| The COVID-19 in recent years has fully demonstrated the importance of advanced pharmaceutical technology to the national economy and people’s health.The development of new drug carriers and delivery methods is an important link in contemporary pharmaceutical technology.The encapsulation and delivery of water-insoluble drug powder are particularly difficult.Especially in the field of traditional Chinese medicine,many pharmaceutical ingredients exist in the form of water-insoluble powder.The preparation method is primitive and rough,limiting the exertion of curative effects.The drug loading rate is low,and the addition of organic solvents is prone to cause biological toxicity in traditional encapsulation methods.On the premise of maintaining biocompatibility,improving the loading rate and realizing controllable delivery of water-insoluble powders are of great significance for reducing the frequency of medication and improving the effect of targeted therapy.In this paper,a new method for encapsulating water-insoluble powders by microfluidic-based bubble template was proposed.Solid powder was encapsulated in the bubbles formed by hydrogel liquid film instead of dissolved in carrier gel,thus avoiding the use of organic solvents and greatly improving the powder loading rate.A numerical model of multiphase flow was established to reveal the interfacial evolution law of the hydrogel liquid film during stretching process.Self-floating powder-in-hydrogel microcapsules（P/H microcapsules）were prepared,and multi-layered powder-in-hydrogel microcapsules（MP/H microcapsules）with multi-responsive capability were prepared by adding magnetic field.The regulation of the size and morphology of the microcapsules was studied and the performance was analyzed.The main contents and conclusions are shown as follows:（1）The device and control system for encapsulating water-insoluble powder by microfluidic-based bubble template method were designed,and the experimental platform for the generation of microcapsules was built.According to the characteristics of bubble template method,the multiphase flow numerical calculation model of liquid film stretching was established.The accuracy of the numerical results was verified by comparing the bubble formation process in model calculation with experimental results.（2）Based on the numerical model,the evolution of gas-liquid interface during the formation of bubble template by liquid film stretching was studied.The formation of bubbles was determined by the competition between liquid film rupture and liquid film necking.Bubble size was related to solution viscosity,interfacial tension,and frame moving velocity.The bubble forming region was determined by capillary number and velocity ratio,and bubble size was also predicted,which provided guidance for the formulation and control of bubble formation process for water-insoluble powder encapsulation in the experiment.（3）The P/H microcapsules were prepared by encapsulating Ca CO3 powder in agarose gel system using microfluidic-based bubble template method.The influencing factors and regulation mechanism of powder-loaded bubbles formation and sol droplets formation were analyzed.It was found that the powder weight,agarose concentration and additive concentration affect the viscosity and surface tension of the solution system,thus affecting the stretching and necking process of liquid film.They were key factors in the formation of bubbles and sol droplets,which can be used to realize precise regulation of geometric morphology.The properties of the obtained P/H microcapsules were characterized.The P/H microcapsules exhibited good mechanical properties and swelling recovery properties.The powder loading rate of P/H microcapsules in wet state could reach 40.11%,which was significantly higher than that of traditional methods（10%）.Moreover,the P/H microcapsules had dual carrier capacity and controlled release ability.The small molecule components were encapsulated in the shell carrier and released by swelling of hydrogel shell and diffusion by concentration gradient.The water-insoluble powder components were encapsulated in the bubble core and presented a stepwise controlled release under ultrasound exposure.（4）The MP/H microcapsules were prepared by encapsulating Ca CO3/Fe3O4 mixed magnetic powder in sodium alginate/chitosan gel system using magnetic-assisted microfluidic bubble template method.The influencing factors and regulation rules of powder-loaded bubbles formation and the cross-linking of hydrogel shell were analyzed.The increase of powder weight,chitosan concentration and PF127 concentration increased the bubble size.The calcium alginate shell thickness was determined by diffusion depth of calcium ions driven by osmotic pressure,which can be regulated by the concentration of sodium alginate and calcium chloride.The MP/H microcapsules showed good mechanical properties and swelling recovery performance.The MP/H microcapsules with different shell layers maintained high powder loading rate.Based on the self-floating performance,magnetic response and ultrasonic response characteristics,the controllable positioning and programmed release of MP/H microcapsules were realized.Moreover,the multi-layered characteristics could achieve long-term and sequential release,which provided a new way for drug delivery. |
