Insights into kinetics, release, and behavioral effects of brain-targeted hybrid nanoparticles for cholesterol delivery in Huntington's disease.

Animals Brain Cholesterol Huntington Disease / drug therapy Kinetics Nanoparticles
Blood-brain barrier Cholesterol Huntington Nanoparticles

Journal

Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908

Informations de publication

Date de publication:
10 02 2021
Historique:
received: 28 10 2020
revised: 23 12 2020
accepted: 28 12 2020
pubmed: 8 1 2021
medline: 8 7 2021
entrez: 7 1 2021
Statut: ppublish

Résumé

Supplementing brain cholesterol is emerging as a potential treatment for Huntington's disease (HD), a genetic neurodegenerative disorder characterized, among other abnormalities, by inefficient brain cholesterol biosynthesis. However, delivering cholesterol to the brain is challenging due to the blood-brain barrier (BBB), which prevents it from reaching the striatum, especially, with therapeutically relevant doses. Here we describe the distribution, kinetics, release, and safety of novel hybrid polymeric nanoparticles made of PLGA and cholesterol which were modified with an heptapeptide (g7) for BBB transit (hybrid-g7-NPs-chol). We show that these NPs rapidly reach the brain and target neural cells. Moreover, deuterium-labeled cholesterol from hybrid-g7-NPs-chol is released in a controlled manner within the brain and accumulates over time, while being rapidly removed from peripheral tissues and plasma. We confirm that systemic and repeated injections of the new hybrid-g7-NPs-chol enhanced endogenous cholesterol biosynthesis, prevented cognitive decline, and ameliorated motor defects in HD animals, without any inflammatory reaction. In summary, this study provides insights about the benefits and safety of cholesterol delivery through advanced brain-permeable nanoparticles for HD treatment.

Identifiants

DOI: 10.1016/j.jconrel.2020.12.051 PMID: 33412229
pubmed: 33412229
pii: S0168-3659(20)30775-6
doi: 10.1016/j.jconrel.2020.12.051
pii:
doi:

Substances chimiques

Cholesterol 97C5T2UQ7J

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

587-598

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Giulia Birolini (G)

Department of Biosciences, University of Milan, via G. Celoria 26, 20133 Milan, Italy; Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", via F. Sforza 35, 20122 Milan, Italy.

Marta Valenza (M)

Department of Biosciences, University of Milan, via G. Celoria 26, 20133 Milan, Italy; Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", via F. Sforza 35, 20122 Milan, Italy. Electronic address: marta.valenza@unimi.it.

Ilaria Ottonelli (I)

Nanotech Lab, Te.Far.T.I. Center, Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi, 103, 41125 Modena, Italy; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, via G. Campi 289, 411214 Modena, Italy.

Alice Passoni (A)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156 Milan, Italy.

Monica Favagrossa (M)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156 Milan, Italy.

Jason T Duskey (JT)

Nanotech Lab, Te.Far.T.I. Center, Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi, 103, 41125 Modena, Italy; Umberto Veronesi Foundation, 20122 Milan, Italy.

Mauro Bombaci (M)

Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", via F. Sforza 35, 20122 Milan, Italy.

Maria Angela Vandelli (MA)

Nanotech Lab, Te.Far.T.I. Center, Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi, 103, 41125 Modena, Italy.

Laura Colombo (L)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156 Milan, Italy.

Renzo Bagnati (R)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156 Milan, Italy.

Claudio Caccia (C)

Unit of Medical Genetics and Neurogenetics, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Via Celoria 11, 20131 Milan, Italy.

Valerio Leoni (V)

Laboratory of Clinical Pathology, Hospital of Desio, ASST-Monza, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy.

Franco Taroni (F)

Unit of Medical Genetics and Neurogenetics, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Via Celoria 11, 20131 Milan, Italy.

Flavio Forni (F)

Nanotech Lab, Te.Far.T.I. Center, Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi, 103, 41125 Modena, Italy.

Barbara Ruozi (B)

Nanotech Lab, Te.Far.T.I. Center, Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi, 103, 41125 Modena, Italy.

Mario Salmona (M)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via Mario Negri 2, 20156 Milan, Italy.

Giovanni Tosi (G)

Nanotech Lab, Te.Far.T.I. Center, Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi, 103, 41125 Modena, Italy.

Elena Cattaneo (E)

Department of Biosciences, University of Milan, via G. Celoria 26, 20133 Milan, Italy; Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", via F. Sforza 35, 20122 Milan, Italy. Electronic address: elena.cattaneo@unimi.it.

Articles similaires

Evaluating the efficacy of telesurgery with dual console SSI Mantra Surgical Robotic System: experiment on animal model and clinical trials.

Sudhir Prem Srivastava, Vishwajyoti Pascual Srivastava, Avinesh Singh et al.
1.00
Robotic Surgical Procedures Animals Humans Telemedicine Models, Animal

Odour generalisation and detection dog training.

Lyn Caldicott, Thomas W Pike, Helen E Zulch et al.
1.00
Animals Odorants Dogs Generalization, Psychological Smell

FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.

Minle Li, Xuan Chen, Pengfei Qu et al.
1.00
Animals TOR Serine-Threonine Kinases Colorectal Neoplasms Colitis Mice

Use of organic material provided by an automatic enrichment device by weaner pigs and its influence on tail lesions.

Philipp Heseker, Jeanette Probst, Stefanie Ammer et al.
1.00
Animals Tail Swine Behavior, Animal Animal Husbandry

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Insights into kinetics, release, and...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Insights into kinetics, release, and...
questionsmedicales.fr › Lipides › Lipides membranaires › Stérols › Cholestérol › Insights into kinetics, release, and...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie de Huntington › Insights into kinetics, release, and...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Cinétique › Insights into kinetics, release, and...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Nanoparticules › Insights into kinetics, release, and...