Microfluidics-based production of chitosan-gellan nanocomplexes encapsulating caffeine

Electrostatic complexes produced by interactions between polysaccharides have promising applications in the medical, pharmaceutical and food fields. In this light, for the development of such particles, microfluidics emerges as a promising technique in which processes occur at a strict laminar flow regime, allowing diffusion-dominated transport and particle formation in highly-controlled conditions. As a proof of concept, we compared bulk versus microfluidic (different devices simulating a range of residence times) processes for the production of electrostatic complexes of gellan with either chitosan (molecular weight ∼ 28 kDa) or hydrolyzed chitosan (molecular weight ∼ 3 kDa). Regardless of the process, polysaccharide solutions (pH 4.5) were mixed in pre-defined concentrations (polysaccharide ratios) to form electrostatic complexes that were used to encapsulate caffeine. These complexes were characterized by zeta potential measurements and particle size distribution. Overall, microfluidics produced complexes with improved characteristics such as lower polydispersity index (PDI ∼ 0.1) and mean size (∼200 nm) when compared to the conventional bulk process (PDI ∼ 0.3 and mean size ∼ 400 nm). Moreover, hydrolyzed chitosan (HC) contributed to an even smaller size and PDI value of the complexes. Such outcome is associated with the lower molecular weight and higher solubility of HC when comparing to conventional chitosan, which in turn improves electrostatic complexation. Caffeine could also be encapsulated in all complexes, but the highest encapsulation efficiency was achieved using microfluidics (70%) and with the geometry that provided a longer residence time. Therefore, we were able to demonstrate that microfluidics is clearly an effective strategy for generating electrostatic complexes with improved properties. Ultimately, this technique demonstrated a high potential for the production of vehicles of bioactive compounds.