title: Dextran-protamine coated nanostructured lipid carriers as mucus-penetrating nanoparticles for lipophilic drugs.
abstract: The main objectives of the present study were (i) to evaluate the effect of the mucus layer on saquinavir-loaded nanostructured lipid carriers (SQV-NLCs) uptake and (ii) to evaluate the mucopenetrating properties of dextran-protamine (Dex-Prot) coating on NLCs as per SQV permeability enhancement. Three different NLC formulations differing on particle size and surfactant content were obtained and coated with Dex-Prot complexes. SQV permeability was then evaluated across Caco-2 cell monolayers (enterocyte-like model) and Caco-2/HT29-MTX cell monolayers (mucus model). In the Caco-2 monolayers, Dex-Prot-NLCs increased up to 9-fold SQV permeability in comparison to uncoated nanoparticles. In the Caco-2/HT29-MTX monolayers, Dex-Prot-NLCs presenting a surface charge close to neutrality significantly increased SQV permeability. Hence, Dex-Prot complex coating is a promising strategy to ensure successful nanoparticle mucus-penetration, and thus, an efficient nanoparticle oral delivery. To our knowledge, this is the first time that Dex-Prot coating has been described as a nanoparticle muco-penetration enhancer across the intestinal mucus barrier.
authors.affiliation: Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Beloqui
authors.affiliation: Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Solinís
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Brussels 1200, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: des Rieux
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Brussels 1200, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
authors.affiliation: Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain. Electronic address: alicia.rodriguez@ehu.es.
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez-Gascón
mesh_terms: D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical; D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers; D020895:Enterocytes / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007408:Intestinal Absorption; D009093:Mucus / Q000378:metabolism*; D049329:Nanostructures; D036103:Nanotechnology; D010316:Particle Size; D010539:Permeability; D011479:Protamines / Q000737:chemistry*; D019258:Saquinavir / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D003911:Dextrans; D004337:Drug Carriers; D011479:Protamines; D013501:Surface-Active Agents; D019258:Saquinavir
keywords: Caco-2; HT29-MTX; Mucus; NLCs; Permeability; Saquinavir