Year: 2025
Type: article
Abstract: Cubosomes—colloidal dispersions of lipid inverted bicontinuous cubic phases—are promising nanosystems for advanced drug delivery applications. Here we report on a microfluidic hydrodynamic flow-focusing approach for solvent exchange that enables the preparation of cubosomes with tunable size. The approach involves a preliminary step where the lipid phytantriol, the main building block, is first dissolved in ethanol to create a precursor solution. This precursor is subsequently flowed through the central channel of a cross-shaped microfluidic device, where it is focused by two lateral streams of water containing the stabilizer Pluronic F127. As water and ethanol mix, the polarity shift forces phytantriol to self-assemble into cubosomes, while the laminar-flow conditions imposed by the microchannels provide controlled mixing conditions. By adjusting the flow rate ratio (QR) between the water-F127 side streams and the phytantriol-ethanol precursor, we control the width of the precursor stream—the region through which solvent molecules exchange. This manipulation thus directly governs the mixing time, influencing the kinetics of lipid self-assembly, which ultimately determines particle size. This technique allows for the tuning of cubosome sizes from 195 nm down to 125 nm, with size decreasing monotonically as QR increases. Although variability is still significant, largely due to pumping instability and the use of a commercial microfluidic device not specifically designed for this application, the trends are statistically significant for every precursor-concentration series (Kendall tau=-0.53 to -0.73, p<0.011). Further customization of the apparatus is expected to improve reproducibility and scalability. The results obtained with this microfluidic method differ markedly from those obtained by bulk solvent exchange, which shows only a weak and generally non-significant trend toward larger particle size at higher dilution ratios. In addition, the polydispersity index is consistently moderate, with an interquartile range of 0.15–0.19. Particle characterization was performed using dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (cryo-TEM), showing the typical size range, inner structure and morphology of cubosomes.
Source: Langmuir
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4415283136