Study On Synthesis, Characterization And Controlled Release Properties Of Novel Dendrimer Derivatives Using As Drug Carriers

Synthesis and characterization of novel polymers used in drug controlled release have attracted much attentions in the field of bioscience and material science. The polymer systems that present a phase transition in response to external stimuli such as temperature, pH, ionic strength, and electric field has been studied, and shown potential applications in the controlled drug release systems. Externally modulated or self-regulating drug-delivery systems have been used as novel approaches to deliver drugs as required. In this thesis, functional star polymers were prepared via a combination of poly (N, N-dimethylaminoethyl methacrylate) (PDMA) which can respond to the change of external environment, and those compound including dendrimer and β-cyclodextrin (β-CD), which can form molecular inclusion complexes. The macromolecular structures of those polymers were characterized through various advanced technologies. The relationship between star polymers' environmental sensitivity and their compositions was investigated. The process and mechanism of controlled drug delivery were studied to understand the supra-molecular inclusion and the related drug release behavior of polymers under different experimental conditions. Furthermore, AB_x cyclodextrin derivatives containing reactive monomers were synthesized, which can be used to prepare hyperbranched polymer.At first, polyamidoamine(PAMAM) dendrimers with generations 0.5 to 5.0 were synthesized on the basis of alternatively repeating of the exhaustive Michael addition and the exhaustive amidation reactions. 6-o-Tosyl-β-cyclodextrin (β-CD-6-OTs) was prepared by the reaction of β-CD with p-toluenesulfonyl chloride in the presence of sodium hydroxide using water as the solvent. β-CD-6-OTs obtained above was further aminated by ethylenediamine. The dendrimer derivatives (PAMAM-β-CD) consisting of a dendritic PAMAM core and β-CD grafts were synthesized by amidation reaction. Their macromolecular structures were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, element analysis, DSC, TGA and particle size analyses. The results indicated that the dendrimer derivatives had been synthesized, and the particle sizes of PAMAM-β-CD were lager than that of PAMAM dendrimers. Sulfate-Phenol experiments showed that the proportions of β-CD in 3.0G and 5.0G PAMAM-β-CD were respectively 80.5(wt)% and 77.8(wt)%.Then 3.0G and 5.0G PAMAM-β-CD were acylated by chloroacetyl chloride to...