Effects of liposomal encapsulation on the antioxidant activity of lipophilic prodrugs of idebenone.
BACKGROUND
Increasing the lipophilicity and/or amphiphilicity of drugs is a potential strategy to improve loading and retention in lipid-based carriers, such as liposomes or lipid nanoparticles.


OBJECTIVE
Idebenone (IDE), an antioxidant compound structurally related to coenzyme Q, or amphiphilic prodrugs of IDE with lipoamino acids, were loaded in neutral or negatively charged SUVET unilamellar liposomes to achieve a controlled release.


METHODS
Technological properties of these systems in the presence of loaded drugs were evaluated in terms of vesicle size, homogeneity, and surface charge, as well as in vitro drug release. The effect of liposomal carrier on the in vitro antioxidant activity of the prodrugs was evaluated from using different biochemical assays on murine astrocyte cultures.


CONCLUSIONS
Although a good loading efficiency was obtained, liposomes were not able to release efficiently the encapsulated drugs, at least in the in vitro serum-free conditions used for the biological tests. However, in some cases, such as in the comet assay, encapsulation of IDE prodrugs in liposomes allowed for the improvement of their protective activity, compared to the free compounds, against the oxidative damage induced on cultured astrocytes.


CONCLUSIONS
Experimental in vitro data suggested that the high affinity shown by these lipophilic IDE derivatives for the liposomal carriers negatively affect their biological activity.
Pignatello
Rosario
R
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, Catania, Italy. r.pignatello@unict.it
Acquaviva
Rosaria
R
Campisi
Agata
A
Raciti
Giuseppina
G
Musumeci
Teresa
T
Puglisi
Giovanni
G
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D020552:Comet Assay; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers; D008081:Liposomes; D011355:Prodrugs / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D004337:Drug Carriers; D008081:Liposomes; D011355:Prodrugs; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D004247:DNA; C036619:idebenone