Lipid nanoparticles for administration of poorly water soluble neuroactive drugs

• Published in: Biomedical microdevices 2017-09, Vol.19 (3), p.44, Article 44
• Main Authors: Esposito, Elisabetta, Drechsler, Markus, Mariani, Paolo, Carducci, Federica, Servadio, Michela, Melancia, Francesca, Ratano, Patrizia, Campolongo, Patrizia, Trezza, Viviana, Cortesi, Rita, Nastruzzi, Claudio
• Format: Article
• Language: English
• Subjects: Animals; Benzamides - chemistry; Benzamides - metabolism; Biocompatibility; Biological and Medical Physics; Biomedical engineering; Biomedical Engineering and Bioengineering; Biophysics; Brain; Brain - metabolism; Cannabinoids; Carbamates - chemistry; Carbamates - metabolism; Central nervous system; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug delivery; Drug delivery systems; Drug Liberation; Drugs; Engineering; Engineering Fluid Dynamics; Formulations; Glycerides - chemistry; Hydrolysis; Intranasal administration; Kinetics; Lipids; Lipids - chemistry; Male; Mental disorders; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; Nervous system; Palmitic acid; Particle Size; Polyoxyethylene sorbitan monooleate; Polysorbates - chemistry; Progesterone; Rats; Rats, Wistar; Solubility; Stearin; Tissue Distribution; Triglycerides - chemistry; Tristearin; Water - chemistry
• ISSN: 1387-2176; 1572-8781
• DOI: 10.1007/s10544-017-0188-x

This study describes the potential of solid lipid nanoparticles and nanostructured lipid carriers as nano-formulations to administer to the central nervous system poorly water soluble drugs. Different neuroactive drugs, i.e. dimethylfumarate, retinyl palmitate, progesterone and the endocannabinoid hydrolysis inhibitor URB597 have been studied. Lipid nanoparticles constituted of tristearin or tristearin in association with gliceryl monoolein were produced. The nanoencapsulation strategy allowed to obtain biocompatible and non-toxic vehicles, able to increase the solubility of the considered neuroactive drugs. To improve URB597 targeting to the brain, stealth nanoparticles were produced modifying the SLN surface with polysorbate 80. A behavioural study was conducted in rats to test the ability of SLN containing URB597 given by intranasal administration to alter behaviours relevant to psychiatric disorders. URB597 maintained its activity after nanoencapsulation, suggesting the possibility to propose this kind of vehicle as alternative to unphysiological mixtures usually employed for animal and clinical studies.