Bittner B, Kissel T
Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany.
J Microencapsul. 1999 May-Jun;16(3):325-41. doi: 10.1080/026520499289059.
Bovine serum albumin (BDA) loaded microspheres with a spherical shape and smooth surface structure were successfully prepared from poly(lactide-co-glycolide) using an ultrasonic nozzle installed in a Niro laboratory spray dryer. Process and formulation parameters were investigated with respect to their influence on microsphere characteristics, such as particle size, loading capacity, and release properties. Preparation of microspheres in yields of more than 50% was achieved using an ultrasonic atomizer connected to a stream of carrier air. Microsphere characteristics could be modified by changing several technological parameters. An increased polymer concentration of the feed generated larger particles with a significantly reduced initial release of the protein. Moreover, microspheres with a smooth surface structure were obtained from the organic polymer solution with the highest viscosity. Microparticles with a low BSA loading showed a large central cavity surrounded by a thin polymer layer in scanning electron microspheres. A high protein loading led to an enlargement of the shell layer, or even to dense particles without any cavities. A continuous in vitro release pattern of BSA was obtained from the particles with low protein loading. Glass transition temperatures (Tg) of the microspheres before and after lyophilization did not differ from those of the BSA loaded particles prepared by spray drying with a rotary atomizer. Analysis of the polymer by gel permeation chromatography indicated that ultrasonication had no effect on polymer molecular weight. Molecular weight and polydispersity of the pure polymer, placebo microspheres prepared by spray drying, and placebo microspheres prepared using the ultrasonic nozzle were in the same range. In conclusion, ultrasonic atomization represents a versatile and reliable technique for the production of protein loaded biodegradable microspheres without inducing a degradation of the polymer matrix. Particle characteristics can be modified by adjusting formulation parameters and atomization conditions in a simple manner.
使用安装在尼鲁实验室喷雾干燥器中的超声喷嘴，成功地从聚（丙交酯 - 乙交酯）制备出具有球形且表面结构光滑的负载牛血清白蛋白（BDA）的微球。研究了工艺和配方参数对微球特性的影响，如粒径、载药量和释放特性。使用连接到载气流的超声雾化器实现了产率超过50%的微球制备。通过改变几个工艺参数可以改变微球特性。进料中聚合物浓度的增加会产生更大的颗粒，蛋白质的初始释放量显著降低。此外，从具有最高粘度的有机聚合物溶液中获得了具有光滑表面结构的微球。扫描电子显微镜显示，低牛血清白蛋白载量的微粒有一个被薄聚合物层包围的大中心腔。高蛋白质载量导致壳层增大，甚至形成没有任何腔的致密颗粒。低蛋白质载量的颗粒呈现出牛血清白蛋白的连续体外释放模式。冻干前后微球的玻璃化转变温度（Tg）与通过旋转雾化器喷雾干燥制备的负载牛血清白蛋白颗粒的玻璃化转变温度没有差异。通过凝胶渗透色谱对聚合物的分析表明，超声处理对聚合物分子量没有影响。纯聚合物、喷雾干燥制备的空白微球和使用超声喷嘴制备的空白微球的分子量和多分散性在相同范围内。总之，超声雾化是一种通用且可靠的技术，用于生产负载蛋白质的可生物降解微球，而不会导致聚合物基质降解。通过简单地调整配方参数和雾化条件可以改变颗粒特性。
