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The Study of the New-Nanopharmaceutical-The Dispersibility of Carbon Nanotubes as Drug Carriers

Author: SiYunYun
Tutor: JingQiuFang；MiLiLi
School: East China University of Science and Technology
Course: Pharmaceutical Engineering
Keywords: PEGed-polymers carbon nanotubes dispersion stability drug-loading property evaluation
CLC: TB383.1
Type: Master's thesis
Year: 2012
Downloads: 164
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Abstract


Carbon nanotubes(CNTs), as the potential carrier of nano-materials, had large specific surface areas that could be filled with the desired molecules, ranging from small molecules to proteins. It aslo had a high aspect ratio which provided multiple attachment sites for various functionalization groups. It was readily taken up by Cells and could reach the cell nuclei. However, the sidewall of CNTs was hydrophobic, which made CNTs uridissolved in water and organic solvents. The dispersion of CNTs was an essential precondition of their application. The purpose of the study was to obtain water-solubility CNTs used as a novel tumor targeted nano-carrier by combining the advantages of hydrophilic PEG derivatives with folic acid & cholesterol. The Cholesterol-PEG and FA-PEG polymers were synthesized to modificate CNTs and other surfactants were used as comparison. Berberine was selected as model drug to evaluate the properbility of CNTs as drug carriers.The effects of different reaction solvents and temperature on the yield of Monocholesterylsuccinate were determined. Then cholesterol-modified PEG was synthesized under gentle conditions. The effect of reaction time on the the substitution degree of folate was studied. The stability of dispersions of carbon nanotubes (SWNTs and MWNTs) was studied by functionalizing with five different modifiers (TPGS, Tween 80, Cremophor, Cholesterol-PEG and Folate-PEG polymers) in water. The concent of CNTs dispersed in water was determined. The optimum dispersion rate as the mass ratio (CNTs/modifier) ranging from 0 to 1 was studied. The binding of Berberine to nanotubes was investigated under different conditions including various pH, temperature, and the initial added amount of drug. Then, its vivro release in buffers (pH=5.5 and 6.8) was evaluated.The polymers (cholesterol and folate modified PEG) were characterized by IR and 1HNMR. It was found that the concentration of SWNTs could achieve 50μg/mL in solution and MWNTs was 230μg/mL using Cholesterol-PEG as modifier (the mass ratio of CNTs/modifier was 1/8). Using Surfactants could enhance the CNTs solubility and thus embodied well dispersion stability of CNTs. The optimized conditions of drug-loading were pH 9.0,4℃. The drug-loading ratio of SWNT reached 5.5, but the five different modifiers had few effects on the relative drug-loading rate(expressed by the mass ratio of drug-loading and CNTs dispersed in solution). Under the conditions of same volume, the absolute drug-loading rate(expressed by the mass ratio of drug-loading and CNTs added in solution) of SWNT improved by 41.8% and MWNT by 9.1% using Cholesterol-PEG as modifier. The higher release rate and content of BER from CNTs was obtained in an acidic solution at pH=5.5 compared with pH6.8. The pH-dependent drug release from CNTs could be exploited for drug delivery applications since the micro-environments of extracellular tissues of tumors are acidic, potentially facilitating active drug release from CNTs delivery vehicles.

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