title: Influence of chronobiology on the nanoparticle-mediated drug uptake into the brain.
abstract: Little attention so-far has been paid to the influence of chronobiology on the processes of nanoparticle uptake and transport into the brain, even though this transport appears to be chronobiologically controlled to a significant degree. Nanoparticles with specific surface properties enable the transport across the blood-brain barrier of many drugs that normally cannot cross this barrier. A clear dependence of the central antinociceptive (analgesic) effects of a nanoparticle-bound model drug, i.e., the hexapeptide dalargin, on the time of day was observable after intravenous injection in mice. In addition to the strongly enhanced antinociceptive effect due to the binding to the nanoparticles, the minima and maxima of the pain reaction with the nanoparticle-bound drug were shifted by almost half a day compared to the normal circadian nociception: The maximum in the pain reaction after i.v. injection of the nanoparticle-bound dalargin occurred during the later rest phase of the animals whereas the normal pain reaction and that of a dalargin solution was highest during the active phase of the mice in the night. This important shift could be caused by an enhanced endo- and exocytotic particulates transport activity of the brain capillary endothelial cells or within the brain during the rest phase.
authors: Institut für Pharmazeutische Technologie, Goethe-Universität Frankfurt, Max-von-Laue-Str. 9, Frankfurt D-60439, Germany. Kreuter@em.uni-frankfurt.de.
authors: Jörg
authors: J
authors: Kreuter
references: Pharmacol Ther. 2004 Oct;104(1):29-45
references: 15500907
references: J Drug Target. 2002 Jun;10(4):317-25
references: 12164380
references: PLoS One. 2012;7(3):e32568
references: 22396775
references: J Drug Target. 2011 Feb;19(2):125-32
references: 20387992
references: J Control Release. 2007 Mar 12;118(1):54-8
references: 17250920
references: Nature. 2002 Aug 29;418(6901):935-41
references: 12198538
references: J Control Release. 2012 Jul 20;161(2):264-73
references: 21872624
references: Chronobiol Int. 2009 Aug;26(6):1019-68
references: 19731105
references: J Control Release. 2009 Jul 1;137(1):78-86
references: 19285109
references: Stroke. 1990 Oct;21(10):1464-9
references: 2219212
references: Eur J Pharm Biopharm. 2009 Feb;71(2):251-6
references: 18805484
references: J Biol Rhythms. 2004 Oct;19(5):400-13
references: 15534320
references: Eur J Immunol. 2004 Nov;34(11):2955-63
references: 15376193
references: J Pharm Pharmacol. 1996 Feb;48(2):136-46
references: 8935161
references: Pharmacol Ther. 2006 Sep;111(3):629-51
references: 16480770
references: J Microencapsul. 2013;30(1):49-54
references: 22676632
references: Chronobiol Int. 1999 Nov;16(6):767-77
references: 10584177
references: Br J Pharmacol. 1999 Oct;128(3):569-76
references: 10516634
references: Adv Drug Deliv Rev. 2007 Aug 31;59(9-10):825-7
references: 17825947
references: Neurosci Lett. 1981 Jan 1;21(1):45-50
references: 6259560
references: J Control Release. 2007 Jan 22;117(1):51-8
references: 17150277
references: Brain Res. 1995 Mar 13;674(1):171-4
references: 7773690
references: Adv Drug Deliv Rev. 2014 May;71:2-14
references: 23981489
references: Expert Opin Drug Deliv. 2005 Jul;2(4):667-81
references: 16296793
references: Annu Rev Pharmacol Toxicol. 2014;54:339-61
references: 24160700
references: Science. 1977 Nov 18;198(4318):756-8
references: 561998