Self-assembling lisofylline-fatty acid conjugate for effective treatment of diabetes mellitus.
Nanomedicine
; 15(1): 175-187, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30300750
ABSTRACT
Lisofylline is an anti-inflammatory agent with proven anti-diabetic activity. Its high solubility and rapid metabolism results in poor bioavailability and short half-life, limiting its clinical utility. We have synthesized Lisofylline-Linoleic acid (LSF-LA) conjugate which self-assembled into micelles (156.9 nm; PDI 0.187; CMC 1 µg/mL; aggregation number 54) without any surfactant and showed enhanced cellular uptake. It protected MIN6 insulinoma cells from cytokine induced cell death and enhanced insulin production under inflammatory conditions. It also suppressed the proliferation of activated peripheral blood mononuclear cells and reduced the production of inflammatory cytokines, IFN-γ and TNF-α. LSF-LA micelles exhibited reduced protein binding, significantly higher half-life (5.7-fold) and higher apparent volume of distribution (5.3-fold) than free LSF. In T1D animals, reduced blood glucose levels were observed at a reduced dose (~15 mg/kg, once daily of LSF-LA micelles vs. 25 mg/kg, twice daily of free LSF) that was further confirmed by immunohistochemical analysis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pentoxifilina
/
Anti-Inflamatórios não Esteroides
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Ácido Linoleico
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Substâncias Protetoras
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Diabetes Mellitus Experimental
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Insulinoma
Limite:
Animals
Idioma:
En
Revista:
Nanomedicine
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Índia