The Use of a Microfluidic Device to Encapsulate a Poorly Water-Soluble Drug CoQ10 in Lipid Nanoparticles and an Attempt to Regulate Intracellular Trafficking to Reach Mitochondria

Abstract

A number of drugs that are currently on the market, as well as new candidates for drugs, are poorly water soluble. Because of this, a need exists to develop drug formulations that will permit the expanded use of such drugs. The use of liposomes and lipid nanoparticles for drug delivery has attracted attention as a technique for solubilizing molecules that are poorly water soluble, but this technique faces serious scale-up risks. In this study, we report on attempts to encapsulate Coenzyme Q₁₀ (CoQ₁₀) as a model of a poorly water-soluble drug in an MITO-Porter, a liposome for mitochondrial delivery using a microfluidic device (a CoQ₁₀-MITO-Porter [μ]). The physical properties of the CoQ₁₀-MITO-Porter [μ] including homogeneity, size, and preparation volume were compared with those for a CoQ₁₀-MITO-Porter prepared by the ethanol dilution method (a CoQ₁₀-MITO-Porter [ED]). In the case where a microfluidic device was used, a small-sized CoQ₁₀-MITO-Porter was formed homogeneously, and it was possible to prepare it on a large scale. Intracellular observations using HeLa cells showed that the CoQ₁₀-MITO-Porter [μ] was efficiently internalized by cells to reach mitochondria. These results indicate that the CoQ₁₀-MITO-Porter [μ] represents a potential candidate for use in mitochondrial nanomedicine.

Keywords: drug delivery system(s); lipid nanoparticle(s) (LNP); liposome(s); microfluidics; nanotechnology; poorly water-soluble drug(s).