Dental Tribune India

Editorial on Dexamethasone: Why Nano−Dexa formulations are the need of the hour in Covid times

By Rajeev Chitguppi, Dental Tribune South Asia
August 04, 2020

Nano-formulations of dexamethasone administered either IV or via inhalation may help to improve COVID-19 treatment outcomes. This editorial summarizes how we can improve our Covid-19 treatment options further by potentiating the already established anti-edema activity and anti-fibrotic effects of free dexamethasone via nanomedicine.

Evidence in recent times has shown that a significant number of severe Covid-19 cases and related fatalities are due to an overreaction of the immune system leading to hyperinflammation and macrophage activation, which in turn results in an overproduction of proinflammatory cytokines (eg. IL-1β, IL-6, and TNF-α) also known as a cytokine storm. This process also results in coagulation abnormalities, which contribute to organ failure and fatalities. Even the RECOVERY trial results indicate that the health status of patients at 1-week post-COVID-19 infection is primarily debilitated NOT by viral replication but by immunological phenomena.

Dexamethasone the first drug to show life-saving efficacy in patients infected with COVID-19.

  1. Dexamethasone reduces COVID-19 deaths by 35% in ICU patients who need mechanical ventilation.
  2. In non-ventilated patients on oxygen therapy, dexamethasone reduces the mortality rate by 20%.
  3. Moreover, shorter hospitalization time and a higher probability of hospital discharge within 28 days.

Dexamethasone enjoys the evidence of being the first and the only drug so far to significantly improve survival chances in COVID-19 patients. Another advantage for dexamethasone is it's a very well-known, well studied, and extensively used drug, which is widely available and very cheap.

It can be tried as a nanomedicine to be administered either IV or by inhalation.

  1. Arikayce, a nanomedicine formulation, gives better clinical results than free amikacin because the nanoformulation enables it to target the pulmonary macrophages more efficiently. Similarly, if we develop a nano-DEXA formulation its pulmonary delivery may outperform free dexamethasone in targeting alveolar macrophages as a strategy to intervene in the (sub)acute phase of COVID-19.
  2. IV nanoformulations can help in efficient and selective delivery of Dexamethasone to the inflammation-initiating and inflammation -propagating phagocytic cells in the lung, in the blood, and in myeloid and lymphoid tissues. This will reduce the production of proinflammatory cytokines, matrix-degrading enzymes and other molecules that lead to edema formation and progressive tissue damage in COVID-19.

Either way - administration by IV or inhalation -  the nano-Dexa particles can be made to accumulate in macrophages, which will only potentiate further the already established anti-edema activity and anti-fibrotic effects of dexamethasone.

Nano-formulation of medicines costs time and money. But if the targeted delivery of nano-Dexa in COVID-19 patients leads to better clinical outcomes, eg. reduced hospital stay, reduced requirement for ICU and mechanical ventilation, apart from higher survival chances and reduced long-term residual effects fo the patients, the higher cost of the medicine would be justifiable.
A recent publication Dexamethasone nanomedicines for Covid-19 details the mechanisms by which nano-Dexa formulations can significantly change the treatment outcomes currently observed in Covid-19.

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