Shmool Talia A, Hooper Philippa J, Kaminski Schierle Gabriele S, van der Walle Christopher F, Zeitler J Axel
Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, UK.
Biopharmaceutical Development, AstraZeneca, Granta Park, Cambridge CB21 6GH, UK.
Pharmaceutics. 2019 Jun 20;11(6):291. doi: 10.3390/pharmaceutics11060291.
Biodegradable poly lactic-co-glycolic acid (PLGA) microspheres can be used to encapsulate peptide and offer a promising drug-delivery vehicle. In this work we investigate the dynamics of PLGA microspheres prepared by freeze-drying and the molecular mobility at lower temperatures leading to the glass transition temperature, using temperature-variable terahertz time-domain spectroscopy (THz-TDS) experiments. The microspheres were prepared using a water-in-oil-in-water (w/o/w) double-emulsion technique and subsequent freeze-drying of the samples. Physical characterization was performed by morphology measurements, scanning electron microscopy, and helium pycnometry. The THz-TDS data show two distinct transition processes, T g , β in the range of 167-219 K, associated with local motions, and T g , α in the range of 313-330 K, associated with large-scale motions, for the microspheres examined. Using Fourier transform infrared spectroscopy measurements in the mid-infrared, we were able to characterize the interactions between a model polypeptide, exendin-4, and the PLGA copolymer. We observe a relationship between the experimentally determined T g , β and T g , α and free volume and microsphere dynamics.
可生物降解的聚乳酸-乙醇酸共聚物（PLGA）微球可用于包裹肽，并提供一种有前景的药物递送载体。在这项工作中，我们使用变温太赫兹时域光谱（THz-TDS）实验，研究了通过冷冻干燥制备的PLGA微球的动力学以及在导致玻璃化转变温度的较低温度下的分子流动性。微球采用水包油包水（w/o/w）双乳液技术制备，随后对样品进行冷冻干燥。通过形态测量、扫描电子显微镜和氦比重瓶法进行物理表征。THz-TDS数据显示，对于所研究的微球，在167-219 K范围内有两个不同的转变过程，即与局部运动相关的Tg,β，以及在313-330 K范围内与大规模运动相关的Tg,α。通过中红外傅里叶变换红外光谱测量，我们能够表征模型多肽艾塞那肽-4与PLGA共聚物之间的相互作用。我们观察到实验测定的Tg,β和Tg,α与自由体积和微球动力学之间的关系。
