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Study of Polymeric Micelle Drug Delivery System Based on the Amphiphilic Polyphosphazene Containing β-CD as a Segment

Author: WangRongJuan
Tutor: QiuLiZuo
School: Zhejiang University
Course: Pharmacy
Keywords: Polymeric micelles Cyclodextrin Polyethylene glycol Polylactic acid Polycaprolactone Doxorubicin
CLC: R96
Type: Master's thesis
Year: 2010
Downloads: 327
Quote: 1
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Abstract

Subject to beta-cyclodextrin (beta-CD) as the center, in its primary hydroxyl group position on the introduction of polyethylene glycol monomethyl ether - polylactic acid or polyethylene glycol monomethyl ether - polycaprolactone polymer chain, has been based on the beta-CD of the amphiphilic polymer spel / CDs and SPEC / CdS. The structure of the polymer with FT-IR, 1H NMR and GPC were characterized. Pyrene fluorescence spectrometry research Spel / CDs and SPEC / CDS in aqueous solution Micellization Behavior of the critical micelle concentration (CMC) in the 0.00092-0.01mg/ml range, and with the increase in the length of the hydrophobic segment The polymeric micelles CMC reduced. Doxorubicin as a model drug, the use of thin-film dispersion method and emulsion - solvent evaporation method drug-loaded micelles, different drug drug loading and encapsulation efficiency. The results show that the film dispersion method micelles smaller particle size, drug loading and high encapsulation efficiency, but are vulnerable to water-soluble polymer material; emulsion - solvent evaporation method of drug-loaded micelle dose and high encapsulation efficiency and is not water-soluble polymer material. For emulsion - the drug solvent evaporation method, the effects of different dosing ratio of different materials on the drug situation in detail. With the growth of the hydrophobic polymeric micelles entrapment efficiency and drug increased volume. Transmission electron microscopy show that the the micelles form of regular spherical and uniformly distributed, in the 100 - 300 nm between. The in vitro release experiments showed that doxorubicin in vitro release of pH-sensitive, faster at low pH (pH = 5.0) release. In addition, with the reduction of the shortening of the hydrophobic polymer material and drug release rate has accelerated. Compared with a hydrophobic polymer material PLA hydrophobic PCL polymer under normal physiological conditions (pH = 7.4) showed slow drug release behavior. Study material in vitro cytotoxicity using MTT assay results show that the synthesis Spel / CDs and spec / CDS basic non-cytotoxic, the material has good biocompatibility. MTT assay and flow cytometry and laser confocal microscopy to examine the drug-loaded micelles in vitro cytotoxicity results showed that the drug-loaded micelles in vitro cytotoxicity has been enhanced with the growth of the hydrophobic chain. Compared with free drug doxorubicin, the drug-loaded micelles the resistant strains MCF-7/ADR cytotoxic significantly improved, can reverse the resistance of the drug-resistant strains of drug-loaded micelles to a certain extent. ScS use of R-123 in the intracellular accumulation of the polymer itself for the inhibition of P-gp protein, the results showed that the polymer sPEL / CDs and SPEC / CDs having a strong inhibition of P-gp protein, its effect of suppressing CsA inhibition of P-gp protein as well as or better than CsA. With the lengthening of the hydrophobic chain inhibitory effect of strengthening and hydrophobic PCL polymer micelle effect is more obvious. Rat pharmacokinetic experiments show that the micellar can extend the half-life of doxorubicin, can significantly increase the AUC, has a long cycle capacity. Drug-loaded polymeric micelles the ICR mice lungs B16 cell growth has a significant inhibitory effect as passive tumor targeting vector delivery system, the class is based on beta-CD in the amphiphilic polymer (SpEL / CDs and SPEC / CDS) has a good prospect worthy of in-depth study.

Study of Polymeric Micelle Drug Delivery System Based on the Amphiphilic Polyphosphazene Containing β-CD as a Segment

Abstract

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