Microfluidic assembly of Turtle-Like shaped solid lipid nanoparticles for lysozyme delivery

After two decades of research in the field of nanomedicine, nanoscale delivery systems for biologicals are becoming clinically relevant tools. Microfluidic-based fabrication processes are replacing conventional tech-niques based on precipitation, emulsion, and homogenization. Here, the focus is on solid lipid nanoparticles (SLNs) for the encapsulation and delivery of lysozyme (LZ) as a model biologic. A thorough analysis was con-ducted to compare conventional versus microfluidic-based production techniques, using a 3D-printed device. The efficiency of the microfluidic technique in producing LZ-loaded SLNs (LZ SLNs) was demonstrated: LZ SLNs were found to have a lower size (158.05 +/- 4.86 nm vs 180.21 +/- 7.46 nm) and higher encapsulation efficacy (70.15 +/- 1.65 % vs 53.58 +/- 1.13 %) as compared to particles obtained with conventional methods. Cryo-EM studies highlighted a peculiar turtle-like structure on the surface of LZ SLNs. In vitro studies demonstrated that LZ SLNs were suitable to achieve a sustained release over time (7 days). Enzymatic activity of LZ entrapped into SLNs was challenged on Micrococcus lysodeikticus cultures, confirming the stability and potency of the biologic. This sys-tematic analysis demonstrates that microfluidic production of SLNs can be efficiently used for encapsulation and delivery of complex biological molecules.

Automated summary

After 20 years of research, nanoscale delivery systems for biologicals in nanomedicine have become clinically relevant. Microfluidic-based production of solid lipid nanoparticles (SLNs) is shown to be efficient in encapsulating and delivering lysozyme (LZ), with smaller size and higher encapsulation efficacy compared to conventional methods. This study demonstrates the potential of microfluidic production of SLNs for encapsulation and delivery of complex biological molecules.