Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Désormeaux, A. et al.

Antiviral efficacy, intracellular uptake and pharmacokinetics of free and liposome-encapsulated 2',3'-dideoxyinosine.

OBJECTIVE: To evaluate the effect of liposome encapsulation on the in vitro antiviral efficacy, intracellular uptake and in vivo pharmacokinetics of 2',3'-dideoxyinosine ( ddl). METHODS: The accumulation of free and liposome-encapsulated ddl was determined in murine monocyte-macrophage RAW 264.7 cells and human premonocytoid U937 cells. The antiviral efficacy was evaluated in U937 cells infected with HIVIIIB. Tissue distribution and pharmacokinetics of free and liposomal ddl were determined in female Sprague-Dawley rats following the administration of a single intravenous bolus dose (3 mg ddl/kg). RESULTS: The entrapment of ddl in liposomes results in a lower drug accumulation in both U937 and RAW 264.7 cells. A lower antiviral efficacy against HIVIIIB replication in U937 cells was observed on encapsulation of ddl in liposomes. Improved pharmacokinetics were observed on entrapment of ddl in liposomes. Higher drug levels were found in plasma for the liposomal formulation. The systemic clearance of the liposomal drug was 120 times lower than that of free drug. Liposome encapsulation of ddl greatly enhanced the drug accumulation in organs of the reticuloendothelial system. CONCLUSION: The encapsulation of ddl in liposomes modified the tissue distribution and plasma pharmacokinetics of the antiviral agent resulting in a marked improvement of drug biodisponibility. The antiviral efficacy of liposomal ddl was lower than that of free drug in HIVIIIB-infected U937 cells.[1]

References

Antiviral efficacy, intracellular uptake and pharmacokinetics of free and liposome-encapsulated 2',3'-dideoxyinosine. Désormeaux, A., Harvie, P., Perron, S., Makabi-Panzu, B., Beauchamp, D., Tremblay, M., Poulin, L., Bergeron, M.G. AIDS (1994) [Pubmed]

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