Optimization and in vivo toxicity evaluation of G4.5 PAMAM Dendrimer-Risperidone complexes

PRIETO M. JIMENA; DEL RIO ZABALA, NAHUEL; MAROTTA HERNAN; CARREÑO GUTIERREZ H; AREVALO AREVALO ROSARIO ; CHIARAMONI NADIA SILVIA; ALONSO, SILVIA DEL VALLE

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2014 vol. 2

1932-6203

Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubilityin aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (.90%). Sincenew strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers asnanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence onsolvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone moleculesper dendrimer) was achieved with a mixture of chloroform:methanol 50:50 v/v solution pH 3. In addition, to explore thepossible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development ofdopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiologicalchanges were studied through histological sections stained with hematoxylin-eosin to observe possible morphologicalbrain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changeswere observed when larvae were treated with the complex.