Esterase-Mediated Sustained Release of Peptide-Based Therapeutics from a Self-Assembled Injectable Hydrogel
| Autor: | Helena C. Parkington, Tanesh D. Gamot, Susan E. Northfield, Simon Bowles, Robert E Widdop, Rachel L. Minehan, Harold A. Coleman, Richard A. Hughes, Qingqing Lin, Ketav Kulkarni, Marie-Isabel Aguilar, Denham Hopper, Mark P. Del Borgo |
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| Rok vydání: | 2021 |
| Předmět: |
Materials science
Cell Survival Peptide Endogeny Rats Sprague-Dawley Neurotrophic factors In vivo Pregnancy Materials Testing Animals General Materials Science Cells Cultured chemistry.chemical_classification Neurons Molecular Structure Esterases Hydrogels Small molecule Rats Drug Liberation chemistry Self-healing hydrogels Drug delivery Biophysics Female Peptides Function (biology) |
| Zdroj: | ACS applied materialsinterfaces. 13(49) |
| ISSN: | 1944-8252 |
| Popis: | A synthetic strategy for conjugating small molecules and peptide-based therapeutics, via a cleavable ester bond, to a lipidated β3-tripeptide is presented. The drug-loaded β3-peptide was successfully co-assembled with a functionally inert lipidated β3-tripeptide to form a hydrogel. Quantitative release of lactose from the hydrogel, by the action of serum esterases, is demonstrated over 28 days. The esterase-mediated sustained release of the bioactive brain-derived neurotrophic factor (BDNF) peptide mimics from the hydrogel resulted in increased neuronal survival and normal neuronal function of peripheral neurons. These studies define a versatile strategy for the facile synthesis and co-assembly of self-assembling β3-peptide-based hydrogels with the ability to control drug release using endogenous esterases with potential in vivo applications for sustained localized drug delivery. |
| Databáze: | OpenAIRE |
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