Preparation And Oral Bioavailability Study Of Curcumin Nanocrystals By Microfluidics

Objective:Curcumin has a wide range of physiological activities,but as an insoluble drug,its bioavailability is very low and its application is hindered.In this study,the strategy of nanoparticle technology was used to enhance drug solubility and improve its bioavailability.Content:In this study,a new type of stainless steel SAR microfluidic chip was designed and manufactured.Using polyvinylpyrrolidone K30 as stabilizer,curcumin nanocrystals were prepared by anti-solvent precipitation method.The properties of curcumin nanocrystals were characterized by property investigation,in vitro dissolution experiment and in vivo pharmacokinetic study.Methods:Based on the current reports,the structure of the microfluidic chip was designed using Auto CAD software,and stainless steel was selected as the preparation material to manufacture a stainless steel SAR microfluidic chip.Before using the metal microfluidic chip to prepare curcumin nanocrystals,based on the COMSOL Multiphysics5.6 software,the"Laminar Fluid Flow"and"Transport of Diluted Species"modules were used to study the mixing performance of the metal ring chip.Through the screening of organic solvents and stabilizers,suitable organic solvents and stabilizers were selected.Taking the particle size as the evaluation index,the box-Behnken experimental design with three factors and three levels was carried out from the concentration of curcumin,the amount of stabilizer,and the flow rate ratio of the aqueous phase and organic phase.The preparation route was optimized,and two kinds of curcumin nanocrystals with different particle sizes were prepared.The morphology,particle size,PDI and Zeta potential of the two nanocrystals were observed and measured,and compared with curcumin raw materials,in vitro dissolution experiments and oral pharmacokinetic experiments in rats were carried out to evaluate the biological properties of nanocrystal preparations.Results:Through the analysis of the simulation results,when the total flow rate was greater than 5m L/min and the ratio of water phase to organic phase was greater than 4/1,the metal microfluidic chip could achieve a fast and uniform mixing effect.At the same time,acetone,which was the best solution for curcumin,was selected as the solvent,and polyvinyl pyrrolidone K30,which was the most favorable for the stability of nanocrystals,was selected as the stabilizer.After single factor experiment and Box-Behnken experimental design,nanocrystals with two-particle sizes were prepared according to the optimized route obtained.In TEM images,the two nanocrystals are uniformly distributed and round.The small particle size of nanocrystal was 59.29±0.56nm,PDI was0.131±0.024,and Zeta potential was-17.36±2.38m V.The big particle size of nanocrystal was 168.40±3.10nm,the PDI was 0.058±0.028,and the Zeta potential was-19.80±2.74m V.Compared with curcumin,the C_max and AUC_0-∞of curcumin nanocrystals were increased by 4.47 and 3.64 times and 4.26 and 3.14 times respectively.Conclusions:In this study,the performance of the microfluidic mixer was simulated by COMSOL Multiphysics 5.6 software,and it was proved that the microfluidic channel can realize the mixed flow of two fluids.Using this micromixer,after optimization by Box-Behnken experiment,two-particle size curcumin nanocrystals were successfully prepared.In vitro dissolution experiments and oral pharmacokinetic studies in rats showed that curcumin nanocrystals could significantly increase the solubility and in vitro dissolution rate of curcumin,and significantly improve its oral bioavailability.