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

Fang Yi Su, Er-Tuan 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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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. Invitro 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 invivo 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.

Original languageEnglish
Pages (from-to)3641-3649
Number of pages9
JournalBiomaterials
Volume35
Issue number11
DOIs
Publication statusPublished - Apr 2014

Keywords

  • Biodistribution
  • Chemotherapy-induced neutropenia
  • Glucose utilization
  • Oral protein delivery
  • Translational medicine

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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