Preparation and performance of pH-responsive 5-Fu/chitosan sustained-release microspheres based on microfluidic technology

T-shaped droplet microfluidic device was used for preparing 5-Fu-loaded chitosan microspheres. • 5-Fu-loaded chitosan microspheres exhibit pH-responsive release patterns and sustainable release characteristics for up to 60 days. • The average particle size of the microspheres is 3.90 ± 0.57 μm, and the particle size distribution is narrow. • Drug-loaded microspheres of different particle sizes have different drug release rates and cycles. Microsphere formulations are a promising drug delivery system for targeted response and prolonged sustained release. However, conventional emulsification crosslinking methods for microsphere preparation usually result in a broad particle size distribution, large particle size, poor uniformity, and consequently erratic drug release kinetics. In this investigation, chitosan microspheres encapsulating 5-Fluorouracil (5-Fu CS-MS) were fabricated using a T-type droplet microfluidic device, and the formulation was optimized by single-factor experiments. The resulting microspheres had a consistent drug release profile, a smooth surface, high monodispersity, and a uniform particle size distribution with an average particle size of 3.90 ± 0.57 μm. The polymer-drug interaction in 5-Fu CS-MS was analyzed using FTIR and XRD. The XPS and EDS results confirmed the occurrence of a Schiff base reaction between glutaraldehyde (GA) and chitosan (CS), indicating successful encapsulation. TGA results revealed that the cross-linking reaction enhanced the thermal stability of the microspheres. Biocompatibility assessments using Human umbilical vein endothelial cells (HUVEC) line demonstrated the safety and compatibility of the fabricated microspheres. More importantly, the in vitro release results illustrated a pH-responsive drug release profile and sustained release of 5-Fu CS-MS for a period up to 60 days. In summary, the CS sustained-release microspheres produced using the microfluidic technique have the potential for intelligent response, precise drug delivery, and prolonged sustained release of small-molecule drugs. Download: Download high-res image (197KB) Download: Download full-size image