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Controlling the bioactivity of a peptide hormone in vivo by reversible self-assembly
- Source :
- Nature Communications, Vol 8, Iss 1, Pp 1-9 (2017), Nature Communications
- Publication Year :
- 2017
- Publisher :
- Nature Portfolio, 2017.
-
Abstract
- The use of peptides as therapeutic agents is undergoing a renaissance with the expectation of new drugs with enhanced levels of efficacy and safety. Their clinical potential will be only fully realised once their physicochemical and pharmacokinetic properties have been precisely controlled. Here we demonstrate a reversible peptide self-assembly strategy to control and prolong the bioactivity of a native peptide hormone in vivo. We show that oxyntomodulin, a peptide with potential to treat obesity and diabetes, self-assembles into a stable nanofibril formulation which subsequently dissociates to release active peptide and produces a pharmacological effect in vivo. The subcutaneous administration of the nanofibrils in rats results in greatly prolonged exposure, with a constant oxyntomodulin bioactivity detectable in serum for at least 5 days as compared to free oxyntomodulin which is undetectable after only 4 h. Such an approach is simple, cost-efficient and generic in addressing the limitations of peptide therapeutics.<br />The clinical potential of peptide therapeutic agents can only be fully realised once their physicochemical and pharmacokinetic properties are precisely controlled. Here the authors show a reversible peptide self-assembly strategy to control and prolong the bioactivity of a native peptide hormone in vivo.
- Subjects :
- Male
0301 basic medicine
Injections, Subcutaneous
Peptide Hormones
Science
General Physics and Astronomy
Peptide
Pharmacology
Peptide hormone
Article
General Biochemistry, Genetics and Molecular Biology
Rats, Sprague-Dawley
Mice
03 medical and health sciences
chemistry.chemical_compound
Pharmacokinetics
In vivo
Animals
Obesity
lcsh:Science
chemistry.chemical_classification
Multidisciplinary
Chemistry
The Renaissance
General Chemistry
Rats
Mice, Inbred C57BL
Oxyntomodulin
Glucose
030104 developmental biology
Drug delivery
lcsh:Q
Self-assembly
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....2249dc88053f30adac25eb2f0ad6d102