Optimization and in vitro toxicity evaluation of G4 PAMAM dendrimer-risperidone complexes

M. JIMENA PRIETO; TEMPRANA FACUNDO; DEL RIO ZABALA, NAHUEL; MAROTTA HERNAN; ALONSO SILVIA

Beijing

Congreso; International Biophysics Congress and 12°Chinese Biophysics Congress; 2011

Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90 %). As new strategies to improve treatments efficiency are needed, we have estudied cationic G4 PAMAM dendrimers performance to act as efficient nanocarriers for this therapeutic drug. In this line, we explored dendrimer-risperidone complexation dependance on solvent, temperature, pH and salt concentration as well as in vitro cytotoxicity measured on L929 cell line and human red blood cells. Best dendrimer risperidone incorporation was achieved when a mixture of 70:30 and 90:10 v/v chloroform:methanol was used, obtaining 17 and 32 risperidone molecules per dendrimer, respectively. No cytotoxicity on L929 cells was found when dendrimer concentration was below 3 x 10-2 µM and risperidone concentration below 5.1 µM. Also no significant haemolysis or morphological changes were observed on human red blood cells. Finally, attempting to obtain an efficient drug delivery system for risperidone incorporation in G4 PAMAM dendrimers was optimized improving drug solubility with low cytotoxicity.