Long-acting injectable medicine is a potential route to Covid therapy

A study conducted by the researchers from the University of Liverpool has shown the potential of repurposing an existing and cheap drug into a long-acting injectable therapy that could be used to treat Covid-19.

In a paper published in the journal Nanoscale, researchers from the University’s Centre of Excellence for Long-acting Therapeutics (CELT) demonstrate the nanoparticle formulation of niclosamide, a highly insoluble drug compound, as a scalable long-acting injectable antiviral candidate. The team started repurposing and reformulating identified drug compounds with the potential for COVID-19 therapy candidates within weeks of the first lockdown. Niclosamide is just one of the drug compounds identified and proved highly effective against SARS-CoV-2 in myriad laboratory studies.

Using their expertise in the fields of materials chemistry, long-acting drug delivery, and pharmacology, CELT scientists used nanoprecipitation to form dispersible solid drug nanoparticle formulations of niclosamide that can be stored as solids, reconstituted with water, and utilised as long-acting injectables. Their research has demonstrated sustained circulating drug concentrations may be maintained for the duration of early infection after a single injection.

CELT is co-directed by pharmacologist Professor Andrew Owen and materials chemist Professor Steve Rannard at the University of Liverpool.

Professor Steve Rannard said: “Repurposing drug compounds is much more than using existing medicines for a new disease. The existing active drug compound needs to be shown to be active at a significant level, then reformulated to address new challenges. The conventional route of administration may also not be relevant and modifying the way the patient receives the drug compound is highly critical to efficacy. Niclosamide is an ideal candidate to be taken forward as a potential long-acting injectable therapeutic to treat Covid-19.

“This is still in early-stage development but the CELT team are currently working with a contract manufacturing organisation to take this forward towards scale-up and clinical manufacture. This work is progressing well and if successful, human trials would be next. We envisage a future `Test-and-Treat’ scenario where infected people are treated at the point of diagnosis with the full course of therapy in one injection.”

Professor Andrew Owen said: “Repurposing of medicines for SARS-CoV-2 has yielded mixed results, with some clear successes for immunomodulatory drugs such as dexamethasone, and work underway to repurpose drugs like favipiravir and molnupiravir that were designed for other viruses.

“The ultimate utility of our long-acting injectable can only be determined inadequately powered and well-controlled randomised clinical trials but unlike other drugs that have been explored for repurposing niclosamide target concentrations may be achievable in humans. The formulation has shown great promise in preclinical studies at a time when it is increasingly evident that drugs are urgently required to complement the vaccines.