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Lipid nanoparticles for administration of poorly water soluble neuroactive drugs

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Abstract

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.

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Abbreviations

CNS:

Central nervous system

SLN:

solid lipid nanoparticles

NLC:

nanostructured lipid carriers

DMF:

dimethyl fumarate

RP:

retinyl palmitate

PRG:

progesterone

P80:

polysorbate 80

cryo-TEM:

cryogenic transmission electron microscopy

PCS:

photon correlation spectroscopy

EE:

encapsulation efficiency

LC:

loading capacity

PTSD:

post-traumatic stress disorder

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Acknowledgements

This work was funded by "FIRB 2010. Fondo per gli Investimenti della Ricerca di Base" from the Ministry of the University and Research of Italy (code RBFR10XKHS).

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Authors and Affiliations

  1. Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara, 19, I-44121, Ferrara, Italy

    Elisabetta Esposito, Rita Cortesi & Claudio Nastruzzi

  2. BIMF/ Soft Matter Electronmicroscopy, University of Bayreuth, Bayreuth, Germany

    Markus Drechsler

  3. Department of Life and Environmental Sciences and CNISM, Università Politecnica delle Marche, I-60100, Ancona, Italy

    Paolo Mariani & Federica Carducci

  4. Department of Science, Roma Tre University, 00146, Rome, Italy

    Michela Servadio, Francesca Melancia & Viviana Trezza

  5. Department of Physiology and Pharmacology, Sapienza University of Rome, 00185, Rome, Italy

    Patrizia Ratano & Patrizia Campolongo

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  1. Elisabetta Esposito
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Correspondence to Elisabetta Esposito.

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Esposito, E., Drechsler, M., Mariani, P. et al. Lipid nanoparticles for administration of poorly water soluble neuroactive drugs. Biomed Microdevices 19, 44 (2017). https://doi.org/10.1007/s10544-017-0188-x

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