Advances in study of novel absorption enhancers based on tight junctions.
- Author:
An KANG
1
;
Yan LIANG
;
Hai-ping HAO
;
Lin XIE
;
Guang-ji WANG
Author Information
1. Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Biological Availability;
Cell Adhesion Molecules;
metabolism;
Cholera Toxin;
pharmacology;
Claudin-1;
Cytoskeleton;
metabolism;
Decanoic Acids;
pharmacology;
Drug Delivery Systems;
Enterotoxins;
pharmacology;
Humans;
Intestinal Absorption;
drug effects;
Membrane Proteins;
metabolism;
Nitric Oxide Donors;
pharmacology;
Occludin;
Phosphoproteins;
metabolism;
Receptors, Cell Surface;
metabolism;
Tight Junctions;
metabolism;
physiology;
Zonula Occludens-1 Protein
- From:
Acta Pharmaceutica Sinica
2007;42(11):1122-1128
- CountryChina
- Language:Chinese
-
Abstract:
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.
