期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 499, 期 1-2, 页码 81-89出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2015.12.046
关键词
Nose-to-brain delivery; NLC; Nanoparticles; Lipid nanoparticles; CPP; Olfactory mucosa
资金
- Ministerio de Economia y Competitividad [SAF2013-42347-R]
- University of the Basque Country (UPV/EHU) [UFI 11/32]
- FEDER funds
- University of the Basque Country
- Fonds National de la Recherche Scientifique (FNRS/FRSM)
- European Regional Development Fund - Project FNUSA-ICRC [CZ.1.05/1.1.00/02.0123]
- 7th Framework Programme of the European Union [316345]
Drug access to the CNS is hindered by the presence of the blood-brain barrier (BBB), and the intranasal route has risen as a non-invasive route to transport drugs directly from nose-to-brain avoiding the BBB. In addition, nanoparticles (NPs) have been described as efficient shuttles for direct nose-to-brain delivery of drugs. Nevertheless, there are few studies describing NP nose-to-brain transport. Thus, the aim of this work was (i) to develop, characterize and validate in vitro olfactory cell monolayers and (ii) to study the transport of polymeric-and lipid-based NPs across these monolayers in order to estimate NP access into the brain using cell penetrating peptide (CPPs) moieties: Tat and Penetratin (Pen). All tested poly(D,L-lactide-co-glycolide) (PLGA) and nanostructured lipid carrier (NLC) formulations were stable in transport buffer and biocompatible with the olfactory mucosa cells. Nevertheless, 0.7% of PLGA NPs was able to cross the olfactory cell monolayers, whereas 8% and 22% of NLC and chitosan-coated NLC (CS-NLC) were transported across them, respectively. Moreover, the incorporation of CPPs to NLC surface significantly increased their transport, reaching 46% of transported NPs. We conclude that CPP-CS-NLC represent a promising brain shuttle via nose-to-brain for drug delivery. (C) 2015 Elsevier B.V. All rights reserved.
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