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 in | YAKUGAKU ZASSHI Vol. 131; no. 2; pp. 307 - 314 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English Japanese |
Published |
Japan
The Pharmaceutical Society of Japan
01.02.2011
Pharmaceutical Society of Japan |
Subjects | |
Online Access | Get full text |
ISSN | 0031-6903 1347-5231 |
DOI | 10.1248/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. |
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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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Cites_doi | 10.1016/j.ijpharm.2007.11.061 10.1152/jappl.1990.68.1.220 10.1016/0006-2952(91)90405-T 10.1152/ajpgi.2000.279.4.G660 10.1016/j.jconrel.2007.10.017 10.1089/jam.2006.19.47 10.1016/0005-2736(93)90159-W 10.1211/0022357021778367 10.1016/S0378-5173(99)00100-3 10.1016/j.ijpharm.2007.02.004 10.1248/bpb.28.510 10.1023/A:1022485816755 10.1016/0168-3659(93)90179-9 10.1016/S0169-409X(01)00231-9 10.2165/00003088-200342130-00003 10.1002/jps.20616 10.1016/S0955-2863(01)00208-X 10.1016/S0378-5173(99)00030-7 10.1152/ajpcell.2001.281.2.C388 10.1016/j.jconrel.2006.09.001 10.1023/A:1012160102740 10.1016/j.jconrel.2006.08.015 10.1002/jps.21462 10.1023/A:1016207809199 10.1016/S0939-6411(01)00149-7 |
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References_xml | – reference: 2) Davis S. S., Illum L., Clin. Pharmacokinet., 42, 1107-1128 (2003). – reference: 13) Chen-Quay S.-C., Eiting K. T., Li A. W.-A., Lamharzi N., Quay S. C., J. Pharm. Sci., 98, 606-619 (2009). – reference: 16) Seki T., Kanbayashi H., Nagao T., Chono S., Tabata Y., Morimoto K., J. Pharm. Sci., 95, 1393-1401 (2006). – reference: 12) Antonini J., Reasor M., Biochem. Pharmacol., 42, 151-156 (1991). – reference: 1) Gonda I., J. Aerosol Med., 19, 47-53 (2006). – reference: 24) McEwan G., Jepson M., Hirst B., Simmons N., Biochem. Biophys. Acta., 1148, 51-60 (1993). – reference: 18) Yang T., Hussain A., Bai S., Khalil I. A., Harashima H., Ahsan F., J. Control. Release, 115, 289-297 (2006). – reference: 23) Dodane V., Khan M. A., Merwin J. R., Int. J. Pharm., 182, 21-32 (1999). – reference: 3) Thanou M., Verhoef J. C., Junginger H. E., Adv. Drug Deliv. Rev., 5, 117-126 (2001). – reference: 7) Wang J., Sakai S., Deguchi Y., Bi, D., Tabata Y., Morimoto K., J. Pharm. Pharmacol., 54, 181-188 (2002). – reference: 21) Ohtake K., Maeno T., Ueda H., Natsume H., Morimoto Y., Pharm. Res., 20, 153-160 (2003). – reference: 14) Miyamoto M., Natsume H., Iwata S., Ohtake K., Yamaguchi M., Kobayashi D., Sugibayashi K., Yamashita M., Morimoto Y., Eur. J. Pharm. Biopharm., 52, 21-30 (2001). – reference: 20) Karczewski J., Groot J., Am. J. Physiol. Gastrointest. Physiol., 279, G660-G665 (2000). – reference: 15) Gao Y., He L., Katsumi H., Sakane T., Fujita T., Yamamoto A., Int. J. Pharm., 354, 126-134 (2008). – reference: 6) Natsume H., Iwata S., Ohtake K., Miyamoto M., Yamaguchi M., Hosoya K., Kobayashi D., Sugibayashi K., Morimoto Y., Int. J. Pharm., 185, 1-12 (1999). – reference: 11) Seki T., Kanbayashi H., Nagao T., Chono S., Tomita M., Hayashi M., Tabata Y., Morimoto K., Biol. Pharm. Bull., 28, 510-514 (2005). – reference: 22) Ranaldi G., Marigliano I., Vespignani I., Perozzi G., Sambuy Y., J. Nutr. Biochem., 13, 157-167 (2002). – reference: 19) Watson C. J., Rowland M., Warhurst G., Am. J. Physiol. Cell Physiol., 281, C388-C397 (2001). – reference: 17) Schipper N. G. M., Olsson S., Hoogstraate J. A., deBoer A. G., Vårum K. M., Artursson P., Pharm. Res., 14, 923-929 (1997). – reference: 9) Seki T., Fukushi N., Chono S., Morimoto K., J. Control. Release, 125, 246-251 (2008). – reference: 10) Kanatani I., Ikai T., Okazaki A., Jo J., Yamamoto M., Imamura M., Kanematsu A., Yamamoto S., Ito N., Ogawa O., Tabata Y., J. Control. Rlease, 116, 75-82 (2006). – reference: 4) Marttin E., Verhoef J. C., Romeijin S. G., Merkus F. W. H. M., Pharm. Res., 12, 1151-1157 (1995). – reference: 5) Merkus F. W. H. M., Schiepper N. G. M., Hermens W. A. J. J., Romeijin V. S. G., Verhoef J. C., J. Control. Release, 24, 201-208 (1993). – reference: 8) Seki T., Kanbayashi H., Chono S., Tabata Y., Morimoto K., Int. J. Pharm., 338, 213-218 (2007). – reference: 25) Peterson M., Gruenhaupt D., J. Appl. Physiol., 68, 220-227 (1990). – ident: 15 doi: 10.1016/j.ijpharm.2007.11.061 – ident: 25 doi: 10.1152/jappl.1990.68.1.220 – ident: 12 doi: 10.1016/0006-2952(91)90405-T – ident: 20 doi: 10.1152/ajpgi.2000.279.4.G660 – ident: 9 doi: 10.1016/j.jconrel.2007.10.017 – ident: 1 doi: 10.1089/jam.2006.19.47 – ident: 24 doi: 10.1016/0005-2736(93)90159-W – ident: 7 doi: 10.1211/0022357021778367 – ident: 6 doi: 10.1016/S0378-5173(99)00100-3 – ident: 8 doi: 10.1016/j.ijpharm.2007.02.004 – ident: 11 doi: 10.1248/bpb.28.510 – ident: 21 doi: 10.1023/A:1022485816755 – ident: 5 doi: 10.1016/0168-3659(93)90179-9 – ident: 3 doi: 10.1016/S0169-409X(01)00231-9 – ident: 2 doi: 10.2165/00003088-200342130-00003 – ident: 16 doi: 10.1002/jps.20616 – ident: 22 doi: 10.1016/S0955-2863(01)00208-X – ident: 23 doi: 10.1016/S0378-5173(99)00030-7 – ident: 19 doi: 10.1152/ajpcell.2001.281.2.C388 – ident: 10 doi: 10.1016/j.jconrel.2006.09.001 – ident: 17 doi: 10.1023/A:1012160102740 – ident: 18 doi: 10.1016/j.jconrel.2006.08.015 – ident: 13 doi: 10.1002/jps.21462 – ident: 4 doi: 10.1023/A:1016207809199 – ident: 14 doi: 10.1016/S0939-6411(01)00149-7 |
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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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