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Updated: Sep 17, 2025
Author Spotlight: Developing a Disposable Dosator for Preclinical Testing of Dry Powder Inhalers in Small Animal Models
Published on: August 18, 2023
Development of an inhalable dry powder formulation for inhibition of SARS-CoV-2
Justin Stella1, Anja Germann2, Oliver Janka3
1Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus C4 1, 66123 Saarbrücken, Germany.
Abstract:
Coronaviruses, including SARS-CoV-2, can cause significant lung damage and may result in multiple organ failure. The severity of COVID-19 is determined by the virus's entry into lung tissue and subsequent replication. This entry is facilitated by the angiotensin-converting enzyme 2 (ACE2) in combination with the serine protease TMPRSS2, which is a critical step. To reduce viral replication, it is necessary to prevent the uptake of the virus directly at the main route of transmission, which is the deposition of the virus as an aerosol in the respiratory tract. To reduce viral uptake into lung cells, an inhalable dry powder formulation was developed. The formulation contains camostat, a clinically proven serine protease inhibitor that inhibits the cellular uptake mechanisms on the lung surface. Camostat was spray-dried together with the mucolytic agent N-acetylcysteine to produce co-amorphous microparticles with sufficient solubility after deposition. Microparticles with properties suited for deposition in the deep part of the respiratory tract can be produced by using appropriate spray-drying parameters. The use of L-leucine enabled suitable aerodynamic properties and storage stability due to reduced interaction with environmental water. The geometric particle diameter, determined using laser light diffraction, decreased with L-leucine content which was found forming a partially crystalline L-leucine shell. The disintegration behavior of the microparticle formulation simulated under lung-like conditions indicated fast disintegration. A pseudo-viral in vitro assay demonstrated low acute toxicity in combination with a high activity. Cell viability and proliferation were not affected by camostat concentrations up to 11.1 μg/mL. The IC50 values of the two dry powder formulations tested on a HEK293T/ACE2-TMPRSS2 cell line were 0.008 μg/mL and 0.019 μg/mL, respectively, which is at least 100 times lower than the cytotoxic concentration. This dry powder formulation serves as a prototype microparticle matrix for incorporating nanoscale drug carriers in the future.
Insights
An inhalable dry powder formulation containing camostat and N-acetylcysteine was developed to inhibit SARS-CoV-2 entry into lung cells. This novel formulation shows high antiviral activity with low toxicity, offering a promising strategy for COVID-19 treatment.
Area of Science:
- Pharmaceutical Sciences
- Virology
- Respiratory Medicine
Background:
- Coronaviruses like SARS-CoV-2 cause severe lung damage and organ failure by entering lung cells.
- Viral entry is facilitated by angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2.
- Preventing viral uptake in the respiratory tract is crucial for reducing replication and disease severity.
Purpose of the Study:
- To develop an inhalable dry powder formulation for inhibiting SARS-CoV-2 uptake into lung cells.
- To create a formulation with camostat, a serine protease inhibitor, and N-acetylcysteine, a mucolytic agent.
- To optimize microparticle properties for deep lung deposition and therapeutic efficacy.
Main Methods:
- Spray-drying camostat and N-acetylcysteine to form co-amorphous microparticles.
- Incorporating L-leucine to achieve suitable aerodynamic properties and storage stability.
- Evaluating microparticle disintegration, particle size, and aerodynamic performance.
- Assessing *in vitro* antiviral activity and cytotoxicity using pseudo-viral assays and cell lines.
Main Results:
- Microparticles demonstrated fast disintegration under simulated lung conditions.
- L-leucine content influenced particle size and aerodynamic properties, forming a protective shell.
- The dry powder formulation exhibited high antiviral activity with IC50 values significantly lower than cytotoxic concentrations.
- Camostat concentrations up to 11.1 μg/mL did not affect cell viability or proliferation.
Conclusions:
- The developed inhalable dry powder formulation effectively inhibits SARS-CoV-2 cellular uptake.
- The formulation shows promising *in vitro* efficacy and low toxicity, suitable for respiratory delivery.
- This microparticle matrix serves as a prototype for future drug delivery systems targeting respiratory viruses.
