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A reanalysis of nanoparticle tumor delivery using classical pharmacokinetic metrics.

作者信息

Price Lauren S L, Stern Stephan T, Deal Allison M, Kabanov Alexander V, Zamboni William C

机构信息

Carolina Center of Cancer Nanotechnology Excellence (C-CCNE), University of North Carolina, Chapel Hill, NC, USA.

Translational Oncology and Nanoparticle Drug Development (TOND2I) Lab, University of North Carolina, Chapel Hill, NC, USA.

出版信息

Sci Adv. 2020 Jul 15;6(29):eaay9249. doi: 10.1126/sciadv.aay9249. eCollection 2020 Jul.


DOI:10.1126/sciadv.aay9249
PMID:32832614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7439617/
Abstract

Nanoparticle (NP) delivery to solid tumors has recently been questioned. To better understand the magnitude of NP tumor delivery, we reanalyzed published murine NP tumor pharmacokinetic (PK) data used in the Wilhelm . study. Studies included in their analysis reporting matched tumor and blood concentration versus time data were evaluated using classical PK endpoints and compared to the unestablished percent injected dose (%ID) in tumor metric from the Wilhelm . study. The %ID in tumor was poorly correlated with standard PK metrics that describe NP tumor delivery (AUC/AUC ratio) and only moderately associated with maximal tumor concentration. The relative tumor delivery of NPs was ~100-fold greater as assessed by the standard AUC/AUC ratio than by %ID in tumor. These results strongly suggest that PK metrics and calculations can influence the interpretation of NP tumor delivery and stress the need to properly validate novel PK metrics against traditional approaches.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/eb5866cec728/aay9249-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/98980cd21550/aay9249-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/e91a74c3de13/aay9249-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/2896cabe424c/aay9249-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/c778edc57f0b/aay9249-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/eb5866cec728/aay9249-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/98980cd21550/aay9249-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/e91a74c3de13/aay9249-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/2896cabe424c/aay9249-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/c778edc57f0b/aay9249-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d392/7439617/eb5866cec728/aay9249-F5.jpg

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本文引用的文献

[1]
Distinguishing Pharmacokinetics of Marketed Nanomedicine Formulations Using a Stable Isotope Tracer Assay.

ACS Pharmacol Transl Sci. 2020-3-13

[2]
Pharmacokinetics and Pharmacodynamics Modeling and Simulation Systems to Support the Development and Regulation of Liposomal Drugs.

Pharmaceutics. 2019-3-7

[3]
A Safe-by-Design Strategy towards Safer Nanomaterials in Nanomedicines.

Adv Mater. 2019-1-30

[4]
Evaluation of the efficiency of tumor and tissue delivery of carrier-mediated agents (CMA) and small molecule (SM) agents in mice using a novel pharmacokinetic (PK) metric: relative distribution index over time (RDI-OT).

J Nanopart Res. 2014-11-1

[5]
Formulation and physiologic factors affecting the pharmacology of carrier-mediated anticancer agents.

Expert Opin Drug Metab Toxicol. 2015

[6]
Effects of tumor microenvironment heterogeneity on nanoparticle disposition and efficacy in breast cancer tumor models.

Clin Cancer Res. 2014-12-1

[7]
Application of pharmacokinetic and pharmacodynamic analysis to the development of liposomal formulations for oncology.

Pharmaceutics. 2014-3-18

[8]
Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers.

J Clin Oncol. 2013-5-13

[9]
Statistics corner: A guide to appropriate use of correlation coefficient in medical research.

Malawi Med J. 2012-9

[10]
Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology.

Cancer Res. 2013-2-19

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