Background: Particle size is a key parameter for drug-delivery nanoparticle design. It is believed that the size of a nanoparticle may have important effects on its ability to overcome the transport barriers in biological tissues. Nonetheless, such effects remain poorly understood. Using a multiscale model, this work investigates particle size effects on the tissue distribution and penetration efficacy of drug-delivery nanoparticles.

Results: We have developed a multiscale spatiotemporal model of nanoparticle transport in biological tissues. The model implements a time-adaptive Brownian Dynamics algorithm that links microscale particle-cell interactions and adhesion dynamics to tissue-scale particle dispersion and penetration. The model accounts for the advection, diffusion, and cellular uptakes of particles. Using the model, we have analyzed how particle size affects the intra-tissue dispersion and penetration of drug delivery nanoparticles. We focused on two published experimental works that investigated particle size effects in in vitro and in vivo tissue conditions. By analyzing experimental data reported in these two studies, we show that particle size effects may appear pronounced in an in vitro cell-free tissue system, such as collagen matrix. In an in vivo tissue system, the effects of particle size could be relatively modest. We provide a detailed analysis on how particle-cell interactions may determine distribution and penetration of nanoparticles in a biological tissue.

Conclusion: Our work suggests that the size of a nanoparticle may play a less significant role in its ability to overcome the intra-tissue transport barriers. We show that experiments involving cell-free tissue systems may yield misleading observations of particle size effects due to the absence of advective transport and particle-cell interactions.


Chemical and Biochemical Engineering


Part of the research presented in this work is supported by the National Science Foundation CBET-CDS&E grant 1609642. The rest of the support came through the PI's startup fund at Missouri S&T.

Keywords and Phrases

Brownian Dynamics; Diffusion; Drug Delivery; Porous Media; Tumor

International Standard Serial Number (ISSN)


Document Type

Article - Journal

Document Version

Final Version

File Type





© 2017 BioMed Central Ltd., All rights reserved.

Creative Commons Licensing

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Publication Date

01 Nov 2017

PubMed ID