Treatment of chemotherapy-induced neutropenia in a rat model by using multiple daily doses of oral administration of G-CSF-containing nanoparticles

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• 作者：Fang-Yi Su ; Er-Yuan Chuang ; Po-Yen Lin ; Yi-Chun Chou ; Chiung-Tong Chen ; Fwu-Long Mi ; Shiaw-Pyng Wey ; Tzu-Chen Yen ; Kun-Ju Lin ; Hsing-Wen Sung
• 关键词：Chemotherapy-induced neutropenia ; Translational medicine ; Oral protein delivery ; Biodistribution ; Glucose utilization
• 刊名：Biomaterials
• 出版年：April, 2014
• 年：2014
• 卷：35
• 期：11
• 页码：3641-3649
• 全文大小：2541 K

文摘

Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(纬-glutamic acid) conjugated with diethylene triamine pentaacetic acid (纬PGA-DTPA) was prepared for oral delivery of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor. The therapeutic potential of this NP system for daily administration of G-CSF to treat neutropenia associated with chemotherapy was evaluated in a rat model. In聽vitro results indicate that the procedures of NP loading and release preserved the structural integrity and bioactivity of the G-CSF molecules adequately. Those results further demonstrated the enzymatic inhibition activity of 纬PGA-DTPA towards G-CSF against intestinal proteases. Additionally, the in聽vivo biodistribution study clearly identified accumulations of G-CSF in the heart, liver, bone marrow, and urinary bladder, an indication of systemic absorption of G-CSF; its relative bioavailability was approximately 13.6%. Moreover, significant glucose uptake was observed in bone marrow during G-CSF treatment, suggesting increased bone marrow metabolism and neutrophil production. Consequently, neutrophil count in the blood increased in a sustained manner; this fact may help a patient's immune system recover from the side effects of chemotherapy.