Terahertz Spectroscopy: An investigation of the Structural Dynamics of Freeze-Dried Poly Lactic-co-glycolic Acid Microspheres

Abstract

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 characterisation was performed by morphology measurements, scanning electron microscopy, and helium pycnometry. The THz-TDS data show two distinct transition processes, $T_{\text{g},\beta}$ in the range of $167-219,$K, associated with local motions, and $T_{\text{g},\alpha}$ 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 characterise the interactions between a model polypeptide, exendin-4, and the PLGA copolymer. We observe a relationship between the experimentally determined $T_{\text{g},\beta}$ and $T_{\text{g},\alpha}$ and free volume and microsphere dynamics.