Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Cheng, Yi-Hsien1, 2
  • He, Chunla1
  • Riviere, Jim E1, 3
  • Monteiro-Riviere, Nancy A2
  • Lin, Zhoumeng1, 2
  • 1 Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, United States. , (United States)
  • 2 Nanotechnology Innovation Center of Kansas State (NICKS), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, United States. , (United States)
  • 3 1Data Consortium, Kansas State University, Manhattan, Kansas 66506, United States. , (United States)
Type
Published Article
Journal
ACS Nano
Publisher
American Chemical Society
Publication Date
Mar 24, 2020
Volume
14
Issue
3
Pages
3075–3095
Identifiers
DOI: 10.1021/acsnano.9b08142
PMID: 32078303
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

Report this publication

Statistics

Seen <100 times