# Stochastic Modeling of Tissue Injury, Edema and Targeted Drug Delivery

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $190,000

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Masud, Arif
 Targeted drug delivery using a nano-sized carrier is a multi-faceted problem that aims at achieving
maximum efficacy with minimum dose of medicine. This problem gets compounded in biological systems
due to their inherent uncertainty and spatiotemporal inhomogeneity. The sources of uncertainty are both
aleatory and epistemic, stemming from natural variability, information uncertainty, and modeling
approximations at multiple levels. Information uncertainty arises from sparse and imprecise data on
hydrodynamic effects and drug transport via blood flow, propensity of the targeted tissue to absorb the
drug, clinical measurement and imaging data .,processing errors, and qualitative information. Model
uncertainty arises due to unknown model parameters, model form assumptions, and solution approximation
errors. Unlike deterministic analysis typically employed in engineered systems, modeling and analysis
methods for biological systems need to be grounded in stochastic methods and associated robust
numerical formulations. These models can then be employed to carry out simulation-based statistical
analysis of the effect of the various combinations of the modeled parameters thereby establishing risk
informed decision guidelines.
 We hypothesize that size and shape of drug carriers play a significant role in increasing the number of
drug carriers reaching targeted, injured tissue and, in turn, drugs available for treatments. A mathematical
framework for stochastic models and associated computer code will be developed to simulate an ischemic
vascular injury and subsequent edema in perivascular tissue and optimize geometry of drug carriers with
minimal trials-and-error. We will examine the hypothesis by validating the developed mathematical model
with drug carriers both in vitro and in vivo with a two-pronged approach. We will develop a variational
framework for coupling stochastic PDEs for drug delivery and reduce dimensionality of the stochastic
system via a novel fine-scale modeling concept. The mathematical framework will be validated via
experimentation of drug carrier transport to targeted tissue using in vitro microfluidic and in vivo mouse
models of the acute limb ischemia. The in vivo mouse model will generate data for the development of the
mathematical model and for its calibration and validation. The new method and the computer codes will be
applied to optimize adhesion and transendothelial migration of drug carriers to a target vascular wall,
accounting for optimal particle size and shape. These studies will be of direct relevance to improving quality
of patient care and health.

## Key facts

- **NIH application ID:** 10252849
- **Project number:** 5R01GM135921-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** ARIF MASUD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $190,000
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10252849

## Citation

> US National Institutes of Health, RePORTER application 10252849, Stochastic Modeling of Tissue Injury, Edema and Targeted Drug Delivery (5R01GM135921-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10252849. Licensed CC0.

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