Brain microvascular endothelial cells, supported by pericytes and astrocytes endfeet, are responsible for the low permeation of large hydrosoluble drugs through the blood-brain barrier (BBB), causing difficulties for effective pharmacological therapies. In recent years, different strategies for promoting brain targeting have aimed to improve drug delivery and activity at this site, including innovative nanosystems for drug delivery across the BBB. In this context, an in vitro approach based on a simplified cellular model of the BBB provides a useful tool to investigate the effect of nanoformulations on the trans-BBB permeation of molecules. This study describes the development of a double-layer BBB, consisting of co-cultured commercially available primary rat brain microvascular endothelial cells and astrocytes. A multiparametric approach for the validation of the model, based on the measurement of the transendothelial electrical resistance and the apparent permeability of a high molecular weight dextran, is also described. As proof of concept for the employment of this BBB model to study the effect of different nanoformulations on the translocation of fluorescent molecules across the barrier, we describe the use of fluorescein isothiocyanate (FITC), loaded into ferritin nanoparticles. The ability of ferritins to improve the trans-BBB permeation of FITC was demonstrated by flux measurements and confocal microscopy analyses. The results suggest this is a useful system for validating nanosystems for delivery of drugs across the BBB.
In vitro permeation of FITC-loaded ferritins across a rat blood-brain barrier : A model to study the delivery of nanoformulated molecules / L. Fiandra, S. Mazzucchelli, M. Truffi, M. Bellini, L. Sorrentino, F. Corsi. - In: JOURNAL OF VISUALIZED EXPERIMENTS. - ISSN 1940-087X. - 2016:114(2016 Aug).
|Titolo:||In vitro permeation of FITC-loaded ferritins across a rat blood-brain barrier : A model to study the delivery of nanoformulated molecules|
MAZZUCCHELLI, SERENA (Secondo)
CORSI, FABIO RUGGERO MARIA (Ultimo)
|Parole Chiave:||bioengineering; blood-brain barrier; ferritin nanoparticles; fluorescent molecules; in vitro models; issue 114; nanomedicine; trans-BBB delivery; animals; astrocytes; blood-brain barrier; cells, cultured; ferritins; fluorescein; pericytes; rats; neuroscience (all); chemical engineering (all); immunology and microbiology (all); biochemistry, genetics and molecular biology (all)|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore BIO/13 - Biologia Applicata
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore MED/18 - Chirurgia Generale
|Data di pubblicazione:||ago-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3791/54279|
|Appare nelle tipologie:||01 - Articolo su periodico|