Complexation of amiodarone and nimodipine with hydroxypropyl-beta cyclodextrin as potential anti-leishmania agents in a combination formula with hexadecylphosphocholine.

GLISONI RJ.; DELGADO MURCIA G.; SOSNIK A.

Mar del Plata, Argentina

Congreso; Reunión Conjunta 2016 SAIC-SAI-SAFE NANOMED-AR; 2016

SAIC-SAI-SAFE NANOMED-AR

Introduction/Goal. Leishmaniasis is a zoonotic disease caused by the parasites infection of the genus Leishmania which induces cutaneous, mucocutaneous or visceral involvements. In the world, there are more than 350 million people at risk of disease and each year about 2 million new cases are reported. The treatment can be performed with pentavalent antimonial, amphotericin B, pentamidine or hexadecylphosphocholine (HPC), which can throw serious adverse events and increased resistance, why it is urgent the research for new therapeutic tools or improving the existing ones. The amiodarone (AMI) and nimodipine (NMP) drugs have shown in vitro activity against trypanosomatides but in vivo activity against L. panamensis, the main causative agent of cutaneous leishmaniasis in Colombia, has not been yet evaluated. Because both drugs have a very poor solubility in aqueous media (260 and 0.5µg/mL, respectively) and before the evaluation of its effectiveness in an in vivo model of infection, it is that it was investigated the complexation ability of HPβCD to improve the aqueous solubility of AMI and NMP as an approach to develop a pre-nanoformulation for topical treatment of cutaneous leishmaniasis in combination with HPC, which it is well known to be irritant topically. Outstanding Results. Increments up to 37 and 271 times for AMI and NMP were achieved in the presence of HPβCD (10% w/v). On the other hand, the complexes obtained were fully characterized by different techniques (size and Z-pot by DLS, ATR/FTIR, XRD and SEM). The average size ranged from 145-175nm (PDI= 0.09-0.62). The physical stability of the complexes in solution (4°C) was preserved up to 1 month. Conclusions. The solubility of AMI and NMP in aqueous medium has been successfully increased by complexation with HPβCD. HPC meanwhile could also be complexed. Overall results support the next stage of evaluation in an in vivo model of infection of Leishmania with potential additional pharmacokinetic advantages.