School of Pharmacy

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Prof. Moein Moghimi has article published in the Journal of Drug Targeting

Professor Moein Moghimi has article published in the Journal of Drug Targeting

Pharmacokinetic analysis reveals limitations and opportunities for nanomedicine targeting of endothelial and extravascular compartments of tumors

Abstract

Targeting of nanoparticles to tumors can potentially improve specificity of imaging and treatments.  We have developed a multicompartmental pharmacokinetic model in order to analyze some of the factors that control efficiency of targeting to intravascular (endothelium) and extravascular (tumor cells and stroma) compartments.  We make the assumption that transport across tumor endothelium is an important step for subsequent nanoparticle accumulation in the tumor (area-under-the-curve, AUC) regardless of entry route (interendothelial and transendothelial routes) and study this through a multicompartmental simulation.  Our model reveals that increasing endothelial targeting efficiency has a much stronger effect on the AUC than increasing extravascular targeting efficiency.  Furthermore, our analysis reveals that both extravasation and intratumoral diffusion rates need to be increased in order to significantly increase the AUC of extravascular-targeted nanoparticles.  Increasing the nanoparticle circulation half-life increases the AUC independently of extravasation and intratumoral diffusion.  Targeting the extravascular compartment leads to a buildup in the first layer surrounding blood vessels at the expense of deeper layers (binding site barrier).  This model explains some of the limitations of tumor targeting, and provides important guidelines for the design of targeted nanomedicines.

 

More information can be found here

published on: 21 January 2019