# Targeted Drug Delivery to Adipose Tissue Macrophages in Obesity

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $397,666

## Abstract

PROJECT SUMMARY
The rising worldwide incidence of obesity is inflicting a massive toll on our healthcare system due to
complications of type 2 diabetes, heart disease, and stroke. Recent evidence shows that chronic, low-grade
inflammation is the causal link between obesity and its associated pathologies. Visceral adipose tissue is the
initiating site, where pro-inflammatory macrophages are harbored in large numbers. These cells release
cytokines that alter local and systemic physiology, inducing glucose intolerance, insulin resistance, and
cardiovascular dysfunction. Therefore, pro-inflammatory macrophage cells in adipose tissue present an
obvious target for clinical intervention. We recently developed a novel strategy to efficiently deliver therapeutic
cargo to adipose tissue macrophages using polysaccharides delivered through the peritoneum. We observe
exceptionally high targeting efficiency (up to 63% of the injected dose) in mouse models of obesity.
Remarkably, when these polysaccharides are conjugated to anti-inflammatory prodrugs, a single dose reduces
gene expression of pro-inflammatory cytokines both in adipose tissue and blood. The delivery vehicle
(polysaccharides), linkers, and drugs are all FDA-approved such that these compounds could potentially be
rapidly translated to clinical testing. The goal of this proposal is to thoroughly and rationally develop these
nanomaterials-based prodrugs through mechanistic studies to understand the delivery process and the
physiological impact. We will perform quantitative biodistribution, cellular uptake, and multiscale imaging
studies to maximize delivery efficiency and further widen the therapeutic window. We will further apply cellular
and genomics assays in rodent models of obesity to test efficacy toward reducing local and systemic
inflammation, diabetic phenotype, and off-target side effects that are expected to be minimized compared with
free drug counterparts. Finally, we will optimize the delivery rate using chemical linkers and controlled-release
formulations to to generate a lead compound ready for translational studies by the conclusion of the award
period. Our highly multidisciplinary team is well suited to succeed in all aspects of this proposed work. Our
team includes experts in nanomaterials chemistry (Andrew Smith), animal models of obesity and diabetes
(Kelly Swanson), macrophage and obesity biology (Erik Nelson), quantitative imaging and biodistribution
(Wawrzyniec Dobrucki), veterinary pathology (Matthew Wallig), and translatable controlled release materials
(Benjamin Keselowsky). Success in this proposal will specifically provide a new therapy that can decouple
obesity from its comorbidities by inhibiting systemic inflammation, and more broadly yield families of anti-
inflammatory compounds with widened therapeutic windows due to high delivery efficiency to specific cells and
tissues. This preventative therapeutic strategy may similarly benefit patients suffering from the ever-e...

## Key facts

- **NIH application ID:** 9985808
- **Project number:** 5R01DK112251-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Andrew Michael Smith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,666
- **Award type:** 5
- **Project period:** 2016-09-19 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985808

## Citation

> US National Institutes of Health, RePORTER application 9985808, Targeted Drug Delivery to Adipose Tissue Macrophages in Obesity (5R01DK112251-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9985808. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*