Establishment And Characterization Of Graphene Based Colon-specific Drug Delivery System

In recent years, the incidence of inflammatory bowel disease(IBD) in China is increasing. However, the pathogenesis of IBD is not yet fully understood. A lifetime administration of drug with adverse reaction for the maintenance of the health-related quality of life is often necessary for its unknown aetiology, which makes the patients painful and destroys their normal life heavily. Since graphene had the characteristics of low toxicity, high specific surface area, good biocompatibility and easy functionalization, in this thesis, we established and characterized two colon-specific drug delivery systems, rGO-F127(Pluronic F127)-SASP and GPAs(graphene-PEGareogels)-SASP, by π-π interaction between graphene layer and salazosulfapyridine(SASP) molecular. We expected the research results could offer scientific basis for realizing the colon-specific delivery of SASP with the targeting carriers of graphene and its derivatives. The main research contents were as follows:1. The colon-specific drug delivery system of rGO-F127-SASP was obtained towards the processes of water-solubility modifying graphene oxide(GO) by adding Pluronic F127, reduction of GO with hydrazine hydrate, and loading free drug SASP. The structure was characterized and the drug loading property was studied. The research results demonstrated that the best initial drug concentration was 2 mg/mL, drug loading content of carrier was 0.348 +/- 0.030 mg/mg, and drug loading efficiency was 17.4 +/- 1.5%. Moreover, this drug delivery system had properties of pH sensitivity, sustained release, high large intestinal cumulative release percent of 72.4%, and high cumulative release percent of 91.6%.2. The colon-specific drug delivery system of GPAs-SASP was manufactured by the processes of preparing GO suspension, obtaining GO sol by adding reinforcing agent of PEG and reducing agent of VC, gelatinization after warming up without stirring, gaining GPAs by freeze-drying, and loading free drug SASP. The structure was also characterized and drug loading property was studied. The research results indicated that the best initial PEG concentration was 0.6 mg/ mL which could promote the formation of GPAs and enhance its mechanical strength; the best initial drug concentration was 2 mg/m L, drug loading content was 0.494 +/- 0.014 mg/mg, and drug loading efficiency was 24.7 +/- 0.7%. In addition, this drug delivery system also had properties of pH sensitivity, sustained release, high large intestinal cumulative release percent of 78.4%, and high cumulative release percent of 92.7%. The use of GPAs-SASP would be safer than the direct uses of SASP and other reported nanoparticles, and GPAs-SASP composite was relatively biocompatible material with reduced cytotoxicity compared with other reports.