Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10228295 | Biomaterials | 2014 | 9 Pages |
Abstract
Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with diethylene triamine pentaacetic acid (γPGA-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 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 γPGA-DTPA towards G-CSF against intestinal proteases. Additionally, the in 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.
Keywords
Related Topics
Physical Sciences and Engineering
Chemical Engineering
Bioengineering
Authors
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,