本文選題：PLGA納米粒　切入點：脂質(zhì)微泡　出處：《重慶醫(yī)科大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：第一部分包裹紫杉醇的高分子納米粒與脂質(zhì)微泡復(fù)合體的制備研究 目的利用生物素-親和素技術(shù)制備一種包裹紫杉醇的新型載藥微泡，并對其連接效果、理化性質(zhì)進行檢測。 方法采用單乳化法制備包裹紫杉醇的PLGA-COOH納米粒（Pac-PLGA），檢測其包封率與載藥量，采用碳二亞胺共價連接法將其與鏈霉親和素相連，免疫熒光檢測鏈霉親和素與Pac-PLGA的連接情況。采用機械振蕩法制備生物素化的脂質(zhì)微泡（BIO-MB）及普通脂質(zhì)微泡（MB）。連接分為2組：生物素-親和素組（SA-Pac-PLGA+BIO-MB），對照組（Pac-PLGA+MB）。用激光共聚焦顯微鏡分別觀察2組在不同時間點脂質(zhì)微泡與Pac-PLGA的連接情況。 結(jié)果Pac-PLGA的平均粒徑為(131.1±29.7)nm，掃描電鏡觀察呈球形，大小均勻，分散度好。高效液相色譜法測得PLGA納米粒對紫杉醇的包封率為(85±2.1)%，載藥量為（4.25±0.16）%，熒光檢測鏈霉親和素成功地與Pac-PLGA連接。激光共聚焦觀察生物素-親和素組Pac-PLGA較多地連接在BIO-MB的表面。而對照組MB表面未見Pac-PLGA的聚集。 結(jié)論本實驗成功地制備出包裹紫杉醇的新型載藥微泡，有望為惡性腫瘤的治療提供一種理想的藥物載體和靶向給藥系統(tǒng)。 第二部分包裹紫杉醇的高分子納米粒與脂質(zhì)微泡復(fù)合體在小鼠肝臟的定位釋放研究 目的探討新型載藥微泡在一定聲強的超聲定位輻照下，紫杉醇及PLGA納米粒在小鼠肝臟的定位釋放情況。 方法利用生物素-親和素技術(shù)制備包裹紫杉醇的新型載藥微泡。將實驗小鼠分為3組：載紫杉醇PLGA納米粒組（Pac-PLGA納米粒組）、載紫杉醇PLGA納米粒與超聲脂質(zhì)微泡混合組（混合組）、包裹紫杉醇的新型載藥微泡組，經(jīng)尾靜脈注入小鼠體內(nèi)后，3組小鼠均用相同聲強的超聲經(jīng)體表定點輻照小鼠肝臟1min，于處理1h后斷頸處死取肝組織，用高效液相色譜法測定小鼠肝臟組織中紫杉醇的濃度，用激光共聚焦顯微鏡觀察小鼠肝組織切片每高倍視野下（x400）熒光標(biāo)記的Pac-PLGA納米粒的數(shù)量。 結(jié)果高效液相色譜法測得新型載藥微泡組小鼠肝組織中的紫杉醇含量為（5.335土1.087）ug/g,高于混合組（4.067土0.954）ug/g和Pac-PLGA納米粒組（2.908土0.925）ug/g,p均0.01，且混合組高于Pac-PLGA納米粒組（p0.01）。激光共聚焦觀察每高倍視野下（x400）熒光標(biāo)記的Pac-PLGA納米粒的數(shù)量，Pac-PLGA納米粒組數(shù)量為(17.590土5.811)個，混合組數(shù)量為(31.227土7.177）個，新型載藥微泡組數(shù)量為(47.500土7.301)個，，新型載藥微泡組Pac-PLGA納米粒數(shù)量高于其余各組（p0.01），且混合組高于Pac-PLGA納米粒組（p0.01）。 結(jié)論新型載藥微泡組小鼠肝組織中的紫杉醇含量及PLGA納米粒的數(shù)量明顯高于其余各組。新型載藥微泡能夠提高靶組織區(qū)內(nèi)的藥物濃度及PLGA納米粒的數(shù)量，從而提高疾病的治療效果。
[Abstract]:Preparation of macromolecular nanoparticles and lipid microvesicles coated with paclitaxel. Aim to prepare a novel paclitaxel encapsulated microbubble by biotin-avidin technique, and to determine its binding effect and physicochemical properties. Methods Pac-PLGA, a paclitaxel coated PLGA-COOH nanoparticles, was prepared by single emulsification method. The encapsulation efficiency and drug loading of paclitaxel were determined. The carbodiimide covalent bonding method was used to bind paclitaxel to streptavidin. The connection between streptavidin and Pac-PLGA was detected by immunofluorescence. Biotin lipid microbubbles BIO-MBs and ordinary lipid microbubbles were prepared by mechanical oscillation method. The connections were divided into two groups: biotin group, SA-Pac-PLGA BIO-MBN group, control group, pac-PLGA MBM. The connection between lipid microbubbles and Pac-PLGA at different time points was observed by light confocal microscope. Results the average diameter of Pac-PLGA was 131.1 鹵29.7nm.The Pac-PLGA was spherical and uniform in size. High performance liquid chromatography (HPLC) showed that the encapsulation efficiency of PLGA nanoparticles to paclitaxel was 85 鹵2.1 and the drug load was 4.25 鹵0.16.The fluorescent detection of Streptomycin was successfully connected to Pac-PLGA. Laser confocal observation showed that Pac-PLGA in biotin / avidin group was more concatenated. The Pac-PLGA aggregation was not observed on the surface of BIO-MB in the control group. Conclusion the microbubbles coated with paclitaxel were successfully prepared in this experiment, which is expected to provide an ideal drug carrier and targeted drug delivery system for the treatment of malignant tumors. The second part: localization and release of paclitaxel encapsulated polymer nanoparticles and lipid microvesicles in mouse liver. Objective to investigate the localization release of paclitaxel and PLGA nanoparticles in the liver of mice. Methods A novel paclitaxel coated microbubble was prepared by biotin avidin technique. The experimental mice were divided into three groups: pac-PLGA nanoparticles group, pac-PLGA nanoparticles group, paclitaxel-loaded PLGA nanoparticles mixed with ultrasonic lipid microbubbles, the experimental mice were divided into three groups: paclitaxel loaded PLGA nanoparticles group, pac-PLGA nanoparticles group, paclitaxel loaded PLGA nanoparticles and ultrasonic lipid microbubbles. Group A (mixed group, paclitaxel coated microbubble group), After injected into the tail vein of mice, the liver of all the three groups were irradiated with the same sound intensity ultrasound at the fixed point of the body surface for 1 min. After 1 hour of treatment, the liver tissues were killed and the concentration of paclitaxel in the liver tissue of the mice was determined by high performance liquid chromatography (HPLC). The number of Pac-PLGA nanoparticles labeled with X 400) in mouse liver tissue sections was observed by laser confocal microscopy. Results the content of paclitaxel in the liver tissue of mice in the new drug loaded microbubble group was determined by HPLC, which was higher than that in the mixed group (4.067 鹵0.954g / g) and the Pac-PLGA nanoparticles group (0.925g / g / g), and the content of paclitaxel in the liver tissue of the mixed group was higher than that of the Pac-PLGA nano-particle group (p 0.01g), and the content of paclitaxel was higher in the mixed group than that in the Pac-PLGA nanoparticles group (p 0.01). The number of Pac-PLGA nanoparticles labeled with fluorescence in each high-power field of vision was 17.590 鹵5.811, and the number of Pac-PLGA nanoparticles was 5.811. The number of mixed group was 31.227 鹵7.177, the number of new drug loaded microbubble group was 47.500 鹵7.301), the number of Pac-PLGA nanoparticles in new drug loaded microbubble group was higher than that of other groups, and the mixing group was higher than Pac-PLGA group. Conclusion the contents of paclitaxel and the number of PLGA nanoparticles in liver tissue of the new drug loaded microbubble group were significantly higher than those in the other groups, and the new drug loaded microbubbles could increase the concentration of drug and the number of PLGA nanoparticles in the target tissue. So as to improve the therapeutic effect of the disease.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R318.08

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