Release of bioactive peptides from polyurethane films in vitro and in vivo: Effect of polymer composition

Zhang, Jing, Woodruff, Trent M., Clark, Richard J., Martin, Darren J. and Minchin, Rodney F. (2016) Release of bioactive peptides from polyurethane films in vitro and in vivo: Effect of polymer composition. Acta Biomaterialia, 41 264-272. doi:10.1016/j.actbio.2016.05.034


Author Zhang, Jing
Woodruff, Trent M.
Clark, Richard J.
Martin, Darren J.
Minchin, Rodney F.
Title Release of bioactive peptides from polyurethane films in vitro and in vivo: Effect of polymer composition
Journal name Acta Biomaterialia   Check publisher's open access policy
ISSN 1742-7061
1878-7568
Publication date 2016-09-01
Sub-type Article (original research)
DOI 10.1016/j.actbio.2016.05.034
Open Access Status Not yet assessed
Volume 41
Start page 264
End page 272
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Formatted abstract
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 30 min. Using a blend of T80A and E5-325, therapeutic plasma levels of PMX53 were observed up to 9 days 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.
Keyword Polyurethane
Drug release
Peptide
Anti-inflammatory
C5A Receptor Antagonist
Segmented Polyurethanes
Immune-Response
Drug-Delivery
C-Terminus
Inhibition
Cancer
Complement
Inflammation
Metaanalysis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
Australian Institute for Bioengineering and Nanotechnology Publications
 
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