title: Effects of superporous hydrogels on paracellular drug permeability and cytotoxicity studies in Caco-2 cell monolayers.
abstract: The aim of this study was to evaluate the effect of superporous hydrogel (SPH) and SPH composite (SPHC) as permeation enhancers for peptide drug delivery on Caco-2 cell monolayers. Moreover, the cytotoxic effects of these polymers were also studied using trypan blue test, MTT assay and propidium iodide staining. Transepithelial electrical resistance (TEER) studies revealed that both SPH and SPHC polymers were able to decrease TEER values to about 40% of initial values, indicating the ability of these polymers to open tight junctions. Recovery studies of TEER showed that the effects of polymers on Caco-2 cell monolayers were reversible, indicating viability of the cells after incubation with polymers. Both polymers were able to enhance the transport of the hydrophilic marker 14C-mannitol up to 2.7 and 3.8-fold in comparison to the control group. The cumulative transport of fluorescein isothiocyanate labelled dextrans with a molecular weight of 4400 Da (FD4) and 19600 Da (FD20) was enhanced by SPH and SPHC polymers by opening of tight junctions; however, this enhancement was inversely proportional to the molecular weight of marker compounds. Cytotoxicity studies confirmed that the transport enhancing properties of SPH and SPHC polymers were not caused by damage of the Caco-2 cell monolayers. The cells were able to exclude trypan blue as well as propidium iodide after incubation with SPH and SPHC polymers. MTT assay showed that the number of viable cells was higher than 95% after incubation with SPH and SPHC polymers. This indicates that the mitochondrial metabolic activities of the cells were preserved after application of the polymers.
authors.affiliation: Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
authors.forename: Farid A
authors.initials: FA
authors.lastname: Dorkoosh
authors.forename: Dewi
authors.initials: D
authors.lastname: Setyaningsih
authors.forename: Gerrit
authors.initials: G
authors.lastname: Borchard
authors.forename: Morteza
authors.initials: M
authors.lastname: Rafiee-Tehrani
authors.forename: J Coos
authors.initials: JC
authors.lastname: Verhoef
authors.forename: Hans E
authors.initials: HE
authors.lastname: Junginger
mesh_terms: D000180:Acrylic Resins; D000465:Algorithms; D000970:Antineoplastic Agents; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D003911:Dextrans / Q000493:pharmacokinetics; D004553:Electric Conductivity; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D008353:Mannitol / Q000493:pharmacokinetics; D008970:Molecular Weight; D010539:Permeability; D016062:Porosity; D011419:Propidium; D013778:Tetrazolium Salts; D013844:Thiazoles; D014343:Trypan Blue
chemical_list: D000180:Acrylic Resins; D000970:Antineoplastic Agents; D004396:Coloring Agents; D003911:Dextrans; D020100:Hydrogels; D013778:Tetrazolium Salts; D013844:Thiazoles; D011419:Propidium; D008353:Mannitol; C006903:carbopol 940; C022616:thiazolyl blue; D014343:Trypan Blue