Encapsulation of drugs with anti-Trypanosoma cruzi activity in lipid liposomes

REIGADA C; DI GIROLAMO F; GALCERAN F; MARTÍNEZ SAYÉ M; CARRILLO C; TORRES P; GLISONI R; CAMMARATA A; LABADIÉ G; MIRANDA MR; PEREIRA CA

Congreso; Molecular Parasitology Meeting; 2022

Marine Biology Laboratory Woods Hole

Trypanosoma cruzi is the etiological agent of Chagas disease which affects around 7 million people, mainly in Latin America. With the need to develop new therapeutic alternatives, we have recently identified different drugs, approved for use in humans, with trypanocidal activity through a combined strategy of in silico and in vitro techniques, which include the antihistamine loratadine (LTD) and the retinoid isotretinoin (ISO), used for acne treatment. We have shown that these compounds act through the inhibition of the proline transporter TcAAAP069 (LTD) or the polyamine permease TcPAT12 (ISO). With the aim of reducing toxicity and improving efficacy of ISO and LTD on the intracellular stages of T. cruzi we formulated ISO or LTD-loaded lipid liposomes. The formulations were prepared with phosphatidylcholine and cholesterol in absoluteethanol and coated with chitosan, to obtain more stable and bioadhesive liposomal vesicles. The characterization of LTD, ISO and free drug liposomes indicated a mean particle size of 300-400 nm, a size distribution (polydispersity index, PDI) of 0.1-0.2, and a zeta potential of approximately +2 mV. The encapsulation efficiency of ISO and LTD in liposomes was about 50 %. We also start with the evaluation of the trypanocidal activity of ISO-loaded liposomes against T. cruzi epimastigotes. The IC50 value was 7.5 μM being most effective than free ISO (IC50 = 30.6 μM), and the empty liposomes presented low toxicity. The trypanocidal activity of the formulations in the different stages of the parasite is still in evaluation.