Microfluidics for nanomedicines manufacturing: An affordable and low-cost 3D printing approach

During the last decade, an innovative lab on a chip technology known as microfluidics became popular in the pharmaceutical field to produce nanomedicines in a scalable way. Nevertheless, the predominant barriers for new microfluidics users are access to expensive equipment and device fabrication expertise. 3D printing technology promises to be an enabling new field that helps to overcome these drawbacks expanding the realm of microfluidics. Among 3D printing techniques, fused deposition modeling allows the production of devices with relatively inexpensive materials and printers. In this work, we developed two different microfluidic chips designed to obtain a passive micromixing by a "zigzag" bas-relief and by the presence of "split and recombine" channels. Computational fluid dynamics studies improved the evaluation of the mixing potential. A fused deposition modeling 3D printer was used to print the developed devices with polypropylene as manufacturing material. Then, two different model nanocarriers (i.e., polymeric nanoparticles and liposomes), loading cannabidiol as model drug, were formulated evaluating the influence of manufacturing parameters on the final nanocarrier characteristics with a design of experiments approach (2-level full factorial design). Both the chips showed an effective production of nanocarriers with tunable characteristics and with an efficient drug loading. These polypropylene-based microfluidic chips could represent an affordable and low-cost alternative to common microfluidic devices for the effective manufacturing of nanomedicines (both polymer- and lipid-based) after appropriate tuning of manufacturing parameters