Evaluation of Insulin Permeability and Effects of Absorption Enhancers on Its Permeability by an in Vitro Pulmonary Epithelial System Using Xenopus Pulmonary Membrane

The permeability of insulin across Xenopus pulmonary membrane and the effects of various absorption enhancers on insulin permeability were examined using an in vitro Ussing chamber technique. Absorption enhancers used in this study were sodium caprate (NaCap), sodium glycocholate (NaGC), sodium sali...

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Veröffentlicht in:Biological & pharmaceutical bulletin 2001, Vol.24(4), pp.385-389
Hauptverfasser: YAMAMOTO, Akira, TANAKA, Hideaki, OKUMURA, Shigeki, SHINSAKO, Keiko, ITO, Mayuko, YAMASHITA, Masahiro, OKADA, Naoki, FUJITA, Takuya, MURANISHI, Shozo
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container_issue 4
container_start_page 385
container_title Biological & pharmaceutical bulletin
container_volume 24
creator YAMAMOTO, Akira
TANAKA, Hideaki
OKUMURA, Shigeki
SHINSAKO, Keiko
ITO, Mayuko
YAMASHITA, Masahiro
OKADA, Naoki
FUJITA, Takuya
MURANISHI, Shozo
description The permeability of insulin across Xenopus pulmonary membrane and the effects of various absorption enhancers on insulin permeability were examined using an in vitro Ussing chamber technique. Absorption enhancers used in this study were sodium caprate (NaCap), sodium glycocholate (NaGC), sodium salicylate (NaSal) and ethylenediaminetetraacetic acid disodium salt (EDTA). The permeability of insulin across Xenopus pulmonary membrane significantly increased in the presence of NaCap and NaGC, while EDTA and NaSal did not enhance the permeability. In addition, the enhancing effect of NaGC increased as the concentrations of these enhancers increased. Transmembrane resistance (Rm) of Xenopus lung was markedly decreased in the presence of these enhancers, and NaCap showed a greater effect on Rm than NaGC. Furthermore, the amount of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) released from the apical side of the Xenopus pulmonary membrane increased in the presence of these enhancers. These results indicate that NaCap and NaGC improve the pulmonary absorption of insulin, but they are toxic to the pulmonary membrane. These findings suggest that this method is useful for estimating the permeability characteristics of peptides across the pulmonary membrane and for evaluating the effects of various additives on their permeability and their membrane toxicity.
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Endocrine system ; Hypoglycemic Agents - pharmacokinetics ; In Vitro Techniques ; insulin ; Insulin - pharmacokinetics ; L-Lactate Dehydrogenase - metabolism ; Lung - drug effects ; Lung - enzymology ; Lung - metabolism ; Medical sciences ; Membranes - enzymology ; Membranes - metabolism ; Patch-Clamp Techniques ; peptide delivery ; Permeability ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. 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Absorption enhancers used in this study were sodium caprate (NaCap), sodium glycocholate (NaGC), sodium salicylate (NaSal) and ethylenediaminetetraacetic acid disodium salt (EDTA). The permeability of insulin across Xenopus pulmonary membrane significantly increased in the presence of NaCap and NaGC, while EDTA and NaSal did not enhance the permeability. In addition, the enhancing effect of NaGC increased as the concentrations of these enhancers increased. Transmembrane resistance (Rm) of Xenopus lung was markedly decreased in the presence of these enhancers, and NaCap showed a greater effect on Rm than NaGC. Furthermore, the amount of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) released from the apical side of the Xenopus pulmonary membrane increased in the presence of these enhancers. These results indicate that NaCap and NaGC improve the pulmonary absorption of insulin, but they are toxic to the pulmonary membrane. These findings suggest that this method is useful for estimating the permeability characteristics of peptides across the pulmonary membrane and for evaluating the effects of various additives on their permeability and their membrane toxicity.</description><subject>Absorption</subject><subject>absorption enhancer</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Female</subject><subject>General pharmacology</subject><subject>Hormones. Endocrine system</subject><subject>Hypoglycemic Agents - pharmacokinetics</subject><subject>In Vitro Techniques</subject><subject>insulin</subject><subject>Insulin - pharmacokinetics</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Lung - drug effects</subject><subject>Lung - enzymology</subject><subject>Lung - metabolism</subject><subject>Medical sciences</subject><subject>Membranes - enzymology</subject><subject>Membranes - metabolism</subject><subject>Patch-Clamp Techniques</subject><subject>peptide delivery</subject><subject>Permeability</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. 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Endocrine system</topic><topic>Hypoglycemic Agents - pharmacokinetics</topic><topic>In Vitro Techniques</topic><topic>insulin</topic><topic>Insulin - pharmacokinetics</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>Lung - drug effects</topic><topic>Lung - enzymology</topic><topic>Lung - metabolism</topic><topic>Medical sciences</topic><topic>Membranes - enzymology</topic><topic>Membranes - metabolism</topic><topic>Patch-Clamp Techniques</topic><topic>peptide delivery</topic><topic>Permeability</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. 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These findings suggest that this method is useful for estimating the permeability characteristics of peptides across the pulmonary membrane and for evaluating the effects of various additives on their permeability and their membrane toxicity.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>11305600</pmid><doi>10.1248/bpb.24.385</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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subjects Absorption
absorption enhancer
Animals
Biological and medical sciences
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Female
General pharmacology
Hormones. Endocrine system
Hypoglycemic Agents - pharmacokinetics
In Vitro Techniques
insulin
Insulin - pharmacokinetics
L-Lactate Dehydrogenase - metabolism
Lung - drug effects
Lung - enzymology
Lung - metabolism
Medical sciences
Membranes - enzymology
Membranes - metabolism
Patch-Clamp Techniques
peptide delivery
Permeability
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
pulmonary absorption
Xenopus laevis
Xenopus lung
title Evaluation of Insulin Permeability and Effects of Absorption Enhancers on Its Permeability by an in Vitro Pulmonary Epithelial System Using Xenopus Pulmonary Membrane
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