공현준 (University of Illinois-Urbana-Champaign)

한빛사논문

조회264

University of Illinois-Urbana-Champaign

CV File 296 kb

Proc. Natl. Acad. Sci. USA, May 28 2024, 121 (22) | https://doi.org/10.1073/pnas.2314533121 Modeling of spatiotemporal dynamics of ligand-coated particle flow in targeted drug delivery processes

Shoaib A. Goraya^a, Shengzhe Ding^b, Ryan C. Miller^b, Mariam K. Arif^c, Hyunjoon Kong^b,d,1, and Arif Masud^a,d,1

^aDepartment of Civil and Environmental Engineering, University ofIllinois Urbana-Champaign, Urbana, IL 61801;

^bDepartment of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801;

^cFeinberg School of Medicine, Northwestern University, Chicago, IL 60611; and

^dDepartment of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61801

¹To whom correspondence may be addressed. : Hyunjoon Kong, Arif Masud

Abstract

Nanoparticles tethered with vasculature-binding epitopes have been used to deliver the drug into injured or diseased tissues via the bloodstream. However, the extent that blood flow dynamics affects nanoparticle retention at the target site after adhesion needs to be better understood. This knowledge gap potentially underlies significantly different therapeutic efficacies between animal models and humans. An experimentally validated mathematical model that accurately simulates the effects of blood flow on nanoparticle adhesion and retention, thus circumventing the limitations of conventional trial-and-error-based drug design in animal models, is lacking. This paper addresses this technical bottleneck and presents an integrated mathematical method that derives heavily from a unique combination of a mechanics-based dispersion model for nanoparticle transport and diffusion in the boundary layers, an asperity model to account for surface roughness of endothelium, and an experimentally calibrated stochastic nanoparticle-cell adhesion model to describe nanoparticle adhesion and subsequent retention at the target site under external flow. PLGA- b-HA nanoparticles tethered with VHSPNKK peptides that specifically bind to vascular cell adhesion molecules on the inflamed vascular wall were investigated. The computational model revealed that larger particles perform better in adhesion and retention at the endothelium for the particle sizes suitable for drug delivery applications and within physiologically relevant shear rates. The computational model corresponded closely to the in vitro experiments which demonstrates the impact that model-based simulations can have on optimizing nanocarriers in vascular microenvironments, thereby substantially reducing in vivo experimentation as well as the development costs.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-23)
연구진국외 연구진
분야 바이오·의료융합 > 바이오소재

댓글 작성 로그인

CV 열람하기

연락처 보기