Extravasation of macromolecules.
Macromolecules can extravasate across the normal endothelium by transcapillary pinocytosis as well as by passage through interendothelial cell junctions, gaps or fenestrae. The main biological factors that control extravasation of a solute include regional differences in the capillary structures, the disease state of the organ or tissue, and the rate of blood and lymph supply. Physicochemical properties that are of profound significance in the extravasation of macromolecules are molecular size, shape, charge and hydrophilic/lipophilic balance (HLB) characteristics. Extravasation of small drugs, proteins, oligonucleotides and genes can be controlled by conjugating or forming complexes with macromolecular carriers. This requires a thorough understanding of the relationship between the chemical structures, physicochemical properties and the pharmacokinetics of both carrier and active molecules. This review article discusses the extravasation of macromolecules from the view points of pharmacokinetics and drug delivery systems, with the main emphasis on the extravasation across the liver, kidney and tumor capillaries.
Takakura
Y
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Mahato
RI
Hashida
M