Gastric retention and stability of lipidized Bowman-Birk protease inhibitor in mice

被引：19

作者：

Wang, J ^{[1
]}

Shen, WC ^{[1
]}

机构：

[1] Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90033 USA

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2000年 / 204卷 / 1-2期

关键词：

Bowman-Birk protease inhibitor; polypeptide lipidization; gastric retention; gastrointestinal absorption;

D O I：

10.1016/S0378-5173(00)00489-0

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Bowman-Birk protease inhibitor (BBI) was modified with a reversible lipidizing agent. The palmitoylated product, Pal-BBI, and BBI were iodinated and orally administered to mice using a gavage needle. A prolonged retention of Pal-BBI was found in the stomach. Furthermore, a significant amount of Pal-BBI was detected as intact polypeptide in the stomach of mice fed with Pal-BBI, while only degradation products were detected with BBI. There was also a significant increase of radioactivity in the blood and liver in mice 1.5 h post-administration of Pal-BBI. These results indicate that lipidized polypeptide can have a longer retention and lower digestion in the stomach. They also suggest that the Pal-BBI may have a higher gastrointestinal absorption than the origin;ll polypeptide. (C) 2000 Elsevier Science B.V. All rights reserved.

引用

页码：111 / 116

页数：6

共 17 条

[1] Synthesis, development and in vitro evaluation of drug delivery systems with protective effect against degradation by pepsin [J].

Bernkop-Schnürch, A ;

Kirchmayer, R ;

Kratzel, M .

JOURNAL OF DRUG TARGETING, 1999, 7 (01) :55-63

[2] THE BOWMAN-BIRK INHIBITOR - TRYPSIN-INHIBITOR AND CHYMOTRYPSIN-INHIBITOR FROM SOYBEANS [J].

BIRK, Y .

INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH, 1985, 25 (02) :113-131

[3] WATER-SOLUBLE FATTY-ACID DERIVATIVES AS ACYLATING AGENTS FOR REVERSIBLE LIPIDIZATION OF POLYPEPTIDES [J].

EKRAMI, HM ;

KENNEDY, AR ;

SHEN, WC .

FEBS LETTERS, 1995, 371 (03) :283-286

[4] REDUCTION AND REACTIVATION OF BOWMAN-BIRK SOYBEAN INHIBITOR [J].

HOGLE, JM ;

LIENER, IE .

CANADIAN JOURNAL OF BIOCHEMISTRY, 1973, 51 (07) :1014-1020

[5] Comparison of pharmacokinetic parameters of a polypeptide, the Bowman-Birk protease inhibitor (BBI), and its palmitic acid conjugate [J].

Honeycutt, L ;

Wang, J ;

Ekrami, H ;

Shen, WC .

PHARMACEUTICAL RESEARCH, 1996, 13 (09) :1373-1377

[6] PROTECTION OF GASTRIC-MUCOSA AGAINST ETHANOL-INDUCED INJURY BY INTRAGASTRIC BOLUS ADMINISTRATION OF EPIDERMAL GROWTH-FACTOR COMBINED WITH HYDROXYPROPYLCELLULOSE [J].

ITOH, M ;

IMAI, S ;

JOH, T ;

KAWAI, T ;

KATSUMI, K ;

YOKOCHI, K ;

TAKEUCHI, T .

JOURNAL OF CLINICAL GASTROENTEROLOGY, 1992, 14 :S127-S130

[7]

Jones M. K., 1999, Frontiers in Bioscience, V4, pD303

[8]

KENNEDY AR, 1994, CANCER RES, V54, pS1999

[9] Effect of intragastric administration of beta-endorphin on thyrotropin-releasing hormone and somatostatin release into gastric lumen of rats [J].

Konagaya, T ;

Kusugami, K ;

Yamamoto, H ;

Nishio, Y ;

Kaneko, H ;

Nagai, H ;

Mitsuma, T .

JOURNAL OF GASTROENTEROLOGY, 1998, 33 (01) :27-31

[10]

Lee V.H.L., 1991, PEPTIDE PROTEIN DRUG

← 1 2 →