title: Cannabinoid antagonist in nanostructured lipid carriers (NLCs): design, characterization and in vivo study.
abstract: This study describes the preparation, characterization, and in vivo evaluation in rats of nanostructured lipid carriers (NLCs) encapsulating rimonabant (RMN) as prototypical cannabinoid antagonist. A study was conducted in order to optimize NLC production by melt and ultrasonication method. NLCs were prepared by alternatively adding the lipid phase into the aqueous one (direct protocol) or the aqueous phase into the lipid one (reverse protocol). RMN-NLCs have been characterized by cryogenic transmission electron microscopy (cryo-TEM), X-ray, photon correlation spectroscopy (PCS) and sedimentation field flow fractionation (SdFFF). Reverse NLCs were treated with polysorbate 80. RMN release kinetics have been determined in vitro by dialysis method. In vivo RMN biodistribution in rats was evaluated after intranasal (i.n.) administration of reverse RMN-NLC. The reverse protocol enabled to prevent the lost of lipid phase and to achieve higher RMN encapsulation efficacy (EE) with respect to the direct protocol (98% w/w versus 67% w/w). The use of different protocols did not affect NLC morphology and dimensional distribution. An in vitro dissolutive release rate of RMN was calculated. The in vivo data indicate that i.n. administration of RMN by reverse NLC treated with polysorbate 80 increased RMN concentration in the brain with respect to the drug in solution. The nanoencapsulation protocol presented here appears as an optimal strategy to improve the low solubility of cannabinoid compounds in an aqueous system suitable for in vivo administration.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ravani
authors.affiliation: BIMF/Soft Matter Electron Microscopy, University of Bayreuth, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Drechsler
authors.affiliation: Department of Life and Environmental Sciences and CNISM, Università Politecnica delle Marche, I-60100 Ancona, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mariani
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Contado
authors.affiliation: Department of Applied Physics, Aalto University, 00076 Aalto, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Ruokolainen
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Roma, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ratano
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Roma, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.affiliation: Department of Science, Roma Tre University, 00146 Roma, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Trezza
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy. Electronic address: nas@unife.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Nastruzzi
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Cortesi
mesh_terms: D000818:Animals; D063387:Cannabinoid Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D053769:Nanocapsules / Q000737:chemistry / Q000627:therapeutic use; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant
chemical_list: D063387:Cannabinoid Receptor Antagonists; D008055:Lipids; D053769:Nanocapsules; D010880:Piperidines; D011720:Pyrazoles; D000077285:Rimonabant
keywords: Cryogenic transmission electron microscopy; Drug delivery; Nanostructured lipid carriers; Photon correlation spectroscopy; Rimonabant