Cyclodextrin-Based Delivery System for a Nitrosyl Ruthenium Complex: Potential Application against Leishmania braziliensis

Leishmaniasis treatment faces challenges including high drug toxicity and resistance. To address these, researchers developed a supramolecular delivery system (RuNO@CD) by encapsulating the antileishmanial ruthenium nitrosyl complex (RuNO) within 2-hydroxypropyl-β-cyclodextrin (HP-βCD). This encapsulation significantly improved RuNO's aqueous solubility (from 6.1 to 65 mmol/L) and ensured long-term stability. The system forms stable nanoaggregates and allows for controlled nitric oxide (NO) release, with the cyclodextrin cavity acting as a steric barrier during chemical reduction by L-glutathione. Under blue-light irradiation, the system maintained effective photolytic NO release. Biocompatibility tests in RAW 264.7 macrophages confirmed low toxicity, and the complex achieved a 70% reduction in intracellular Leishmania braziliensis amastigotes. Overall, this strategy successfully optimizes the pharmacological profile of RuNO, offering a promising candidate for improved leishmaniasis therapy.