Abstract
The purpose of this study was to evaluate the effects of cyclodextrins (CyDs) to stabilize exnatide in the microencapsulation medium and influence on the pharmaceutical properties of exenatide loaded PLGA microsphere. Three CyDs interacted differently with exenatide by investigation using ultraviolet, fluorescence and circular dichroism spectroscopy. The binding affinities of CyDs to the hydrophobic tryptophan residues of exenatide increased in following order: α-CyD < β-CyD < γ-CyD. It was consistent with orders of W/O interface stabilizing and anti-adsorption effects. However, the stabilizing effect of β-CyD on liquid-state and freeze-drying of exenatide was greater than that of γ-CyD. The negative values of ΔH0, ΔS0, and ΔG0 indicated that the exenatide–CyDs complex formation was a favorable exothermic and spontaneous processes that increased the order in the complex with structural rigidity. Furthermore, it was also shown that β-CyD improved encapsulation efficiency, in vitro extended release, and in vivo pharmacokinetic and pharmacodynamic properties of prepared PLGA microspheres.
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