title: Nanoparticle transport across in vitro olfactory cell monolayers.
abstract: 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.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain; Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium.
authors.forename: Oihane
authors.initials: O
authors.lastname: Gartziandia
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain.
authors.forename: Susana Patricia
authors.initials: SP
authors.lastname: Egusquiaguirre
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium; Integrated Center for Cell Therapy and Regenerative Medicine, International Clinical Research Center (FNUSA-ICRC), St. Anne's University Hospital Brno, Pekařská 53, Brno 656 91, Czech Republic.
authors.forename: John
authors.initials: J
authors.lastname: Bianco
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain.
authors.forename: Manoli
authors.initials: M
authors.lastname: Igartua
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Hernandez
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium. Electronic address: ana.beloqui@uclouvain.be.
authors.forename: Ana
authors.initials: A
authors.lastname: Beloqui
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D019344:Lactic Acid / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles; D009297:Nasal Mucosa / Q000378:metabolism; D009831:Olfactory Mucosa / Q000166:cytology / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D057846:Cell-Penetrating Peptides; D008055:Lipids; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan
keywords: CPP; Lipid nanoparticles; NLC; Nanoparticles; Nose-to-brain delivery; Olfactory mucosa