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Synthesis of pH-responsive Polymeric Nanoparticles for Drug Delivery Application

Author: WeiFuMiao
Tutor: BiHong
School: Anhui University
Course: Polymer Chemistry and Physics
Keywords: pH responsive random copolymer micelle nanogel drug carrier
CLC: TQ460.7
Type: Master's thesis
Year: 2011
Downloads: 162
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Abstract


The application of smart responsive polymeric nanoparticles in drug delivery system (DDS) has drawn wide attention by the development of polymeric science and modern medicine in recent years. It has many advantages such as controlling the drug release rate, decreasing the administration frequency, lowering side effect and toxicity of drugs, improving the therapeutic effect as well as widening administration routes.The main contents of this paper were as follows:1. A series of different compositions of random terpolymer P(S-co-2VP-co-nBMA were synthesized via radical polymerization by changing the monomer feed ratio. The structure and composition of the copolymers were characterized by FT-IR, NMR and GPC measurements. The pH-responsive self-assembly behavior of random terpolymer in THF/H2O solution was studied. UV-vis spectrophotometer (UV), dynamic light scattering (DLS) and transmission electron microscopy (TEM) have been used to study the corresponding self-assembly behavior of P(S-co-2VP-co-nBMA) in THF/H2O as a function of copolymer composition and pH value. The morphologies change from unimers to solid nanoparticles, further to core-shell structured micelles and then to larger aggregates as pH value of solution increased. Particularly, at pH 5 the random terpolymer self-assembled into well-defined core-shell structured nanosphere with hydrophobic PS/PnBMA segments as the mixed core, hydrophilic P2VP segments as the shell. In addition, norfloxacin (NFLX) was chosen as a model drug to study the drug carry and release behavior of the polymeric micelles. NFLX was loaded in the micelles by dialysis method and the drug loading content and drug loading efficiency were 5.5% and 33.2%, respectively. The drug release behavior at different pH values (2.0 HCl solution and 7.4 phosphate buffer solution) was monitored by UV spectrometer. Results showed that the rate of drug release was rapid under acidic conditions, while there was nearly no drug release under neutral conditions.2. Different size of nanogel P(DMAEMA-co-HEMA) has been prepared via inverse emulsion polymerization by changing the crosslinker contents. The structure and morphologies of the nanogel were characterized by FT-IR, NMR and TEM. The transmittance of the solution was characterized by UV and the results demonstrated that there was obvious swelling phenomenon of the nanogel under acidic conditions. HEK 293 A cells were chosen as models to investigate the cytotoxicity of the nanogels by MTT assay. The results indicated that the cytotoxicity of the nanogels were concentration-dependent. In order to explore the possibility of the nanogel as the drug carrier owing to its pH responsive property, DOX was chosen as the model drug and the drug loading content was 11.4%. The release behavior of the nanogels at pH of 5.0 and 7.4 monitored by UV spectroscopy revealed that the lower pH value triggered more rapid drug release rate than neutral medium, owing to the swelling of nanogel.

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