title: Thiolated polycarbophil/glutathione: defining its potential as a permeation enhancer for oral drug administration in comparison to sodium caprate.
abstract: Thiolated polyacrylates were shown to be permeation enhancers with notable potential. The aim of this study was to evaluate the permeation enhancing properties of a thiolated polycarbophil/glutathione (PCP-Cys/GSH) system for oral drug application in comparison to a well-established permeation enhancer, namely sodium caprate. In vitro permeation studies were conducted in Ussing-type chambers with sodium fluoresceine (NaFlu) and fluoresceine isothiocyanate labeled dextran (molecular mass 4 kDa; FD4) as model compounds. Bioavailability studies were carried out in Sprague Dawley rats with various formulations. Moreover, cytotoxic effects of both permeation enhancers were compared. Permeation enhancement ratios of 1% sodium caprate were found to be 3.0 (FD4) and 2.3 (NaFlu), whereas 1% PCP-Cys/0.5% GSH displayed enhancement ratios of 2.4 and 2.2. Both excipients performed at a similar level in vivo. Sodium caprate solutions increased oral bioavailability 2.2-fold (FD4) and 2.3-fold (NaFlu), while PCP-Cys hydrogels led to a 3.2-fold and 2.2-fold enhancement. Cell viability experiments revealed a significantly higher tolerance of Caco-2 cells towards 0.5% PCP-Cys (81% survival) compared to 0.5% sodium caprate (5%). As PCP-Cys is not absorbed from mucosal membranes due to its comparatively high molecular mass, systemic side-effects can be excluded. In conclusion, both systems displayed a similar potency for permeation enhancement of hydrophilic compounds. However, PCP-Cys seems to be less harmful to cultured cells.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 52, Josef-Möller-Haus, 6020 Innsbruck, Austria.
authors.forename: Glen
authors.initials: G
authors.lastname: Perera
authors.forename: Jan
authors.initials: J
authors.lastname: Barthelmes
authors.forename: Anja
authors.initials: A
authors.lastname: Vetter
authors.forename: Christof
authors.initials: C
authors.lastname: Krieg
authors.forename: Cindy
authors.initials: C
authors.lastname: Uhlschmied
authors.forename: Günther K
authors.initials: GK
authors.lastname: Bonn
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage* / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003545:Cysteine / Q000008:administration & dosage; D003652:Decanoic Acids / Q000008:administration & dosage* / Q000737:chemistry; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage; D005079:Excipients / Q000008:administration & dosage; D019793:Fluorescein / Q000008:administration & dosage / Q000493:pharmacokinetics; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D003652:Decanoic Acids; D003911:Dextrans; D004337:Drug Carriers; D005079:Excipients; D020100:Hydrogels; D013438:Sulfhydryl Compounds; C031071:decanoic acid; C030312:calcium polycarbophil; D005978:Glutathione; D003545:Cysteine; D019793:Fluorescein