title: Mucus permeating carriers: formulation and characterization of highly densely charged nanoparticles.
abstract: The GI mucus layer represents a significant block to drug carriers absorption. Taking an example from nature, virus-mimicking nanoparticles (NPs) with highly densely charged surface were designed with the aim to improve their mucus permeation ability. NPs were formulated by combining chitosan with chondroitin sulfate and were characterized by particle size, ζ-potential and hydrophobicity. The interaction occurring between NPs and diluted porcine intestinal mucus was investigated by a new method. Furthermore, the rotating tube technique was exploited to evaluate the NPs permeation ability in fresh undiluted porcine intestinal mucus. NPs (400-500 nm) presenting a slightly positive (4.02 mV) and slightly negative (-3.55 mV) ζ-potential resulted to be hydrophobic and hydrophilic, respectively. On the one hand the hydrophobic NPs undergo physico-chemical changes when incubated with mucus, namely the size increased and the ζ-potential decreased. On the other hand, the hydrophilic NPs did not significantly change size and net charge during incubation with mucus. Both types of NPs showed a 3-fold higher diffusion ability compared to the reference 50/50 DL-lactide/glycolide copolymer NPs (136 nm, -23 mV, hydrophilic). Based on these results, this work gives valuable information for the further design of mucus-penetrating NPs.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Irene
authors.initials: I
authors.lastname: Pereira de Sousa
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Corinna
authors.initials: C
authors.lastname: Steiner
authors.affiliation: Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmutzler
authors.affiliation: Newcastle University, Institute for Cell and Molecular Biosciences, Newcastle upon Tyne, United Kingdom.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Wilcox
authors.affiliation: Nanomi B.V., EJ Oldenzaal, The Netherlands.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Veldhuis
authors.affiliation: Newcastle University, Institute for Cell and Molecular Biosciences, Newcastle upon Tyne, United Kingdom.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Pearson
authors.affiliation: Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Huck
authors.affiliation: Institute of Zoology, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Willi
authors.initials: W
authors.lastname: Salvenmoser
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria. Electronic address: Andreas.Bernkop@uibk.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D002809:Chondroitin Sulfates / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D057927:Hydrophobic and Hydrophilic Interactions; D007413:Intestinal Mucosa / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D053758:Nanoparticles; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D013552:Swine
chemical_list: D004337:Drug Carriers; D011108:Polymers; D002809:Chondroitin Sulfates; D048271:Chitosan
keywords: Chitosan; Chondroitin sulfate; Diffusion; Hydrophobicity; Mucus; Mucus-penetrating particles