994) The colloidal domain—where physics, chemistry, biology and technology meet. VCH Publishers, USA

    Google Scholar 

  • Fukui S, Schwarz R, Rapaport SI, Takada Y, Smith QR (1991) Blood-brain barrier transport of kynurenines: implications for brain synthesis and metabolism. J Neurochem 56:2007–2017

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis G (1995) Engineering liposomes for drug delivery: progress and problems. Trends Biotechnol 13:527–537

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis G, Florence AT (1993) Liposomes in drug delivery: clinical, diagnostic and ophthalmic potential. Drugs 45:15–28

    Article  PubMed  CAS  Google Scholar 

  • Hutamekain P, Farkas AE, Orbok A, Wilhelm I, Nagyoszi P, Veszelka S et al (2008) Effect of nicotine and polyaromtic hydrocarbons on cerebral endothelial cells. Cell Biol Int 32:198–209

    Article  Google Scholar 

  • Iden DL, Allen TM (2001) In vitro and in vivo comparison of immunoliposomes made by conventional coupling techniques with those made by a new post-insertion approach. Biochim Biophys Acta 1513:207–216

    Article  PubMed  CAS  Google Scholar 

  • Joshi JV, Aswal VK, Goyal PS (2007) Combined SANS and SAXS studies on alkali metal dodecyl sulphate micelles. J Phys Condens Matter 19:196219

    Article  Google Scholar 

  • Kakudo T, Chaki S, Futaki S, Nakase I, Akaji K, Kawakami T, Maruyama K, Kamiya H, Harashima H (2004) Transferrinmodified liposomes equipped with a pH-sensitive fusogenic peptide: an artificial viral-like delivery system. Biochemistry 43:5618–5628

    Article  PubMed  CAS  Google Scholar 

  • Kincses ZST, Toldi J, Vécsei L (2010) Kynurenines, neurodegeneration and Alzheimer’s disease. J Cell Mol Med 14:2045–2054

    Article  PubMed  CAS  Google Scholar 

  • Lindman B, Wennerström H (1980) Topics in current chemistry. Springer, Berlin, p 87

    Google Scholar 

  • Mastrobattista E, Crommelin DJ, Wilschut J, Storm G (2002) Targeted liposomes for delivery of protein-based drugs into the cytoplasm of tumor cells. J Liposome Res 12:57–65

    Article  PubMed  CAS  Google Scholar 

  • Mori N, Ohta S (1992) Comparison of anticonvulsant effects of valproic acid entrapped in positively and negatively charged liposomes in amygdaloid-kindled rats. Brain Res 593:329–331

    Article  PubMed  CAS  Google Scholar 

  • Mori N, Kurokouchi A, Osonoe K, Saitoh H, Ariga K, Suzuki K, Iwata Y (1995) Liposome-entrapped phenytoin locally suppresses amygdaloid epileptogenic focus created by db-cAMP/EDTA in rats. Brain Res 703:184–190

    Article  PubMed  CAS  Google Scholar 

  • Németh H, Robotka H, Kis Z, Rózsa É, Janáky T, Somlai C, Marosi M, Farkas T, Toldi J, Vécsei L (2004) Kynurenine administered together with probenecid markedly inhibits pentylenetetrazol-induced seizures. Anelectrophysiological and behavioural study. Neuropharmacology 47:916–925

    Article  PubMed  Google Scholar 

  • Ostro MJ, Cullis PR (1989) Use of liposomes as injectable-drug delivery systems. Am J Hosp Pharm 46:1576–1587

    PubMed  CAS  Google Scholar 

  • Pardridge WM (1998) CNS drug design based on principles of blood–brain barrier transport. J Neurochem 70:1781–1792

    Article  PubMed  CAS  Google Scholar 

  • Pardridge WM (2002) Drug and gene delivery to the brain: the vascular route. Neuron 36:555–558

    Article  PubMed  CAS  Google Scholar 

  • Robotka H, Németh H, Somlai C, Vécsei L, Toldi J (2005) Systemically administered glucosamine-kynurenic acid, but not pure kynurenic acid, is effective in decreasing the evoked activity in area CA1 of the rat hippocampus. Eur J Pharamcol 513:75–80

    Article  CAS  Google Scholar 

  • Sas K, Párdutz Á, Toldi J, Vécsei L (2010) Dementia, stroke and migraine—some common pathological mechanisms. J Neurol Sci 299:55–65

    Article  PubMed  Google Scholar 

  • Stauffer D, Jan N, He Y, Pandey RB, Marangoni DG, Smith-Palmer T (1994) Micelle formation, relaxation time, and three-phase coexistence in a microemulsion model. J Chem Phys 100:6934–6944

    Article  CAS  Google Scholar 

  • Stilbs P, Walderhaug H, Lindman B (1983) Micellar fluidity. A deuterium nuclear magnetic resonance spin relaxation study of the anisotropic reorientation of solubilized trans-Decalin-d18. J Phys Chem 87:4762–4769

    Article  CAS  Google Scholar 

  • Szleifer I, Ben-Shaul A, Gelbart WM (1987) Statistical thermodynamics of molecular organization in mixed micelles and bilayers. J Chem Phys 86:7094–7110

    Article  CAS  Google Scholar 

  • Wilhelm I, Farkas AE, Nagyoszi P, Varo G, Balint Z, Vegh GA et al (2007) Regulation of cerebral endothelial cell morphology by extracellular calcium. Phys Med Biol 52:6261–6274

    Article  PubMed  CAS  Google Scholar 

  • Wilhelm I, Fazakas C, Krizbai IA (2011) In vitro models of the blood-brain barrier. Acta Neurobiol Exp 71:113–128

    Google Scholar 

  • Zádori D, Klivényi P, Plangár I, Toldi J, Vécsei L (2011a) Endogenous neuroprotection in chronic neurodegenerative disorders: with particular regard to the kynurenines. J Cell Mol Med 15:701–717

    Article  PubMed  Google Scholar 

  • Zádori D, Nyiri G, Szőnyi A, Szatmári I, Fülöp F, Toldi J et al (2011b) Neuroprotective effects of a novel kynurenic acid analogue in a transgenic mouse model of Huntington’s disease. J Neural Transm 118:865–875

    Article  PubMed  Google Scholar 

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Acknowledgments

The Project named “TÁMOP-4.2.1/B-09/1/KONV-2010-0005—Creating the Center of Excellence at the University of Szeged” is supported by the European Union and co-financed by the European Regional Fund.

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Authors and Affiliations

  1. Supramolecular and Nanostructured Materials Research Group of the Hungarian Academy of Sciences, Faculty of Medicine, Institute of Medical Chemistry, and Nanomedicine Program, University of Szeged, Aradi v.t.1, Szeged, 6720, Hungary

    V. Hornok, T. Bujdosó & I. Dékány

  2. Deparment of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, 6726, Hungary

    J. Toldi, K. Nagy & I. Demeter

  3. Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, 6726, Hungary

    C. Fazakas & I. Krizbai

  4. Faculty of Medicine, Institute of Neuroscience, University of Szeged, Semmelweis u 6, Szeged, 6720, Hungary

    L. Vécsei

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  1. V. Hornok
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  2. T. Bujdosó
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  3. J. Toldi
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  4. K. Nagy
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  5. I. Demeter
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  6. C. Fazakas
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  7. I. Krizbai
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  8. L. Vécsei
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  9. I. Dékány
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Correspondence to I. Dékány.

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Hornok, V., Bujdosó, T., Toldi, J. et al. Preparation and properties of nanoscale containers for biomedical application in drug delivery: preliminary studies with kynurenic acid. J Neural Transm 119, 115–121 (2012). https://doi.org/10.1007/s00702-011-0726-2

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  • DOI: https://doi.org/10.1007/s00702-011-0726-2

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