Microfluidic Preparation of Nanoparticles Using Poly(ethylene Glycol)-distearoylphosphatidylethanolamine for Solubilizing Poorly Soluble Drugs

Microfluidic systems have shown promise for the production of nanoparticles from mixtures of aqueous and organic solutions, including liposomes, oil-in-water nanoemulsions, and lipid nanoparticles. They offer important practical advantages, including low reagent consumption, parallelization, and automation, and are ideally suited to high-throughput optimization and scale-up. In this study, we developed a new method for the formulation of nanoparticles of poorly soluble drug compounds. The nanoparticles, prepared by microfluidic mixing using only poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE), were highly stable and uniform in size. By mixing an organic solution of poorly soluble cyclosporine A and PEG-DSPE with water in the microfluidic device, amorphous cyclosporine A nanoparticles (CsA-NPs), with an encapsulation efficiency of approximately 90% and a particle size of 100–200 nm, were obtained. Analysis of the microfluidic process parameters revealed that particle size distribution was significantly controlled by the flow rate ratio. The obtained CsA-NPs were stable for up to 150 days at room temperature, and the pharmacokinetic profile was similar to that of the commercial formulation containing Cremophor EL, which has been reported to induce serious adverse effects after intravenous administration. These findings provide a useful technical platform for the safe solubilization of poorly soluble compounds and their subsequent pharmaceutical development.