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.
BackgroundLead-exposed workers may suffer adverse health effects under the currently regulated blood lead (BPb) levels. However, a probabilistic assessment about lead exposure-associated anemia risk is lacking. The goal of this study was to examine the association between lead exposure and anemia risk among factory workers in Taiwan.MethodsWe first collated BPb and indicators of hematopoietic function data via health examination records that included 533 male and 218 female lead-exposed workers between 2012 and 2014. We used benchmark dose (BMD) modeling to estimate the critical effect doses for detection of abnormal indicators. A risk-based probabilistic model was used to characterize the potential hazard of lead poisoning for job-specific workers by hazard index (HI). We applied Bayesian decision analysis to determine whether BMD could be implicated as a suitable BPb standard.ResultsOur results indicated that HI for total lead-exposed workers was 0.78 (95% confidence interval: 0.50–1.26) with risk occurrence probability of 11.1%. The abnormal risk of anemia indicators for male and female workers could be reduced, respectively, by 67–77% and 86–95% by adopting the suggested BPb standards of 25 and 15 μg/dL.ConclusionsWe conclude that cumulative exposure to lead in the workplace was significantly associated with anemia risk. This study suggests that current BPb standard needs to be better understood for the application of lead-exposed population protection in different scenarios to provide a novel standard for health management. Low-level lead exposure risk is an occupational and public health problem that should be paid more attention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-017-4315-7) contains supplementary material, which is available to authorized users.
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