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A Novel Sustained-Release Formulation of Recombinant Human Growth Hormone and Its Pharmacokinetic, Pharmacodynamic and Safety Profiles
Wei, Yi1,2; Wang, Yuxia1; Kang, Aijun3; Wang, Wei4; Ho, Sa V.4; Gao, Junfeng3; Ma, Guanghui1; Su, Zhiguo1
关键词PELA microspheres narrow size distribution growth hormone controlled release high bioactivity safety
刊名MOLECULAR PHARMACEUTICS
2012-07-01
DOI10.1021/mp300126t
9期:7页:2039-2048
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental ; Pharmacology & Pharmacy
资助者973 project ; National Natural Science Foundation of China ; 973 project ; National Natural Science Foundation of China
研究领域[WOS]Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]POLY-DL-LACTIDE-POLY(ETHYLENE GLYCOL) MICROSPHERES ; PREMIX MEMBRANE EMULSIFICATION ; NARROW SIZE DISTRIBUTION ; IN-VITRO DEGRADATION ; ACID) MICROPARTICLES ; PROCESS PARAMETERS ; MICROCAPSULES ; MICROENCAPSULATION ; STABILITY ; DEFICIENCY
英文摘要

An effective and safe formulation of sustained-release rhGH for two months using poly(monomethoxypolyethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA) microspheres was developed to reduce the frequency of medication. The rhGH-loaded PELA microspheres with a narrow size distribution were successfully prepared by a double emulsion method combined with a premix membrane emulsification technique without any exogenous stabilizing excipients. The narrow size distribution of the microspheres would guarantee repeatable productivity and release behavior. Moreover, the amphiphilic PELA improved the bioactivity retention of protein drugs since it prevented protein contact with the oil/water interface and the hydrophobic network, and modulated diffusion of acidic degradation products from the carrier system. These PELA microspheres were compared in vivo with commercial rhGH solution, conventional poly(D,L-lactic acid) (PLA) and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres. Administration of rhGH-PELA could extend the duration of rhGH release (for up to 56 days) and increase area under the curve (AUC) compared to rhGH solution, PLA or PLGA microspheres in Sprague-Dawley (SD) rats. In addition, rhGH-PELA microspheres induced a greater response in total insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) than other rhGH formulations. With a hypophysectomized SD rat model, the pharmacological efficacy of rhGH-PELA microspheres was shown to be better than that from daily administration of rhGH solutions over 6 days based on body weight gain and width of the tibial growth plate. Histological examination of the injection sites indicated a significantly milder inflammatory response than that observed after injection of PLA and PLGA microspheres. Neither anti-rhGH antibodies nor the toxic effects on heart, liver and kidney were detectable after administration of rhGH-PELA microspheres in SD rats. These results suggest that rhGH-PELA microspheres have the potential to be clinically effective and safe when administered only once every two months, a dose regimen for better patient acceptance and compliance.

语种英语
所属项目编号2009CB930300 ; 20820102036 ; 51173187
资助者973 project ; National Natural Science Foundation of China ; 973 project ; National Natural Science Foundation of China
WOS记录号WOS:000305917600019
Citation statistics
Cited Times:17[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63003
Collection实验动物科学部
作者单位1.Pfizer Inc, BioTherapeut R&D, Chesterfield, MO 63017 USA
2.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
3.Chinese Acad Sci, Grad Sch, Beijing 100190, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Dept Lab Anim Sci, Beijing 100191, Peoples R China
Recommended Citation
GB/T 7714
Wei, Yi,Wang, Yuxia,Kang, Aijun,et al. A Novel Sustained-Release Formulation of Recombinant Human Growth Hormone and Its Pharmacokinetic, Pharmacodynamic and Safety Profiles[J]. MOLECULAR PHARMACEUTICS,2012,9(7):2039-2048.
APA Wei, Yi.,Wang, Yuxia.,Kang, Aijun.,Wang, Wei.,Ho, Sa V..,...&Su, Zhiguo.(2012).A Novel Sustained-Release Formulation of Recombinant Human Growth Hormone and Its Pharmacokinetic, Pharmacodynamic and Safety Profiles.MOLECULAR PHARMACEUTICS,9(7),2039-2048.
MLA Wei, Yi,et al."A Novel Sustained-Release Formulation of Recombinant Human Growth Hormone and Its Pharmacokinetic, Pharmacodynamic and Safety Profiles".MOLECULAR PHARMACEUTICS 9.7(2012):2039-2048.
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