Poly(l-threonine-co-l-threonine Succinate) Thermogels for Sustained Release of Lixisenatide.
Biomacromolecules
; 25(8): 4946-4955, 2024 08 12.
Article
en En
| MEDLINE
| ID: mdl-38949062
ABSTRACT
Negatively charged poly(l-Thr-co-l-Thr succinate) (PTTs) was developed as a new thermogel. Aqueous PTT solutions underwent thermogelation over a concentration range of 6.0-8.3 wt %. Dynamic light scattering, FTIR, 1H NMR, and COSY spectra revealed the partial strengthening of the ß-sheet conformation and the dehydration of PTTs during the transition. Extendin-4 was released from the PTTs thermogel with a large initial burst release, whereas positively charged lixisenatide significantly reduced its initial burst release to 25%, and up to 77% of the dose was released from the gel over 14 days. In vivo study revealed a high plasma concentration of lixisenatide over 5 days and hypoglycemic efficacy was observed for type II diabetic rats over 7-10 days. The biocompatible PTTs were degraded by subcutaneous enzymes. This study thus demonstrates an effective strategy for reducing the initial burst release of protein drugs from thermogels with the introduction of electrostatic interactions between the drug and the thermogel.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
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Geles
Límite:
Animals
Idioma:
En
Revista:
Biomacromolecules
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos