# Targeted delivery of TB therapeutics

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $251,250

## Abstract

Project Abstract:
 Tuberculosis (TB) causes an estimated 10 million new cases each year and remains one of the leading
causes of infectious death. While the current “short” chemotherapy regimen is generally effective, it must be
delivered for an extended period and the evolution of resistant clones is common. Treatment options for drug-
resistant infections requires the use of less effective or more toxic agents. Current evidence suggests that limited
drug exposure within the TB granuloma is responsible for these deficiencies. Thus, concentrating TB drugs
within the granuloma has been a long-standing goal that could enhance bacterial clearance, reduce the
emergence of drug resistance, and facilitate the use of second-line drugs that are limited by their systemic
toxicity. Our group has developed a flexible delivery platform technology for the high efficiency encapsulation of
compounds within glucan particles (GP), which are avidly taken up by macrophages via glucan receptors,
selectively targeting cargo to these cells. Using this strategy, we found that we can efficiently concentrate both
isoniazid and clofazimine in Mtb-infected macrophages ex vivo, increasing the potency of these drugs by up to
100-fold. We now plan to expand these studies by optimizing the encapsulation and delivery of additional drugs
using the ex vivo macrophage model, and perform a proof of principle animal study to determine if we can
effectively target drugs to the site of infection and enhance bacterial killing. If successful, this exploratory project
will lay the groundwork for a longer-term project with the potential to transform TB therapy.

## Key facts

- **NIH application ID:** 10128706
- **Project number:** 1R21AI151842-01A1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** CHRISTOPHER M SASSETTI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $251,250
- **Award type:** 1
- **Project period:** 2020-12-17 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128706

## Citation

> US National Institutes of Health, RePORTER application 10128706, Targeted delivery of TB therapeutics (1R21AI151842-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10128706. Licensed CC0.

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