Transfer Investigations of Lipophilic Drugs from Lipid Nanoemulsions to Lipophilic Acceptors: Contributing Effects of Cholesteryl Esters and Albumin as Acceptor Structures.

Sabrina Knoke,Heike Bunjes

doi:10.3390/ph14090865

Abstract

When studying the release of poorly water-soluble drugs from colloidal drug delivery systems designed for intravenous administration, the release media should preferentially contain lipophilic components that represent the physiological acceptors present in vivo. In this study, the effect of different acceptor structures was investigated by comparing the transfer of fenofibrate, retinyl acetate, and orlistat from trimyristin nanoemulsion droplets into lipid-containing hydrogel particles, as well as to bovine serum albumin (BSA). A nanodispersion based on trimyristin and cholesteryl nonanoate was incorporated into the hydrogel particles (mean diameter ~40 µm) in order to mimic the composition of lipoproteins. The course of transfer observed utilizing the lipid-containing hydrogel particles as an acceptor was in relation to the lipophilicity of the drugs: the higher the logP value, the slower the transfer. There was no detectable amount of the drugs transferred to BSA in liquid solution, demonstrating clearly that albumin alone does not contribute substantially as acceptor for the lipophilic drugs under investigation in this study. In contrast, cholesteryl nonanoate contributes to a much greater extent. However, in all cases, the partition equilibrium of the drugs under investigation was in favor of the trimyristin emulsion droplets.

Highlights

The liquid and liquid crystalline state, as well as the integrity of the nanoparticles, could be preserved during hydrogel bead production, and the resulting system was successfully applied as lipophilic acceptor in transfer studies
The partition equilibrium of the drugs under investigation was found to be in favor of the trimyristin emulsion droplets
Given that there is no officially approved method to investigate the release of lipophilic drugs from nanosized carriers, the hydrogel-bead-based setup can be helpful in order to compare the contribution of different lipophilic acceptors to the release performance of colloidal drug delivery systems

Summary

Introduction

To overcome issues arising from the poor water solubility of many newly discovered drugs, lipid-based colloidal dispersions are under investigation as a promising formulation approach for the parenteral administration of these substances [1]. Such dispersions may, e.g., be liposomes, nanoemulsions, or may contain solid or liquid crystalline nanoparticles [2,3,4]. Information on the release behavior (or drug retention properties, respectively) of the lipid carrier particles is crucial for quality control, as well as to predict in vivo behavior. Since there is no officially approved test, efforts are being made to design appropriate setups for release testing of nanoparticulate drug carriers [5]

Methods

Results

Conclusion