Effects of Sperminated Pullulans on the Pulmonary Absorption of Insulin

Sperminated pullulans (SP) having different molecular weights (MWs) were prepared, and the enhancing effect on the pulmonary absorption of insulin in rats was examined. SP acted as enhancers of insulin absorption when a 0.1% solution was applied with insulin simultaneously and their enhancing effect...

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Published inYAKUGAKU ZASSHI Vol. 131; no. 2; pp. 307 - 314
Main Authors MORIMOTO, Kazuhiro, MARU, Hiroto, EGAWA, Yuya, UEDA, Hideo, MORIMOTO, Yasunori, KIMURA, Soichiro, SEKI, Toshinobu, FUKUSHI, Nanako, CHONO, Sumio
Format Journal Article
LanguageEnglish
Japanese
Published Japan The Pharmaceutical Society of Japan 01.02.2011
Pharmaceutical Society of Japan
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ISSN0031-6903
1347-5231
DOI10.1248/yakushi.131.307

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Abstract Sperminated pullulans (SP) having different molecular weights (MWs) were prepared, and the enhancing effect on the pulmonary absorption of insulin in rats was examined. SP acted as enhancers of insulin absorption when a 0.1% solution was applied with insulin simultaneously and their enhancing effects depended on the MW of the SP; the same solutions exhibited low toxicity in the in vivo LDH leaching test. In the in vitro experiments using Calu-3 cells, tight junction-opening effects and a toxic effect of SP in the MTT assay were observed at lower concentrations compared with the in vivo experiments. A mucus layer might interfere with the interaction between SP and the cell surface and might suppress both these effects and toxicity. SP having a high MW will be useful for preparing safe and efficient formulations of peptide and protein drugs. The change in the localization of the tight junction proteins may be related to the permeation-enhancing mechanism of SP.
AbstractList Sperminated pullulans (SP) having different molecular weights (MWs) were prepared, and the enhancing effect on the pulmonary absorption of insulin in rats was examined. SP acted as enhancers of insulin absorption when a 0.1% solution was applied with insulin simultaneously and their enhancing effects depended on the MW of the SP; the same solutions exhibited low toxicity in the in vivo LDH leaching test. In the in vitro experiments using Calu-3 cells, tight junction-opening effects and a toxic effect of SP in the MTT assay were observed at lower concentrations compared with the in vivo experiments. A mucus layer might interfere with the interaction between SP and the cell surface and might suppress both these effects and toxicity. SP having a high MW will be useful for preparing safe and efficient formulations of peptide and protein drugs. The change in the localization of the tight junction proteins may be related to the permeation-enhancing mechanism of SP. [INTRODUCTION]Since the pulmonary alveoli have a large surface area and a rich blood supply, pulmonary administration of peptide and protein drugs is one possible way to avoid the problems associated with parenteral formulations, such as tissue invasion, and also to improve patient compliance. 1)
Sperminated pullulans (SP) having different molecular weights (MWs) were prepared, and the enhancing effect on the pulmonary absorption of insulin in rats was examined. SP acted as enhancers of insulin absorption when a 0.1% solution was applied with insulin simultaneously and their enhancing effects depended on the MW of the SP; the same solutions exhibited low toxicity in the in vivo LDH leaching test. In the in vitro experiments using Calu-3 cells, tight junction-opening effects and a toxic effect of SP in the MTT assay were observed at lower concentrations compared with the in vivo experiments. A mucus layer might interfere with the interaction between SP and the cell surface and might suppress both these effects and toxicity. SP having a high MW will be useful for preparing safe and efficient formulations of peptide and protein drugs. The change in the localization of the tight junction proteins may be related to the permeation-enhancing mechanism of SP.Sperminated pullulans (SP) having different molecular weights (MWs) were prepared, and the enhancing effect on the pulmonary absorption of insulin in rats was examined. SP acted as enhancers of insulin absorption when a 0.1% solution was applied with insulin simultaneously and their enhancing effects depended on the MW of the SP; the same solutions exhibited low toxicity in the in vivo LDH leaching test. In the in vitro experiments using Calu-3 cells, tight junction-opening effects and a toxic effect of SP in the MTT assay were observed at lower concentrations compared with the in vivo experiments. A mucus layer might interfere with the interaction between SP and the cell surface and might suppress both these effects and toxicity. SP having a high MW will be useful for preparing safe and efficient formulations of peptide and protein drugs. The change in the localization of the tight junction proteins may be related to the permeation-enhancing mechanism of SP.
Sperminated pullulans (SP) having different molecular weights (MWs) were prepared, and the enhancing effect on the pulmonary absorption of insulin in rats was examined. SP acted as enhancers of insulin absorption when a 0.1% solution was applied with insulin simultaneously and their enhancing effects depended on the MW of the SP; the same solutions exhibited low toxicity in the in vivo LDH leaching test. In the in vitro experiments using Calu-3 cells, tight junction-opening effects and a toxic effect of SP in the MTT assay were observed at lower concentrations compared with the in vivo experiments. A mucus layer might interfere with the interaction between SP and the cell surface and might suppress both these effects and toxicity. SP having a high MW will be useful for preparing safe and efficient formulations of peptide and protein drugs. The change in the localization of the tight junction proteins may be related to the permeation-enhancing mechanism of SP.
Author SEKI, Toshinobu
MARU, Hiroto
EGAWA, Yuya
MORIMOTO, Yasunori
KIMURA, Soichiro
MORIMOTO, Kazuhiro
CHONO, Sumio
UEDA, Hideo
FUKUSHI, Nanako
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Snippet Sperminated pullulans (SP) having different molecular weights (MWs) were prepared, and the enhancing effect on the pulmonary absorption of insulin in rats was...
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SubjectTerms absorption enhancer
Animals
Cell Survival - drug effects
Cells, Cultured
Chemistry, Pharmaceutical
Claudin-1
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Glucans - chemistry
Glucans - pharmacology
Glucans - toxicity
insulin
Insulin - metabolism
Lung - metabolism
Male
Membrane Proteins - metabolism
Molecular Weight
Occludin
pulmonary absorption
Rats
Rats, Wistar
sperminated pullulan
Stimulation, Chemical
Tight Junctions - metabolism
Title Effects of Sperminated Pullulans on the Pulmonary Absorption of Insulin
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