Trypanocidal activity of liposomal isotretinoin and loratadine formulations

Abstract

We previously identified the antihistamine loratadine (LTD) and the medication for severe acne isotretinoin (ISO), as repositioned drugs for Chagas disease that showed strong activity against Trypanosoma cruzi. In this study, we evaluated the trypanocidal efficiency of LTD and ISO using liposomes that increase their low water solubility and facilitate their internalization allowing the reduction of the drug effective dose.Liposomes were prepared with phosphatidylcholine and cholesterol, and coated with chitosan. The average diameter, polydispersity index and Zeta-potential of LTD, ISO and unloaded liposomes were characterized by dynamic light scattering. The drug encapsulation efficiency in vesicles was determined by high performance liquid chromatography. Their trypanocidal effects were evaluated on the T. cruzi parasites.ISO and LTD liposomes inhibited epimastigote proliferation and trypomastigote viability of T. cruzi, and both formulations were significantly more potent than benznidazole, the drug currently used to treat Chagas disease. We also showed that the storage stability of ISO, that represents a relevant issue, was improved after encapsulated it in liposomes.This encapsulation of LTD and ISO in liposomes that significantly increased their trypanocidal effect and stability, encourage the use of carriers as drug delivery systems.