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Improved Approach Of Curcumin In The Anti-cancer Treatment

Posted on:2013-09-05Degree:MasterType:Thesis
Country:ChinaCandidate:N ZhangFull Text:PDF
GTID:2234330371476131Subject:Drug analysis
Abstract/Summary:PDF Full Text Request
Curcumin (curcumin) is a kind of yellow polyphenol extracted from turmeric, Curcuma or rhizoma, which boost anti-tumor activities in vitro and in vivo through m μ Ltiple mechanisms. It can inhibit the proliferation of tumor cells and induce in vitro apoptosis of various cancers, including bladder,breast, lung, pancreas, prostate, cervix, head and neck, ovarian, kidney, brain, bone marrow and skin cancers.As for its great efficacy in the cell experiments of both chemotherapy and γ-ray treatment, Curcumin has also been used in the prevention and treatment of many types of cancer in vivo.However, due to its poor water solubility, the bioavailability is also relatively low, which limits its use as an anti-cancer drug. With the design of two different drug delivery systems, Cur-2-ME synergistic administration and CNT-Cur system,this study aims to improve the bioavailability of Curcumin in order to achieve the purpose of enhanced efficacy and targeting therapy.As for Cur-2-ME synergistic administration, lung cancer SPC-A1cells were applied, and studies of SRB,flow cytometry, PTEN and Western-blotting were conducted for the synergistic efficacy, and the res μ Lts indicated that the two drug combing wo μ Ld not generate a new chemical substance, may block the cells in the G2/M phase, and inhibit the tumor cell proliferation through Akt signaling pathway (non-PTEN pathway),all of which laid the foundation in finding the cheap, safe and efficient anti-cancer drug combinations.As for the CNT-Cur drug delivery system,SWNT was first functionalized and combined with the polypeptide NGR covalently, making it more conducive for drug loading and tumor targeting. Then, through the solid nanoparticle preparation methods, CNT-Cur drug delivery system was obtained, and its in vitro and in vivo tumor-inhibitory activities were studied in order to provide more data for synergistic enhancement of Curcumin and CNT.The surface functionalization of CNT was analysed using infrared spectrum,and the res μ Lts of TEM and TGA suggested that the NGR polypeptide may exist in the layer of materials attached to the SWNT surface. Through the use of surfactants PVP and soybean lecithin, a significant increase in solubility of the functionalized SWNT in water was observed, thereby the loading of Curcumin in the system was enhanced accordingly. Particle size and zeta potential of the CNT-Cur nanoparticles were stable at around120nm and-12mV, respectively, indicating that it was abvailable for intravenous injection and in vivo drug absorption, while X-ray diffraction res μ Lts showed that there was free Curcumin existing in the system.UV spectrophotometer res μ Lts showed that the CNT and the concentration of Curcumin in the system were688.3μ g/mL and1.88mg/ml, respectively, and in vitro release experiments showed a combination of both burst-release and sustained-release,which meaned that the system co μ Ld reach a relatively high concentration fast and remain above the therapeutic concentration for a certain period of time.Prostate cancer PC-3cells and S180tumor loaded SD mice were applied for the in vivo and in vitro pharmacodynamics study, respectively, the CNT toxicity, inhibitory effects of CNT,Curcumin, the CNT-Cur system, and all groups combined with808nm laser were investigated, and pathological changes of tumor and other tissues were observed. The res μ Lts showed that CNT boosted a certain degree of renal toxicity in vivo, but Curcumin inhibited it, and the preparation of CNT-Cur combined with808nm laser significantly inhibited tumors, with significant differences between corresponding groups, suggesting that the purpose of a combination of chemotherapy and heat therapy was achieved.
Keywords/Search Tags:Curcumin, 2-methoxyestradiol, CNT, Synergistic enhancement, Drug delivery system, heat therapy
PDF Full Text Request
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