The Fabrication And Release Properties Of Microcapsules For Controlled Release In Intestinal Via Droplet-based Microfluidics

The incidence of gastro-intestinal diseases(such as gastroenteritis,stomach cancer,colon cancer,etc.)is rising every year due to unreasonable diet and lifestyle habits,drug abuse,or genetic factors.Acute gastroenteritis often attacks rapidly,and causes dehydration and electrolyte imbalance in the body.If the treatment is not timely,acute gastroenteritis can cause a series of complications and seriously endanger the patient's health.When acute gastroenteritis attacks,it is desired that the plasma drug concentration reaching the therapeutic level immediately after drug administration.Thus,a burst-release of large amounts of drugs is necessary.After the first step of burst release,it is desired that the plasma drug concentration could maintain a safe and effective range over a long period of time to ensure curative effect and inhibit complications.At this time,a sustained-release mode must be achieved.If the burst release mode and the sustained release mode are orderly combined in a single drug delivery carrier which could achieve sequential release,it will be more beneficial to treating acute diseases such as gastroenteritis reasonably and effectively.The pH of the gastrointestinal system varies widely.Certain drugs often become unstable or inactivated when experience such large changes in pH conditions during the medication.There are a variety of enzymes in the stomach.This enzymes can easily damage drugs which are sensitive to enzymes,thus reduces the efficacy of these drugs.In addition,some drugs often have different physicochemical properties,such as hydrophilicity and hydrophobicity,but the synergy of multiple drugs is often necessary during treatment.Considering the above characteristics of the treatment of acute gastroenteric diseases,we designed a controlled release microcapsule system which could release drugs in intestinal tract.The microcapsule system was prepared by the double droplet capillary device designed in this experiment,and showing good release effect under simulated gastrointestinal tract conditions.The microcapsule system provides a new idea and method for drug development for treating gastrointestinal diseases.The results obtained in this experiment are as follows:1.We designed and assembled a microfluidic device for preparing double droplets,and double droplets were successfully prepared by adjusting the flow rate,solvent ratio and material concentration of each phase.When the volume ratio of dichloromethane and ethyl acetate is 1:4 and the material concentration is 100 mg/m L,monodisperse double droplets can be prepared by adjusting the flow rate of inner phase,middle phase,outer phase to 3 ?L/min,15 ?L/min,and 120 ?L/min,respectively.2.We prepared a controlled-release microcapsule system for intestinal tract based on the optimized droplet generation conditions above.This microcapsule system can realize the coencapsulation of drugs with different physicochemical properties(hydrophilic or hydrophobic).The microcapsules do not decompose in the pH conditions of the stomach,while decomposed in intestinal pH conditions,so that this microcapsules can achieve targeted intestinal release.When the microencapsulated drug is released under the simulated conditions of the gastrointestinal tract,the amount of the drug released can reach a relatively high concentration(50% or more)in an hour,and release in a sustained release manner when staying in the intestinein.This is consistent with the characteristics of acute gastroenterology medications,and the controlled release of the microcapsules was good under simulated gastrointestinal conditions.