Blood-brain barrier disruption following the internal carotid arterial perfusion of alkyl glycerols

Hwa Jeong Lee, Yun Zhang, William M. Pardridge

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Non ionic, amphipathic molecules form vesicles and this property correlates with the disruption of membranes. In the present studies, high mM concentrations of aliphatic alcohols, 1-O-hexyldiglycerol (HDG) and 1-O-heptyltriglycerol (HTG), are shown to cause enhanced drug transport into brain via disruption of the blood-brain barrier (BBB) in vivo, as determined with an internal carotid artery perfusion method. The intravenous administration of comparable concentrations of HDG or HTG caused no increase in BBB transport of drug. The enhanced transport of drug showed a dependency on molecular weight as 45 mM HTG increased the transport of sucrose, 360 Da, but did not increase the transport of arginine vasopressin (AVP), 1084 Da, although AVP transport across the BBB was increased by 80 mM HDG or HTG. Quasielastic light scattering measurements provided evidence for the formation of vesicular structures in aqueous solutions containing high mM concentrations of the HDG or HTG. In summary, these studies demonstrate BBB disruption following the internal carotid arterial infusion of high mM concentrations of membrane active alkyl glycerols.

Original languageEnglish
Pages (from-to)463-467
Number of pages5
JournalJournal of Drug Targeting
Volume10
Issue number6
DOIs
StatePublished - Sep 2002

Keywords

  • Blood-brain barrier
  • Drug targeting
  • Vasopressin
  • Vinblastine

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