title: Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone complexes.
abstract: 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%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex.
authors.affiliation: Biomembrane Laboratory, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina ; IMBICE-CONICET, CCT La Plata, Argentina.
authors.forename: Maria Jimena
authors.initials: MJ
authors.lastname: Prieto
authors.affiliation: Biomembrane Laboratory, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina ; IMBICE-CONICET, CCT La Plata, Argentina.
authors.forename: Nahuel Eduardo
authors.initials: NE
authors.lastname: del Rio Zabala
authors.affiliation: Biomembrane Laboratory, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina ; IMBICE-CONICET, CCT La Plata, Argentina.
authors.forename: Cristian Hernán
authors.initials: CH
authors.lastname: Marotta
authors.affiliation: Department of Cell Biology and Pathology, Institute of Neuroscience of Castilla y Leon, School of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Hector
authors.initials: H
authors.lastname: Carreño Gutierrez
authors.affiliation: Department of Cell Biology and Pathology, Institute of Neuroscience of Castilla y Leon, School of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Arévalo Arévalo
authors.affiliation: Biomembrane Laboratory, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina ; IMBICE-CONICET, CCT La Plata, Argentina.
authors.forename: Nadia Silvia
authors.initials: NS
authors.lastname: Chiaramoni
authors.affiliation: Biomembrane Laboratory, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina ; IMBICE-CONICET, CCT La Plata, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: del Valle Alonso
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D064032:Calbindin 2 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004337:Drug Carriers; D015870:Gene Expression; D006863:Hydrogen-Ion Concentration; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018967:Risperidone / Q000737:chemistry / Q000494:pharmacology*; D012997:Solvents; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D064032:Calbindin 2; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D012997:Solvents; D029961:Zebrafish Proteins; C576513:calb2b protein, zebrafish; D014446:Tyrosine 3-Monooxygenase; D018967:Risperidone