A modular microfluidic platform for the synthesis of biopolymeric nanoparticles entrapping organic actives

Microreactors have been shown to be a powerful tool for the production of nanoparticles (NPs); however, there is still a lack of understanding of the role that the microfluidic environment plays in directing the nanoprecipitation process and the synthetized nanoparticles size and morphology. We fabricated a novel capillary microfluidic device using a newly designed modular apparatus by assembling commercial stainless steel microcapillary tubes for HPLC through a cross junction. In this way, we realized a flow-focusing-based microdevice in which the dispersed organic phase is continuously focused by the continuous phase using a couple of syringe pumps. Our device is substantially distinct from others because of its modularity and flexibility, having the possibility to allocate, in its geometry, microchannels of different length, material, or internal diameter; moreover, it could be used to prepare NPs from different classes of pristine polymers independently from their nature (natural or synthetic ones), and no limitation can be envisaged due to the hydrophobic and hydrophilic character of the applied polymers. Using this capillary microfluidic flow-focusing device we fabricated monodisperse fluorescent-loaded nanoparticles from biodegradable polymers (i.e., poly-lactic-co-glycolic-acid and chitosan) with a one-step procedure. A flourescent probe (6 - coumarin) was incorporated within the biodegradable matrix of the particles. Various operating conditions, such as the polymer molecular weight and concentration, flow rate ratio, type of solvent phase, τmix, microreactor-focusing channel diameters and length, and temperature have been investigated. Their influences on the formation of NPs, have been correlated to the final particle size distribution, ranging from 20 to 300 nm, and morphological characteristics. NPs’ characterization was performed by Dynamic light scattering (DLS), size and Z-potential, and by means scanning electron microscopy (SEM), morphology. This technique allows the fast, low cost, easy, and automated synthesis of polymeric nanoparticles and it may become a useful approach in the progression from laboratory scale to pilot-line scale processes. The presence of the fluorescent probe enables to carry out preliminary studies of cellular uptake, transport and translocation of nanoparticles in cell cultures and in vivo systhems, in order to produce NPs containing organic actives for medical applications and ''plant medicine''. In the future, we will approach fluid dynamics and modeling studies to analyze the microfluidic behavior and mixing process within the capillary microchannels. These results may expand the current understanding of the nanoprecipitation mechanism of biopolymeric NPs and the role exerted by the microfluidic environment