Therapeutic Efficacy of Cytosine Arabinoside Trapped in Liposomes

Mayhew, E.; Rustum, Youcef M.; Szoka, Francis C.

doi:10.1007/978-1-4684-4241-0_15

Cited by 17 publications

(17 citation statements)

References 14 publications

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“…DOPE for in vitro and cholesterol for in vivo studies. Stabilization of anionic and neutral liposomes in blood by cholesterol has been known for a long time [18]. It is therefore obvious that for systemic gene delivery, one has to consider the stability of liposome-DNA complexes in blood, various components of which are known to react with macromolecular complexes.…”

Section: Resultsmentioning

confidence: 99%

Stabilization of cationic liposome‐plasmid DNA complexes by polyamines and poly(ethylene glycol)‐phospholipid conjugates for efficient in vivo gene delivery

et al. 1997

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Stable complexes of cationic liposomes with plasmid DNA were prepared by (1) including a small amount of poly(ethylene glycol)-phospholipid conjugate or (2) condensing the DNA with polyamines prior to the formation of liposomeplasmid complexes. These preparations were stable for months at 4°C and gave reproducible high transfection activity for in vivo gene delivery after intravenous injection in mice. Under these conditions, the expression of marker gene (luciferase) was primarily in the lungs (reaching values up to 3 ng expression per mg tissue protein), but also in other tissues to a lesser extent. Non-stabilized formulations lost all their transfection activity in 4 days. In these formulations cholesterol, not dioleoylphosphatidylethanolamine, was the helper lipid effective for sustaining high transfection activity in vivo. These new developments in formulation technology should enhance the potential for liposome-mediated gene therapy.

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Section: Resultsmentioning

confidence: 99%

Stabilization of cationic liposome‐plasmid DNA complexes by polyamines and poly(ethylene glycol)‐phospholipid conjugates for efficient in vivo gene delivery

et al. 1997

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“…This finding may be explained by tighter packing of PE molecules in the bilayer as compared with the PC of the same fatty acid composition [24]. Liposomes prepared from phospholipids of low transition temperature usually require Chol to achieve plasma stability [25]. It was recently shown that equimolar mixtures of DOPE and Chol containing various amounts of PEG-lipids form liposomes under physiological conditions [26,27].…”

Section: Resultsmentioning

confidence: 99%

Liposomes with detachable polymer coating: destabilization and fusion of dioleoylphosphatidylethanolamine vesicles triggered by cleavage of surface‐grafted poly(ethylene glycol)

Kirpotin

Hong

Mullah³

et al. 1996

FEBS Letters

194

112

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Plasma-stable liposomes (100 nm) were prepared from dioleoylphosphatidylethanolamine (DOPE) and 3--6 tool% of a new disulfide-linked poly(ethylene glycol)-phospbolipid conjugate (mPEG-DTP-DSPE). In contrast to similar preparations containing non-cleavable PEG-phospholipid conjugate, thiolytic cleavage of the grafted polymer chains facilitated rapid and complete release of the liposome contents. Furthermore, the detachment of PEG from DOPE liposomes resulted in liposomal fusion. Finally, while formulation of pH-sensitive DOPE/ cholesterol hemisuccinate liposomes with mPEG-DTP-DSPE abolished the pH sensitivity, cleavage of the PEG chains completely restored this property. These are the first examples of new useful properties of liposomes grafted with cleavable polymer.

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“…Our strategy to achieve these goals was based on the following prior observations. (i) The inclusion of cholesterol (Chol) and solid-phase phospholipids such as sphingomyelin and distearoyl phosphatidylcholine has been shown to increase liposome stability in plasma as determined by the degree of retention of various liposome-encapsulated markers in vitro (16)(17)(18). (ii) The same solid-phase phospholipids (sphingomyelin or distearoyl phosphatidylcholine) in the form of small sonicated liposomes are cleared more slowly after intravenous injection than those made with fluid phospholipids such as egg yolk phosphatidylcholine (PtdCho) (19)(20)(21)(22).…”

mentioning

confidence: 99%

Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.

Gabizón

Papahadjopoulos

1988

Proc. Natl. Acad. Sci. U.S.A.

1,001

488

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The rapid clearance of circulating liposomes from the bloodstream, coupled with their high uptake by liver and spleen, has thus far been an obstacle to any attempts at targeting to tumors. We have assessed the impact of liposome composition on their clearance from the circulation in normal and tumor-bearing mice and on their uptake by tumors and various normal tissues. By selective changes in lipid composition, while maintaining a mean particle diameter of '100 nm, we have achieved up to a 60-fold increase in the fraction of recovered dose present in blood 24 hr after i.v. i 'ection. Concomitantly, there was a decrease by a factor of 4 of the recovered dose localizing in the liver and spleen, the major organs of the reticuloendothelial system. Parallel experiments in tumor-bearing mice demonstrated a 25-fold increase of the liposome concentration in the tumor when formulations with long and short blood residence time were compared. The most favorable results were obtained with liposomes containing a small molar fraction of a negatively charged glycolipid, such as monosialoganglioside or phosphatidylinositol, and a solidphase neutral phospholipid as the bulk component. The biodistribution of such formulations is of considerable therapeutic potential in cancer for increasing the concentration of cytotoxic agents in tumors while minimizLing the likelihood of toxicity to the reticuloendothelial system. Liposome encapsulation has been proven useful for reducing the toxicity of certain drugs (1-6) as well as for enhancing the efficacy of macrophage-activating factors (7,8) and drugs directed against parasites residing within the reticuloendothelial system (RES) (9)(10)(11)(12). The propensity of the RES to remove liposomes from the circulation has thus far limited the prospect oftargeting liposomes to tissues other than liver, spleen, and lung (13-15).Designing liposomes with prolonged circulation time would require a reduction of the rate of their clearance by the RES and of the leakage of liposome contents in the bloodstream. Our strategy to achieve these goals was based on the following prior observations. (i) The inclusion of cholesterol (Chol) and solid-phase phospholipids such as sphingomyelin and distearoyl phosphatidylcholine has been shown to increase liposome stability in plasma as determined by the degree of retention of various liposome-encapsulated markers in vitro (16-18). (ii) The same solid-phase phospholipids (sphingomyelin or distearoyl phosphatidylcholine) in the form of small sonicated liposomes are cleared more slowly after intravenous injection than those made with fluid phospholipids such as egg yolk phosphatidylcholine (PtdCho) (19)(20)(21)(22). (iii) The inclusion of certain gangliosides, which confer to the liposome surface a negative charge and increased hydrophilicity, synergizes with Chol to enhance liposome stability in plasma (23) and prolongs liposome half-life in blood with a concomitant decrease in liver and spleen uptake (24). In addition, inclusion of phosphatidylinositol (P...

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Therapeutic Efficacy of Cytosine Arabinoside Trapped in Liposomes

Cited by 17 publications

References 14 publications

Stabilization of cationic liposome‐plasmid DNA complexes by polyamines and poly(ethylene glycol)‐phospholipid conjugates for efficient in vivo gene delivery

Stabilization of cationic liposome‐plasmid DNA complexes by polyamines and poly(ethylene glycol)‐phospholipid conjugates for efficient in vivo gene delivery

Liposomes with detachable polymer coating: destabilization and fusion of dioleoylphosphatidylethanolamine vesicles triggered by cleavage of surface‐grafted poly(ethylene glycol)

Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.

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