PMID- 23795867
OWN - NLM
STAT- MEDLINE
DCOM- 20140305
LR  - 20211021
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Print)
IS  - 1543-8384 (Linking)
VI  - 10
IP  - 8
DP  - 2013 Aug 5
TI  - Sustained release of matrix metalloproteinase-3 to trabecular meshwork cells 
      using biodegradable PLGA microparticles.
PG  - 3023-3032
LID - 10.1021/mp4001052 [doi]
AB  - Accumulation of extracellular matrix (ECM) materials in the trabecular meshwork 
      (TM) is believed to be a contributing factor to intraocular pressure (IOP) 
      elevation, a risk factor/cause of primary open angle glaucoma, a major blinding 
      disease. Matrix metalloproteinase-3 (MMP-3) is one of the proteinases that can 
      effectively degrade ECM elements such as fibronectin, and MMP-3 delivery to the 
      TM represents a promising approach for IOP reduction and treatment of glaucoma. 
      In this study, we tested the feasibility of using polymeric microparticles to 
      achieve a slow and sustained release of active MMP-3 to cultured human TM cells. 
      beta-Casein, with molecular weight (24 kDa) and hydrophobicity similar to those of 
      the active MMP-3 fragment (19.2 kDa), was first employed as a model for initial 
      testing. beta-casein was encapsulated into poly(lactic-co-glycolic acid) (PLGA) 
      microparticles using a double emulsion procedure at an encapsulation efficiency 
      of approximately 45%. The PLGA microparticles were chosen given their 
      biocompatibility and the proven capacity of sustained release of encapsulated 
      molecules. The release test conducted in the culture medium showed a slow and 
      sustained release of the protein over 20 days without a significant initial burst 
      release. Active MMP-3 was subsequently encapsulated into PLGA microparticles with 
      an encapsulation efficiency of approximately 50%. A biofunctional assay utilizing 
      human TM cells was set up in which the reduction of fibronectin was used as an 
      indicator of enzyme activity. It was observed that fibronectin staining was 
      markedly reduced by the medium collected from MMP-3-microparticle-treated 
      cultures compared to that from blank- and beta-casein-microparticle controls, which 
      was validated using a direct MMP-3 activity assay. The controlled release of 
      MMP-3 from the microparticles resulted in sustained degradation of fibronectin up 
      to 10 days. This proof-of-concept undertaking represents the first study on the 
      controlled and sustained release of active MMP-3 to TM cells via encapsulation 
      into PLGA microparticles as a potential treatment of glaucoma.
FAU - Turturro, Sanja
AU  - Turturro S
AD  - Department of Ophthalmology and Visual Sciences, University of Illinois at 
      Chicago, Chicago, IL 60612, United States.
FAU - Sunoqrot, Suhair
AU  - Sunoqrot S
AD  - Department of Biopharmaceutical Sciences, University of Illinois at Chicago, 
      Chicago, IL 60612, United States.
FAU - Ying, Hongyu
AU  - Ying H
AD  - Department of Ophthalmology and Visual Sciences, University of Illinois at 
      Chicago, Chicago, IL 60612, United States.
FAU - Hong, Seungpyo
AU  - Hong S
AD  - Department of Biopharmaceutical Sciences, University of Illinois at Chicago, 
      Chicago, IL 60612, United States.
FAU - Yue, Beatrice Y J T
AU  - Yue BYJT
AD  - Department of Ophthalmology and Visual Sciences, University of Illinois at 
      Chicago, Chicago, IL 60612, United States.
LA  - eng
GR  - P30 EY001792/EY/NEI NIH HHS/United States
GR  - R01 EY018828/EY/NEI NIH HHS/United States
GR  - EY001792/EY/NEI NIH HHS/United States
GR  - EY018828/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130718
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Glaucoma/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Lactic Acid/*chemistry
MH  - Matrix Metalloproteinase 3/chemistry/*metabolism/pharmacokinetics
MH  - Microscopy, Electron, Scanning
MH  - Particle Size
MH  - Polyglycolic Acid/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Trabecular Meshwork/*cytology/metabolism
PMC - PMC3762706
MID - NIHMS507802
EDAT- 2013/06/26 06:00
MHDA- 2014/03/07 06:00
PMCR- 2014/08/05
CRDT- 2013/06/26 06:00
PHST- 2013/06/26 06:00 [entrez]
PHST- 2013/06/26 06:00 [pubmed]
PHST- 2014/03/07 06:00 [medline]
PHST- 2014/08/05 00:00 [pmc-release]
AID - 10.1021/mp4001052 [doi]
PST - ppublish
SO  - Mol Pharm. 2013 Aug 5;10(8):3023-3032. doi: 10.1021/mp4001052. Epub 2013 Jul 18.