Biosurfactants as stabilizers of niclosamide nanocrystals: Enhancing stability, solubility, and cytotoxicity profiling

Abstract

Biosurfactants are surface-active compounds of biological origin, stable over a wide range of temperature, pH, and salinity. In this work, the ability of the biosurfactants rhamnolipid (RAM), sophorolipid (SOFO) and surfactin (SURF) to stabilize a nanocrystal suspension of niclosamide (NCL) in water, and to enhance the drug solubility were evaluated. The performances were compared with those of the synthetic surfactants tween 80 (TW) and soluplus (SOLU). Overall, RAM, SOFO, and SURF proved to be as effective as TW and SOFO in terms of NCL nanocrystal suspension stabilization. Formulations containing 3 % (w/w) surfactant exhibited the best stability at 4 °C and 25 °C. The three biosurfactants also led to an improvement of aqueous NCL solubility, even when a slurry of the micronized drug was used without nanocrystal formulation. The best performance was observed for the SURF 3 % (w/w) nanocrystal formulation (1157.48 μg/mL), which released more than twice the amount of NCL compared to the best synthetic surfactant formulation (TW 3 % (w/w), 542.57 μg/mL), and 622 times more than the pure solid drug (1.86 μg/mL). Cell viability was not compromised by the surfactants alone, indicating that the formulation cytotoxic effect is related to the enhanced solubilization of NCL. Consistently, the NCL/SURF formulation was the most effective, achieving a maximum cytotoxicity effect of 80 % at a concentration of 1000 nM, while the other formulations reached a maximum effect of 71 % at concentrations starting from 1500 nM. Nevertheless, when the balance between formulation stability, drug release enhancement, and cytotoxicity is considered the three biosurfactants studied in this work showed significant potential advantages relative to synthetic analogues that can be explored in pharmaceutical development.