PMID- 26257128
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20220309
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 25
DP  - 2015 Oct
TI  - Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite.
PG  - 35-42
LID - S1742-7061(15)30046-5 [pii]
LID - 10.1016/j.actbio.2015.08.002 [doi]
AB  - Polymer excipients, such as low molar mass poly(ethylene glycol) (PEG), have 
      shown contradictory effects on protein stability when co-encapsulated in 
      polymeric nanoparticles. To gain further insight into these effects, 
      platelet-derived growth factor (PDGF-AA) was encapsulated in polymeric 
      nanoparticles with vs. without PEG. PDGF-AA is a particularly compelling protein, 
      as it has been demonstrated to promote cell survival and induce the 
      oligodendrocyte differentiation of neural stem/progenitor cells (NSPCs) both in 
      vitro and in vivo. Here we show, for the first time, the controlled release of 
      bioactive PDGF-AA from an injectable nanoparticle/hydrogel drug delivery system 
      (DDS). PDGF-AA was encapsulated, with high efficiency, in 
      poly(lactide-co-glycolide) nanoparticles, and its release from the drug delivery 
      system was followed over 21 d. Interestingly, the co-encapsulation of low 
      molecular weight poly(ethylene glycol) increased the PDGF-AA loading but, 
      unexpectedly, accelerated the aggregation of PDGF-AA, resulting in reduced 
      activity and detection by enzyme-linked immunosorbent assay (ELISA). In the 
      absence of PEG, released PDGF-AA remained bioactive as demonstrated with NSPC 
      oligodendrocyte differentiation, similar to positive controls, and significantly 
      different from untreated controls. This work presents a novel delivery method for 
      differentiation factors, such as PDGF-AA, and provides insights into the 
      contradictory effects reported in the literature of excipients, such as PEG, on 
      the loading and release of proteins from polymeric nanoparticles. STATEMENT OF 
      SIGNIFICANCE: Previously, the polymer poly(ethylene glycol) (PEG) has been used 
      in many biomaterials applications, from surface coatings to the encapsulation of 
      proteins. In this work, we demonstrate that, unexpectedly, low molecular weight 
      PEG has a deleterious effect on the release of the encapsulated protein 
      platelet-derived growth factor AA (PDGF-AA). We also demonstrate release of 
      bioactive PDGF-AA (in the absence of PEG). Specifically, we demonstrate the 
      differentiation of neural stem and progenitor cells to oligodendrocytes, similar 
      to what is observed with the addition of fresh PDGFAA. A differentiated 
      oligodendrocyte population is a key strategy in central nervous system 
      regeneration. This work is the first demonstration of controlled PDGF-AA release, 
      and also brings new insights to the broader field of protein encapsulation.
CI  - Copyright (c) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights 
      reserved.
FAU - Elliott Donaghue, Irja
AU  - Elliott Donaghue I
AD  - Department of Chemical Engineering and Applied Chemistry, University of Toronto, 
      Canada; Institute of Biomaterials and Biomedical Engineering, University of 
      Toronto, Canada.
FAU - Shoichet, Molly S
AU  - Shoichet MS
AD  - Department of Chemical Engineering and Applied Chemistry, University of Toronto, 
      Canada; Institute of Biomaterials and Biomedical Engineering, University of 
      Toronto, Canada; Department of Chemistry, University of Toronto, Canada. 
      Electronic address: molly.shoichet@utoronto.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150806
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (platelet-derived growth factor A)
RN  - 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - B697894SGQ (polyethylene glycol 400)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Delayed-Action Preparations
MH  - *Drug Delivery Systems
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Hydrogel, Polyethylene Glycol Dimethacrylate/*chemistry
MH  - Male
MH  - Multipotent Stem Cells/cytology/drug effects
MH  - Nanoparticles/*chemistry
MH  - Neural Stem Cells/cytology/drug effects
MH  - Platelet-Derived Growth Factor/*pharmacology
MH  - Polyethylene Glycols/chemistry
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Controlled release
OT  - Drug delivery
OT  - Hydrogel
OT  - Nanoparticle
OT  - Neural stem cell
OT  - Oligodendrocyte
OT  - PDGF-AA
OT  - PEG
OT  - PLGA
OT  - Protein delivery
OT  - Spinal cord injury
EDAT- 2015/08/11 06:00
MHDA- 2016/06/15 06:00
CRDT- 2015/08/11 06:00
PHST- 2015/06/01 00:00 [received]
PHST- 2015/07/28 00:00 [revised]
PHST- 2015/08/05 00:00 [accepted]
PHST- 2015/08/11 06:00 [entrez]
PHST- 2015/08/11 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
AID - S1742-7061(15)30046-5 [pii]
AID - 10.1016/j.actbio.2015.08.002 [doi]
PST - ppublish
SO  - Acta Biomater. 2015 Oct;25:35-42. doi: 10.1016/j.actbio.2015.08.002. Epub 2015 
      Aug 6.