Article

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

ABSTRACT 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.

0 Followers
 · 
82 Views
  • Source
    [Show abstract] [Hide abstract]
    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 · 4.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is an opportunity to augment the therapeutic potential of drug combinations through use of drug delivery technology. This report summarizes data obtained using a novel liposomal formulation with coencapsulated doxorubicin and vincristine. The rationale for selecting these drugs is due in part to the fact that liposomal formulations of doxorubicin and vincristine are being separately evaluated as components of drug combinations. Doxorubicin and vincristine were coencapsulated into liposomes using two distinct methods of drug loading. A manganese-based drug loading procedure, which relies on drug complexation with a transition metal, was used to encapsulate doxorubicin. Subsequently the ionophore A23187 was added to induce formation of a pH gradient, which promoted vincristine encapsulation. Plasma elimination studies in mice indicated that the drug:drug ratio before injection [4:1 doxorubicin:vincristine (wt:wt ratio)] changed to 20:1 at the 24-h time point, indicative of more rapid release of vincristine from the liposomes than doxorubicin. Efficacy studies completed in MDA MB-435/LCC6 tumor-bearing mice suggested that at the maximum tolerated dose, the coencapsulated formulation was therapeutically no better than liposomal vincristine. This result was explained in part by in vitro cytotoxicity studies evaluating doxorubicin and vincristine combinations analyzed using the Chou and Talalay median effect principle. These data clearly indicated that simultaneous addition of vincristine and doxorubicin resulted in pronounced antagonism. These results emphasize that in vitro drug combination screens can be used to predict whether a coformulated drug combination will act in an antagonistic or synergistic manner.
    Clinical Cancer Research 02/2004; 10(2):728-38. DOI:10.1158/1078-0432.CCR-1131-03 · 8.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pour améliorer les paramètres pharmacologiques d'un photosensibilisateur de seconde génération, la méta-tétra(hydroxyphényl)chlorine (mTHPC), plusieurs formules liposomales commerciales ont été élaborées, parmi elles le Foslip, qui correspond à la mTHPC dans des liposomes conventionnels. L'objectif de ce travail est d'étudier les caractéristiques photophysiques et photobiologiques du Foslip. L'exposition des suspensions de Foslip à de petites doses de lumière (10 mJ) a conduit à une baisse significative de la fluorescence, qui a cependant été restaurée après destruction des liposomes. Nous attribuons cette caractéristique au quenching de fluorescence photoinduite. Cet effet a été mis en évidence uniquement pour les concentrations locales élevées de mTHPC dans des bicouches lipidiques. Les résultats ont été interprétés en supposant une migration d'énergie entre les molécules rapprochées de mTHPC avec sa dissipation consécutive par les molécules du photoproduit se comportant comme des pièges d'énergie. Le quenching de fluorescence photoinduite ainsi que les techniques de polarisation et de chromatographie liquide ont été appliquées successivement pour estimer le taux de redistribution des molécules de mTHPC des liposomes vers les protéines du plasma et les membranes lipidiques. Les processus de redistribution de la mTHPC après injection intratumorale de mTHPC dans un modèle de récidive de cancer du sein sont en corrélation avec les résultats obtenus dans une étude in vitro de la redistribution du Foslip dans les liposomes DPPC. Il a été démontré que le phénomène de quenching de fluorescence photoinduite doit être pris en compte lors de l'utilisation de techniques optiques pour l'étude des applications in vivo et in vitro des formulations liposomales de mTHPC.

Preview

Download
2 Downloads
Available from