ASSESSMENT OF MUTAGENICITY OF POLYMERIC NANOPARTICLES OF COPPER (II) COMPLEX BY THE BACTERIAL REVERSE MUTATION TEST (AMES TEST)

RESENDE, FLÁVIA APARECIDA; ALEIXO, NADIA ANDRADE; BARUD, HERNANE DA SILVA; ISLAN, GERMAN A; CASTRO GR

Congreso; XVII CONGRESO LATINOAMERICANO DE GENÉTICA; 2021

Asociación Latinoamericana de Genética (ALAG)

CuCl2(INH)2.H2O (I1) complex, a copper (II) complex with isoniazid, is a potential candidate for antituberculosis therapy and it was encapsulated in polymeric nanoparticles (PN) made ofpolymethacrylate copolymers (i.e., Eudragit®, EU). Considering the preclinical requirements, in thisstudy we determined the mutagenic potential of PN produced by nanoprecipitation of EU in presence of poloxamer 188, based on the residual charges of EU, NE30D (neutral), S100 (carboxylated), and E100 (aminated). Mutagenic activity was evaluated by the Salmonella/microsome assay (Ames test), which uses bacteria as sensitive indicators of DNA damage, and a rat liver homogenate (S9 microsomal fraction) for metabolic conversion of carcinogens to their active mutagenic forms. In the present study, the Ames test was performed using TA98, TA100, TA97 and TA102 strains of Salmonella Typhimuriumin in experiments with (+S9) and without (-S9) metabolic activation system. The results obtained showed that PNNE30D, PN-S100, and PN-E100 did not induce any increase in the number of revertant colonies relativeto the negative control, indicating the absence of mutagenic activity, who contributed to the search for new safe formulations with biological activities. The absence of mutagenic effects in bacterial systems is encouraging, because although many compounds have considerable pharmacological activities, some undesirable properties such as mutagenicity, carcinogenicity and toxicity may restrict their use as therapeutic agent. In this context, it is important to continue the pharmacological and toxicological investigations of PN with I1 in order to determine themechanism(s) of action to guarantee their safer and more effective application to human health.