# Microneedle Delivery of Zanamivir for the Treatment of Influenza Infections

> **NIH NIH R44** · TSRL, INC. · 2024 · $998,663

## Abstract

Abstract
Yearly influenza epidemics strike millions of people, causing up to 500,000 deaths. Fatality caused by most
seasonal influenza viruses is <0.03%, but with significant mortality in the young and the elderly populations.
When a new pathogenic influenza strain enters the population, a pandemic could kill tens of millions of people
with a negative economic impact estimated to be over 150 billion dollars. Due to the incomplete efficacy of the
current vaccines, effective drug treatment is necessary. Presently, influenza treatment is only somewhat
effective, and some influenza strains are resistant to the currently marketed therapeutics, adamantanes and the
neuraminidase inhibitor Tamiflu®. However, while zanamivir (ZAN, Relenza®) remains highly active against
oseltamivir-resistant influenza strains, its therapeutic impact is severely limited by its route of administration, via
oral inhalation, which renders it unsuitable for patients with a compromised respiratory system. Therefore,
development of a novel delivery alternative for ZAN as we propose here, is poised to address a significant unmet
medical need.
Transdermal drug delivery offers a number of improvements over other delivery systems. The drug directly enters
the systemic circulation, circumventing absorption and first-pass barriers typical for oral delivery. It avoids skin
puncture by syringe needles, eliminating pain and patient visits to a clinician. Transdermal delivery of ZAN could
allow large numbers of patients to be reached during an influenza outbreak, which will be particularly important
in light of the added risk during the ongoing COVID-19 pandemic. While ZAN itself cannot cross the human skin
barrier at therapeutic rates, Microneedle (MN) - enhanced transdermal delivery is an elegant, efficient, and
painless method for increasing the skin permeation of many drugs, including ZAN. Our novel drug-device
combination product, TSR-066, consists of a swellable MN patch, which will continuously deliver ZAN over 5
days. This CRP proposal will support optimization and scale-up of the ZAN MN formulation and subsequent IND-
enabling toxicology studies in minipigs. We have obtained agreement with the FDA on the preclinical studies
needed in order to open the IND, as well as on the Phase I clinical development plans and the 505(b)2 regulatory
strategy. In addition to the experimental work proposed here, we will develop a robust IP expansion strategy for
the current ZAN MN product, as well as future product candidates that stand to benefit from MN-enabled delivery.
The end result of this work will be a novel, transdermal delivery approach for ZAN, which will expand its reach
into patient groups for which Relenza® is contraindicated and allow for simple administration for ZAN for both
treatment and prevention of the flu. We have assembled a team of expert advisors and collaborators to ensure
successful completion of this research plan.

## Key facts

- **NIH application ID:** 10823342
- **Project number:** 5R44AI129122-08
- **Recipient organization:** TSRL, INC.
- **Principal Investigator:** Elke Lipka
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $998,663
- **Award type:** 5
- **Project period:** 2017-03-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823342

## Citation

> US National Institutes of Health, RePORTER application 10823342, Microneedle Delivery of Zanamivir for the Treatment of Influenza Infections (5R44AI129122-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10823342. Licensed CC0.

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