Dissertation > Excellent graduate degree dissertation topics show

The Study of Self-assembled Tumor-targeted Novel Drug Carrier Derived from Pullulan Conjugate

Author: TangHongBo
Tutor: ZhangQiQing；LiuLingRong；ZhuTaiWen
School: Peking Union Medical College , China
Course: Biomedical Engineering
Keywords: Acetyl pullulan Folic acid Dialysis Tumor targeting Nano - drug carriers
CLC: R94
Type: PhD thesis
Year: 2010
Downloads: 396
Quote: 1
Read: Download Dissertation

Abstract

With the rapid development of nanotechnology, tumor targeting nano drug carriers to become one of the hot, high expression of the surface of certain cancer cells to folate receptor targeted therapy provides a theoretical basis. In this study, acetyl Pullulanase folic acid even assembly (FPA) for material preparation and to study tumor targeting white assembling nano-drug carriers, the preparation of a new type of epirubicin nano pharmaceutical preparations, evaluation Prussian Fundamentalists self-assembly body as the feasibility of nano-drug carriers. In this study, pullulan main chain, the hydrophobic acetyl pullulan synthesized by acetylation reaction (PA), then N, N'-dicyclohexyl carbodiimide (DCC) as a coupling agent, - dimethylaminopyridine (DMAP) as a catalyst, folic acid and PA coupling synthetic FPA; hydrogen nuclear magnetic resonance (1H-NMR) method were used to characterize the structure of the PA and FPA, FPA nanoparticles prepared by the dialysis method (FPANs FPA) and packet contained epirubicin nanoparticles (FPA / EPI) and the application transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to observe the morphology of the nanoparticles, dynamic light scattering (DLS) was measured grain diameter and particle size distribution; investigated FPANs and FPA / EPI particle size in aqueous solution and the potential in different media; investigated FPANs and FPA / EPI stability in aqueous solution; flow cytometry to detect cervical cancer Hela cells on FPA / EPI pickup, and to study the uptake mechanism; ships blank FPANs and acetyl 普鲁兰纳米 particles (PANs) 200mg/kg tail vein injected into ICR mice, and the animals were observed for signs, body weight and appetite changes, investigated its security in vivo; FPA / EPI (EPI equivalent dose of 10mg/kg) intravenously to Wistar rats, determination of the trend of changes in the plasma concentrations after administration, and to calculate its pharmacokinetics pharmacokinetic parameters, and compared with the free drug EPI effects of the sustained-release effect in vivo; cervical cancer Hela xenograft animal models, the FPA / EPI intravenous tumor model animals to study the in vivo distribution characteristics as well as anti-tumor effect and apoptosis of tumor cells detected by TUNEL assay. The results showed that successfully synthesized FPA folic acid degree of substitution of 0.235; the applications dialysis prepared FPANs and FPA / EPI, nano-particles were uniform spherical, electrically neutral FPANs particle size (204.2 ± 10.9) nm, the dispersion (PDI) to 0.172 ± 0.036 after the drug particle size and dispersion were (273.4 ± 11.0) nm and 0.165 ± 0.026 in the aqueous solution FPANs and FPA / epi particle size and particle size distribution within three months change significantly; FPA / EPI folic acid receptor-mediated enter the cell, with a significant dose response relationship; FPANs and PANs intravenous injection into mice animals signs, body weight, food intake, and major organs showed no obvious toxic side effects; FPA / EPI half-life (t1 / 2), mean residence time (MRT0-24h) and the plasma concentration - area under the curve (AUC 0-24h) respectively 1.57,1.33 and 3.95 times the free drug; vein 2h after injection of drug accumulation in tumor animal liver, spleen and lung, compared with the free drug in the tumor tissue and liver FPA / EPI longer Date maintain a high drug content and a significant reduction in the content of the stomach and intestines; FPA / EPI tail vein injection Hela xenograft into nude mice, administration, at a dose of 5.0mg/kg and 7.5mg/kg, relative tumor proliferation rate of 81.38% and 37.72%, respectively, tumor weight inhibition rates were 32.37% and 61.19%, with a significant dose-response relationship, EPI and FPA / EPI can induce apoptosis in Hela cells. The results of this study show that tumor targeting Prussian Rankine self-assembled nano-drug carriers stability in vitro and in vivo better security, a sustained release of the drug, to change its distribution characteristics in vivo, reducing the drugs on the part of the organ toxicity, tumor targeting and better anti-tumor effect and dose-effect relationship. Prussian Fundamentalists self-assembly can be used as a promising tumor targeting nano-drug carriers.

The Study of Self-assembled Tumor-targeted Novel Drug Carrier Derived from Pullulan Conjugate

Abstract

Related Dissertations