FORMULATION OF LIPID NANOCAPSULES LOADED PRAZIQUANTEL AND BENZNIDAZOLE BY A PHASE INVERSION TECHNIQUE. A NOVEL THERAPY FOR NEGLECTED PARASITIC DISEASES?

ARRÚA C.; BASTIAT G.; SALOMON C.

Congreso; 4ta Reunión Internacional de Ciencias Farmacéuticas; 2016

FORMULATION OF LIPID NANOCAPSULES LOADED PRAZIQUANTEL AND BENZNIDAZOLE BY A PHASE INVERSION TECHNIQUE. A NOVEL THERAPY FOR NEGLECTED PARASITIC DISEASES?Arrua E.1,2, Bastiat G.3, Salomon C.1,2 arruacarolina@gmail.com1IQUIR-CONICET, Rosario, Argentina. 2Área Técnica Farmacéutica, Departamento Farmacia. Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR. 3MINT, INSERM U1066, IBS-CHU, Angers, France;Benznidazole (BZN) and praziquantel (PZQ)-loaded lipid nanocapsules (LNC) were developed in size of approximately 50 nm by means of a convenient and simple methodology. Preparation of BZN and PZQ-loaded LNC was based on a phase inversion method that allows the preparation of very small nanocapsules by a thermal manipulation of an oil/water system. Briefly, a solution of BZN or PZQ in acetone were incorporated in Labrafac and sonicated for 15 minutes. Then, these were heated to evaporate completely acetone. This phase was mixed with Lipoid® S75-3, sodium chloride, Kolliphor® HS15 and heated under magnetic stirring up to 90 oC ensuring that the phase inversion temperature is passed. The cooling step was then performed until an exact temperature of 50 oC was reached, again, completely passing the phase inversion zone. This cycle was repeated twice before adding 5ml of distilled water at 04 oC. The hydrodynamic diameter, polydispersity index and zeta potential of LNC were determined by dynamic light scattering using a Zetasizer® Nanoseries DTS 1060. BZN and PZQ-loaded LNC were diluted 1:60 (v/v) in deionized water in order to ensure convenient scatter intensity on the detector; each measurement was done in triplicate at 25°C. It was evaluated the activation of the complement system in normal human serum by measuring the residual haemolytic system capacity after being in contact with the non-loaded LNC and containing hydrophobic drugs. To this suspension they were diluted to a final concentration of 5 mg/ml of LNC. Average diameter of the LNC was similar to that obtained in the absence of drugs, 50 nm, polydispersity index less than 0.07, which would indicate homogeneous size distribution. It is observed that activation of the complement system by the drug-loaded LNC was similar to that obtained with the non-loaded LNC, which may be because the drug would be found encapsulated in the LNC core. In addition, the drug-loaded LNC similar results regarding the surviving cells for 24 and 48 hours after the start. Studies are currently under way to further investigate the in vivo performance of these LNC.