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Sustained-release G-CSF microspheres using a novel solid-in-oil-in-oil-in-water emulsion method

Authors Liu G, Hong X, Jiang M, Yuan W

Received 18 May 2012

Accepted for publication 14 June 2012

Published 17 August 2012 Volume 2012:7 Pages 4559—4569


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Guang Liu,1 Xiaoyun Hong,2 Mier Jiang,1 Weien Yuan2

Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China

Background: The main treatments for cancers are still chemotherapy and radiotherapy for intermediate-stage cancer and terminal cancer. However, the therapeutic methods often result in a decreased neutrophilic granulocyte count and other side effects. In this study, in order to improve the neutrophilic granulocyte levels in the blood after radiotherapy and chemotherapy, we developed a sustained-release granulocyte colony–stimulating factor (G-CSF) microsphere formulation using a novel solid-in-oil-in-oil-in-water (S/O/O/W) emulsification method.
Methods: G-CSF was loaded into dextran nanoparticles by freezing-induced phase separation, and then the G-CSF–loaded nanoparticles were encapsulated into sustained-release poly(lactic-co-glycolic acid) microspheres using S/O/O/W emulsification. The control microspheres were also prepared through W/O/W emulsification. The performance of the two microsphere formulations was investigated both in vitro and in vivo.
Results: The microspheres for the controlled release of G-CSF in a zero-order or near-zero-order pattern were provided for 2 weeks. The in vitro cumulative G-CSF release kept over 90% of its bioactivity, which was proved by a NFS-60 cell line growth assay. The microspheres of the control group fabricated by W/O/W emulsification maintained less then half of its bioactivity. The in vivo efficacy of microspheres made using the S/O/O/W method was higher than those using the W/O/W method.
Conclusion: These results suggested that the microspheres prepared by the S/O/O/W method had increased neutrophil activity compared to those prepared by W/O/W.

Keywords: microspheres, bioactivity, G-CSF, stability, sustained release

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