8 Sept 2023 • 15% – 19% of AIDS-related mortality worldwide is caused by HIV–associated cryptococcal disease. The gold standard therapy for cryptococcal meningitis has traditionally been intravenous (IV) amphotericin B plus flucytosine for 1–2 weeks or liposomal amphotericin at 10 mg/kg once .

However, IV amphotericin has been reported to be associated with potentially life-threatening toxicities such as kidney impairment, anemia, thrombophlebitis, and electrolyte abnormalities.

Along with its adverse effect profile, administering IV amphotericin is logistically challenging, requiring hospitalization and rigorous laboratory monitoring.

A novel lipid nanocrystal (LNC) oral amphotericin B has been developed as an alternative to IV- administered amphotericin comprising 3 components: amphotericin B, calcium, and phosphatidylserine, a natural phospholipid derived from soy.

• When the LNC is administered, target cells like macrophages engulf and transport LNCs to sites of infection.

• Once the LNC is captured intracellularly, the low intracellular calcium concentration triggers nanocrystals to open, releasing the drug inside the cell.

• Because LNC amphotericin is locked up inside the solid nanocrystal particle, the body is protected from amphotericin toxicity.

An open-label, phase 2, randomized trial to evaluate the anti-fungal efficacy of oral LNC amphotericin in HIV-associated cryptococcal meningitis demonstrated similar CSF anti-fungal activity and 18-week survival when compared to the standard 7-day course of IV amphotericin with flucytosine. Also, the toxicity associated with LNC amphotericin formulation was reportedly better than IV formulations.

Researchers speculate that if LNC amphotericin with flucytosine can treat a 100% fatal fungal infection of the brain in severely immunocompromised individuals with HIV, treatment of other fungal infections should be possible, however further clinical trials will be necessary to confirm the same.

Source: OXFORD | Read full story