Inhaled steroids coated with liposomes may help COVID-19 patients

Using corticosteroids to dampen severe lung inflammation in COVID-19 patients has been hotly debated. Although people with asthma use inhalers regularly to combat and prevent asthma attacks, steroids can dampen the immune response, making patients less equipped to fend off a severe viral infection. Now, corticosteroids are regularly used to treat COVID-19 patients, and some researchers suspect that regular corticosteroid use by asthma patients protects them from severe infection. 

Corticosteroids can cause side effects like weight gain, and patients don’t always remember to take them daily as prescribed. Kameswari Konduri, the cofounder of VGSK Technologies Inc., found a way to improve patient compliance and limit side effects: a delivery system that only requires a single dose every week. The delivery system propels corticosteroids deep into the lungs, where COVID-19 infects a subset of lung cells, making it a contender for delivering COVID-19 treatments. Recently, Konduri reported preliminary evidence in mice and cell lines that her product may help COVID-19 patients breathe easier, and it may even stop viral replication (1).

Konduri’s delivery system, dubbed ProLung-budesonide, coats the corticosteroid budesonide in a modified lipid that protects it from quickly degrading, allowing for lower, longer lasting doses (2). She previously demonstrated that the liposomal delivery system reduced asthma-induced inflammation when administered weekly, achieving results similar to daily treatment with uncoated inhaled budesonide. 

In her recent preprint article posted on bioRxiv, Konduri described using a mouse model of asthma to determine where ProLung-budesonide localized in the lung. These mice were not infected with COVID-19 since mice only develop mild disease, making them ineffective models for characterizing the human inflammatory response to COVID-19.

Konduri imaged lung tissue using electron microscopy to determine if ProLung-budesonide was effectively administered to mouse lungs for a sustained period. To her surprise, ProLung-budesonide localized to type II pneumocytes, the cells deep in the lungs where COVID-19 binds the ACE2 receptor, for up to ten days after initial treatment.

Konduri contacted the Division of Microbiology and Infectious Disease at NIH, which helps researchers test new therapeutics with potential to treat COVID-19. Researchers at the NIH assisted in using a range of doses of ProLung-budesonide to treat animal cells infected with COVID-19, and calculated efficacy using the amount of virus and viable cells after treatment. They compared the drug’s efficacy to that of a protease inhibitor known to decrease COVID-19 replication in mammalian cells. ProLung-budesonide decreased viral replication by 90% when used at half the concentration of the protease inhibitor.

“It’s an interesting study,” said Michael Wechsler, a pulmonologist from National Jewish Health who was not involved in this study, in an email. But “it’s hard to know what the effect of corticosteroids on viral replication is in humans and in the setting of actual infection.”

Konduri is consulting with the Division of Microbiology and Infectious Disease at the NIH to move forward with a clinical trial. She’s filling out paperwork right now. Starting a clinical trial is a daunting task in the time of COVID-19. She needs to raise the funds for the trial, and also needs to find a way to manufacture enough ProLung-budesonide for the inhalers; manufacturers are overwhelmed right now due to pandemic-related challenges. 

But she isn’t ready to give up yet.

“This entity is actually inhibiting the viral replication from occurring, so it could be a good therapy for COVID. Getting into the clinical trial phase needs a lot of support, and that’s what we’re hoping to get,” she said.

References 

1. Konduri, K.S. et al. ProLung™-budesonide Inhibits SARS-CoV-2 Replication and Reduces Lung Inflammation. bioRxiv (2021).
2. Konduri, K.S. et al. Efficacy of liposomal budesonide in experimental asthma. J Allergy Clin Immunol 2, 321-327 (2003).