Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy

Joseph M Caster; Stephanie K Yu; Artish N Patel; Nicole J Newman; Zachary J Lee; Samuel B Warner; Kyle T Wagner; Kyle C Roche; Xi Tian; Yuanzeng Min; Andrew Z Wang

doi:10.1016/j.nano.2017.03.002

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Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy

Journal article

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Peer reviewed

Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy

Joseph M Caster, Stephanie K Yu, Artish N Patel, Nicole J Newman, Zachary J Lee, Samuel B Warner, Kyle T Wagner, Kyle C Roche, Xi Tian, Yuanzeng Min, …

Nanomedicine, Vol.13(5), pp.1673-1683

07/2017

DOI: 10.1016/j.nano.2017.03.002

PMCID: PMC5483200

PMID: 28300658

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https://www.ncbi.nlm.nih.gov/pmc/articles/5483200View

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Abstract

Nanoparticle (NP) chemotherapeutics can improve the therapeutic index of chemoradiotherapy (CRT). However, the effect of NP physical properties, such particle size, on CRT is unknown. To address this, we examined the effects of NP size on biodistribution, efficacy and toxicity in CRT. PEG-PLGA NPs (50, 100, 150 nm mean diameters) encapsulating wotrmannin (wtmn) or KU50019 were formulated. These NP formulations were potent radiosensitizers in vitro in HT29, SW480, and lovo rectal cancer lines. In vivo, the smallest particles avoided hepatic and splenic accumulation while more homogeneously penetrating tumor xenografts than larger particles. However, smaller particles were no more effective in vivo. Instead, there was a trend toward enhanced efficacy with medium sized NPs. The smallest KU60019 particles caused more small bowel toxicity than larger particles. Our results showed that particle size significantly affects nanotherapeutics' biodistrubtion and toxicity but does not support the conclusion that smaller particles are better for this clinical application.

Nanoparticles

Particle Size

Tissue Distribution

Rectal Neoplasms

Animals

Heterografts

Humans

Mice

Polymers

Chemoradiotherapy

Androstadienes - pharmacokinetics

Details

Title: Subtitle: Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy
Creators: Joseph M Caster - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: jcaster@unch.unc.edu
Stephanie K Yu - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Artish N Patel - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Nicole J Newman - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Zachary J Lee - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Samuel B Warner - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Kyle T Wagner - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Kyle C Roche - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Xi Tian - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Yuanzeng Min - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Andrew Z Wang - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Resource Type: Journal article
Publication Details: Nanomedicine, Vol.13(5), pp.1673-1683
DOI: 10.1016/j.nano.2017.03.002
PMID: 28300658
PMCID: PMC5483200
NLM abbreviation: Nanomedicine
ISSN: 1549-9634
eISSN: 1549-9642
Publisher: United States
Grant note: R01 CA178748 / NCI NIH HHS
Language: English
Date published: 07/2017
Academic Unit: Radiation Oncology
Record Identifier: 9984047727502771

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