Inkjet printing of lipoplexes: A feasibility study

Pharmaceutical inkjet printing has emerged as a versatile and precise technique for the production and functionalization of personalized 3D-printed drug delivery systems. This study focuses on the feasibility of inkjet printing for lipoplexes as efficient nucleic acid delivery systems. Lipoplexes are soft matter nanoparticles with liquid-crystalline inner structure encapsulating and protecting nucleic acids. Upon jetting, shear forces acting on the shear sensitive lipoplexes may induce changes in size and nucleic acid encapsulation. In order to investigate possible effects of inkjet printing on the intactness of nanoparticles, we investigated two structural different lipoplex formulations, composed of custom lipid composites and DNA. A set of characterization methods was applied to screen for printing induced changes, including dynamic and electrophoretic light scattering, nanoparticle tracking analysis, imaging flow cytometry, as well as gel electrophoresis. Moreover, lipoplex functionality studies were performed. The study demonstrates that lipoplexes can be successfully printed while retaining their structural integrity and nucleic acid encapsulation efficiency. Furthermore, transfection experiments revealed maintained functionality of the lipid nanoparticles after printing. Finally, we tested the feasibility of printing lipoplexes on a model surface in precise patterns. To the best of our knowledge, this is the first study that proved the suitability of lipoplexes as bioink for inkjet printing. This study establishes a foundational framework for integrating this advanced technology into future biomedical and pharmaceutical processing of lipoplexes in 3D printed medical devices and medicinal products. • Proof of concept for lipoplex formulations as suitable ink for inkjet printing. • Deep characterization of lipoplex properties and functionality after printing. • Comparative analysis of lipoplexes via NTA, DLS and imaging flow cytometry. • Proof of concept for surface decoration with lipoplexes using inkjet printing.