title: 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.
abstract: 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 5-10h. Nano-CT provided a nondestructive, high-resolution, and three-dimensional analysis method to characterize the porous microsphere.
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong, China.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510000, Guangdong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, Anhui 230000, China.
authors.forename: Dajiang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, Anhui 230000, China. Electronic address: wuzy@ustc.edu.cn.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong, China.
authors.forename: Zhefei
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong, China.
authors.forename: Qixing
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong, China.
authors.forename: Zhuying
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong, China. Electronic address: 874477522@qq.com.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510000, Guangdong, China. Electronic address: chuanbin_wu@126.com.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry; D006244:Hardness; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013499:Surface Properties; D014054:Tomography / Q000379:methods; D014965:X-Rays
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid
keywords: PLGA microspheres; Pore structure; Scanning electron microscopy (SEM); Surface protein interconnectivity; Transmission hard X-ray nano-tomography (nano-CT)