Quality by design (QbD) liposomes engineering using 3D printed Tesla microfluidic arrays.

Microfluidic arrays have been successfully implemented for the design and development of liposome nanoparticles. In this study we have applied a Quality by Design (QbD) approach to investigate the effect of 3D printed Tesla microfluidic designs (direct and serpentine shape) on the liposome nanoparticles in comparison with conventional ultrasonication methodology. Critical processing parameters (CPP) such as the shape, length and channel width of the Tesla arrays were also studied. Furthermore, the effect of critical material attributes (CMA), including the length of the phosphatidylcholine (PC) carbon chain and the lipid:cholesterol ratio on the produced nanoparticles was investigated. The obtained findings revealed that both CPP and CMA play a key role in the formation of liposome nanoparticles. The liposome size was decreasing with a descending order for plain array > Tesla _(serpentine) > Tesla _(direct) > ultrasonication. However, improved Tesla arrays with narrow channel width (200 μm) produced the smallest liposome particle size (74 nm). The PC carbon chain length was critical for the obtained particle size where Lipoid S75 produced smaller nanoparticles when compared to Lipoid E80. The increase of cholesterol content resulted in liposome size reduction and decreased zeta-potential.