title: Nano-carrier systems: Strategies to overcome the mucus gel barrier.
abstract: The present review provides an overview of nanotechnology-based strategies to overcome various mucus gel barriers including the intestinal, nasal, ocular, vaginal, buccal and pulmonary mucus layer without destroying them. It focuses on the one hand on strategies to improve the mucus permeation behavior of particles and on the other hand on systems avoiding the back-diffusion of particles out of the mucus gel layer. Nanocarriers with improved mucus permeation behavior either exhibit a high density of positive and negative charges, bearing mucolytic enzymes such as papain and bromelain on their surface or display a slippery surface due to PEG-ylation. Furthermore, self-nanoemulsifying-drug-delivery-systems (SNEDDS) turned out to exhibit comparatively high mucus permeating properties. Strategies in order to avoid back-diffusion are based on thiolated polymers reacting to a higher extent with cysteine subunits of the mucus at pH 7 in deeper mucus regions than at pH 5 being prevalent in luminal mucus regions of the intestinal and vaginal mucosa. Furthermore, particles changing their zeta potential from negative to positive once they have reached the epithelium seem to be promising carriers. The summarized knowledge should provide a good starting point for further developments in this field.
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Innsbruck, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Dünnhaupt
authors.affiliation: Chemical Process & Energy Resources Research Institute, Centre for Research and Technology Hellas, Thessaloniki, Greece.
authors.forename: O
authors.initials: O
authors.lastname: Kammona
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH, Innsbruck, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Waldner
authors.affiliation: Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece; Chemical Process & Energy Resources Research Institute, Centre for Research and Technology Hellas, Thessaloniki, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Kiparissides
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: A
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D065567:Absorption, Physiological / Q000187:drug effects; D000818:Animals; D004058:Diffusion; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000639:trends; D004655:Emulsions; D005100:Expectorants / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009092:Mucous Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009093:Mucus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D049329:Nanostructures / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000008:administration & dosage / Q000378:metabolism; D010539:Permeability; D010599:Pharmacokinetics; D059748:Proteolysis; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005100:Expectorants; D010447:Peptide Hydrolases
keywords: Back-diffusion; Innovative strategies; Mucus barrier; Mucus penetration; Nanocarriers; Proteolytic enzymes