PMID- 25218676
OWN - NLM
STAT- MEDLINE
DCOM- 20150731
LR  - 20220321
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 193
DP  - 2014 Nov 10
TI  - Microencapsulation of protein drugs for drug delivery: strategy, preparation, and 
      applications.
PG  - 324-40
LID - S0168-3659(14)00621-X [pii]
LID - 10.1016/j.jconrel.2014.09.003 [doi]
AB  - 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 100mum 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.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Ma, Guanghui
AU  - Ma G
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140910
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Biocompatible Materials)
RN  - 0 (Capsules)
RN  - 0 (Drug Carriers)
RN  - 0 (Peptides)
RN  - 0 (Recombinant Proteins)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Animals
MH  - Biocompatible Materials/*chemistry
MH  - Capsules
MH  - Chitosan/chemistry
MH  - Drug Carriers/*chemistry
MH  - Drug Compounding/instrumentation/*methods
MH  - Equipment Design
MH  - Humans
MH  - Lactic Acid/chemistry
MH  - Microspheres
MH  - Particle Size
MH  - Peptides/*administration & dosage/pharmacokinetics
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Protein Stability
MH  - Recombinant Proteins/*administration & dosage/pharmacokinetics
MH  - Surface Properties
OTO - NOTNLM
OT  - Bioactivity
OT  - Membrane emulsification
OT  - Microcapsule
OT  - Microsphere
OT  - Protein drug
OT  - Uniform size
EDAT- 2014/09/15 06:00
MHDA- 2015/08/01 06:00
CRDT- 2014/09/15 06:00
PHST- 2014/03/14 00:00 [received]
PHST- 2014/09/01 00:00 [revised]
PHST- 2014/09/03 00:00 [accepted]
PHST- 2014/09/15 06:00 [entrez]
PHST- 2014/09/15 06:00 [pubmed]
PHST- 2015/08/01 06:00 [medline]
AID - S0168-3659(14)00621-X [pii]
AID - 10.1016/j.jconrel.2014.09.003 [doi]
PST - ppublish
SO  - J Control Release. 2014 Nov 10;193:324-40. doi: 10.1016/j.jconrel.2014.09.003. 
      Epub 2014 Sep 10.