title: The accumulation of drugs within large unilamellar vesicles exhibiting a proton gradient: a survey.
abstract: We have shown previously that transmembrane proton gradients can be used to efficiently accumulate biogenic amines [M.B. Bally et al. (1988) Chem. Phys. Lipids 47, 97-107] and doxorubicin [L.D. Mayer, M.B. Bally and P.R. Cullis (1986) Biochim. Biophys. Acta 857, 123-126] to high concentrations within liposomes. To determine the generality of this loading procedure, representative drugs from a variety of different classes (antineoplastics, local anaesthetics, antihistamines, etc.) were examined as to their ability to redistribute in response to a proton gradient. While the majority of drugs examined, all of which are weak bases, were accumulated by large unilamellar vesicles exhibiting a pH gradient (interior acid) the extent of uptake varied considerably between different pharmaceuticals. These differences are discussed in the context of various factors which will likely influence drug accumulation including its membrane/water partition coefficient and its solubility in the intravesicular medium.
authors.affiliation: Department of Biochemistry, University of British Columbia, Vancouver, Canada.
authors.forename: T D
authors.initials: TD
authors.lastname: Madden
authors.forename: P R
authors.initials: PR
authors.lastname: Harrigan
authors.forename: L C
authors.initials: LC
authors.lastname: Tai
authors.forename: M B
authors.initials: MB
authors.lastname: Bally
authors.forename: L D
authors.initials: LD
authors.lastname: Mayer
authors.forename: T E
authors.initials: TE
authors.lastname: Redelmeier
authors.forename: H C
authors.initials: HC
authors.lastname: Loughrey
authors.forename: C P
authors.initials: CP
authors.lastname: Tilcock
authors.forename: L W
authors.initials: LW
authors.lastname: Reinish
authors.forename: P R
authors.initials: PR
authors.lastname: Cullis
mesh_terms: D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers; D008081:Liposomes / Q000378:metabolism; D008567:Membranes, Artificial; D008942:Mitoxantrone / Q000493:pharmacokinetics; D010713:Phosphatidylcholines / Q000378:metabolism; D013999:Timolol / Q000493:pharmacokinetics
chemical_list: D000779:Anesthetics, Local; D000970:Antineoplastic Agents; D006634:Histamine H1 Antagonists; D008051:Lipid Bilayers; D008081:Liposomes; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D013999:Timolol; D008942:Mitoxantrone