The introduction of Dexamethasone

Description

Dexamethasone is an organic compound with the chemical formula C22H29FO5. As a corticosteroid, it is similar to a natural hormone produced by adrenal glands. This drug is often used to replace this chemical when the body does not make enough of it. Dexamethasone has been widely used for the treatment of several diseases and in patients under chronic treatment[1].

Dex-P and Dex

Dexamethasone phosphate (Dex-P) is the pro-drug of Dexamethasone (Dex), being converted to Dex by the action of alkaline phosphatase. They are synthetic glucocorticoids derived from cortisol, an endogenous glucocorticoid with anti-inflammatory action. These drugs are thirty times more potent than cortisol and have a lower mineralocorticoid effect due to the presence of a flour atom in its structure. The more important difference between Dex and Dex-P is the higher aqueous solubility of Dex-P.

Uses

In recent decades, Dex has been widely used in several diseases due to its anti-inflammatory and immunosuppressive activity. It comes as an oral tablet, oral solution, eye drops, and ear drops. It's also available as an injectable solution or an intraocular solution given after surgery. This drug is used in patients with solid tumors to inhibit tumor progression, and as an adjuvant in chemotherapy, to reduce vomit, nausea, and fatigue; in ocular disease. Additionally, they are used for treating several allergy episodes and in local inner ear therapies. The application of these glucocorticoids in occlusive airway conditions such as asthma attacks is interesting; It is used to enhance lung maturation on fetuses and in patients with affected lungs due to the infection with COVID-19[2]. Dex arrives at the pulmonary alveolar sacs, interacting with the pulmonary surfactant. These surfactants form a monolayer in the alveolar sacs that contain lipids and proteins, composed of 80% phosphatidylcholine (PC). This film has the function of decreasing the surface tension in the interface during breathing.

Biocompatible

All types of dexamethasone were biocompatible in lower concentrations (0.03–300 µM)[3]. However, with increasing concentrations of dexamethasone, the viability of the cells in each group decreased, albeit to a differing extent. DEX-lab and DEX-med were safe up to 2000 µM (784 µg/mL; 0.0784 mg/mL), while DPS treatment was only safe up to 900 µM (464 µg/mL; 0.464 mg/mL; DPS-lab) and 1000 µM (516 µg/mL; 0.516 mg/mL; DPS-med).

References

[1] Formica F, et al. Cartilage-targeting dexamethasone prodrugs increase the efficacy of dexamethasone. Journal of Controlled Release, 2018; 295: 118-129.

[2] Cámara C, et al. Dexamethasone and Dexamethasone Phosphate: Effect on DMPC Membrane Models. Pharmaceutics, 2023; 15: 844.

[3] Gao Z, et al. Dexamethasone for Inner Ear Therapy: Biocompatibility and Bio-Efficacy of Different Dexamethasone Formulations In Vitro. Biomolecules, 2021; 11: 1896.