Tuning of Hydrogel Architectures by Ionotropic Gelation in Microfluidics: Beyond Batch Processing to Multimodal Diagnostics

Microfluidics is emerging as a promising tool to control physicochemical properties of nanoparticles and to accelerate clinical translation. Indeed, microfluidic-based techniques offer more advantages in nanomedicine over batch processes, allowing fine-tuning of process parameters. In particular, the use of microfluidics to produce nanoparticles has paved the way for the development of nano-scaled structures for improved detection and treatment of several diseases. Here, ionotropic gelation is implemented in a custom-designed microfluidic chip to produce different nanoarchitectures based on chitosan-hyaluronic acid polymers. The selected biomaterials provide biocompatibility, biodegradability and non-toxic properties to the formulation, making it promising for nanomedicine applications. Furthermore, results show that morphological structures can be tuned through microfluidics by controlling the flow rates. Aside from the nanostructures, the ability to encapsulate gadolinium contrast agent for magnetic resonance imaging and a dye for optical imaging is demonstrated. In conclusion, the polymer nanoparticles here designed revealed the dual capability of enhancing the relaxometric properties of gadolinium by attaining Hydrodenticity and serving as a promising nanocarrier for multimodal imaging applications.