PMID- 27245428
OWN - NLM
STAT- MEDLINE
DCOM- 20171020
LR  - 20171117
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 41
DP  - 2016 Sep 1
TI  - Release of bioactive peptides from polyurethane films in vitro and in vivo: 
      Effect of polymer composition.
PG  - 264-72
LID - S1742-7061(16)30252-5 [pii]
LID - 10.1016/j.actbio.2016.05.034 [doi]
AB  - Thermoplastic polyurethanes (TPUs) are widely used in biomedical applications due 
      to their excellent biocompatibility. Their role as matrices for the delivery of 
      small molecule therapeutics has been widely reported. However, very little is 
      known about the release of bioactive peptides from this class of polymers. Here, 
      we report the release of linear and cyclic peptides from TPUs with different hard 
      and soft segments. Solvent casting of the TPU at room temperature mixed with the 
      different peptides resulted in reproducible efflux profiles with no evidence of 
      drug degradation. Peptide release was dependent on the size as well as the 
      composition of the TPU. Tecoflex 80A (T80A) showed more extensive release than 
      ElastEon 5-325, which correlated with a degree of hydration. It was also shown 
      that the composition of the medium influenced the rate and extent of peptide 
      efflux. Blending the different TPUs allowed for better control of peptide efflux, 
      especially the initial burst effect. Peptide-loaded TPU prolonged the plasma 
      levels of the anti-inflammatory cyclic peptide PMX53, which normally has a plasma 
      half-life of less than 30min. Using a blend of T80A and E5-325, therapeutic 
      plasma levels of PMX53 were observed up to 9days following a single 
      intraperitoneal implantation of the drug-loaded film. PMX53 released from the 
      blended TPUs significantly inhibited B16-F10 melanoma tumor growth in mice 
      demonstrating its bioactivity in vivo. This study provides important findings for 
      TPU-based therapeutic peptide delivery that could improve the pharmacological 
      utility of peptides as therapeutics. STATEMENT OF SIGNIFICANCE: Therapeutic 
      peptides can be highly specific and potent pharmacological agents, but are poorly 
      absorbed and rapidly degraded in the body. This can be overcome by using a matrix 
      that protects the peptide in vivo and promotes its slow release so that a 
      therapeutic effect can be achieved over days or weeks. Thermoplastic 
      polyurethanes are a versatile family of polymers that are biocompatible and used 
      for medical implants. Here, the release of several peptides from a range of 
      polyurethanes was shown to depend on the type of polymer used in the 
      polyurethane. This is the first study to examine polyurethane blends for peptide 
      delivery and shows that the rate and extent of peptide release can be fine-tuned 
      using different hard and soft segment mixtures in the polymer.
CI  - Copyright (c) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights 
      reserved.
FAU - Zhang, Jing
AU  - Zhang J
AD  - School of Biomedical Sciences, University of Queensland, St Lucia, Queensland 
      4072, Australia.
FAU - Woodruff, Trent M
AU  - Woodruff TM
AD  - School of Biomedical Sciences, University of Queensland, St Lucia, Queensland 
      4072, Australia.
FAU - Clark, Richard J
AU  - Clark RJ
AD  - School of Biomedical Sciences, University of Queensland, St Lucia, Queensland 
      4072, Australia.
FAU - Martin, Darren J
AU  - Martin DJ
AD  - Australian Institute for Bioengineering and Nanotechnology, University of 
      Queensland, St Lucia, Queensland 4072, Australia.
FAU - Minchin, Rodney F
AU  - Minchin RF
AD  - School of Biomedical Sciences, University of Queensland, St Lucia, Queensland 
      4072, Australia. Electronic address: r.minchin@uq.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160528
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg))
RN  - 0 (Biocompatible Materials)
RN  - 0 (Peptides)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Polyurethanes)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biocompatible Materials/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Drug Liberation
MH  - Male
MH  - Melanoma, Experimental/pathology
MH  - Mice, Inbred C57BL
MH  - Peptides/chemistry/*pharmacology
MH  - Peptides, Cyclic/pharmacokinetics/pharmacology
MH  - Polyurethanes/*chemistry
MH  - Temperature
OTO - NOTNLM
OT  - Anti-inflammatory
OT  - Drug release
OT  - Peptide
OT  - Polyurethane
EDAT- 2016/06/02 06:00
MHDA- 2017/10/21 06:00
CRDT- 2016/06/02 06:00
PHST- 2016/01/11 00:00 [received]
PHST- 2016/04/26 00:00 [revised]
PHST- 2016/05/03 00:00 [accepted]
PHST- 2016/06/02 06:00 [entrez]
PHST- 2016/06/02 06:00 [pubmed]
PHST- 2017/10/21 06:00 [medline]
AID - S1742-7061(16)30252-5 [pii]
AID - 10.1016/j.actbio.2016.05.034 [doi]
PST - ppublish
SO  - Acta Biomater. 2016 Sep 1;41:264-72. doi: 10.1016/j.actbio.2016.05.034. Epub 2016 
      May 28.