Preparation And Delivery Performance Of Drug Carriers Based On Saccharomyces Cerevisiae

Berberine hydrochloride possesses good therapeutic effects on intestinal diseases,but its oral bioavailability is limited by poor solubility and low acid tolerance.In this study,yeast cell microcapsules(YCMs)are prepared as carriers of berberine hydrochloride(BRH),and the physicochemical,morphological,and conformational characteristics of BRH-loaded YCMs(BRH-YCMs)are analyzed.The drug solubility and in vitro release behavior of encapsulated BRH are also evaluated under various p H conditions.The carrier was further modified with cationic lipid membrane.The experimental results showed the unmodified YCMs-BRH archieved sustained release effectively,and the modified YCMs-BRH could reduce drug loss and improve drug availability in an acidic environment.The research contents and main results are as follows:(1)The berberine hydrochloride loaded yeast microcapsules were prepared and optimized: the preparation conditions were to first dissolve berberine hydrochloride in hot water at 80 °C,and the yeast microcapsules pretreated with 10%(volume fraction)ethanol in advance and lyophilized were added under heating at 50 °C under lower speed stirring.The drug loading time is 16 h,and the drug concentration is 5 mg/m L,that is,m(yeast microcapsules): m(berberine hydrochloride)= 5:1,and the loading efficiency was 8.71 ± 0.39%.(2)The drug sustained-release system and p H-responsive release system of BRH-YCMs were established.Compared with the original drug,YCMs could help achieve sustained drug release.For p H-responsive release,the BRH-YCMs are relatively stable in simulated gastric juice,and the drug release after 4 h is only13.20±4.23%,which facilitates the gut-targeted release of berberine hydrochloride.(3)The surface modification of yeast microcapsules was further explored: The non-phospholipid lipid membranes prepared from aqueous phase and buffer solution were successfully coated on the surface of yeast microcapsules with a 1:1 mass ratio,and an ion-responsive release system was established for sensing phosphate ions in intestinal juice.The yeast microcapsules modified with water phase lipid film had a drug release rate of only 8.82±0.33% within the first 4 hours in the simulated gastric acid environment,and inn simulated intestinal fluid,the final release rate of lipid film modified BRH-YCMs at 48 h was 65.27±3.96%.It shows that the surface modification of the YCM carrier effectively reduces the loss of drugs in gastric juice and improves the utilization of drugs in the intestine.(4)The antibacterial properties of yeast microcapsules loaded with the model antibiotics kanamycin sulfate against Escherichia coli were studied.The drug-loading amount was 157.18±0.92 mg/g.And the antibacterial effect of 50 μg/m L drug-loading microcapsules was equivalent to that of the original drug,and could last for 72 h,indicating that yeast microcapsules can be used as a sustained-release drug carrier.In conclusion,this study prepared an oral drug delivery system based on Saccharomyces cerevisiae cells.It has the distinct characteristics of intestinal microenvironment responsive release.This study provides new strategies and materials for the design and preparation of new oral drug carriers.