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

DIGIROLAMO FABIO; CARRILLO, CAROLINA; CAMMARATA, AGOSTINA; PEREIRA, CA; REIGADA, CHANTAL; SAYE, MELISA; GLISONI, ROMINA; MIRANDA, MARIANA; GALCERAN, FACUNDO; TORRES, PABLO; LABADIE, GUILLERMO

Woods hole

Congreso; Molecular Parasitology Meeting MPM XXXIII; 2022

Marine biological laboratory

Trypanosoma cruzi is the etiological agent of Chagas disease which affects around 7million people, mainly in Latin America. With the need to develop new therapeuticalternatives, 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 theinhibition of the proline transporter TcAAAP069 (LTD) or the polyamine permeaseTcPAT12 (ISO). With the aim of reducing toxicity and improving efficacy of ISO and LTDon 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 liposomalvesicles. The characterization of LTD, ISO and free drug liposomes indicated a meanparticle size of 300-400 nm, a size distribution (polydispersity index, PDI) of 0.1-0.2, anda zeta potential of approximately +2 mV. The encapsulation efficiency of ISO and LTDin liposomes was about 50 %. We also start with the evaluation of the trypanocidalactivity of ISO-loaded liposomes against T. cruzi epimastigotes. The IC50 value was 7.5µM being most effective than free ISO (IC50 = 30.6 µM), and the empty liposomespresented low toxicity. The trypanocidal activity of the formulations in the differentstages of the parasite is still in evaluation.