Computed Tomography-Guided Screening of Surfactant Effect on Blood Circulation Time of Emulsions: Application to the Design of an Emulsion Formulation for Paclitaxel

Abstract

PURPOSE: In an effort to apply the imaging techniques currently used in disease diagnosis for monitoring the pharmacokinetics and biodisposition of particulate drug carriers, we sought to use computed tomography (CT) scanning methodology to investigate the impact of surfactant on the blood residence time of emulsions. METHODS: We prepared the iodinated oil Lipiodol emulsions with different compositions of surfactants and investigated the impact of surfactant on the blood residence time of emulsions by CT scanning. RESULTS: The blood circulation time of emulsions was prolonged by including Tween 80 or DSPE-PEG (polyethylene glycol 2000) in emulsions. Tween 80 was less effective than DSPE-PEG in terms of prolongation effect, but the blood circulating time of emulsions was prolonged in a Tween 80 content-dependent manner. As a proof-of-concept demonstration of the usefulness of CT-guided screening in the process of formulating drugs that need to be loaded in emulsions, paclitaxel was loaded in emulsions prepared with 87 or 65% Tween 80-containing surfactant mixtures. A pharmacokinetics study showed that paclitaxel loaded in 87% Tween 80 emulsions circulated longer in the bloodstream compared to those in 65% Tween 80 emulsions, as predicted by CT imaging. CONCLUSIONS: CT-visible, Lipiodol emulsions enabled the simple evaluation of surfactant composition effects on the biodisposition of emulsions.