Quantitative three-dimensional analysis of poly (lactic-co-glycolic acid) microsphere using hard X-ray nano-tomography revealed correlation between structural parameters and drug burst release

• The PLGA microspheres were fabricated using a double-emulsion method.
• Size, shape, and distribution of pores and protein were clearly observed with nano-CT.
• Interconnected and surface connected pores could be clearly distinguished in nano-CT.
• Nano-CT, a non-destructive, high resolution 3D method to access the PLGA microsphere.

The objective of this study was to investigate the use of transmission hard X-ray nano-computed-tomography (nano-CT) for characterization of the pore structure and drug distribution in poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating bovine serum albumin and to study the correlation between drug distribution and burst release. The PLGA microspheres were fabricated using a double-emulsion method. The results of pore structure analysis accessed with nano-CT were compared with those acquired by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Surface pore interconnectivity and surface protein interconnectivity were obtained using combined nano-CT and pixel analysis. The correlation between surface protein interconnectivity with the initial burst release across various tested formulations was also analyzed. The size, shape, and distribution of the pores and protein could be clearly observed in the whole microsphere using nano-CT, whereas only the sectional information was observed using SEM or CLSM. Interconnected pores and surface connected pores could be clearly distinguished in nano-CT, which enables the quantitative analysis of surface pore interconnectivity and surface protein interconnectivity. The surface protein interconnectivity in different formulations correlated well with the burst release at 5–10 h. Nano-CT provided a nondestructive, high-resolution, and three-dimensional analysis method to characterize the porous microsphere.

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