On the mechanism and dynamics of uptake and permeation of polyether-copolyester dendrimers across an in vitro blood-brain barrier model.

Abstract:

:Dendrimers have emerged as a promising drug delivery system due to their well defined size, tailorability, and multifunctional nature. However, their application in brain delivery is relatively a new area of research. The present study was aimed at evaluating the uptake and permeation of polyether-copolyester (PEPE) dendrimers across the blood-brain barrier model and exploring the underlying mechanisms. Saturation was observed in the uptake of rhodamine B labeled PEPE dendrimers by brain vascular endothelial (bEnd.3) cells at high concentrations. Clathrin and caveolin inhibitors produced partial inhibition of the dendrimer uptake, signifying contribution of both pathways in the uptake process. PEPE dendrimers were able to cross in vitro BBB model in high amounts with P(app) of 19.7 +/- 1.9 x 10(-6) cm/s and 38.6 +/- 4.1 x 10(-6) cm/s for den-1-(G2)-400 and den-2-(G2)-400, respectively; and only 11-14% reduction in transendothelial electrical resistance during initial 4 h. The results of this study suggest that architecture of dendrimers plays a major role not only in influencing the extent and mechanism of uptake by bEnd.3 cells but also permeation across the BBB model. =

journal_name

J Pharm Sci

authors

Dhanikula RS,Hammady T,Hildgen P

doi

10.1002/jps.21669

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

3748-60

issue

10

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)33095-7

journal_volume

98

pub_type

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