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Poly(Ethylene Glycol) Grafted Amphiphilic Polyphosphazenes: Self-assembly Behavior and Applications in Drug Delivery Systems

Author: ZhengCheng
Tutor: ZhuKangJie；QiuLiZuo
School: Zhejiang University
Course: Polymer Chemistry and Physics
Keywords: Polymer Polyphosphazene Amphiphilic copolymer Polymeric micelles Drug Delivery System Doxorubicin
CLC: O634.51
Type: PhD thesis
Year: 2009
Downloads: 608
Quote: 1
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Abstract

Paper Select polyphosphazene polymer backbone as to different molecular weight polyethylene glycol as a hydrophilic side chain, try glycine ethyl ester, p-aminobenzoic acid ethyl ester and cholesterol in three different amino compound as a hydrophobic substituent group, synthesized a series of different physical and chemical properties of amphiphilic graft polyphosphazenes. Substituent ratio established controllable high yield amphipathic polymeric graft polyphosphazene synthesis methods, by NMR, UV spectroscopy, gel permeation chromatography and differential scanning calorimetry analysis of the copolymer was characterized. Right amphiphilic graft polyphosphazene in aqueous self-assembly behavior has been systematically studied. By pyrene fluorescence probe method of the copolymer in aqueous critical micelle concentration, the results showed that the copolymer with hydrophobic substituents content increases the critical micelle concentration decreased. The main form of the copolymer assembly by transmission electron microscope observation, which showed that the polyethylene glycol chain is hydrophilic amphiphilic copolymer in aqueous solution can spontaneously assemble to form aggregates of different structures: the hydrophobic glycine ethyl ester group amphiphilic graft polyphosphazene, when a higher degree of substitution of glycine ethyl ester, it appears as rod-like micelles, with glycine ethyl ester copolymer decreased gradually, micellar system simultaneously with rod and two forms spherical micelles, to further reduce the content of glycine ethyl ester group of the copolymer a form spherical micelles only. For p-aminobenzoic acid ethyl ester as a hydrophobic group amphiphilic graft polyphosphazenes, when higher levels of the hydrophilic chain of the copolymer, in the form of spherical micelles; hydrophilic content decreased when a certain value the amphiphilic copolymer is a polymer vesicles. For the molecular weight of the hydrophilic PEG 1100 chains of amino-substituted ethyl amphiphilic graft polyphosphazenes, when PEG content for a specific level in the water to form the shape of the self-assembly fatally stability at different concentrations obtained by using different solvents dialysis differentiated morphology assembling, improve the assembly of the polymer concentration from the mesh structure will change to spherical particles. Very hydrophobic amino cholesterol, and therefore hydrophobic amino substituent cholesterol amphiphilic graft polyphosphazene only the hydrophilic segment content is high only when the water to form a stable spherical micelles. Polyphosphazenes amphiphilic graft micelles to solubilize hydrophobic drugs, hydrophobic micellar drug loading ability composition of the copolymer, and to set the type of drug preparation method of micelles; glycine ethyl ester as a hydrophobic group amphiphilic graft group polyphosphazenes micelles containing the drug in a package shape may change significantly, wherein the low content of glycine ethyl ester copolymer micelles in the carrier blank after drug originally has a rod into all of spherical nano-micelles drug-loaded micelles, and glycine ethyl ester copolymers with higher levels of drug-loaded micelles with morphology is related to the amount of drug, drug loading is low when the drug-loaded micelles are still showing consistent with blank spherical micelles, while When the drug loading increased to a certain extent on the drug-loaded micelles into a hollow sphere. Drug-loaded micelles having different pH values ??in the release medium vitro results suggest that drug-loaded micelles with release characteristics, at a lower pH, the release rate will be significantly accelerated. By the p-amino benzoic acid ethyl ester substituted polyphosphazenes amphiphilic graft polymers formed vesicles can be used to carry water-soluble anticancer drugs, the loaded water-soluble polymer vesicles in vitro drug release behavior findings Description vesicles drug release process follows Fickian diffusion mechanism. , Contained micelles and vesicles in vitro antitumor activity evaluation results show amphiphilic graft polyphosphazene containing micelles can effectively inhibit tumor cell growth, glycine ethyl ester as a hydrophobic group amphiphilic polyphosphazene nitrile containing micelles adriamycin-resistant MCF-7 breast cancer cells IC50 of free drug is unencapsulated third control group; while packets containing water-soluble amphiphilic poly anticancer drugs phosphazene copolymer vesicles on HepG2 cells than the IC50 of the drug substance used directly in the control group 17 times. By studying tumor cells amphiphilic graft polyphosphazene drug-loaded micelles intake, we found that doxorubicin-resistant MCF-7 breast cancer cell uptake of drug-loaded micelles is more efficient than the free drug uptake efficiency of its much higher 4 hours with the carrier micelles in cells incubated with doxorubicin fluorescence intensity up to the same concentration of free drug in the control group three times. Containing micelles can significantly change the resistance to doxorubicin doxorubicin MCF-7 cells in the distribution of doxorubicin carried by the micelles easier access to the nucleus; Furthermore, experimental results show that drug-loaded micelle particle Take micelles can significantly affect the rate of uptake by cells, incubated for 4 hours micelles smaller particle uptake by tumor cells in an amount of large particle size 1.9 times micelles. Using a rat carrageenan-induced acute inflammation model investigated in cholesterol amino substituent amphiphilic micelles containing polyphosphazene inflammatory therapeutic properties. The same dose of the drug solution compared to the control group, the copolymer micelles containing group treatment is better than the corresponding control group. In short, amphiphilic graft polyphosphazene micellar pharmaceutical controlled release drug delivery system in particular in the field of anticancer drugs has delivered a strong application potential and broad prospects for development, worthy of further study.

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