Engineering a nifurtimox nanosuspension: toward improved pharmaceutical attributes

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Drug Delivery

Background:

• Chagas disease, caused by Trypanosoma cruzi, is treated with Nifurtimox (NFX), a drug with poor solubility and erratic bioavailability.
• NFX's Biopharmaceutics Classification System class II/IV status necessitates strategies to enhance its dissolution and absorption.

Purpose of the Study:

• To develop and characterize a Nifurtimox nanosuspension (NFX-NS) using nanocrystals (NFX-NCs).
• To enhance NFX solubility and dissolution for improved therapeutic efficacy and pediatric administration.

Main Methods:

• NFX-NS was prepared via top-down, solvent-free wet milling, followed by lyophilization.
• Physicochemical characterization, solubility, dissolution, and in vitro biological evaluations were performed.

Main Results:

• The NFX-NS formulation achieved a particle size of ~200 nm with good stability (>120 days).
• NFX nanocrystals showed a tenfold increase in aqueous solubility and significantly improved dissolution rates.
• In vitro studies demonstrated enhanced anti-T. cruzi activity and improved biocompatibility of NFX-NCs.

Conclusions:

• NFX-NS represents the first nanocrystal-based formulation of NFX.
• This novel formulation effectively addresses NFX's solubility challenges, offering a promising alternative for Chagas disease treatment, particularly in pediatric populations.