Formation of particulate lipid lyotropic liquid crystalline nanocarriers using a microfluidic platform

Hypothesis: Non-lamellar lyotropic liquid crystal nanoparticles (LLCNPs) are gaining significant interest in the fields of drug delivery and nanomedicine. Traditional, top-down formulation strategies for LLCNPs are typically low-throughput, can lack controllability and reproducibility in the particle size distribution, and may be unsuitable for loading more fragile therapeutics. The development of a controllable, reproducible, scalable, and high-throughput strategy is urgently needed. Experiments: Monoolein (MO)-based LLCNPs with various stabilizers (F127, F108, and Tween 80) and phytantriol (PT)-F127 cubosomes were produced at various flow conditions via a bottom-up method using a microfluidic platform. Findings: This simple enabling strategy was used to formulate LLCNPs with lower polydispersity compared to the traditional top-down homogenization method. Significantly, particle size could be quantitatively controlled by varying the overall flow-rate; a scaling law was identified between nanoparticle mean size and the total flow rate (Q) of meansize∼Q-0.15 for MO cubosomes and meansize∼Q-0.19 for PT cubosomes (at a fixed flow rate ratio). Effective size control was achieved for a range of cubosome formulations involving different lipids and stabilizers. The formulation of stable, drug-loaded cubosomes with high encapsulation efficiency using this method was exemplified using calcein as a model drug. This work will further promote the utilisation of LLCNPs in nanomedicine and facilitate their clinical translation.