title: Triggered release of doxorubicin following mixing of cationic and anionic liposomes.
abstract: In many applications, an ability of liposomes to retain drug and then rapidly release it at some later time would be of benefit. In this work, we investigate the ability of cationic large unilamellar vesicles (LUV) to promote rapid release of doxorubicin from anionic LUV. It is shown that the addition of cationic liposomes containing cholesterol, dioleoylphosphatidylethanolamine (DOPE), distearoylphosphatidylcholine (DSPC) and the cationic lipid N,N-dioleyl-N,N-dimethylammonium chloride (DODAC) to doxorubicin-containing LUV composed of cholesterol, DOPE, DSPC and the anionic lipid dioleoyphosphatidylglycerol (DOPG) can result in release of more than 90% of the drug in times of 30 s or less. Further, it is shown that these release characteristics are exquisitely dependent on the presence of DOPE and cholesterol. In the absence of DOPE, much slower release rates are observed, with maximum release levels of 50% after a 2-h incubation at 20 degrees C. Remarkably, threshold levels of more than 10 mol% cholesterol are required before any appreciable release is observed. [31P]NMR spectroscopy and freeze-fracture electron microscopy studies reveal that systems giving rise to rapid release of doxorubicin exhibit limited formation of inverted hexagonal (H(II)) phase, suggesting that these lipids facilitate drug release by formation of local regions of non-bilayer structure. It is concluded that drug release triggered by mixing anionic and cationic liposomes could be of utility in drug delivery applications.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, 2146 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3. igorvj@interchange.ubc.ca
authors.forename: Igor V
authors.initials: IV
authors.lastname: Zhigaltsev
authors.forename: Norbert
authors.initials: N
authors.lastname: Maurer
authors.forename: Kim F
authors.initials: KF
authors.lastname: Wong
authors.forename: Pieter R
authors.initials: PR
authors.lastname: Cullis
mesh_terms: D000838:Anions; D002412:Cations; D002784:Cholesterol; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005614:Freeze Fracturing; D008081:Liposomes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D000838:Anions; D002412:Cations; D008081:Liposomes; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D000644:Quaternary Ammonium Compounds; C015831:dimethyldioctadecylammonium; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; D004317:Doxorubicin; D002784:Cholesterol