Preparation of Glucagon-Like Peptide-1 Loaded PLGA Microspheres : Characterizations, Release Studies and Bioactivities in Vitro/in Vivo
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概要
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The gut hormone glucagon-like peptide-1 (GLP-1) is proposed for treatment of Type II diabetes mellitus. However, the short half life of GLP-1 in vivo is a major limitation for its application due to the frequent invasive administrations. To provide a optimal formulation to overcome this limitation, we developed a GLP-1 entrapped microspheres to achieve sustained release GLP-1 for 4-week. GLP-1 was stabilized by GLP-1-zinc complexation with zinc carbonate and encapsulated in poly(D, L-lactic-co-glycolic acid) (PLGA) with S/O/O solvent extraction to obtain GLP-1 loaded PLGA microspheres (MS). The characteristics of MS were evaluated as follows: The surface morphyology was assessed by scanning electron microscopy (SEM); The drug encapsulation efficiency and GLP-1 controlled release profile was tested by HPLC; The sustained release of GLP-1 MS in vivo and pharmacological efficacy were studied in normal mice and streptozotocin (STZ)-induced diabetic mice model after subcutaneous administration of GLP-1 MS. GLP-1-zinc complexation significantly reduced initial burst release from 37.2 to 7.5%. The controlled release bioactive GLP-1 in vitro was achieved for 4-week period by zinc complexation and addition of ZnCO_3. The optimal and complete cumulative release of GLP-1 from MS was increased from 23 to 63% in 28d by using low MW PLGA (MW 14000). The in vivo testing in normal mice and diabetic mice suggest that this zinc-stabilized technique combined with S/O/O method in the presence of water insoluble antacid additive ZnCO_3 preserve the biological activity of GLP-1. GLP-1 MS formulation achieved controlled released in vivo for 28d and exhibit sustained long term pharmacological efficacy to decrease blood glucose level in diabetic mice. This GLP-1 MS formulation provides a practical formulation for long-term sustained delivery of GLP-1 to treat Type II diabetes.
- 公益社団法人日本薬学会の論文
- 2008-02-01
著者
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LU Ying
Department of Computer and Communications Engineering, St. John's University
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Lu Ying
Department Of Pharmaceutics School Of Pharmacy Second Military Medical University
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Lu Ying
Department Of Computer And Communications Engineering St. John's University
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Zhang Guoqing
Department Of Pharmacy East Hospital Of Hepatobiliary Surgery
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ZHANG HE
Department of Emergency, Qilu Hospital of Shandong University
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Zhang He
Department Of Pharmaceutics School Of Pharmacy Second Military Medical University
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Yin Dongfeng
Department Of Pharmaceutics School Of Pharmacy Second Military Medical University
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ZOU Hao
Department of Pharmaceutics, School of Pharmacy, Second Military Medical University
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SUN Duxin
Division of Pharmaceutics, College of Pharmacy, Ohio State University
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ZHONG Yanqiang
Department of Pharmaceutics, School of Pharmacy, Second Military Medical University
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Zhong Yanqiang
Department Of Pharmaceutics School Of Pharmacy Second Military Medical University
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Zou Hao
Department Of Pharmaceutics School Of Pharmacy Second Military Medical University
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Sun Duxin
Division Of Pharmaceutics College Of Pharmacy Ohio State University
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