Preparation of Nanostructured Lipid Drug Delivery Particles Using Microfluidic Mixing

Background: Cubosomes are highly ordered self-assembled lipid particles analogous to liposomes, but with internal liquid crystalline structure. They are receiving interest as stimuli responsive delivery particles, but their preparation typically requires high energy approaches such as sonication which is not favourable in many applications. Objective: Here we investigated the impact of microfluidic preparation on particle size distribution and internal structure of cubosomes prepared from two different lipid systems, phytantriol and glyceryl monooleate (GMO). Methods: The impact of relative flow rates of the aqueous and organic streams, the total flow rate and temperature were investigated in a commercial microfluidic system. The particle size distribution and structure were measured using dynamic light scattering and small angle X-ray scattering respectively. Results: Phytantriol based particles were robust to different processing conditions, while cubosomes formed using GMO were more sensitive to composition both locally and globally, which reflects their preparation using other techniques. Conclusion: Thus, in summary microfluidics represents a reproducible and versatile method to prepare complex lipid particle dispersions such as cubosomes.