Insulin-cell penetrating peptide hybrids with improved intestinal absorption efficiency

被引:104
作者
Liang, JF [1 ]
Yang, VC
机构
[1] Stevens Inst Technol, Dept Chem & Biol Chem, Hoboken, NJ 07030 USA
[2] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA
关键词
cell-penetrating peptide; diabetes; oral insulin; Caco-2 cell monolayer; TAT; drug delivery;
D O I
10.1016/j.bbrc.2005.07.142
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cell-penetrating peptide (CPP) was linked to insulin to form insulin-CPP hybrids. The intestinal absorption efficiency of CPP hybridized insulin was 6-8 times increased compared to normal insulin as tested on Caco-2 cell monolayer, a widely used in vitro model for intestinal absorption. Insulin-CPP hybrid transportation seemed to be through an active and transcytosis-like mechanism. Importantly, insulin in hybrids kept intact after they passed through the Caco-2 cell monolayer. This study provides a new clue for oral insulin development. (C) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:734 / 738
页数:5
相关论文
共 17 条
[1]   P-glycoprotein (P-gp) mediated efflux in Caco-2 cell monolayers: The influence of culturing conditions and drug exposure on P-gp expression levels [J].
Anderle, P ;
Niederer, E ;
Rubas, W ;
Hilgendorf, C ;
Spahn-Langguth, H ;
Wunderli-Allenspach, H ;
Merkle, HP ;
Langguth, P .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1998, 87 (06) :757-762
[2]   Conjugates of antisense oligonucleotides with the Tat and antennapedia cell-penetrating peptides: Effects on cellular uptake, binding to target sequences, and biologic actions [J].
Astriab-Fisher, A ;
Sergueev, D ;
Fisher, M ;
Shaw, BR ;
Juliano, RL .
PHARMACEUTICAL RESEARCH, 2002, 19 (06) :744-754
[3]   Enhanced rectal absorption of insulin-loaded Pluronic® F-127 gels containing unsaturated fatty acids [J].
Barichello, JM ;
Morishita, M ;
Takayama, K ;
Chiba, Y ;
Tokiwa, S ;
Nagai, T .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1999, 183 (02) :125-132
[4]   Basal insulin therapy in type 2 diabetes [J].
Bethel, MA ;
Feinglos, MN .
JOURNAL OF THE AMERICAN BOARD OF FAMILY PRACTICE, 2005, 18 (03) :199-204
[5]   NUCLEAR TRANSLOCATION OF AN EXOGENOUS FUSION PROTEIN CONTAINING HIV TAT REQUIRES UNFOLDING [J].
BONIFACI, N ;
SITIA, R ;
RUBARTELLI, A .
AIDS, 1995, 9 (09) :995-1000
[6]   Hybrid insulin cocrystals for controlled release delivery [J].
Brader, ML ;
Sukumar, M ;
Pekar, AH ;
McClellan, DS ;
Chance, RE ;
Flora, DB ;
Cox, AL ;
Irwin, L ;
Myers, SR .
NATURE BIOTECHNOLOGY, 2002, 20 (08) :800-804
[7]   Modulation of intestinal tight junctions by Zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model [J].
Fasano, A ;
Uzzau, S .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (06) :1158-1164
[8]   Synthesis and characterization of poly(ethylene glycol)-insulin conjugates [J].
Hinds, K ;
Koh, JJ ;
Joss, L ;
Liu, F ;
Baudys, M ;
Kim, SW .
BIOCONJUGATE CHEMISTRY, 2000, 11 (02) :195-201
[9]   Liposomes with phosphatidylethanol as a carrier for oral delivery of insulin: studies in the rat [J].
Kisel, MA ;
Kulik, LN ;
Tsybovsky, IS ;
Vlasov, AP ;
Vorob'yov, MS ;
Kholodova, EA ;
Zabarovskaya, ZV .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2001, 216 (1-2) :105-114
[10]   A new drug carrier, Nα-deoxycholyl-L-lysyl-methylester, for enhancing insulin absorption in the intestine [J].
Lee, S ;
Lee, J ;
Lee, DY ;
Kim, SK ;
Lee, Y ;
Byun, Y .
DIABETOLOGIA, 2005, 48 (03) :405-411