G4.5 Pamam Dendrimer-Risperidone: Biodistribution and Behavioral Changes in In Vivo Model

Abstract

Dendritic polymers are considered as emerging and outstanding carriers as modern medicinal systems due to their derivatisable branched architecture and possibility to modify them in numerous ways. Here, G4.5 PAMAM dendrimers were obtained as carriers of the antipsychotic drug risperidone. Despite their extensive applicability in the pharmaceutical field, the use of dendrimers as carriers in biological systems is constrained due to their inherent associated toxicity. The biocompatibility of dendrimers and dendrimer-risperidone complexes was evaluated in vivo for biological performance. To this end, the pharmacokinetics and biodistribution after oral treatment of free risperidone and dendrimer-risperidone complexes were studied in healthy mice. Also, the behavioral changes such as locomotion, aggression, dominance in male and female mice were evaluated both after a single dose and after daily therapy for 8 days. Also, in vivo effects of risperidone and dendrimer-risperidone complexes on the locomotion of zebrafish larvae were explored. The data obtained suggest that the unmetabolized risperidone complexes increase the arrival to the brain after 90 minutes. On the other hand, behavioral studies showed an increase in the potency of the drug in animals treated with the complexes