Research ArticlePharmaceutics, Drug Delivery and Pharmaceutical TechnologyTransdermal Delivery of Etoposide phosphate (cas 117091-64-2) I: In Vitro and In Vivo Evaluation

Add time:08/25/2019    Source:sciencedirect.com

Cancer chemotherapy frequently requires long periods of multiple intravenous infusions that often results in patients opting out of treatment. The main purpose of this study was to investigate the feasibility of delivering one of these anticancer agents: Etoposide phosphate (cas 117091-64-2) (ETP) transdermally using iontophoresis and a combination of iontophoresis/microporation. The iontophoresis conditions for ETP were first optimized in vitro then tested in vivo in a rabbit model. Both ETP and its active form etoposide (VP) were quantified in dermis (via microdialysis sampling) and in plasma, with a specially developed high-performance liquid chromatography method. In vitro, the amount of total etoposide permeated and the steady state flux increased (p < 0.05) with increase in iontophoretic current densities (100-400 μA/cm2). At 300 μA/cm2, microporation/iontophoresis further improved both parameters by 2- and 2.8-fold, respectively. In vivo, exposure increased proportionally to current density in plasma, whereas dermal concentration dropped significantly at the highest current density. Microporation led to a 50% increase in Cmax and AUClast values in both skin and plasma. In conclusion, a mild current density (300 μA/cm2) and a small surface area (10.1 cm2) achieved and maintained the minimum effective concentration for the entire duration of electrical current delivery; microporation further increased the plasma concentrations at the same current density.

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