Microencapsulation of protein drugs for drug delivery: Strategy, preparation, and applications

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	Microencapsulation of protein drugs for drug delivery: Strategy, preparation, and applications
	Ma, Guanghui 1,2
刊名	JOURNAL OF CONTROLLED RELEASE
	2014-11-10
卷号	193 期号:nov 页码:324-340
关键词	Uniform size Microsphere Microcapsule Membrane emulsification Protein drug Bioactivity
ISSN号	0168-3659
其他题名	J. Control. Release
中文摘要	Bio-degradable poly(lactide) (PLA)/poly(lactide-glycolide) (PLGA) and chitosan microspheres (or microcapsules) have important applications in Drug Delivery Systems (DDS) of protein/peptide drugs. By encapsulating protein/peptide drugs in the microspheres, the serum drug concentration can be maintained at a higher constant value for a prolonged time, or injection formulation can be changed to orally or mucosally administered formulation. PLA/PLGA and chitosan are most often used in injection formulation and oral formulation. However, in the preparation and applications of PLA/PLGA and chitosan microspheres containing protein/peptide drugs, the problems of broad size distribution and poor reproducibility of microspheres, and deactivation of protein during the preparation, storage and release, are still big challenges. In this article, the techniques for control of the diameter of microspheres and microcapsules will be introduced at first, then the strategies about how to maintain the bioactivity of protein drugs during preparation and drug release will be reviewed and developed in our research group. The membrane emulsification techniques including direct membrane emulsification and rapid membrane emulsification processes were developed to prepare uniform-sized microspheres, the diameter of microspheres can be controlled from submicron to 100 mu m by these two processes, and the reproducibility of products can be guaranteed. Furthermore, compared with conventional stirring method, the big advantages of membrane emulsification process were that the uniform microspheres with much higher encapsulation efficiency can be obtained, and the release behavior can be adjusted by selecting microsphere size. Mild membrane emulsification condition also can prevent the deactivation of proteins, which frequently occurred under high shear force in mechanical stirring, sonification, and homogenization methods. The strategies for maintaining the bioactivity of protein drug were developed, such as adding additives into protein solution, using solid drug powder instead of protein solution, and employing hydrophilic poly(lactide)-poly(ethylene glycol) (PELA) as a wall material for encapsulation in PLA/PLGA microspheres/microcapsules; developing step-wise crosslinking process, self-solidification process, and adsorbing protein drug into preformed chitosan microsphere with hollow-porous morphology for encapsulation in chitosan microsphere. As a result, animal test demonstrated that PELA microcapsules with uniform size and containing recombinant human growth hormone (rhGH) can maintain higher blood drug concentration for 2 months, and increased animal weight more apparently only by single dose, compared with PLA and PLGA microcapsules; hollow-porous chitosan microsphere loading insulin decreased blood glucose level largely when it was used as a carrier for oral administration. (C) 2014 Elsevier B.V. All rights reserved.
英文摘要	Bio-degradable poly(lactide) (PLA)/poly(lactide-glycolide) (PLGA) and chitosan microspheres (or microcapsules) have important applications in Drug Delivery Systems (DDS) of protein/peptide drugs. By encapsulating protein/peptide drugs in the microspheres, the serum drug concentration can be maintained at a higher constant value for a prolonged time, or injection formulation can be changed to orally or mucosally administered formulation. PLA/PLGA and chitosan are most often used in injection formulation and oral formulation. However, in the preparation and applications of PLA/PLGA and chitosan microspheres containing protein/peptide drugs, the problems of broad size distribution and poor reproducibility of microspheres, and deactivation of protein during the preparation, storage and release, are still big challenges. In this article, the techniques for control of the diameter of microspheres and microcapsules will be introduced at first, then the strategies about how to maintain the bioactivity of protein drugs during preparation and drug release will be reviewed and developed in our research group. The membrane emulsification techniques including direct membrane emulsification and rapid membrane emulsification processes were developed to prepare uniform-sized microspheres, the diameter of microspheres can be controlled from submicron to 100 mu m by these two processes, and the reproducibility of products can be guaranteed. Furthermore, compared with conventional stirring method, the big advantages of membrane emulsification process were that the uniform microspheres with much higher encapsulation efficiency can be obtained, and the release behavior can be adjusted by selecting microsphere size. Mild membrane emulsification condition also can prevent the deactivation of proteins, which frequently occurred under high shear force in mechanical stirring, sonification, and homogenization methods. The strategies for maintaining the bioactivity of protein drug were developed, such as adding additives into protein solution, using solid drug powder instead of protein solution, and employing hydrophilic poly(lactide)-poly(ethylene glycol) (PELA) as a wall material for encapsulation in PLA/PLGA microspheres/microcapsules; developing step-wise crosslinking process, self-solidification process, and adsorbing protein drug into preformed chitosan microsphere with hollow-porous morphology for encapsulation in chitosan microsphere. As a result, animal test demonstrated that PELA microcapsules with uniform size and containing recombinant human growth hormone (rhGH) can maintain higher blood drug concentration for 2 months, and increased animal weight more apparently only by single dose, compared with PLA and PLGA microcapsules; hollow-porous chitosan microsphere loading insulin decreased blood glucose level largely when it was used as a carrier for oral administration. (C) 2014 Elsevier B.V. All rights reserved.
WOS标题词	Science & Technology ; Physical Sciences ; Life Sciences & Biomedicine
类目[WOS]	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]	Chemistry ; Pharmacology & Pharmacy
关键词[WOS]	HUMAN GROWTH-HORMONE ; MEMBRANE EMULSIFICATION TECHNIQUE ; SIZED CHITOSAN MICROSPHERES ; SOLVENT EVAPORATION METHOD ; LOADED PLGA MICROSPHERES ; ORAL INSULIN DELIVERY ; IN-VITRO ; PLA MICROCAPSULES ; NANOPARTICLES ; STABILITY
收录类别	SCI
原文出处	://WOS:000344229000029
语种	英语
WOS记录号	WOS:000344229000029
公开日期	2015-04-01
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/11807]
专题	过程工程研究所_研究所（批量导入）
作者单位	1.Inst Proc Engn, PLA Key Lab Biopharmaceut Prod & Formulat Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Collaborat Innovat Ctr Chem Sci & Engn Tianjin, Tianjin 300072, Peoples R China
推荐引用方式 GB/T 7714	Ma, Guanghui. Microencapsulation of protein drugs for drug delivery: Strategy, preparation, and applications[J]. JOURNAL OF CONTROLLED RELEASE,2014,193(nov):324-340.
APA	Ma, Guanghui.(2014).Microencapsulation of protein drugs for drug delivery: Strategy, preparation, and applications.JOURNAL OF CONTROLLED RELEASE,193(nov),324-340.
MLA	Ma, Guanghui."Microencapsulation of protein drugs for drug delivery: Strategy, preparation, and applications".JOURNAL OF CONTROLLED RELEASE 193.nov(2014):324-340.