MMSL 2013, 82(2):55-62 | DOI: 10.31482/mmsl.2013.008

SCREENING OF BLOOD-BRAIN BARRIER PENETRATION USING THE IMMOBILIZED ARTIFICIAL MEMBRANE PHOSPHATIDYLCHOLINE COLUMN CHROMATOGRAPHY AT THE PHYSIOLOGICAL PHOriginal article

Jana ®ďárová Karasová ORCID...1,2*, Daniel Jun ORCID...2,3, Kamil Kuča ORCID...2,3
1 Department of Public Health, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
2 University Hospital, Hradec Kralove, Czech Republic
3 Centre of Advanced Studies, Faculty of Military Health Sciences, Trebesska 1575, 50001 Hradec Kralove, Czech Republic

In this study, 21 structurally diverse drugs with examined central nervous system penetration were used for prediction of blood-brain barrier penetration using HPLC-UV instrument. Drugs' chromatographic capacity factors were measured by the immobilized artificial membrane presented by phosphatidylcholine column. The correlation between chromatographic capacity factor, octanol-water partition coefficient (log P) and molecular polar surface area (PSA) were determined at the physiological pH. The correlation factor 0.6677 with respect to log P and 0.7199 in reference to PSA was assigned. The developed in vitro prediction method may be used as a screening tool for blood-brain barrier penetration of drugs with passive transport mechanism.

Keywords: Blood-Brain Barrier; CNS penetration; Immobilized Artificial Membrane; HPLC; Prediction

Received: January 6, 2013; Revised: February 11, 2013; Published: June 5, 2013  Show citation

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®ďárová Karasová, J., Jun, D., & Kuča, K. (2013). SCREENING OF BLOOD-BRAIN BARRIER PENETRATION USING THE IMMOBILIZED ARTIFICIAL MEMBRANE PHOSPHATIDYLCHOLINE COLUMN CHROMATOGRAPHY AT THE PHYSIOLOGICAL PH. MMSL, 82(2), 55-62. doi: 10.31482/mmsl.2013.008
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    References

    1. Tsukita, S.; Furuse, M.; Itoh, M. Multifunctional strance in tight junctions. Nature Rev. Mol. Cell. Biol. 2001, 2, 285-293. Go to original source... Go to PubMed...
    2. Turksen, K.; Troy, T.C. Barriers built on claudins. J. Cell. Sci. 2004, 117, 2435-2447. Go to original source... Go to PubMed...
    3. Yoon, H.Ch.; Kim, S.J.; Shin, B.S.; Lee, K.Ch.; Yoo, S.D. Rapid screening of blood-brain barrier penetration of drugs using the immobilized artificial membrane phosphatidylcholine column chromatography. J. Biomol. Screen. 2006, 11(1), 13-20. Go to original source... Go to PubMed...
    4. Bendels, S.; Kansy, M.; Wagner, B.; Huwyler, J. In silico prediction of brain and CSF permeation of small molecules using PLS regression models. Eur. J. Med. Chem. 2008, 43, 1581-1592. Go to original source... Go to PubMed...
    5. Lorke, D.E.; Kalasz, H.; Petroianu, G.A.; Tekes, K. Entry of oximes into the brain: a review. Curr. Med. Chem. 2008, 15, 743-753. Go to original source... Go to PubMed...
    6. Lorke, D.E.; Hasan, M.Y.; Nurulain, S.M.; Shafiullah, M.; Nagelkerke, N.; Petroianu, G.A. Effect of intrathecal pralidoxime administration upon survival of rats exposed to the organophosphate paraoxon. Neurotoxicology 2008, 29, 663-670. Go to original source... Go to PubMed...
    7. Pardridge, W.M. Transport of small molecules through the blood-brain barrier: biology and methodology. Adv. Drug Deliv. Rev. 1995, 15, 5-36. Go to original source...
    8. Clark, D.E. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena: Prediction of intestinal absorption potential. J Pharm. Sci. 2003, 88, 807-814.
    9. Sakurada, K.; Matsubara, K.; Shimizu, K.; Shiono, H.; Seto, Y.; Teute, K.; Toshibo, M.; Sakai, I.; Mukoyama, H.; Takatori, T. (2003) Pralidoxime iodide (2-PAM) penetrates across the blood brain barrier. Neurochem. Res. 2003, 28, 1401-1407. Go to original source... Go to PubMed...
    10. Mano, Y.; Higuchi, S.; Kamimura, H. Investigation of the high partition of YM992, a novel antidepressant, in rat brain: in vitro and in vivo evidence for the high binding in brain and the high permeability at the BBB. Biopharm. Drug Dispos, 2002, 23, 351-360. Go to original source... Go to PubMed...
    11. Sheen, D.; Artru, A.; Adkinson, K. Principles and applicability of CSF sampling for the assessment of CNS drug delivery and pharmacodynamics. Adv. Drug Deliv. Rev. 2004, 56, 1825-1857. Go to original source... Go to PubMed...
    12. Lüdemanm, L.; Hamm, B.; Zimmer, C. Pharmacokinetic analysis of glioma compartments with dynamic Gd-DTPA-enhanced magnetic resonance imaging. Magn. Reson. Imaging. 2000, 18, 1201-1214. Go to original source... Go to PubMed...
    13. Zheng, G.Z.; Bhatia, P.; Kolasa, T.; Patel, M.; El Kouhen, O.F.; Chang, R.; Uchic, M.E.; Miller, L.; Baker, S.; Lehto, S.G.; Honore, P.; Wetter, J.M.; Marsh, K.C.; Moreland, R.B.; Brioni, J.D.; Stewart, A.O. Correlation between brain/plasma ratios and efficacy in neuropathic pain models of selective metabotropic glutamate receptor 1 antagonists. Bioorg. Med. Chem. Lett. 2006, 16, 4936-4940. Go to original source... Go to PubMed...
    14. Kalász, H.; Hasan, M.Y.; Sheen, R.; Kuca, K.; Petroianu, G.; Ludányi, K.; Gergely, A.; Tekes, K. HPLC analysis of K-48 concentration in plasma. Anal. Bioanal. Chem. 2006, 385, 1062-1067. Go to original source... Go to PubMed...
    15. Lorke, D.E.; Hasan, M.Y.; Nurulain, S.M.; Sheen, R.; Kuca, K.; Petroianu, G.A. Entry of two new asymmetric bispiridium oximes (K-27 and K-48) into the rat brain: comparison with obidoxime. J. Appl. Toxicol. 2007, 27, 482-490. Go to original source... Go to PubMed...
    16. Petroianu, G.A.; Lorke, D.E.; Hasan, Y.M.; Adem, A.; Sheen, R.; Nurulain, S.M.; Kalasz, H. Paraoxon has only a minimal effect on pralidoxime brain concentration in rats. J. Appl. Toxicol. 2007, 27, 350-357. Go to original source... Go to PubMed...
    17. Tekes, K.; Hasan, M.Y.; Sheen, R.; Kuca, K.; Petroianu, G.; Ludányi, K.; Kalász, H. High-performance liquid chromatographic determination of the plasma concentration of K-27, a novel oxime-type cholinesterase reactivator. J. Chromatogr. A. 2006, 1122, 84-87. Go to original source... Go to PubMed...
    18. Petroianu, G.A.; Nurulain, S.M.; Nagelkerke, N.; Shafiullah, M.; Kassa, J.; Kuca, K. Five oximes (K-27, K-48, obidoxime, HI-6 and trimedoxime) in comparison with pralidoxime: survival in rats exposed to methyl-paraoxon. J. Appl. Toxicol. 2007, 27, 453-457. Go to original source... Go to PubMed...
    19. Di, L.; Kerns, E.H.; Fan, K.; McConell, O.J.; Carter, G.T. (2003) High throughput artificial membrane permeability assay for blood-brain barrier. Eur. J. Med. Chem. 2003, 38, 223-232. Go to original source... Go to PubMed...
    20. Suomalainen, P.; Johans, C.; Sőderlung, T.; Kinnunen, P.K. Surface activity profiling of drug applied to the prediction of blood-brain barrier permeability. J. Med. Chem. 2004, 47, 1783-1788. Go to original source... Go to PubMed...
    21. Palm, K.; Luthman, K.; Ungell, A.L.; Strandlung, G.; Beigi, F.; Lundahl, P. Evaluation of dynamic polar molecular surface area as predictor of drug absorption: comparison with other computational and experimental predictors. J. Med. Chem. 1998, 41, 5382-5392. Go to original source... Go to PubMed...
    22. Zhu, C.; Jiang, L.; Chen, T.M.; Hwang, K.K. A comparative study of artificial membrane permeability assay for high throughput profiling of drug absorption potential. Eur. J. Med. Chem. 2002, 37, 399-407. Go to original source... Go to PubMed...
    23. Brioni, J.D.; Stewart, A.O. Correlation between brain/plasma ratios and efficacy in neuropathic pain models of selective metabotropic glutamate receptor 1 antagonists. Bioorg. Med. Chem. Lett. 2006, 16, 4936-4940.

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