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Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications.
J Control Release. 2014 Nov 10; 193:324-40.JC

Abstract

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 100μm 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 2months, 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.

Authors+Show Affiliations

State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, No. 1 Bei-Er-Tiao, Zhong-Guan-Cun, Beijing 100190, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), No.92 Weijin Road, Nankai District, Tianjin 300072, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25218676

Citation

Ma, Guanghui. "Microencapsulation of Protein Drugs for Drug Delivery: Strategy, Preparation, and Applications." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 193, 2014, pp. 324-40.
Ma G. Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications. J Control Release. 2014;193:324-40.
Ma, G. (2014). Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications. Journal of Controlled Release : Official Journal of the Controlled Release Society, 193, 324-40. https://doi.org/10.1016/j.jconrel.2014.09.003
Ma G. Microencapsulation of Protein Drugs for Drug Delivery: Strategy, Preparation, and Applications. J Control Release. 2014 Nov 10;193:324-40. PubMed PMID: 25218676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications. A1 - Ma,Guanghui, Y1 - 2014/09/10/ PY - 2014/03/14/received PY - 2014/09/01/revised PY - 2014/09/03/accepted PY - 2014/9/15/entrez PY - 2014/9/15/pubmed PY - 2015/8/1/medline KW - Bioactivity KW - Membrane emulsification KW - Microcapsule KW - Microsphere KW - Protein drug KW - Uniform size SP - 324 EP - 40 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 193 N2 - 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 100μm 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 2months, 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. SN - 1873-4995 UR - https://www.unboundmedicine.com/medline/citation/25218676/Microencapsulation_of_protein_drugs_for_drug_delivery:_strategy_preparation_and_applications_ DB - PRIME DP - Unbound Medicine ER -