Portal de investigação
Engineered albumin-functionalized nanoparticles for improved FcRn binding enhance oral delivery of insulin.
Autores da FMUP
Participantes de fora da FMUP
- Azevedo C
- Nilsen J
- Grevys A
- Andersen JT
- Sarmento B
Unidades de investigação
Abstract
Oral delivery of biopharmaceuticals, as insulin, is hampered by rapid degradation and inefficient absorption in the gastrointestinal tract (GIT). To solve this, a new class of biodegradable poly(lactic-co-glycolic)-poly(ethylene glycol) (PLGA-PEG) mucodiffusive nanoparticles (NPs) was designed. Specifically, these were decorated with site-specific conjugated human albumin, engineered for improved pH dependent binding to the neonatal Fc receptor (FcRn), which naturally mediates transport of albumin across the intestinal epithelium. The designed NPs of monodisperse 150 nm in size were 10% loaded with insulin and their surface was successfully functionalized with human albumin. Importantly, the engineered albumin-functionalized NPs bound human FcRn favorably in a pH dependent manner and showed enhanced transport across polarized cell layers. When orally administered to human FcRn expressing mice induced with diabetes, a reduction of glycemia was measured as a function of receptor targeting, with up to around 40% reduction after 1 h post-delivery. Thus, biodegradable PLGA-PEG NPs decorated with human albumin for improved FcRn-dependent transport offer a novel attractive strategy for delivery of encapsulated biopharmaceuticals across intestinal barriers.
Copyright © 2020 Elsevier B.V. All rights reserved.
Dados da publicação
- ISSN/ISSNe:
- 1873-4995, 0168-3659
- Tipo:
- Article
- Páginas:
- 161-173
Journal of Controlled Release Elsevier
Documentos
- Não há documentos
Filiações
Keywords
- Engineered albumin variants; FcRn binding; Glycemic decrease; Intestinal permeability; PLGA-PEG nanoparticles; Type 1 diabetes mellitus
Proyectos asociados
Ameaça aos princípios bioéticos na pratica médica no Brasil: Duas Décadas dos Processos ético-profissionais (1988-2008)
Investigador Principal: Rui Manuel Lopes Nunes
Estudo Clínico Académico . 2019
Citar a publicação
Azevedo C,Nilsen J,Grevys A,Nunes R,Andersen JT,Sarmento B. Engineered albumin-functionalized nanoparticles for improved FcRn binding enhance oral delivery of insulin. J. Control. Release. 2020. 327. p. 161-173. IF:9,776. (1).
