Effect of piplartine and cinnamides on Leishmania amazonensis, Plasmodium falciparum and on peritoneal cells of Swiss mice.

CONTEXT: Plants of the Piperaceae family produce piplartine that was used to synthesize the cinnamides. OBJECTIVE: To assess the effects of piplartine (1) and cinnamides (2-5) against the protozoa responsible for malaria and leishmaniasis, and peritoneal cells of Swiss mice. MATERIALS AND METHODS: Cultures of Leishmania amazonensis, Plasmodium falciparum-infected erythrocytes, and peritoneal cells were incubated, in triplicate, with different concentrations of the compounds (0 to 256 µg/mL). The inhibitory concentration (IC50) in L. amazonensis and cytotoxic concentration (CC50) in peritoneal cell were assessed by the MTT method after 6 h of incubation, while the IC50 for P. falciparum-infected erythrocytes was determined by optical microscopy after 48 or 72 h of incubation; the Selectivity Index (SI) was calculated by CC50/IC50. RESULTS: All compounds inhibited the growth of microorganisms, being more effective against P. falciparum after 72 h of incubation, especially for the compounds 1 (IC50 = 3.2 µg/mL) and 5 (IC50 = 6.6 µg/mL), than to L. amazonensis (compound 1 = 179.0 µg/mL; compound 5 = 106.0 µg/mL). Despite all compounds reducing the viability of peritoneal cells, the SI were <10 to L. amazonensis, whereas in the cultures of P. falciparum the SI >10 for the piplartine (>37.4) and cinnamides 4 (>10.7) and 5 (= 38.4). DISCUSSION AND CONCLUSION: The potential of piplartine and cinnamides 4 and 5 in the treatment of malaria suggest further pre-clinical studies to evaluate their effects in murine malaria and to determine their mechanisms in cells of the immune system.

Acetylated cashew gum-based nanoparticles for transdermal delivery of diclofenac diethyl amine.

Nanoprecipitation and dialysis methods were employed to obtain nanoparticles (NPs) of acetylated cashew gum (ACG). NPs synthesized by dialysis showed greater average size compared to those synthesized by nanoprecipitation, but they presented improved stability and yield. NPs were loaded with diclofenac diethylamine and the efficiency of the drug incorporation was over 60% for both methods, for an ACG:NP a weight ratio of 10:1. The cytotoxicity assay demonstrated that the NPs had no significant effect on the cell viability, verifying their biocompatibility. The release profile for the diclofenac diethylamine associated with the ACG-NPs showed a more controlled release compared to the free drug and a Fickian diffusion mechanism was observed. Transdermal permeation reached 90% penetration of the drug.