Back to Search
Start Over
Release of bioactive peptides from polyurethane films in vitro and in vivo: Effect of polymer composition
- Source :
- Acta Biomaterialia. 41:264-272
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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. 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.
- Subjects :
- Male
0301 basic medicine
Materials science
Biocompatibility
Polyurethanes
Melanoma, Experimental
Biomedical Engineering
Biocompatible Materials
Peptide
02 engineering and technology
Peptides, Cyclic
Biochemistry
Biomaterials
03 medical and health sciences
chemistry.chemical_compound
In vivo
Animals
Organic chemistry
Amino Acid Sequence
Molecular Biology
Cell Proliferation
Polyurethane
chemistry.chemical_classification
Temperature
General Medicine
Polymer
021001 nanoscience & nanotechnology
Small molecule
Cyclic peptide
Mice, Inbred C57BL
Drug Liberation
030104 developmental biology
chemistry
Drug delivery
Biophysics
Peptides
0210 nano-technology
Biotechnology
Subjects
Details
- ISSN :
- 17427061
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Acta Biomaterialia
- Accession number :
- edsair.doi.dedup.....3d450b44ff07e20c8c719d4e09ba1412