title: The role of the extracellular matrix in tissue distribution of macromolecules in normal and pathological tissues: potential therapeutic consequences.
abstract: The interstitial space is a dynamic microenvironment that consists of interstitial fluid and structural molecules of the extracellular matrix, such as glycosaminoglycans (hyaluronan and proteoglycans) and collagen. Macromolecules can distribute in the interstitium only in those spaces unoccupied by structural components, a phenomenon called interstitial exclusion. The exclusion phenomenon has direct consequences for plasma volume regulation. Early studies have assigned a major role to collagen as an excluding agent that accounts for the sterical (geometrical) exclusion. More recently, it has been shown that the contribution of negatively charged glycosaminoglycans might also be significant, resulting in an additional electrostatical exclusion effect. This charge effect may be of importance for drug uptake and suggests that either the glycosaminoglycans or the net charge of macromolecular substances to be delivered may be targeted to increase the available volume and uptake of macromolecular therapeutic agents in tumor tissue. Here, we provide an overview of the structural components of the interstitium and discuss the importance the sterical and electrostatical components have on the dynamics of transcapillary fluid exchange.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway. helge.wiig@biomed.uib.no
authors.forename: Helge
authors.initials: H
authors.lastname: Wiig
authors.forename: Christina
authors.initials: C
authors.lastname: Gyenge
authors.forename: Per Ole
authors.initials: PO
authors.lastname: Iversen
authors.forename: Donald
authors.initials: D
authors.lastname: Gullberg
authors.forename: Olav
authors.initials: O
authors.lastname: Tenstad
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans
chemical_list: D006025:Glycosaminoglycans; C020341:glucosaminoglycans; D003094:Collagen