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Self-assemble Of Dipeptide Derivative And Study On Release Evaluation Of Drug Delivery

Posted on:2015-10-10Degree:MasterType:Thesis
Country:ChinaCandidate:X GongFull Text:PDF
GTID:2284330452966188Subject:Biomedical engineering
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In recent years, due to its distinct advantage in structural diversity, energyefficiency and environmental protection,easy operation,without special devices,“self-assembly” technology has demonstrated a strong advantage and promisingapplication prospect both in the manufacture of nanomaterials, functional moleculardevices, or drug delivery model, wound healing and other tissue engineering.In the field of molecular self-assembly, small molecular peptides, as importantbiologically active substances for a variety of cell functions in vivo, has goodbiocompatibility, controllable degradability and flexible self-assembling properties,which can self-assemble into nanowires, nanotubes, nanospheres, and membranematerials in respond to environmental conditions. And the peptide-based materials orproducts have shown a great potential in biomaterials, tissue engineering and drugrelease for their unique functions, novel self-assembly shapes and excellentbiocompatibility.In this thesis, small molecular peptide derivative, Fmoc-diphenylalanine(Fmoc-FF) was chosen as a model molecule. Through the way of self-assembly,different regulating methods of self-assembly had been designed and the regulationmechanism of self-assembling was analyzed in order to obtain well-performancedpeptide materials with controlled structures, while expanding their potentialapplications.The main researches can be summarized as follows:(1) A variety of surfaces and and pH environment were used to regulate theFmoc-FF self-assembly. It had been found that Fmoc-FF moleculars couldself-assemble into various structures on nylon membranes, polypropylene membranes,nitrocellulose membranes, polytetrafluoroethylene (PTFE) hydrophilic membranes,polyvinylidene fluoridce (PVDF) hydrophilic membranes, and glass sheets accordingto the hydrophilicity, surface roughness, porosity, etc. of the surface; Under pH2~12,morphology of Fmo-FF self-assembled materials shifted from "massive block withoutrules " to "nanofibers" and " nanospheres". Our results reveal that the interface andpH condition can regulate the behavior of Fmoc-FF self-assembly. (2) Polysaccharides regulated self-assembly of Fmoc-FF peptide. Sodium alginate(SA) and chitosan were chosen as “regulator” to regulate the self-assembly ofFmoc-FF molecular. The result showed that, SA played a better role in regulating theself-assembly process. The Fmoc-FF/SA composite hydrogel could self-assemble intonano-fibers, thin films, and "honeycomb" and other structures without altering thesecondary structure of the self-assmbled Fmoc-FF moleculars. By in vitro cell cultureexperiments, both Fmoc-FF and the Fmoc-FF/SA hydrogels exhibited goodbiocompatibility. At the same time, in vitro drug release studies demonstrated that theFmoc-FF/SA hydrogels also had good value in terms of sustained-release of drugs.(3) Graphene oxide (GO) regulated self-assembly of Fmoc-FF peptide. Weprepared GO through improved Hummrs’ method, and then used the GO to regulatethe self-assembly of Fmoc-FF. Different sample preparation methods and GO contentwere chosen as variables, respectively. Results indcated that GO could modulate theself-assembly behavior of Fmoc-FF, and under certain conditions, GO wrapped in thesurface of the self-assembld Fmoc-FF fibers or the like. The hybrid hydrogels showedmuch higher stability compared to pure Fmoc-FF hydrogel, which might be caused by-OH groups, strong π-π interaction etc. Finally, The sustained and controlled drugrelease from the hybrid hydrogels was achieved by varying the concentrations of GOand aging time, and the experiments showed the Fmoc-FF/GO hydrogels were gooddrug carriers, which can further explore the scope of its application.
Keywords/Search Tags:Dipeptide derivatives, self-assembly, polysaccharides, graphene oxide, drug delivery
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