以C60-Phe-PLA为载体材料缓释微球的制备以及体内药效学的初步研究

发布时间：2018-06-06 02:18

  本文选题：C60 + 微球　； 参考：《郑州大学》2014年硕士论文

【摘要】：富勒烯（C60）因其独特的理化性质一直是近十几年的研究热点。C60-苯丙氨酸(C60-Phe)作为C60的衍生物具有较好的水溶性和生物相容性，且其经过光照射之后可以产生活性氧，据此可以对肿瘤进行光疗。米托蒽醌(Mitoxantrone，MTX)是一种蒽醌类抗肿瘤药物，因其不含有氨基糖结构，故不能产生自由基，并且具有抑制脂质过氧化的作用，所以对心脏毒性较低。 本课题拟选用分散-溶媒扩散法制备米托蒽醌多功能载药微球。以米托蒽醌(Mitoxantrone，MTX)作为抗肿瘤模型药物，以C60-Phe-PLA为载体材料制成微球。可以将米托蒽醌(Mitoxantrone，MTX)化疗与C60-Phe-PLA的光疗进行有效的结合。并通过体内药效学实验评价微球的抗肿瘤作用及其缓释作用。 本文研究的主要内容分为三个方面：（一）、以C60-Phe-PLA为载体材料选择模型药物；（二）、以米托蒽醌为模型药物，，C60-Phe-PLA多功能载药微球的制备和表征；（三）、以米托蒽醌为模型药物，C60-Phe-PLA多功能载药微球的药效学评价； 一、以C60-Phe-PLA为载体材料模型药物的选择 本课题采用分散-溶媒扩散法，以C60-Phe-PLA为载体材料，分别制备米托蒽醌、5-氟尿嘧啶以及多西他赛微球，通过微球的载药量进行考察。并且通过正交试验，优化处方。优化处方后，米托蒽醌的载药量为(8.090.15)%，5-氟尿嘧啶的载药量为(0.300.05)%，多西他赛的载药量为(4.720.23)%。因此本实验最终选择水溶性米托蒽醌作为模型药物。 二、以米托蒽醌为模型药物，C60-Phe-PLA多功能载药微球的制备和表征 本课题采用分散-溶媒扩散法制备以米托蒽醌为模型药物，C60-Phe-PLA多功能载药微球。并对载药微球的粒径、微球的载药量以及微球的体外药物释放情况进行考察。结果表明，所制备的载药微球粒径分布在8-20μm左右，药物的载药量为(8.090.15)%，体外药物释放实验表明，该多功能载药微球具有缓释特性。 三、以米托蒽醌为模型药物，C60-Phe-PLA多功能载药微球的药效学评价 米托蒽醌（MTX）的多功能微球在B16-F10黑色素瘤C57BL小鼠模型体内的组织分布实验显示，米托蒽醌的多功能微球主要分布在肿瘤部位，而在心脏、肝、脾、肺、肾各组织基本检测不到米托蒽醌。 B16-F10黑色素瘤C57BL小鼠模型体内药效学实验显示，米托蒽醌的多功能微球光照组的肿瘤体积明显减小，给药后第11天，米托蒽醌多功能微球光照、空白微球光照与非光照和MTX原料药光照与非光照组的T/C值分别为：-7.38%、39.92%、140.07%、29.09%和29.11%。药效学研究结果提示，载米托蒽醌的多功能微球经过532nm激光照射后对B16-F10黑色素瘤的抑制效果更好。 在B16-F10黑色素瘤C57BL小鼠模型体内给药系统的HE染色显示载米托蒽醌的多功能微球对各脏器无明显的损伤。
[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.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943;R96

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