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 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.
Yamamoto
A
A
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan. yamamoto@mb.kyoto-phu.ac.jp
Tanaka
H
H
Okumura
S
S
Shinsako
K
K
Ito
M
M
Yamashita
M
M
Okada
N
N
Fujita
T
T
Muranishi
S
S
D000042:Absorption; D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007328:Insulin / Q000493:pharmacokinetics*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008566:Membranes / Q000201:enzymology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010539:Permeability; D014982:Xenopus laevis
D007004:Hypoglycemic Agents; D007328:Insulin; D007770:L-Lactate Dehydrogenase