The Synthesis, Characterization And Pharmacokinetics Of Scutellarin-PEG Conjugates

Scutellarin is an active ingredient extracted from Erigeron breviscapus, a traditional Chinese herbal medicine. Pharmacological study showed that scutellarin could significantly reduce the blood viscosity, improve the blood flow, decrease the vascular resistance, and inhibit the platelet aggregation and the thrombosis formation. Scutellarin has been used in clinic for the treatment of the paralysis induced by cerebrovascular accidents, e.g. hypertension, cerebral haemorrhage, cerebral thrombosis, polyneuritis and chronic arachnitis. Although commonly used as an oral agent, the low solubility of scutellarin in water leads to its poor bioavailability.In the past decades, PEGylation of biological macromolecules intended to enhance peptide or protein drug delivery as novel strategies becomes available. The most important advantage of polyethylene glycol (PEG) modification is that it greatly increases water solubility, maintains activity, extends the half-life (t_1/2) of most drugs, and results in a improved plasma presence. In contrast to the successful application of PEG to macromolecules for drug delivery, only a few small organic molecule anticancer agents have been conjugated to PEGs, and there was no investigation have been reported about oral absorption of PEG conjugates. Respecting the unique benefit of PEGylation, it's clear that it has enormous potentialities in the modification of small molecule drugs, especially the low solubility effective ingredient in traditional Chinese drug.In our study, the scutellarin as model drug was conjugated to a series of PEG of different molecular weights (200-1000 Da) in order to investigate the absorption variation after PEGylation and the correlation between the change...