alexa Liposomes for the sustained drug release in vivo.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacovigilance

Author(s): Blume G, Cevc G

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Abstract New lipidic carriers suitable for the sustained drug release in vivo are presented. They consist of middle sized, compact phospholipid vesicles with one or up to few lipid bilayers which are sterically stabilized with a small amount of large-head phospholipids. As an example, phosphatidylcholine (PC) liposomes casted with up to 10 mol\% of phosphatidylethanolamine with a covalently attached polyethyleneglycol 5000 headgroup (PE-PEG) are discussed. Such vesicles exhibit a very long circulation time after an i.v. administration in mice; the improvement over pure phosphatidylcholine liposomes within the first 24 h exceeds 8000\%, at this point nearly 25\% of the applied PE-PEG liposomes being still in the circulation. This advantage is a consequence of reduced phagocytosis of the lipidic carriers, as shown by an in vitro assay with blood monocyte cells in the flow cytometric experiments. For example, after 6 h incubation with THP-1 monocyte cells in human plasma the difference between the uptake of standard distearoylphosphatidylcholine (DSPC) and novel liposomes containing 10\% distearoylphosphatidylethanolamine-PEG is by 1000\%. Vesicles with 2.5 mol\% DSPE-PEG are also taken-up via phagocytosis relatively slowly. But the latter vesicles, moreover, retain most of the enclosed model-drug carboxyfluorescein after an incubation in plasma. The rate of permeation of the encapsulated substance from such DSPE-PEG liposomes is below 2.4\% per h. This is by approximately a factor of two less than for pure DSPC liposomes; vesicles with a higher PE-PEG content are inferior in this respect. Long circulation time and high retention of the newly developed liposomes open up ways for the future systemic use as such stabilized drug carriers for the therapeutic applications in vivo.
This article was published in Biochim Biophys Acta and referenced in Journal of Pharmacovigilance

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