title: Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation.
abstract: This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters--co-emulsifier type, aqueous phase type, homogenization temperature--on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution <0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol(®) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Belgrade 11221, Serbia.
authors.forename: Sanela M
authors.initials: SM
authors.lastname: Đorđević
authors.affiliation: Faculty of Technology, University of Niš, Leskovac 16000, Serbia; DCP Hemigal, Leskovac 16000, Serbia.
authors.forename: Nebojša D
authors.initials: ND
authors.lastname: Cekić
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade 11221, Serbia.
authors.forename: Miroslav M
authors.initials: MM
authors.lastname: Savić
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Belgrade 11221, Serbia.
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Isailović
authors.affiliation: ICTM-Institute of Microelectronic Technologies, University of Belgrade, Belgrade 11000, Serbia.
authors.forename: Danijela V
authors.initials: DV
authors.lastname: Ranđelović
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade 11221, Serbia.
authors.forename: Bojan D
authors.initials: BD
authors.lastname: Marković
authors.affiliation: Faculty of Technology, University of Niš, Leskovac 16000, Serbia.
authors.forename: Saša R
authors.initials: SR
authors.lastname: Savić
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade 11221, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Timić Stamenić
authors.affiliation: Institut für Pharmazeutische Technologie, Eberhard-Karls Universität Tübingen, Tübingen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Daniels
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Belgrade 11221, Serbia. Electronic address: snexs@pharmacy.bg.ac.rs.
authors.forename: Snežana D
authors.initials: SD
authors.lastname: Savić
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004355:Drug Stability; D045703:Emulsifying Agents; D004655:Emulsions / Q000737:chemistry*; D054709:Lecithins / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013678:Technology, Pharmaceutical
chemical_list: D045703:Emulsifying Agents; D004655:Emulsions; D054709:Lecithins; D011136:Polysorbates; D013229:Stearic Acids; D020442:Poloxamer; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D018967:Risperidone
keywords: Brain targeting; General factorial design; Parenteral nanoemulsions; Pharmacokinetics; Physical stability; Poorly water-soluble drugs