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Extravasation of macromolecules.

Takakura¹, Mahato, Hashida

¹Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan

Advanced Drug Delivery Reviews

|June 6, 2000

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Macromolecule extravasation across capillaries is controlled by biological factors and physicochemical properties. Understanding these factors is key for effective drug delivery systems targeting organs like the liver, kidney, and tumors.

Area of Science:

Pharmacology
Biophysics
Drug Delivery

Background:

Macromolecules extravasate via pinocytosis or through interendothelial cell junctions.
Capillary structure, organ disease state, and blood/lymph supply influence solute extravasation.
Molecular size, shape, charge, and hydrophilic/lipophilic balance (HLB) are critical physicochemical properties.

Purpose of the Study:

To review macromolecule extravasation from pharmacokinetic and drug delivery perspectives.
To emphasize extravasation mechanisms in liver, kidney, and tumor capillaries.
To explore controlling small drug, protein, oligonucleotide, and gene extravasation using macromolecular carriers.

Main Methods:

Literature review focusing on pharmacokinetics and drug delivery systems.

Related Experiment Videos

Analysis of factors influencing macromolecule transport across endothelium.

Discussion of structure-property-pharmacokinetic relationships for drug carriers.

Main Results:

Extravasation pathways include transcapillary pinocytosis and passage through endothelial junctions.
Biological factors (regional differences, disease, supply rates) and physicochemical properties (size, shape, charge, HLB) significantly impact extravasation.
Conjugating or complexing with macromolecular carriers can control the extravasation of small molecules, proteins, oligonucleotides, and genes.

Conclusions:

A comprehensive understanding of macromolecule extravasation is essential for designing effective drug delivery systems.
Tailoring carrier properties based on structure-property-pharmacokinetic relationships can optimize drug targeting to specific organs like the liver, kidney, and tumors.
This review provides insights into managing macromolecule transport for therapeutic applications.