Meta-Analysis of Nanoparticle Delivery to Tumors Using a Physiologically Based Pharmacokinetic Modeling and Simulation Approach

Numerous studies
have engineered nanoparticles with different physicochemical
properties to enhance the delivery efficiency to solid tumors, yet
the mean and median delivery efficiencies are only 1.48% and 0.70%
of the injected dose (%ID), respectively, according to a study using
a nonphysiologically based modeling approach based on published data
from 2005 to 2015. In this study, we used physiologically based pharmacokinetic
(PBPK) models to analyze 376 data sets covering a wide range of nanomedicines
published from 2005 to 2018 and found mean and median delivery efficiencies
at the last sampling time point of 2.23% and 0.76%ID, respectively.
Also, the mean and median delivery efficiencies were 2.24% and 0.76%ID
at 24 h and were decreased to 1.23% and 0.35%ID at 168 h, respectively,
after intravenous administration. While these delivery efficiencies
appear to be higher than previous findings, they are still quite low
and represent a critical barrier in the clinical translation of nanomedicines.
We explored the potential causes of this poor delivery efficiency
using the more mechanistic PBPK perspective applied to a subset of
gold nanoparticles and found that low delivery efficiency was associated
with low distribution and permeability coefficients at the tumor site
(P < 0.01). We also demonstrate how PBPK modeling
and simulation can be used as an effective tool to investigate tumor
delivery efficiency of nanomedicines.