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Preliminary Study on Hepatocellular Carcinoma Targeting Pectin-based Nanoparticle Delivery System

Author: WangYanMei
Tutor: YanFengXiang; YuCuiYun
School: Nanhua University
Course: Pharmacology
Keywords: pectin nanoparticles ASGPR HCC targeted drug delivery pharmacokinetic 5-FU
CLC: R735.7
Type: Master's thesis
Year: 2013
Downloads: 11
Quote: 0
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Abstract


Objective: In this study, we report a fabrication of natural pectin-based drug deliverysystem, and further report the evaluation of in vitro cytotoxicity, cellular uptake and invivo pharmacokinetic of the5-FU-loaded nanoparticles.Method: In vitro: Inhibited effects of5-fluorouracil (5-FU) and5-FU-loadednanoparticles (5-FU-NPs) on proliferations of HepG2, A549tumor cells was observedby MTT assay and IC50value was calculated; absorption of5-FU and5-FU-NPs byHepG2, A549tumor cells in the120th minute was detected with High PerformanceLiquid Chromatography(HPLC); targeting effect of5-FU and5-FU-NPs on HepG2tumor cells was detected by evaluate the absorption of5-FU and5-FU-NPs by HepG2and A549tumor cells in the120th minute while the HepG2and A549tumor cells wasfist incubated with galactose.in vivo: Pharmacokinetics study using Sprague Dawley (SD) rats. Mice were treatedby tail vein i.v. injection with5-FU or5-FU-NPs at a matched dose of35mg/kg, theblood concentration was detected by HPLC, and the pharmacokinetic parameters wereobtained by running software3p97.Result:5-FU-NPs can significantly inhibit the proliferation of HepG2and A549cellsin a dose-dependent way, and it is more effective than free5-FU (P＜0.05).5-FU-NPscan also inhibit the proliferation of A549cells in a dose-dependent way, but there isno significant difference compared with5-FU (P＞0.05). Results of HPLC show thatthe absorption of5-FU-NPs in HepG2tumor cells is2.36times of free5-FU but inA549tumor cells there is no significant difference (P＞0.05). When incubated withglactose the absorption of5-FU-NPs in HepG2tumor cells is half of without glactosebut approximately the same with free5-FU (P＞0.05); the absorption of5-FU-NPs inA549tumor cells is closely to that of without glactose (P＞0.05). The pharmacokinetic result indicate that the5-FU-NPs effective duration is much longerthan that of free5-FU, and the peak concentration of5-FU-NPs is much lower thanfree5-FU.Conclusion:1. The pectin-based nanoparticles has the excellent biocompatibility, nontoxicity,characteristics;2. The pectin-based nanoparticles have the targeting effect for hepatocellularcarcinoma cells;3. The pectin-based nanoparticles can prolong the biological half-life of5-FU.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Liver tumors
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