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Paolino, Donatella; Iannone, Michelangelo; Cardile, Venera; Renis, Marcella; Puglisi, Giovanni; Rotiroti, Domenicantonio; Fresta, Massimo
Journal of pharmaceutical sciences, July 2004, Volume: 93, Issue: 7Journal Article
The potential therapeutic advantages of the encapsulation of idebenone within pegylated liposomes were investigated in vitro on primary cortical astrocytes of rats. In particular, both the concentration‐dependent effects and the therapeutic effectiveness toward excitotoxic injury, elicited by chronic treatment with ethanol (100 μM) for 12 days, were evaluated. The following parameters were taken into consideration to assay free or liposomally entrapped idebenone: lactic dehydrogenase release, respiratory capacity measured by tetrazolium salt conversion, glutamine synthetase, and the levels of constitutive and inducible 70‐kDa heat shock proteins. To evaluate the effects on astrocytes, three different drug concentrations were used (0.5 μM, 5 μM, and 50 μM). At the highest concentration used (50 μM), a toxic effect of the free and liposomally entrapped drug was observed. Toxic effects seem to be due to a cellular membrane perturbation, as demonstrated by 45Ca2+ permeation. The therapeutic effect of free or liposomally entrapped idebenone on ethanol‐induced injury of primary cortical astrocytes was evaluated as a function of the drug concentration. The drug liposome formulation was much more effective than the free drug in counteracting the ethanol‐induced damage in astrocytes, i.e., 10‐times‐lower doses of liposomally entrapped idebenone are able to provide a greater protective action than the free drug. The improved action of idebenone‐loaded liposomes is probably due to the greater drug bioavailability at the cellular level. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1815–1827, 2004
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