抗结核药物异烟肼缓释复合支架及羟基磷灰石的制备与表征
发布时间：2019-05-29 14:47
【摘要】：在药物释放领域，高分子有着重要的应用。将高分子作为药物载体，一方面能够实现对药物的控制释放；另一方面，许多高分子材料具有可降解的特性，不会在人体内长期存在。在组织工程领域，高分子组织工程支架能够为细胞的粘附生长以及新陈代谢提供类似于细胞外基质的生长空间，且随着细胞的生长而降解。无机钙磷酸盐既能提供骨组织修复中所需的钙、磷等，同时能够对高分子降解所产生的酸性物质进行中和，避免局部过酸而对机体产生伤害。本论文针对药物释放以及组织工程进行了两部分的研究工作：第一部分为“抗结核药物缓释支架材料的制备与表征”，第二部分为“以聚乳酸/明胶复合纤维膜为模板制备羟基磷灰石”。 在本论文第一部分中，以聚乳酸（PLLA）作为基体材料，β-磷酸三钙（β-TCP）作为添加物，载入抗结核药物异烟肼（INH），制备成具有高达96%的孔隙率的均匀组织工程复合支架。对支架的药物释放行为进行评价，PLLA/β-TCP/INH复合支架能够持续80天以上的药物释放。同时对聚乳酸的降解行为以及药物释放过程中支架的性能变化进行表征，聚乳酸在80天的药物释放期间降解不明显，对缓冲液的酸度影响不大，支架的性能变化小。最后研究了PLLA/β-TCP/INH复合支架对成骨细胞生长的影响以及其骨组织修复能力，结果显示，细胞能够很好的在支架上贴附生长，并且动物实验显示骨组织缺损修复良好。可以确定PLLA/β-TCP/INH复合支架能够在进行药物释放治疗骨结核病的同时引导缺损的骨组织进行再生修复。 本论文第二部分对羟基磷灰石的仿生制备进行了研究。将聚乳酸和明胶通过静电纺丝法制备出均匀的复合纤维膜，采用模拟人体体液进行生物矿化后，高温煅烧处理得到羟基磷灰石。控制矿化时间、煅烧温度以及时间，，可获得形貌和结晶性与鹿茸或人小腿胫骨煅烧产物相似的六棱柱形羟基磷灰石。最佳制备条件为：聚乳酸/明胶复合纤维在5倍模拟人体体液中矿化24小时，于1000℃下煅烧1小时。
[Abstract]:In the field of drug release, polymers have important applications. On the one hand, polymer as drug carrier can realize the controlled release of drugs; on the other hand, many polymer materials have degradable properties and will not exist in human body for a long time. In the field of tissue engineering, polymer tissue engineering scaffolds can provide a growth space similar to extracellular matrix for cell adhesion, growth and metabolism, and degrade with the growth of cells. Inorganic calcium phosphate can not only provide calcium, phosphorus and so on in bone tissue repair, but also neutralize the acid produced by polymer degradation, so as to avoid local excessive acid and harm to the body. In this paper, drug release and tissue engineering are studied in two parts: the first part is "preparation and characterization of antituberculosis drug sustained release stents". In the second part, hydroxyapatite was prepared by using polylactic acid / gelatin composite fiber membrane as template. In the first part of this paper, polylactic acid (PLLA) was used as matrix material and 尾-tricalcium phosphate (尾-TCP) as additive to load isoniazid (INH), an antituberculosis drug. Uniform tissue engineering composite scaffolds with porosity of up to 96% were prepared. The drug release behavior of stents was evaluated. PLLA/ 尾-TCP/INH composite stents could release drugs for more than 80 days. At the same time, the degradation behavior of polylactic acid and the performance changes of scaffolds during drug release were characterized. The degradation of polylactic acid during 80 days of drug release was not obvious, but had little effect on the acidity of buffer, and the performance of stents changed little. Finally, the effect of PLLA/ 尾-TCP/INH composite scaffold on the growth of osteoblasts and the ability of bone tissue repair were studied. the results showed that the cells could adhere to the scaffold very well, and the animal experiments showed that the bone tissue defect was repaired well. It can be confirmed that PLLA/ 尾-TCP/INH composite stent can guide the regeneration and repair of defective bone tissue while drug release treatment of bone tuberculosis. In the second part of this paper, the biomimetic preparation of hydroxyapatite was studied. Polylactic acid and gelatin were prepared by electrospinning to prepare uniform composite fiber membrane. Hydroxyapatite was obtained by biomineralization of simulated human body fluid and calcination at high temperature. By controlling the mineralization time, calcination temperature and time, hexagonal hydroxyapatite with morphology and crystallization similar to the calcined products of velvet antler or human calf tibia can be obtained. The optimum preparation conditions were as follows: Polylactic acid / gelatin composite fiber was mineralized in 5 times simulated human body fluid for 24 hours and calcined at 1000 鈩
本文编号：2488004
[Abstract]:In the field of drug release, polymers have important applications. On the one hand, polymer as drug carrier can realize the controlled release of drugs; on the other hand, many polymer materials have degradable properties and will not exist in human body for a long time. In the field of tissue engineering, polymer tissue engineering scaffolds can provide a growth space similar to extracellular matrix for cell adhesion, growth and metabolism, and degrade with the growth of cells. Inorganic calcium phosphate can not only provide calcium, phosphorus and so on in bone tissue repair, but also neutralize the acid produced by polymer degradation, so as to avoid local excessive acid and harm to the body. In this paper, drug release and tissue engineering are studied in two parts: the first part is "preparation and characterization of antituberculosis drug sustained release stents". In the second part, hydroxyapatite was prepared by using polylactic acid / gelatin composite fiber membrane as template. In the first part of this paper, polylactic acid (PLLA) was used as matrix material and 尾-tricalcium phosphate (尾-TCP) as additive to load isoniazid (INH), an antituberculosis drug. Uniform tissue engineering composite scaffolds with porosity of up to 96% were prepared. The drug release behavior of stents was evaluated. PLLA/ 尾-TCP/INH composite stents could release drugs for more than 80 days. At the same time, the degradation behavior of polylactic acid and the performance changes of scaffolds during drug release were characterized. The degradation of polylactic acid during 80 days of drug release was not obvious, but had little effect on the acidity of buffer, and the performance of stents changed little. Finally, the effect of PLLA/ 尾-TCP/INH composite scaffold on the growth of osteoblasts and the ability of bone tissue repair were studied. the results showed that the cells could adhere to the scaffold very well, and the animal experiments showed that the bone tissue defect was repaired well. It can be confirmed that PLLA/ 尾-TCP/INH composite stent can guide the regeneration and repair of defective bone tissue while drug release treatment of bone tuberculosis. In the second part of this paper, the biomimetic preparation of hydroxyapatite was studied. Polylactic acid and gelatin were prepared by electrospinning to prepare uniform composite fiber membrane. Hydroxyapatite was obtained by biomineralization of simulated human body fluid and calcination at high temperature. By controlling the mineralization time, calcination temperature and time, hexagonal hydroxyapatite with morphology and crystallization similar to the calcined products of velvet antler or human calf tibia can be obtained. The optimum preparation conditions were as follows: Polylactic acid / gelatin composite fiber was mineralized in 5 times simulated human body fluid for 24 hours and calcined at 1000 鈩
本文编号：2488004
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