Effects of surfactant-based permeation enhancers on mannitol permeability, histology, and electrogenic ion transport responses in excised rat colonic mucosae.
Int J Pharm
; 539(1-2): 11-22, 2018 Mar 25.
Article
em En
| MEDLINE
| ID: mdl-29341916
ABSTRACT
Surfactant-based intestinal permeation enhancers (PEs) are constituents of several oral macromolecule formulations in clinical trials. This study examined the interaction of a test panel of surfactant-based PEs with isolated rat colonic mucosae mounted in Ussing chambers in an attempt to determine if increases in transepithelial permeability can be separated from induction of mucosal perturbation. The aim was to assess the effects of PEs on (i) apparent permeability coefficient (Papp) of [14C]-mannitol (ii) histology score and (iii) short-circuit current (ΔIsc) responses to a cholinomimetic (carbachol, CCh). Enhancement ratio increases for Papp values followed the order C10â¯>â¯C9â¯=â¯C111â¯>â¯a bile salt blendâ¯>â¯sodium choleateâ¯>â¯sucrose laurateâ¯>â¯Labrasol® >C12E8â¯>â¯C12â¯>â¯Cremophor® A25â¯>â¯C7â¯>â¯sucrose stearateâ¯>â¯Kolliphor® HS15â¯>â¯Kolliphor® TPGS. Exposures that increased the Papp by ≥2-fold over 120â¯min were accompanied by histological damage in 94% of tissues, and by a decreased ΔIsc response to CCh in 83%. A degree of separation between the increased Papp of [14C]-mannitol and histological damage and diminution of the ΔIsc response to CCh was observed at selected concentrations of Labrasol®. Overall, this surfactant-based PE selection caused transcellular perturbation at similar concentrations to those that enhanced permeability.
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1
Base de dados:
MEDLINE
Assunto principal:
Permeabilidade
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Tensoativos
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Transporte de Íons
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Manitol
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article