Yang Y Y, Chia H H, Chung T S
Institute of Materials Research & Engineering, 3 Research Link, Singapore 117602, Singapore.
J Control Release. 2000 Oct 3;69(1):81-96. doi: 10.1016/s0168-3659(00)00291-1.
This study describes the influence of preparation temperature on the various characteristics and release profiles of poly(DL-lactide-co-glycolide) (PLGA) microspheres. The bovine serum albumin (BSA)-loaded microspheres were prepared using the water-in-oil-in-water (w/o/w) technique with poly(vinyl alcohol) as surfactant in the external aqueous phase. We have varied the preparation temperature to observe its effect on microsphere characteristics such as the microsphere shrinking rate during formation, particle size, density, surface and internal morphology, BSA encapsulation efficiency, BSA initial release, microsphere degradation and BSA in vitro release behaviour. During fabrication, a low preparation temperature of 5 degrees C gives the fastest initial but the slowest overall shrinking rate. Microspheres formed at high temperatures of 38 degrees C and 42 degrees C on the other hand have the lowest initial yet the highest overall shrinking rate. Subsequently, microsphere mean size increases and the particle size distribution widens with increase in the preparation temperature. Although all the microspheres have a porous surface as well as internal structure, microspheres fabricated at high temperatures have a uniform internal pore distribution and a very thin dense skin layer, while microspheres fabricated at lower temperatures have a thicker but porous skin layer and bigger pores in the middle of the sphere. Microspheres formed at 33 degrees C are found to give the highest initial burst release. In terms of in vitro release, microspheres fabricated at low temperatures (5 degrees C, 15 degrees C and 22 degrees C) exhibit similar, steady rates. Microspheres formed at higher temperatures however give very low release rates after their initial release. The results obtained suggest that preparation temperature significantly affects microsphere formation, resulting in their structural and protein release profile differences. These differences ultimately work together to affect the initial release and overall release patterns of the microspheres.
本研究描述了制备温度对聚（DL-丙交酯-共-乙交酯）（PLGA）微球的各种特性和释放曲线的影响。采用水包油包水（w/o/w）技术，以聚乙烯醇为外水相表面活性剂，制备了载牛血清白蛋白（BSA）的微球。我们改变制备温度，以观察其对微球特性的影响，如形成过程中的微球收缩率、粒径、密度、表面和内部形态、BSA包封效率、BSA初始释放、微球降解以及BSA的体外释放行为。在制备过程中，5℃的低制备温度导致初始收缩速度最快，但总体收缩速度最慢。另一方面，在38℃和42℃的高温下形成的微球初始收缩速度最低，但总体收缩速度最高。随后，随着制备温度的升高，微球平均尺寸增大，粒径分布变宽。尽管所有微球都具有多孔表面和内部结构，但高温制备的微球内部孔隙分布均匀，致密皮层非常薄，而低温制备的微球皮层较厚但多孔，球中部孔隙较大。发现33℃形成的微球初始突释最高。在体外释放方面，低温（5℃、15℃和22℃）制备的微球表现出相似的稳定释放速率。然而，高温形成的微球在初始释放后释放速率非常低。所得结果表明，制备温度显著影响微球的形成，导致其结构和蛋白质释放曲线存在差异。这些差异最终共同作用，影响微球的初始释放和总体释放模式。
