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控释和纳米药物中的生物大分子:聚丙交酯-乙交酯微球和纳米微球

Biomacromolecules in controlled release and nanomedicine: poly (lactide-co-glycolide) micro and nanospheres
课程网址: http://videolectures.net/nib_stevanovic_nanospheres/  
主讲教师: Magdalena Stevanović
开课单位: 塞尔维亚科学和艺术学院技术科学研究所
开课时间: 2012-02-06
课程语种: 英语
中文简介:
生物大分子如聚乙醇酸、聚乳酸、它们的共聚物和其他聚酯已被用于许多临床应用。主要应用包括药物输送系统、组织工程应用、可吸收缝线和骨科固定装置。在合成聚合物家族中,聚酯因其易于通过酯键水解降解、降解产物通过代谢途径被再吸收以及调整结构以改变降解速率的潜力而对这些应用具有吸引力。 聚(丙交酯-共-乙交酯)(PLGA)或聚(D,L-丙交酯)(PDLLA)颗粒允许药物封装在聚合物基质中,药物在体内的受控和平衡释放的关键要求是其理想的球形和狭窄的尺寸分布。颗粒的大小和形状在其与细胞的粘附和相互作用中起着关键作用。聚合物降解在缓释聚酯系统药物释放中也起着关键作用,因此,为了阐明控制释放的机制,有必要分析这些装置的体外降解行为。 不同的药物(水溶性维生素、蛋白质(辣根过氧化物酶-HRP)、银纳米颗粒)已成功封装到聚酯微球和纳米球中,从而根据活性物质的浓度产生具有各种形态特征的纳米颗粒。体外降解过程和释放试验、细胞毒性、99mTc标记聚酯颗粒以及未使用和使用胶囊药物的PLGA纳米粒的生物分布进行了检查。含有包封抗坏血酸的PLGA纳米球表现出延长的血液循环,伴随着肺、肝和脾的时间依赖性减少,以及肾、胃和肠的增加。所得结果表明,PLGA纳米球和PLGA/抗坏血酸85/15%纳米颗粒均未显著影响HepG2细胞的活力。采用改进的沉淀法成功制备了负载HRP的PDLLA微球,该方法先前用于空白PDLLA和PLGA纳米微球。 已成功制备出具有球形形态、合适粒径、高蛋白质包封率和良好蛋白质稳定性的HRP微球。以糖为还原剂,以聚(α,γ,L-谷氨酸)为封盖剂,通过改进的化学还原法制备银纳米颗粒,并将其额外封装在PLGA颗粒内,以确保其释放,从而延长抗菌效果。 通过X射线衍射、扫描电子显微镜、体视学分析、透射电子显微镜、紫外光谱、即时薄层色谱、差示扫描量热法、傅里叶变换红外光谱和zeta电位测量对样品进行了表征。
课程简介: Biomacromolecules such as poly (glycolic acid), poly (lactic acid), their copolymers and other polyesters have been used in a number of clinical applications. The major applications include drug delivery systems, tissue engineering applications, resorbable sutures and orthopaedic fixation devices. Among the families of synthetic polymers, the polyesters have been attractive for these applications because of their ease of degradation by hydrolysis of ester linkage, degradation products being resorbed through the metabolic pathways and the potential to tailor the structure to alter degradation rates. Poly(lactide‐co‐glycolide) (PLGA) or poly(D,L‐lactide) (PDLLA) particles allow the encapsulation of medicaments within the polymer matrix, and the crucial requirements for the controlled and balanced release of the medicament in the body are their ideal spherical shape and narrow size distribution. The size and shape of particles play the key role in their adhesion and interaction with the cell. Polymer degradation, also, plays a key role in medicament release from sustained release polyester systems, therefore in order to elucidate the mechanism governing release, it appears essential to analyze the in vitro degradation behavior of these devices. Different medicaments (water soluble vitamins, protein (horseradish peroxidase‐HRP), silver nanoparticles) have been successfully encapsulated into polyester micro and nanospheres thus creating nanoparticles with various morphological characteristic depending of the concentration of the active substance. In vitro degradation process and release tests, cytotoxicity, labeling polyester particles by 99mTc and biodistribution of PLGA nanoparticles without and with encapsulated medicament were examined. PLGA nanospheres with encapsulated ascorbic acid exhibit prolonged blood circulation accompanied by time dependent reduction in lung, liver and spleen, and addition in kidney, stomach and intestine. The obtained results indicate that neither PLGA nanospheres nor PLGA/ascorbic acid 85/15% nanoparticles significantly affected the viability of the HepG2 cells. HRP‐loaded PDLLA spheres were successfully prepared by the modified precipitation method that was previously applied for blank PDLLA and PLGA nanospheres. The HRP‐loaded microspheres have been successfully formulated with spherical morphology, suitable particle size, high protein encapsulation efficiency and good protein stability. Silver nanoparticles were prepared by modified chemical reduction method with saccharide as reducing agent and with poly (α, γ, L‐glutamic acid) as capping agent and were additionaly encapsulated within PLGA particles to ensure their release and therefore the antimicrobial effect over an extended period of time. The samples were characterized by X‐ray diffraction, scanning electron microscopy, stereological analysis, transmission electron microscopy, ultraviolet spectroscopy, instant thin layer chromatography, differential scanning calorimetry, fourier‐transform infrared spectroscopy and zeta potential measurements.
关 键 词: 控制释放的机制; 聚合物降解; 纳米颗粒
课程来源: 视频讲座网
数据采集: 2021-12-02:zkj
最后编审: 2021-12-02:zkj
阅读次数: 59