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.

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    • "Liposomes containing highphase transition lipids formed more-stable formulations, which were better able to retain their drug and showed apparent increases in drug-circulation lifetimes. A similar result was also observed by Bally et al. using DOX (Bally et al., 1990). Cell-culture studies showed that empty vesicles did not show any cytotoxic effect on MCF-7 cell lines. "
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    ABSTRACT: Theranostic liposomes carry both the therapeutic active ingredients and the contrast agent into one delivery system. Codelivery of imaging contrast agent and chemotherapeutic drugs can provide real-time validation of the targeting strategy, resulting in an another step forward for individual-based therapy. The aim of this study was the incorporation of different drugs used in the diagnosis and treatment of tumors into one delivery system to develop nanosized, polyethylene glycol (PEG)-coated, different charged theranostic liposomes. Different charged liposomes consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or Phospholipon(®) 90G (PL 90G; Phospholipid GmbH, Cologne, Germany), cholesterol, poly(ethylene glycol)2000/phosphatidyl ethanolamine (PEG(2000)-PE), stearylamine (SA) or dicetyl phosphate (DCP), and diethylenetriamine pentaacetate/PE (DTPA-PE) as bilayer ingredients and 5-florouracil (5-FU) as active substance were prepared by the film technique. Characterization, 5-FU in vitro release, cytotoxicity, and physical stability studies were performed. Particle size of all liposomes was 100-150 nm. Difference was not noted between encapsulation efficiency (EE%) of neutral DPPC and PL 90G liposomes containing 5-FU. EE% of charged DPPC liposomes was higher than that of charged PL 90G liposomes. PL 90G containing liposomes had a higher phospholipid amount than the same formulation of DPPC liposomes. DPPC containing different charged liposomes were selected for cytotoxicity studies. Different charged DPPC liposomes had the same antitumoral activity with the free 5-FU solution on MCF-7 cell lines. Liposome dispersions were more stable from the point of particle-size change and 5-FU leakage during storage at refrigerated temperature. The results of this study are very encouraging for the development of theranostic liposome formulations as a targeted delivery system for drugs, such as 5-FU, used both in therapy and imaging.
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    • "Liposomes containing highphase transition lipids formed more-stable formulations, which were better able to retain their drug and showed apparent increases in drug-circulation lifetimes. A similar result was also observed by Bally et al. using DOX (Bally et al., 1990). Cell-culture studies showed that empty vesicles did not show any cytotoxic effect on MCF-7 cell lines. "

    Full-text · Article · Jan 2013
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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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