Preparation Of Monodisperse Chitosan Microspheres With T-Shaped Microchannel Device And In Vitro Study Of Drug Release

In recent years, biodegradable polymer microspheres is widely applied in the controlled release of drugs, because of its advantages in size, micro-structure, and surface physicochemical properties. Use polymer microspheres as carrier to proceed controlled release of drugs, can maintain a certain concentration of drugs in blood system for a long term, can not only increase the safety and bioavailability of drugs, but also improve the effect of treatment.In this paper,5-Fluorouracil was used as model drug, and T-shaped microchannel devices was used to prepare monodisperse chitosan microspheres. Liquid-liquid two-phase flow pattern as also the related influencing factors was investigated, and the morphology, surface structure, and the particle size distribution was analyzed. Effect of preparation conditions on the sustained release performance was investigated. Drug release kinetics models were used to simulate the profile of in vitro drug release.With different flow rate of Qc and QD, four different How patterns known as laminar, jetting, squeezing, and dripping were observed. With low concentration of chitosan, high ratio of Qc/Qd, and high concentration of surfactant, microspheres with smaller particle size can be obtained. Particle size distribution analysis proved the microspheres was nearly monodiserse system, the dispersion index was lower than0.08.By increasing the concentration of chitosan and cross-linking agent, reducing drug dosage and cross-linking time, and with high molecular weight of chitosan, we obtained5-Fu-chitosan microspheres with better quality. High encapsulation efficiency was obtained by increasing the concentration of chitosan and crosslinking agent, reducing crosslinking time. High molecular weight of chitosan and high drug dosage can also increase the encapsulation efficiency.Composite microspheres was prepared by blending nHA or nSiO2with chitosan. Core-shell microspheres was obtained by coating with PLA. The drug release rate and initial burst release was reduced, and the drug release was extended to48h.Zero order, First order, Higuchi model, Korsemeyar Peppas model, Kopcha model, Hixson Crowell model and corrosion-diffusion model were used to simulate in vitro drug release profile of microspheres. Corrosion-diffusion model and Kopcha model were the best fit, correlation coefficient was above0.999.