title: Thiolated hydroxyethyl cellulose: design and in vitro evaluation of mucoadhesive and permeation enhancing nanoparticles.
abstract: Within this study, HEC-cysteamine nanoparticles with free thiol groups in the range of 117-1548 μmol/g were designed and characterized. Nanoparticles were generated via ionic gelation of the cationic polymer with tripolyphosphate (TPP) followed by covalent crosslinking via disulfide bond formation using H2O2 as oxidant. The mean diameter of the particles was in the range of 270-360 nm, and zeta potential was determined to be +4 to +10 mV. Nanoparticles were evaluated in terms of mucoadhesive, permeation enhancing, and biocompatible properties as well as biodegradability. The particles remained attached to porcine intestinal mucosa up to 70% after 3h of incubation. The more nanoparticles were oxidized; however, the less were their mucoadhesive properties. Nanoparticles applied in a concentration of 0.5% (m/v) with the highest content of free thiol groups improved the transport of fluorescein isothiocyanate dextran 4 (FD4) across Caco-2 cell monolayer 3.94-fold in comparison with control (buffer). In addition, the transport of FD4 was even 1.84-fold enhanced in the presence of 0.5% (m/v) nanoparticles with the lowest free thiol group content. The higher the disulfide bond content within nanoparticles was, to a lower degree nanoparticles were hydrolyzed by cellulase. None of these nanoparticles showed pronounced cytotoxicity. Accordingly, HEC-cysteamine could be a promising excipient for nanoparticulate delivery systems for poorly absorbed drugs.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Deni
authors.initials: D
authors.lastname: Rahmat
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Christiane
authors.initials: C
authors.lastname: Müller
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Jan
authors.initials: J
authors.lastname: Barthelmes
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Gul
authors.initials: G
authors.lastname: Shahnaz
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia.
authors.forename: Ronny
authors.initials: R
authors.lastname: Martien
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: D000269:Adhesives / Q000008:administration & dosage / Q000737:chemistry*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D003543:Cysteamine / Q000008:administration & dosage / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000269:Adhesives; D003911:Dextrans; D005079:Excipients; D011108:Polymers; D013438:Sulfhydryl Compounds; C015219:fluorescein isothiocyanate dextran; D003543:Cysteamine; D002482:Cellulose; C002283:hydroxyethylcellulose; D006861:Hydrogen Peroxide; D016650:Fluorescein-5-isothiocyanate