# Targeted delivery of antifungal drug loaded liposomes to control mucormycosis

> **NIH NIH R21** · UNIVERSITY OF GEORGIA · 2022 · $188,750

## Abstract

PROJECT SUMMARY
 Invasive fungal diseases (IFDs) cause millions of deaths each year and they are refractory to treatment.
Mucormycosis is responsible for 20 to 30% of life threatening invasive fungal disease cases and has been
ranked the third most important fungal disease after aspergillosis and candidiasis, afflicting close to one million
people annually. One species of Mucorales, Rhizopus delemar is responsible for most cases of mucormycosis.
Patients at the greatest risk of developing mucormycosis have weakened immune systems such as HIV/AIDS
patients. The vulnerable population is increasing due to increasing numbers of individuals taking
immunosuppressive drugs for stem cell or organ transplants and medical device implantation. An infected
individual’s medical cost often exceed $100,000. Liposomal amphotericin B (AmB) is the most commonly
prescribed treatment, but AmB has serious limitations due to human organ toxicity, the lack of sufficient
fungicidal effect at safe doses and safety at limited treatment periods, and the emergence of resistant fungi.
Even with treatment, there is still approximately a 30% to 50% mortality rate. We created a transformative
technology in which almost any antifungal drug may be delivered specifically to the fungal cell wall and/or their
secreted exopolysaccharide matrices to increase drug efficacy by orders of magnitude. This technology and
the conceptual framework support it meeting the critical need for dramatically improved antifungal therapeutics.
 We have employed the carbohydrate recognition domain of the C-type lectin receptor Dectin-1 to target
liposomal packaged antifungals to fungal glucans. Antifungals such as Amphotericin B packaged in liposome
penetrate the endothelium, have longer half-lives and less infusion toxicity than detergent solubilized drugs.
We have remarkably strong data showing that Dectin-1-targeted Amphotericin B-loaded liposomes improved
the binding efficiency of liposomal AmB 1,000-fold over untargeted liposomes and killed R. delemar more
efficiently. The deliverables of this high-risk high-reward proposal include (1) demonstrating the potential of
Dectin-1 targeted liposomes loaded with AmB or Anidulafungin (AFG), DEC1-AmB-LLs and DEC1-AFG-LL,
alone and in combination, to inhibit and/or kill R. delemar in vitro as compared to untargeted drug-loaded
liposomes or free drugs and (2) to demonstrate the enhanced efficacy of DEC1-AmB-LL and DEC1-AFG-LL
alone and in combination to treat pulmonary mucormycosis in a neutropenic mouse model, as compared to
untargeted drugs. We believe this research will contribute to an eminent paradigm shift for the treatment of all
IFDs in the clinic, which will stimulate new activity in the antifungal pharmaceutical industry.
 We have an established team of scientists already combining their expertise in diverse areas of science
necessary to carry out these experiments. We have developed an experimental platform to rapidly innovate
and reiteratively tes...

## Key facts

- **NIH application ID:** 10509943
- **Project number:** 1R21AI171787-01
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Richard Brian Meagher
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $188,750
- **Award type:** 1
- **Project period:** 2022-07-20 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10509943

## Citation

> US National Institutes of Health, RePORTER application 10509943, Targeted delivery of antifungal drug loaded liposomes to control mucormycosis (1R21AI171787-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10509943. Licensed CC0.

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