title: Promoting effects of chemical permeation enhancers on insulin permeation across TR146 cell model of buccal epithelium in vitro.
abstract: To find potential enhancers for facilitating the buccal delivery of insulin, a TR146 cell-culture model of buccal epithelium, cultured on commercially available insert plates, was used to evaluate the permeability-enhancing effects of several traditional and new types of chemical enhancers, including N-acetyl-L-cysteine (NAC), sodium deoxycholate (SDC), sodium nitroprusside (SNP), reduced glutathione (GSH), glutamine (Gln), chitosan (CS), L-arginine (Arg), 1-dodecylazacycloheptan-2-one (Azone), and soybean lecithin (SPC) (50 and 10 μg/mL respectively). Permeability studies were performed to determine the enhancing effects of these compounds on insulin permeation across the cell-culture model. The enhancing effects of the enhancers were assessed by calculating the apparent permeability coefficients and enhancement ratio. Cytotoxicity of the permeation enhancers at different concentrations was investigated by using the methylthiazolydiphenyl-tetrazolium bromide (MTT) assay. Results showed that 50 μg/mL of NAC, SDC, GSH, CS, Arg, Azone, SPC, SNP, and 10 μg/mL of SNP had a significant enhancing effect on promoting the transport of insulin across the TR146 cell model. MTT assays showed that 50 μg/mL of Gln, Azone, SDC, SNP, Arg, 10 μg/mL SDC, and Arg had obvious toxic effects on TR146 cells. Therefore, NAC, GSH, CS, SPC, and SNP appear to be safe, effective permeability enhancers that promote the transport of insulin across the TR146 cell-culture model of buccal epithelium and may be potential enhancers for buccal delivery of insulin with both low toxicity and high efficiency.
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Xue
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: Chen
authors.forename: Jing-ru
authors.initials: JR
authors.lastname: Meng
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hou
authors.forename: Hui
authors.initials: H
authors.lastname: Bai
authors.forename: Xing-gang
authors.initials: XG
authors.lastname: Mao
authors.forename: Xiao-xing
authors.initials: XX
authors.lastname: Luo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000327:Adsorption / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002610:Cheek; D048271:Chitosan / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000494:pharmacology
chemical_list: D000277:Adjuvants, Pharmaceutic; D007328:Insulin; D010713:Phosphatidylcholines; D009599:Nitroprusside; C024990:asolectin; D048271:Chitosan; D005978:Glutathione; D000111:Acetylcysteine