Microfluidic fabrication of berberine-loaded nanoparticles for cancer treatment applications

Introduction: Production of chitosan nanoparticles using the ionic gelation method assisted by a microfluidic chip has not been studied extensively. Still, there are some dominant limitations to the production of chitosan nanoparticles utilizing this method and has been reported in previous studies. Aim: To address this issue, the current study introduces a novel approach to diminishing those hurdles and systematically examines different microfluidic production processes which influence the production of chitosan/sodium tripolyphosphate nanoparticles (CSNPs) for drug delivery applications. This study aimed to enhance the anticancer effect of berberine by a unique nanoformulation approach using a microfluidic chip compared to free drug delivery. Method: In this approach, by adjusting the preparation procedures, changing the chitosan concentration and flow rate ratio, and using acidic tripolyphosphate (pH < 4), six types of berberine-loaded CSNPs with different physical properties were fabricated. The drug release profile and cytotoxicity effect of selected samples were investigated using MTT and apoptosis assays, respectively. Results: Finely dispersed berberine loaded chitosan nanoparticles (PDI<0.3) with an average size of (130-200 nm) were produced. By this nanoencapsulation method, the loading content of berberine was enhanced from 11 to 55%. Based on the size and drug loading content, three samples were chosen for In-vitro studies. According to the results of MTT and apoptosis assays it was found that selected berberine-loaded chitosan nanoparticles demonstrated anti-proliferative effects in treated cells compared to free berberine delivery. With the implemented strategy of this study, homogeneous continuous production of CSNPs as a proper drug carrier candidate for drug delivery applications without any limitation was facilitated.

Automated summary

This study introduced a novel approach to overcome limitations in the production of chitosan nanoparticles and systematically examined different microfluidic production processes for drug delivery applications of chitosan/sodium tripolyphosphate nanoparticles. The unique nanoformulation approach using a microfluidic chip successfully enhanced the anticancer effect of berberine, leading to the fabrication of berberine-loaded chitosan nanoparticles with improved physical properties. The study demonstrated anti-proliferative effects of the selected berberine-loaded chitosan nanoparticles compared to free berberine delivery, establishing the potential of homogeneous continuous production of CSNPs for drug delivery applications.