PMID- 9795050
OWN - NLM
STAT- MEDLINE
DCOM- 19981223
LR  - 20190915
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 55
IP  - 2-3
DP  - 1998 Nov 13
TI  - A new preparation method for protein loaded poly(D, L-lactic-co-glycolic acid) 
      microspheres and protein release mechanism study.
PG  - 181-91
AB  - A new method for encapsulating a model protein, lysozyme into hydrophilic 
      uncapped poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres was developed 
      using an oil/water (O/W) single emulsion technique. Lysozyme powder, which was 
      prepared from lyophilization after adjusting a lysozyme solution pH at 3, was 
      molecularly dissolved in a co-solvent system composed of dimethylsulfoxide (DMSO) 
      and methylene chloride. The resulting organic solution containing PLGA was 
      directly emulsified into an aqueous phase, and the organic solvent phase was 
      extracted and evaporated. Various lysozyme-loaded PLGA microspheres having 
      different morphologies were obtained depending on the relative mixing ratio of 
      the two co-solvents used. In vitro release experiments indicated that an initial 
      lysozyme release rate from the microspheres was mainly controlled by ionic 
      interaction between basic amino acid residues in lysozyme and free carboxylate 
      groups in PLGA polymer chain ends, which was probed by incubating the 
      microspheres in a series of media having different NaCl concentrations. However, 
      the protein release leveled off after about 15 days' incubation. To determine the 
      reason for the protein 'no-release' from biodegradable microspheres, a systematic 
      analysis was carried out. By separately adding 0.5 M NaCl, 5 M guanidine HCl, or 
      5 mM sodium dodecyl sulfate into the release media during the non-release period, 
      it was possible to selectively identify a specific protein non-release mechanism: 
      ionic interaction, non-covalent aggregation, and/or surface adsorption, 
      respectively. It was found that non-covalent aggregation and surface adsorption 
      of lysozyme within the microspheres were the main cause of no further release, 
      whereas ionic interaction between degrading polymer and protein played an 
      insignificant role in the later stage of the release period. The greater amount 
      of additional lysozyme release by sodium dodecyl sulfate than by guanidine 
      hydrochloride suggested that protein surface adsorption was a more critical 
      factor in protein release than aggregation.
FAU - Park, T G
AU  - Park TG
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and 
      Technology, 373-1 Kusong-dong Yusong-gu, Taejon 305-701, South Korea. 
      tgpark@sorak.kaist.ac.kr
FAU - Yong Lee, H
AU  - Yong Lee H
FAU - Sung Nam, Y
AU  - Sung Nam Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Drug Carriers)
RN  - 0 (poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer)
RN  - 34346-01-5 (Polyglactin 910)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 3.2.1.17 (Muramidase)
SB  - IM
MH  - *Drug Carriers
MH  - Microscopy, Electron, Scanning
MH  - Microspheres
MH  - Muramidase/*administration & dosage
MH  - Particle Size
MH  - *Polyethylene Glycols
MH  - *Polyglactin 910
EDAT- 1998/10/31 00:00
MHDA- 1998/10/31 00:01
CRDT- 1998/10/31 00:00
PHST- 1998/10/31 00:00 [pubmed]
PHST- 1998/10/31 00:01 [medline]
PHST- 1998/10/31 00:00 [entrez]
AID - S0168-3659(98)00050-9 [pii]
AID - 10.1016/s0168-3659(98)00050-9 [doi]
PST - ppublish
SO  - J Control Release. 1998 Nov 13;55(2-3):181-91. doi: 
      10.1016/s0168-3659(98)00050-9.