Improvement of pulmonary absorption of insulin and other water-soluble compounds by polyamines in rats.
The absorption enhancing effects of polyamines, spermine (SPM), spermidine (SPD) and putrescine (PUT) on the pulmonary absorption of poorly absorbable drugs were studied in rats. Insulin, 5(6)-carboxyfluorescein (CF), and fluorescein isothiocyanate-labeled dextrans (FDs) were chosen as models of poorly absorbable drugs. The absorption of insulin from the lung was enhanced in the presence of SPM and SPD, while PUT had almost no absorption enhancing effect for improving the pulmonary absorption of insulin in rats. SPM also improved the pulmonary absorption of FDs with various molecular weights, although we found almost no significant difference in the pulmonary absorption of CF with or without SPM. As for the pulmonary membrane toxicity of SPM, there was no significant difference in the release of protein and lactate dehydrogenase (LDH) with or without SPM in bronchoalveolar lavage fluid (BALF), indicating that SPM did not cause any membrane damage to the lung tissues. Furthermore, SPM did not affect the stability of insulin in BALF, suggesting that SPM might increase the permeability of insulin across the alveolar epithelium. In conclusion, polyamines, especially SPM can effectively improve the pulmonary absorption of insulin and other macromolecules without any membrane damage to the lung tissues.
He
Lin
L
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan.
Gao
Yang
Y
Lin
Yulian
Y
Katsumi
Hidemasa
H
Fujita
Takuya
T
Yamamoto
Akira
A
D000042:Absorption; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004355:Drug Stability; D019793:Fluorescein / Q000493:pharmacokinetics; D005452:Fluoresceins / Q000493:pharmacokinetics; D007328:Insulin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000187:drug effects; D011073:Polyamines / Q000494:pharmacology* / Q000633:toxicity; D011700:Putrescine / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013095:Spermidine / Q000494:pharmacology / Q000633:toxicity; D013096:Spermine / Q000494:pharmacology / Q000633:toxicity; D014867:Water / Q000737:chemistry
D001786:Blood Glucose; D005452:Fluoresceins; D007328:Insulin; D011073:Polyamines; D014867:Water; D013096:Spermine; C024098:6-carboxyfluorescein; D019793:Fluorescein; D013095:Spermidine; D011700:Putrescine