以乙醇作为聚合物抗溶剂的改良剪切沉淀法制备万古霉素PLGA微球及其性能研究

发布时间：2018-04-28 21:16

本文选题：抗溶剂 + 剪切沉淀法　；参考：《南方医科大学》2017年硕士论文

【摘要】：背景:骨感染是骨科治疗中的难题,而抗感染治疗是当中重要的一环,鉴于长期全身抗生素治疗毒副作用大,近年来局部抗生素治疗受到越来越多的关注,目前局部抗生素治疗迫切需要可以高效包载普遍呈亲水性的抗菌药物的新方法。目的:探讨以乙醇作为聚合物抗溶剂的改良剪切沉淀法制备亲水性药物微球的可行性,研究聚合物浓度,乙醇/甘油容量比,内水相容量,初始载药量和乳化液注射速度等制备参数对万古霉素PLGA微球特性的影响,研究微球的体外释放行为及其生物学性能。方法:以剪切沉淀法为基础通过改良制备条件以制备万古霉素PLGA微球,利用体外洗脱法测定微球的体外释放特性,采用扫描电镜和溶剂萃取技术测定微球的形态特征和万古霉素PLGA微球中药物的含量,通过抗菌实验和降解实验来研究所制备微球的生物学性能。结果:所制备的微球呈圆球形,微球的表面和内部均存在孔洞结构,微球的平均粒径在11.15和27.51 μm之间,微球的包封率最高达89.97%,在制备过程中随着聚合物浓度的增加微球的粒径和包封率增加而载药量减少;随着初始载药量的增加微球的包封率和载药量增加;随着剪切液中乙醇/甘油容积比的降低微球的包封率和载药量降低;随着内水相的增加微球的包封率和载药量降低,微球的粒径增加;随着注射速率的增加微球的粒径、包封率和载药量增加;微球释放实验进行到第30天的时候仅45.9%的药物被释放;抗菌实验结果显示万古霉素PLGA微球抗菌性能一直持续到抗菌实验的第7天;微球体内降解实验结果显示万古霉素PLGA微球在植入SD大鼠的肌肉3个月后完全降解。结论:改良剪切沉淀法成功制备万古霉素PLGA微球,这一方法可以有效地将水溶性药物包载进聚合物微球,通过调整制备参数可以相应地调节微球的粒径、包封率和载药量等特性,这一制备方法将万古霉素包载进微球并不会对万古霉素的抗菌活性产生影响,微球具有良好的释放行为、抗菌性能及体内降解特性。改良剪切沉淀法成功制备万古霉素PLGA微球,这一抗生素缓释系统有望成为骨感染治疗中局部抗生素治疗的理想剂型。
[Abstract]:Background: bone infection is a difficult problem in orthopedic treatment, and anti-infection therapy is an important part of the treatment. In view of the toxicity and side effects of long-term systemic antibiotic therapy, more and more attention has been paid to local antibiotic therapy in recent years. At present, local antibiotic therapy is in urgent need of a new method which can be efficiently encapsulated with commonly hydrophilic antimicrobial agents. Objective: to study the feasibility of preparing hydrophilic drug microspheres by modified shear precipitation method using ethanol as an antisolvent, and to study the concentration of polymer, the ratio of ethanol to glycerol, and the internal water phase capacity. The effects of initial drug loading and emulsion injection rate on the properties of vancomycin PLGA microspheres were investigated. The in vitro release behavior and biological properties of vancomycin PLGA microspheres were studied. Methods: vancomycin PLGA microspheres were prepared on the basis of shear precipitation method. The release characteristics of vancomycin PLGA microspheres were determined by in vitro elution. The morphology of vancomycin PLGA microspheres and the content of vancomycin PLGA microspheres were determined by SEM and solvent extraction. The biological properties of the prepared microspheres were studied by antibacterial and degradation experiments. Results: the prepared microspheres were spherical, and the pore structures were found in the surface and interior of the microspheres. The average diameter of the microspheres was between 11.15 渭 m and 27.51 渭 m, and the average size of the microspheres was between 11.15 渭 m and 27.51 渭 m. The encapsulation efficiency of the microspheres was up to 89.97. The encapsulation efficiency of the microspheres decreased with the increase of the concentration of polymer and the encapsulation efficiency of the microspheres, and the encapsulation efficiency and the drug load increased with the increase of the initial drug loading. With the decrease of ethanol / glycerol volume ratio in shearing solution, the encapsulation efficiency and drug load of microspheres decreased, the encapsulation efficiency and drug loading decreased with the increase of water phase, the particle size of microspheres increased with the increase of injection rate. The encapsulation efficiency and drug loading increased, only 45.9% of the microspheres were released at the 30th day, and the antibacterial properties of vancomycin PLGA microspheres continued until the 7th day. The results of in vivo degradation of vancomycin PLGA microspheres showed that the microspheres were completely degraded 3 months after implantation into SD rats. Conclusion: vancomycin PLGA microspheres were successfully prepared by modified shear precipitation method. This method can effectively encapsulate water-soluble drugs into polymer microspheres. The particle size of vancomycin PLGA microspheres can be adjusted by adjusting the preparation parameters. The encapsulation efficiency and drug loading capacity of vancomycin were not affected by the encapsulation of vancomycin into microspheres, and the microspheres had good release behavior, antibacterial properties and degradation characteristics in vivo. Vancomycin PLGA microspheres were successfully prepared by modified shear precipitation method. This antibiotic sustained-release system is expected to be an ideal dosage form for local antibiotic therapy in the treatment of bone infection.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943

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