Purpose
Lipid-based nanoparticles, designed to mimic cell membrane structures, are extensively employed in drug delivery systems due to their bioavailability and versatility. The monodispersity of these carriers in terms of size is crucial for safe and effective drug or nucleic acid delivery. This study investigated a microfluidic chip-based methodology for the monodisperse fabrication of size-controllable nanoparticles, comparing its performance with conventional methods.

Methods
Variations in flow rates and lipid concentrations resulted in significant differences in the physical properties of lipid nanoparticles (LNPs), including nanoparticle diameter and polydispersity index. Optimal flow rates and lipid concentrations were identified, resulting in nanoparticles of the desired size and with low polydispersity index values. Using these parameters, nucleic acid-loaded LNPs were prepared and compared to liposomes produced via the conventional thin film hydration method, with identical lipid and nucleic acid compositions.

Results
The microfluidic approach enabled the production of monodisperse LNPs that were smaller in size compared to conventional methods. Higher nucleic acid loading was observed in the LNPs, and they exhibited enhanced protection against external enzymatic degradation. In vitro studies involved the transfection of Hela cells with both types of nanoparticles to assess nucleic acid delivery efficiency via RNA interference. The results demonstrated comparable nucleic acid delivery efficiency using LNPs compared to liposomes. Additionally, the biodistribution results demonstrated that LNPs exhibit delayed excretion, suggesting prolonged retention within the body after nanoparticle administration in mice. These findings suggest the potential for long-term in vivo persistence of LNPs, characterized by their high loading capacity.

Conclusion
These results highlight the advantages of using microfluidic-based processes for producing LNPs designed for nucleic acid delivery, particularly in the context of drug development and manufacturing.