Liposomes with entrapped doxorubicin exhibit extended blood residence times

Canadian Liposome Co. Ltd, North Vancouver, Canada.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 04/1990; 1023(1):133-9. DOI: 10.1016/0005-2736(90)90018-J
Source: PubMed


The blood residence time of liposomes with entrapped doxorubicin is shown to be significantly longer than for identically prepared empty liposomes. Liposomal doxorubicin systems with a drug-to-lipid ratio of 0.2 (w/w) were administered at a dose of 100 mg lipid/kg. Both doxorubicin and liposomal lipid were quantified in order to assess in vivo stability and blood residence times. For empty vesicles composed of phosphatidylcholine (PC)/cholesterol (55:45, mole ratio) and sized through filters of 100 nm pore size, 15-25% of the administered lipid dose was recovered in the blood 24 h after i.v. injection. The percentage of the dose retained in the circulation at 24 h increased 2-3-fold when the liposomes contain entrapped doxorubicin. For 100 nm distearoyl PC/chol liposomal doxorubicin systems, as much as 80% of the injected dose of lipid and drug remain within the blood compartment 24 h after i.v. administration.

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    • "The plasma and tissue samples were kept at K20 8C until analysis. A previous HPLC analysis of biological samples carried out by Bally et al. [24] indicated that O98% of the fluorescence detected was due to nonmetabolized DOX after mice receiving liposomal DOX. In our studies, the concentrations of DOX in plasma and tissue samples were assayed by a spectrofluorometric method described by Mayer et al [25]. "
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    ABSTRACT: This paper described the synthesis of a novel galactosylated lipid with mono-galactoside moiety, (5-Cholesten-3beta-yl) 4-oxo-4-[2-(lactobionyl amido) ethylamido] butanoate (CHS-ED-LA), and the targetability of doxorubicin (DOX), a model drug, in liposomes containing 10% mol/mol CHS-ED-LA (galactosylated liposomes, GalL) to the liver was studied. The weighted-average overall drug targeting efficiency (Te(*)) was used to evaluate the liver targetability of GalL DOX. The results showed that GalL DOX gave a relatively high (Te(*))(liver) value of 64.6%, while DOX in conventional liposome (CL DOX) only gave a (Te(*))(liver) value of 21.8%. In the liver, the GalL DOX was mainly taken up by parenchymal cells (88% of the total hepatic uptake). Moreover, preinjection of asialofetuin significantly inhibited the liver uptake of GalL DOX (from 70 to 12% of the total injected dose). It was suggested that liposomes containing such novel galactosylated lipid, CHS-ED-LA, had a great potential as drug delivery carriers for hepatocyte-selective targeting.
    European Journal of Pharmaceutics and Biopharmaceutics 02/2006; 62(1):32-8. DOI:10.1016/j.ejpb.2005.07.004 · 3.38 Impact Factor
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    • "Clinical trials and animal studies, or studies with cells in culture using liposomes as carriers of DOX show a reduction of complications and side effects, enhanced antitumor activity, and improved therapeutic index (Mayer et al, 1989). These advantages are thought to arise from a sustained release of the liposomal drug into the blood stream (Bally et al, 1990). "
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    ABSTRACT: Summary Recently, liposomes have gained a special interest as gene delivery systems: over 30 human clinical trials for gene delivery using cationic liposomes have been approved; all these delivery methods use intratumoral, subcutaneous and other local delivery but not systemic delivery due to the toxicity of cationic lipids. Stealth liposomes (coated with polyethyleneglyc ol to camouflage the liposome and evade detection by the immune system) have a remarkable longevity in body fluids, have negligible toxicity with respect to their lipid components, reduce the toxicity of the encapsulated drug, and can deliver efficiently their doxorubicin payload (DOXIL) or cis-platin to tumor lesions. The mechanism of stealth liposome accumulation in tumors involves their extravasation through gaps in the endothelium of tumor vessels. DOXIL can sustain a much higher concentration of Doxorubicin in tumor tissue compared to free drug administration at comparable doses. Liposomes tagged with folate-PEG or with antibodies can target specific tissues. We propose that "stealth" liposomes, could find future applications to systemically deliver plasmid DNA with therapeutic genes ( p53 , HSV- tk , angiostatin) to primary tumors and their metastases leading to complete cancer eradication. Abbreviations: AUC, area-under-the-plasma concentration vs time curve CHOL, cholesterol CL, cardiolipin DDAB, dimethyldioctadecylammonium bromide DOGS, dioctadecylamidoglycylspermine DOPE, dioleyl phosphatidylethanolamine DOSPA , (2,3-dioleyloxy-N-(20({2,5-bis((3- aminopropyl)amino)-1-oxypentyl}amino)ethyl)- N,N-dimethyl-2,3-bis(9-octadecenyloxy)-1- propanaminium trifluoroacetate DOTMA or lipofectin, N-(1-(2,3-dioleyloxy) propyl)-N, N, N trimethylammonium chloride

  • Supplements to Clinical neurophysiology 01/2006; 59. DOI:10.1016/S1567-424X(09)70005-4
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