Microfluidic manufacture of solid lipid nanoparticles: a case study on tristearin-based systems

Solid lipid nanoparticles are lipid-based carriers and that can be used for a range of drugs and biomolecules. However, most manufacturing methods currently used do not offer easy translation from laboratory to scale-independent production. Within this study, we have investigated the use of microfluidics to produce solid lipid nanoparticles and investigated their protein loading capability. In the development of the process we have investigated and identified the critical process parameters that impact on the production of the SLNs. Solid lipid nanoparticles based on Tristearin and 1,2-Distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjugate-2000 were formulated using on the Nanoasemblr® Benchtop system from Precision Nanosystems and the flow rate ratio and total flow rate were investigated as process parameters and the particle size, PDI, zeta potential, drug loading and drug release was quantified. Our results demonstrate the suitability of microfluidics as a valid method for solid lipid nanoparticles containing protein production. In terms of key process parameters to consider, both the solvent/aqueous ratio (FRR) and total flow rate were shown to have a notable impact on particle size. However, protein loading capacity was similar across all flow rates tested. Within this study we outline a rapid and easy to adopt protocol for the scale-independent production of solid lipid nanoparticles and this process can support the rapid translation of production methods from bench to clinic.