Endothelial endocytic pathways: gates for vascular drug delivery.

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TitleEndothelial endocytic pathways: gates for vascular drug delivery.
Publication TypeJournal Article
Year of Publication2004
AuthorsMuro, S, Koval, M, Muzykantov, V
JournalCurr Vasc Pharmacol
Volume2
Issue3
Pagination281-99
Date Published2004 Jul
ISSN1570-1611
KeywordsAnimals, Biological Transport, Drug Delivery Systems, Endocytosis, Endothelium, Vascular, Humans
Abstract

Vascular endothelium plays strategic roles in many drug delivery paradigms, both as an important therapeutic target itself and as a barrier for reaching tissues beyond the vascular wall. Diverse means are being developed to improve vascular drug delivery including stealth liposomes and polymer carriers. Affinity carriers including antibodies or peptides that specifically bind to endothelial surface determinants, either constitutive or pathological, enhance targeting of drugs to endothelial cells (EC) in diverse vascular areas. In many cases, binding to endothelial surface determinants facilitates internalization of the drug/carrier complex. There are several main endocytic pathways in EC, including clathrin- and caveoli-mediated endocytosis, phagocytosis and macropinocytosis (these two are less characteristic of generic EC) and the recently described Cell Adhesion Molecule (CAM)-mediated endocytosis. The latter may be of interest for intracellular drug delivery to EC involved in inflammation or thrombosis. The metabolism and effects of internalized drugs largely depend on the routes of intracellular trafficking, which may lead to degrading lysosomal compartments or other organelles, recycling to the plasma membrane or transcytosis to the basal surface of endothelium. The latter route, characteristic of caveoli-mediated endocytosis, may serve for trans-endothelial drug delivery. Paracellular trafficking, which can be enhanced under pathological conditions or by auxiliary agents, represents an alternative for transcytosis. Endothelial surface determinants involved in endocytosis, mechanisms of the latter and trafficking pathways, as well as specific characteristics of EC in different vascular areas, are discussed in detail in the context of modern paradigms of vascular drug delivery.

Alternate JournalCurr Vasc Pharmacol
PubMed ID15320826
Grant ListGM61012 / GM / NIGMS NIH HHS / United States
HL 60290 / HL / NHLBI NIH HHS / United States
P01 HL019737-26 / HL / NHLBI NIH HHS / United States
P01 HL019737-290018 / HL / NHLBI NIH HHS / United States
R01 GM061012-05 / GM / NIGMS NIH HHS / United States
R01(HL/GM 71175-01) / GM / NIGMS NIH HHS / United States