Abstract

Vascular targeted nanoparticles have been developed for the delivery of therapeutic and imaging agents in cancer and cardiovascular diseases. However, at authors' knowledge, a comprehensive systematic analysis on their delivery efficiency is still missing. Here, a computational model is developed to predict the vesselwall accumulation of agents released from vascular targeted nanoconstructs. The transport problem for the released agent is solved using a finite volume scheme in terms of three governing parameters: the local wall shear rate S, ranging from 10 to 200 s-1; the wall filtration velocity Vf , varying from 10-9 to 10-7 m/s; and the agent diffusion coefficient D, ranging from 10-12 to 10 -9 m2/s. It is shown that the percentage of released agent adsorbing on the vessel walls in the vicinity of the vascular targeted nanoconstructs reduces with an increase in shear rate S, and with a decrease in filtration velocity Vf and agent diffusivity D. In particular, in tumor microvessels, characterized by lower shear rates (S = 10 s-1) and higher filtration velocities (Vf = 10-7 m/s), an agent with a diffusivity D = 10-12 m2/s (i.e. a 50nm particle) is predicted to deposit on the vessel wall up to 30 % of the total released dose. Differently, drug molecules, exhibiting a smaller size and much higher diffusion coefficient (D = 10-9 m2/s), are predicted to accumulate up to 70 %. In healthy vessels, characterized by higher S and lower Vf , the largest majority of the released agent is redistributed directly in the circulation. These data suggest that drug molecules and small nanoparticles only can be efficiently released from vascular targeted nanoconstructs towards the diseased vessel walls and tissue.

Autore Pugliese

• De Tullio Marco Donato , Pascazio Giuseppe

Tutti gli autori

• de Tullio M.D. , Singh J. , Pascazio G. , Decuzzi P.

Titolo volume/Rivista

COMPUTATIONAL MECHANICS

Anno di pubblicazione

2014

ISSN

0178-7675

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

Non Disponibile

0

Ultimo Aggiornamento Citazioni

2017-04-22 03:20:59

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile