Development of Nutraceutical Emulsions as Risperidone Delivery Systems: Characterization and Toxicological Studies

• Published in: Journal of pharmaceutical sciences 2015-12, Vol.104 (12), p.4142-4152
• Main Authors: Igartúa, Daniela Edith, Calienni, María Natalia, Feas, Daniela Agustina, Chiaramoni, Nadia Silvia, Del Valle Alonso, Silvia, Prieto, María Jimena
• Format: Article
• Language: English
• Subjects: Absorption enhancer; Administration, Oral; Animals; Autism; Biological Availability; Biomaterials; Caco-2 Cells; Chemistry, Pharmaceutical - methods; Danio rerio; Dietary Supplements; Drug Delivery Systems - methods; Emulsions; Emulsions - pharmacology; Female; Heart Rate - drug effects; Humans; Light-scattering; Male; Microdialysis; Microencapsulation; Motor Activity - drug effects; Oral drug delivery; Particle Size; Risperidone; Risperidone - pharmacology; Solubility; Toxicology; Zebrafish
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.24636

Emulsions are gaining increasing interest to be applied as drug delivery systems. The main goal of this work was the formulation of an oil/water nutraceutical emulsion (NE) for oral administration, enriched in omega 3 (ω3) and omega 6 (ω6), and able to encapsulate risperidone (RISP), an antipsychotic drug widely used in the treatment of autism spectrum disorders (ASD). RISP has low solubility in aqueous medium and poor bioavailability because of its metabolism and high protein binding. Coadministration of ω3, ω3, and vitamin E complexed with RISP might increase its bioavailability and induce a synergistic effect on the treatment of ASD. Here, we developed an easy and quick method to obtain NEs and then optimized them. The best formulation was chosen after characterization by particle size, defects of the oil-in-water interface, zeta potential (ZP), and in vitro drug release. The formulation selected was stable over time, with a particle size of around 3µm, a ZP lower than −20mV and controlled drug release. To better understand the biochemical properties of the formulation obtained, we studied in vitro toxicity in the Caco-2 cell line. After 4h of treatment, an increase in cellular metabolism was observed for all RISP concentrations, but emulsions did not change their metabolic rate, except at the highest concentration without drug (25µg/mL), which showed a significant reduction in metabolism respect to the control. Additionally, locomotor activity and heart rate in zebrafish were measured as parameters of in vivo toxicity. Only the highest concentration (0.625µg/mL) showed a cardiotoxic effect, which corresponds to the decrease in spontaneous movement observed previously. As all the materials contained in the formulations were US FDA approved, the NE selected would be good candidate for clinical trials.