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Studies On Amphiphilic Bblock Copolymer And Self-assembly Drug Carrier Micelles

Posted on:2004-04-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:L D DengFull Text:PDF
GTID:1101360092480640Subject:Applied Chemistry
Abstract/Summary:PDF Full Text Request
The nanoparticles with hydrophobic surface were easily adsorbed by protein and phagocytosed by cells of the reticuloendothelial system. Thus, studies on the amphiphilic block copolymer as drug carrier are important both theoretically and practically. Methoxy poly(ethylene glycol)-b-poly(L-lactic acid) diblock copolymer (PELLA) and methoxy poly(ethylene glycol)-b-poly(D,L-lactic acid) diblock copolymer (PEDLLA) were prepared by melt polycondensation.Poly(ethylene glycol)-b-polycaprolactone-b-poly(ethyleneglycol) (PECL) triblock copolymer was synthesized by using TDI as the coupler. The structure,the composition, the molecular weight and the molecular weight distributions , and the properties of the 1 copolymers were characterized by IR, H-NMR, GPC, DSC and WAXD methods. The sizes of the self-assembly micelles of the amphiphilic block copolymers and the effects werestudied by dynamic light scattering (DLS) and UV-visible spectrophotometer (UV). The micelle sizes werelargely influenced bythe hydrophobic chain content in the copolymer, the properties of the solvent and the copolymer concentration in the organic phase. The morphology of the micelles was investigated by transmission electron microscopy. Theresults showed that the micelles appeared spheres with inner core and outer shell. The critical association concentrations (CAC) were determined by pyrene monomer fluorescence probe technology. The degradability of copolymer was studied by the loss of the intrinsic viscosity in the degradation process. The results indicated that the degradation rate of PECL was slower thanthat of PELLA and PEDLLA. The stability of the copolymer micelle dispersion was examined by measuring the critical flocculation concentration, which gradually decreased with increasing the content of thehydrophobic chain in the copolymer. The rheological results showed thatthe viscosity ofthe micelle dispersion with higher content of PEG segments was firstly decreased and then increased with the increasingthe temperature. Otherwise, the variation of viscosity was irregular. The viscosity of the micelle dispersion increased with the increase of the electrolyte (Na 2SO 4) concentrations. Polymer micelles paclitaxel (PMT) was prepared by self-emulsification/solvent evaporation method and solid dispersion technique with amphiphilic block polymers as the carrier material. The size ofthe PMT was in nanoscale andthe size distribution was narrower.The morphology ofthe drug-loaded micelles was 1 investigated by transmission electron microscopy and H-NMR. The drug-loaded micelles showed asphere with inner core and outer shell.The effects on the drug-loaded amount, the entrapment efficiency, the size and the size distribution of PMT were investigated by HPLC, DLS and UV. Redispersion experiment results indicated theproperties of the drug-loaded micelles could be maintained by lyophilization. Any initial burst release was not observed in the release pattern of all the samples. The drug releasing rate and the accumulated releasing amount decreased upon increasing the molecular weight of the hydrophobic chain in the copolymer and the drug-loading amount. The release in vivo showed that PMT restrained the growth of Kunming rice liver cancer H22 and the inhibiting effect was more remarkable with the increase of dosage.
Keywords/Search Tags:poly(ethylene glycol), amphiphilic polymer, block copolymer, poly(lactic acid), polycaprolactones, drug controlled release, paclitaxel
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