Ulcerative colitis-specific delivery of keratinocyte growth factor by neutrophils-simulated liposomes facilitates the morphologic and functional recovery of the damaged colon through alleviating the inflammation

• Published in: Journal of controlled release Vol. 299; pp. 90 - 106
• Main Authors: Zhao, Ying-Zheng, ZhuGe, De-Li, Tong, Meng-Qi, Lin, Meng-Ting, Zheng, Ya-Wen, Jiang, Xue, Yang, Wai-Geng, Yao, Qing, Xiang, Qi, Li, Xiao-Kun, Xu, He-Lin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-04-2019
• Subjects: Inflammation; Keratinocyte growth factor; Liposomes; Neutrophil membrane; Ulcerative colitis; Neutrophil membrane; Inflammation; Keratinocyte growth factor; Liposomes; Ulcerative colitis
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2019.02.034

Keratinocyte growth factor (KGF) was effective to treat ulcerative colitis. However, its poor stability and unspecific distribution toward inflamed bowel were two important obstacles hindering its consistent efficacy. Herein, KGF was firstly encapsulated into the liposomes (KGF-Lips) to improve its stability. Thereafter, the neutrophil membrane vesicle (NEM) was extracted from the activated neutrophil which was isolated from the healthy mice and then activated by lipopolysaccharide. Subsequently, NEM was inlaid in KGF-Lips to construct a neutrophil-like liposome (KGF-Neus). KGF was easily encapsulated into KGF-Neus with a high encapsulation efficiency of 95.3 ± 0.72%. Controlling NEM/lipid ratio at 1:50, KGF-Neus displayed the spherical morphology with Dh of 154.8 ± 2.7 nm, PDI of 0.18, and zeta potential of −2.37 ± 0.14 mV. Moreover, KGF-Neus exhibited good stability of Dh and significantly improved the chemical stability of KGF. Owing to NEM-associated proteins, KGF-Neus were specifically internalized by the inflammatory HUVECs. Moreover, KGF-Neus were specifically homed to the inflamed bowel in dextran sulfate sodium-induced mice after intravenous injection, resulting in the effective recovery of the morphology and function of the bowel. The therapeutic mechanisms of KGF-Neus were highly associated with alleviation of inflammation in colitis. Overall, the neutrophil-like liposome may be an excellent carrier for the colitis-targeted delivery of KGF.
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