Construction And Evaluation Of A New Gastroretentive Drug Delivery System

Objective:To develop chitosan-coated nanomicelles loaded gastroretentive beads to boost emodin inhibition efficacy on gastric tumor cells and extend retention time in stomach.Method:The encapsulation efficiency（EE）,drug loading（DL）,particle size and zeta potential were used as evaluation indexes to screen positively charged nanoscale chitosan coated emodin-loaded micelles with the highest encapsulation efficiency and drug loading.The chitosan-coated emodin-loaded nanomicelles were prepared using thin-film hydration method,and EE,DL,mean particle size,polydispersity index（PDI）,zeta potential and morphology were determined,respectively.In vitro cytotoxicity of emodin-loaded nanomicelles,emodin suspensions and blank nanomicelles was evaluated with human gastric carcinoma SGC-7901 cells by MTT.Nanomicelles-loaded floating mucoadhesive beads（NFM-Beads）were prepared by ionic gelation method,and its mucoadhesion ability was evaluated using eggshell membranes and gastric mucosa isolated from mice.In vitro swelling,degradation and floating ability in simulated gastric fluid were also investigated.FT-IR spectroscopy was applied to identify the formation of nanomicelles and NFM-Beads.Emodin release from NFM-Beads in vitro was fitted to zero order,first order,Higuchi and Ritger-Peppas models to study the release mechanism.In vivo gastroretention behaviour of NFM-Beads was evaluated by BaSO₄-based X-ray imaging exams in rabbit stomach.Results:The emodin-loaded nanomicelle used to prepare NFM-Beads consists of 1.5 mg emodin,140 mg Pluronic F127,10 mg Tween 80 and 6 mL 0.5%chitosan.The EE%was approximately 97.74±1.98%and the DL%was 0.808±0.009%.The size of nanomicells was 206.8²88.6 nm with a PDI of 0.162⁰.295,and its zeta potential was about 30.76±3.92 mV.The blank nanomicelles had null cytotoxicity and emodin-loaded nanomicelles had better inhibition efficacy on human gastric carcinoma SGC-7901 cells compared with emodin suspensions.The swelling ratio of NFM-Beads with 2%（w/v）CMC-Na/nanomicelles ratio 5/1 was the highest and its value was up to 740%;its degradation ratio is lower than other four formulations（p<0.01）;it floated initially about 80%at 5 min and then the floating retained above 70%after 8 h;mucoadhesion of NFM-Beads on both eggshell membranes and mice stomach mucosa was larger than 90%and no significant difference（p>0.05）was observed;emodin release from NFM-Beads in simulated gastric fluid was fitted to anomalous transport mechanism;In vivo gastroretention behaviour of NFM-Beads showed that NFM-Beads can be retained in rabbit stomach for at least 8 h.Conclusion:Compared with its suspension,emodin-loaded nanomicelle can enhance the growth inhibition of emodin on gastric tumor cell SGC-7901;NFM-Beads were successfully prepared,and it can elongate gastric retentive time,as well as its physical and chemical properties can meet the needs of treatment of gastric diseases.The new NFM-Beads system could be an effective approach to improve the therapeutic potency of drug against gastric cancer.