[Advances in study of novel absorption enhancers based on tight junctions].
Hydrophilic low molecular drugs, peptides and proteins, which are always poor in bioavailability, are mainly absorbed through the paracellular way in which the tight junction is the elementary framework. The tight junctions are a multiple unit structure composed of multiprotein complex that affiliates with the underlying apical actomyosin ring. Tight junction proteins are identified including transmembrane proteins (occludin, claudin and JAM) , cytoplasmic plaque proteins (ZO-1, ZO-2, ZO-3 and cingulin) and cytoskeleton. Traditional absorption enhancers can usually impair mucous membranes which constraint the utilization of these enhancers. Recently, with the increasing knowledge of the structure and function of tight junctions, many new absorption enhancers have been developed such as NO donor, CPE, Zot, and so on. In vivo and in vitro studies have shown that these enhancers could be effectively used to increase the absorption of paracellular markers and low bioavailable drug across intestinal epithelium with lower side effect. In short, the transient opening of the tight junctions by these enhancers provides new ideas that could help in novel drug delivery of therapeutic agents.
Kang
An
A
Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Liang
Yan
Y
Hao
Hai-ping
HP
Xie
Lin
L
Wang
Guang-ji
GJ
D000818:Animals; D001682:Biological Availability; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D062445:Claudin-1; D003599:Cytoskeleton / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology; D016503:Drug Delivery Systems; D004731:Endotoxins; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism / Q000502:physiology; D062826:Zonula Occludens-1 Protein
C568108:CLDN1 protein, human; D015815:Cell Adhesion Molecules; D062445:Claudin-1; D003652:Decanoic Acids; D004731:Endotoxins; D004768:Enterotoxins; C407243:F11R protein, human; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C035598:enterotoxin, Clostridium; C077728:zonula occludens toxin, Vibrio cholerae; C031071:decanoic acid; D002772:Cholera Toxin