本文選題：C60 + 微球�。� 參考：《鄭州大學(xué)》2014年碩士論文

【摘要】：富勒烯（C60）因其獨特的理化性質(zhì)一直是近十幾年的研究熱點。C60-苯丙氨酸(C60-Phe)作為C60的衍生物具有較好的水溶性和生物相容性，且其經(jīng)過光照射之后可以產(chǎn)生活性氧，據(jù)此可以對腫瘤進行光療。米托蒽醌(Mitoxantrone，MTX)是一種蒽醌類抗腫瘤藥物，因其不含有氨基糖結(jié)構(gòu)，故不能產(chǎn)生自由基，并且具有抑制脂質(zhì)過氧化的作用，所以對心臟毒性較低。 本課題擬選用分散-溶媒擴散法制備米托蒽醌多功能載藥微球。以米托蒽醌(Mitoxantrone，MTX)作為抗腫瘤模型藥物，以C60-Phe-PLA為載體材料制成微球�？梢詫⒚淄休祯�(Mitoxantrone，MTX)化療與C60-Phe-PLA的光療進行有效的結(jié)合。并通過體內(nèi)藥效學(xué)實驗評價微球的抗腫瘤作用及其緩釋作用。 本文研究的主要內(nèi)容分為三個方面：（一）、以C60-Phe-PLA為載體材料選擇模型藥物；（二）、以米托蒽醌為模型藥物，，C60-Phe-PLA多功能載藥微球的制備和表征；（三）、以米托蒽醌為模型藥物，C60-Phe-PLA多功能載藥微球的藥效學(xué)評價； 一、以C60-Phe-PLA為載體材料模型藥物的選擇 本課題采用分散-溶媒擴散法，以C60-Phe-PLA為載體材料，分別制備米托蒽醌、5-氟尿嘧啶以及多西他賽微球，通過微球的載藥量進行考察。并且通過正交試驗，優(yōu)化處方。優(yōu)化處方后，米托蒽醌的載藥量為(8.090.15)%，5-氟尿嘧啶的載藥量為(0.300.05)%，多西他賽的載藥量為(4.720.23)%。因此本實驗最終選擇水溶性米托蒽醌作為模型藥物。 二、以米托蒽醌為模型藥物，C60-Phe-PLA多功能載藥微球的制備和表征 本課題采用分散-溶媒擴散法制備以米托蒽醌為模型藥物，C60-Phe-PLA多功能載藥微球。并對載藥微球的粒徑、微球的載藥量以及微球的體外藥物釋放情況進行考察。結(jié)果表明，所制備的載藥微球粒徑分布在8-20μm左右，藥物的載藥量為(8.090.15)%，體外藥物釋放實驗表明，該多功能載藥微球具有緩釋特性。 三、以米托蒽醌為模型藥物，C60-Phe-PLA多功能載藥微球的藥效學(xué)評價 米托蒽醌（MTX）的多功能微球在B16-F10黑色素瘤C57BL小鼠模型體內(nèi)的組織分布實驗顯示，米托蒽醌的多功能微球主要分布在腫瘤部位，而在心臟、肝、脾、肺、腎各組織基本檢測不到米托蒽醌。 B16-F10黑色素瘤C57BL小鼠模型體內(nèi)藥效學(xué)實驗顯示，米托蒽醌的多功能微球光照組的腫瘤體積明顯減小，給藥后第11天，米托蒽醌多功能微球光照、空白微球光照與非光照和MTX原料藥光照與非光照組的T/C值分別為：-7.38%、39.92%、140.07%、29.09%和29.11%。藥效學(xué)研究結(jié)果提示，載米托蒽醌的多功能微球經(jīng)過532nm激光照射后對B16-F10黑色素瘤的抑制效果更好。 在B16-F10黑色素瘤C57BL小鼠模型體內(nèi)給藥系統(tǒng)的HE染色顯示載米托蒽醌的多功能微球?qū)Ω髋K器無明顯的損傷。
[Abstract]:Fullerenes (C60), because of their unique physical and chemical properties, have been a hot spot for recent years..C60- phenylalanine (C60-Phe) has better solubility in water and biocompatibility as a derivative of C60, and it can produce living oxygen after light irradiation, and it can be phototherapy for tumor. Mitoxantrone (MTX) is a kind of anthraquinone. Antineoplastic drugs, because they do not contain amino sugar structure, can not produce free radicals, and inhibit the role of lipid peroxidation, so the heart toxicity is low.
Mitoxantrone (Mitoxantrone, MTX) is used as an antitumor model drug and C60-Phe-PLA as the carrier material to prepare microspheres. It can be used to combine the chemotherapy of Mitoxantrone and MTX with the phototherapy of C60-Phe-PLA and through the pharmacodynamics in vivo. The anti-tumor effect and sustained release effect of microspheres were evaluated.
The main contents of this study were divided into three aspects: (1) selecting model drugs with C60-Phe-PLA as the carrier material; (two) the preparation and characterization of C60-Phe-PLA multifunction drug loaded microspheres with mitoxantrone as the model drug; (three) the pharmacodynamic evaluation of C60-Phe-PLA multifunction drug loaded microspheres with mitoxantrone as the model drug;
First, the choice of model drugs with C60-Phe-PLA as the carrier material.
In this study, the dispersive solvent diffusion method was used to prepare mitoxantrone, 5- fluorouracil and docetaxel microspheres with C60-Phe-PLA as the carrier material, and the drug loading of the microspheres was investigated. The prescription was optimized by orthogonal test. The dosage of mitoxantrone was (8.090.15)% and the dose of 5- fluorouracil was (0.300.0 5)%, docetaxel drug loading was (4.720.23)%. Therefore, the final choice of water soluble mitoxantrone as a model drug.
Two, the preparation and characterization of C60-Phe-PLA multifunctional drug loaded microspheres with mitoxantrone as a model drug.
In this study, we used the dispersible solvent diffusion method to prepare the drug loaded microspheres with mitoxantrone (C60-Phe-PLA) as a model drug, and the particle size of the microspheres, the amount of drug loading of the microspheres and the release of the microspheres in vitro. The results showed that the particle size distribution of the microspheres was about 8-20 m, and the drug loading amount was (8.090. 15)%. In vitro drug release experiments showed that the multifunctional drug loaded microspheres exhibited sustained release characteristics.
Three, using mitoxantrone as a model drug, pharmacodynamic evaluation of C60-Phe-PLA multifunctional drug loaded microspheres.
The tissue distribution of multifunction microspheres of mitoxantrone (MTX) in the B16-F10 melanoma C57BL mouse model showed that mitoxantrone's multifunction microspheres were mainly distributed in the tumor site, but the mitoxantrone was not detected in the heart, liver, spleen, lung, and kidney.
The pharmacodynamic test of B16-F10 melanoma C57BL mouse model showed that the tumor volume of the multifunction microspheres of mitoxantrone decreased significantly, and eleventh days after the administration, the multifunction microspheres of mitoxantrone were illuminated, and the T/C values of light and non light and MTX materials were -7.38%, 39.92%, 140.07%, 29.09%, respectively. And 29.11%. pharmacodynamic studies showed that the multifunction microspheres loaded with mitoxantrone had better inhibitory effect on B16-F10 melanoma after 532nm laser irradiation.
HE staining of the drug delivery system in the B16-F10 melanoma C57BL mouse model showed that the mitoxantrone multifunctional microspheres had no obvious damage to the organs.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R943;R96

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本文編號：1984579