| In recent years,with the intensification of the aging population in China,some diseases that threaten the health of the middle-aged and elderly people have drawn wide attention from scientists.The incidence of cerebral thrombosis is more common in the middle-aged and elderly,with acute onset and high clinical hazard.Compared with using the antiplatelet aggregation drug aspirin alone,the combination of aspirin and dipyridamole can improve the safety of medication by reducing the incidence of stroke recurrence and ischemic events significantly,so as to improve brain microcirculation.In traditional oral administration,the drug concentration varies greatly with time and the action time for treatment is short.Droplet microfluidic is a technology that utilizes microstructures to manipulate micro upgraded fluids,rapidly generate droplets through multiple immiscible phases in microchannels.The droplets prepared by microfluidic technology have high monodispersity and controllable size.Therefore,based on droplet microfluidic technology and in combination with the current research requirements for long-term effects,stable encapsulation,and controlled release of pharmaceutical preparations,this article explores drug loaded microcapsules with gastric acid resistance and long-term drug release within 24 h.The specific research content of this study mainly includes the following aspects.Firstly,a glass capillary microfluidic device was independently designed and fabricated,which can prepare triple high order droplets with good monodispersity.The device can prepare different forms of W/O/W/O triple droplets,such as triple droplets containing different numbers of inner water cores,and triple droplets containing different numbers of W/O double cores.In addition,the size of the droplet can also be changed by adjusting the flow rate of each phase.Then,based on the template of the triple emulsion device,the double emulsion template was designed by coning the glass capillary tip by using a program-controlled horizontal stretching instrument and a needle grinding instrument.Using this device,double droplets of polyethylene glycol diacrylate-hydroxypropyl methylcellulose acetate succinate were prepared,and the polyethylene glycol diacrylate(PEGDA)core was solidified by ultraviolet light;The p H responsive hydroxypropyl methylcellulose acetate succinate(HPMCAS)shell was solidified by solvent evaporation to obtain PEGDA-HPMCAS core-shell drug loaded microcapsules.The hydrophilic drug aspirin was encapsulated in the core,and the hydrophobic drug dipyridamole was encapsulated in the shell,achieving the simultaneous encapsulation of two drugs with different hydrophilic and hydrophobic properties with synergistic effects.Finally,the drug release behavior of PEGDA-HPMCAS core-shell drug loaded microcapsules with p H responsiveness in simulated gastric fluid with hydrochloric acid solution at p H 1.5 and in simulated intestinal fluid with PBS solution at p H 7.4 was investigated.The results showed that the microcapsules maintained good integrity and stable drug encapsulation under severe simulated gastric conditions.The HPMCAS shell decomposed within 2 h after entering the simulated intestinal fluid,and the hydrophobic drug dipyridamole encapsulated in the shell was suddenly released;The PEGDA core slowly releases the hydrophilic drug aspirin encapsulated in the simulated intestinal fluid through the network pores of the hydrogel within24 h.Subsequently,the cytotoxicity of core shell microcapsules was further explored.The MTT experiment results showed that the PEGDA core,HPMCAS shell,and the core-shell microcapsules of the microcapsules had no effect on the growth of Hep G2 liver cancer cells;Different concentrations of blank core-shell microcapsules had no effect on the growth of HT-29 colon cancer cells.Studies have confirmed that core shell microcapsules have good biocompatibility and are ideal drug carriers. |