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Nanomedicine and Neurosciences: Advantages, Limitations and Safety Aspects

Book Series: Frontiers in Nanomedicine

Volume 2

by

Giovanni Tosi

DOI: 10.2174/97816810851281170101
eISBN: 978-1-68108-493-0, 2017
ISBN: 978-1-68108-494-7
ISSN: 2405-9129 (Print)
ISSN: 2405-9137 (Online)



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Frontiers in Nanomedicine offers an up-to-date understanding of nanomaterials to readers having clinical or biomolecu...[view complete introduction]

Table of Contents

Foreword

- Pp. i

Frank Boury and Philippe Menei

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Preface

- Pp. II

Giovanni Tosi

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List of Contributors

- Pp. III

Giovanni Tosi

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Nanomedicine and Neurodegenerative Diseases: An Introduction to Pathology and Drug Targets

- Pp. 1-60 (60)

Tasnuva Sarowar and Andreas M. Grabrucker

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Nanoparticles Targeting Mitochondria in Neurodegenerative Diseases: Toxicity and Challenge for Nanotherapeutics

- Pp. 61-100 (40)

Michal Cagalinec

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Neuronal Mechanisms for Nanotopography Sensing

- Pp. 101-114 (14)

Ilaria Tonazzini and Marco Cecchini

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Drug Delivery to the Brain by Liposomal Carrier Systems

- Pp. 115-127 (13)

Anne Mahringer and Gert Fricker

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Neuronopathic LSDs: Quest for Treatments Drives Research in Nanomedicine and Nanotechnology

- Pp. 128-155 (28)

Cinzia M. Bellettato, David J. Begley, Christina Lampe and Maurizio Scarpa

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Targeting Brain Disease in Mucopolysaccharidoses

- Pp. 156-183 (28)

Marika Salvalaio, Laura Rigon, Francesca D’Avanzo, Elisa Legnini, Valeria Balmaceda Valdez, Alessandra Zanetti and Rosella Tomanin

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Functional Validation of Drug Nanoconjugates in vivo

- Pp. 184-198 (15)

Ibane Abasolo, Yolanda Fernández and Simó Schwartz

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How does “Protein Corona” Affect the In vivo Efficiency of Polymeric Nanoparticles? State of Art

- Pp. 199-238 (40)

F. Pederzoli, M. Galliani, F. Forni, M .A. Vandelli, D. Belletti, G. Tosi and B. Ruozi

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Safety of Nanomedicine: Neuroendocrine Disrupting Potential of Nanoparticles and Neurodegeneration

- Pp. 239-262 (24)

Eva Rollerova, Alzbeta Bujnakova Mlynarcikova, Jana Tulinska, Jevgenij Kovriznych, Alexander Kiss and Sona Scsukova

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Subject Index

- Pp. 263-269 (7)

Giovanni Tosi

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Foreword

Although neurosurgery is one of the youngest surgical specialties, it is also the one that has undergone the most dramatic progress in recent years. As neurosurgery interfaces with other surgical areas, in particular ear, nose, throat specialty (ENT), ophthalmology and orthopedic surgery, new subspecialties have aroused such as: otoneurosurgery, neuro-ophthalmology and neuro-orthopedic spinal surgery. More particularly, new surgical approaches have appeared thanks to the improvements made in the areas of medical devices, imaging and information technology.

Nonetheless, surgery of the nervous system and the spine still has to face therapeutic challenges, including the incurability of most cerebral tumors, low back pain and its socioeconomic impact, as well as the neurodisability associated with the evolution of a large number of afflictions of the nervous system. These challenges can only be addressed through a new technological revolution.

For instance, Huntington's disease (HD) is an incurable neurodegenerative genetic disorder manifesting in adulthood and causing motor, psychiatric and cognitive disturbances. It is caused by a mutation in the huntingtin gene (htt), which at first leads to the degeneration of striatal GABAergic neurons and then to other neuronal areas. This mutation (mhtt) is involved in repression of several neuronal genes, particularly brain-derived neurotrophic factor. The use of trophic factors, targeting particularly BDNF in a neuronal protection strategy, may be particularly relevant for the treatment of HD where genetic screening can identify individuals at risk, providing a unique opportunity to intervene early in the onset of striatal degeneration.

The "NBIC convergence" (convergence between Nanotechnology, Biotechnology, Information technology and Cognitive sciences) is a concept that appeared in 2002, in a report from the National Science Foundation. This concept appeared following a reflection on the potential impact of this convergence in the improvement of human capabilities, both at the individual and societal level. While this new concept, in particular its potential applications, has generated a philosophical and ethical debate, it has already been a source of progress in health technologies.

For the first time, this e-book aims to depict the state of the art using nanotechnologies as a promising tool for therapy and diagnosis of neurodegenerative diseases. It focuses on anatomy and pathology of the main related-diseases, and gives a clear overview of the last advances in the so-called nanomedicine as to target the blood brain barrier or to image the brain defects accurately. All main issues linked to the development of new nanomedicine platforms (liposomes, targeting molecules, nanoconjugates…) and their fate, in vivo, (biopharmaceutical performances, interaction with biological media, toxicity…) are clearly presented with a translational approach.

This e-book gives the reader a perfect overview of this very exciting field of medical research. It is intended to help scientists, technologists, and students who may use or need to use some aspects of nanomedicine in their work or who wish to be trained in this emerging and promising area of investigation.

Frank Boury & Philippe Menei
INSERM U1066,
University & University hospital, Angers, France


Preface

The era of nanomedicine is claimed to be effective now, in these years. But we experiment that is not true, in the field of medicine in particular. Obviously, there is a plethora of papers published in the major scientific and highly impacted journals, but it is not enough to claim clearly that medical application of nanotechnology is currently on the edge of technological approaches.

Considering the brain, there are several pathological changes affecting the Central Nervous System (CNS): neurodegenerative (Alzheimer’s, Parkinson’s, retinal degeneration), neurological/neuropsychiatric (epilepsy, amyotrophic lateral sclerosis, autism), brain tumors (gliomas, astrocytomas, etc.) and rare neurometabolic disorders (i.e. inherited Lysosomal Storage Diseases), all considered major contributors to human death. Neurological disease management deeply impacts on patients health, care providers activity and represents a substantial socio-economic burden. Due to the absence of targeted and cost-effective therapies and limited diagnostic tools, the costs to the national health systems are high.

For disease management, it is fundamental to achieve a deeper understanding of basic neurobiology underlying each distinct disorder and as an urgent unmet need, to develop novel targeted therapeutic strategies. Nanomedicine represents a powerful new approach providing novel carriers to deliver drugs to specific sites in the brain as well as to other organs (lung/liver/ breast/ tumor sites). Only a joint multidisciplinary research coordination effort can facilitate the full development of nanomedicine as valuable treatment and diagnosis strategy for these diseases.

This book provides for the first step in order to “fill in the blanks” with a part of aspects which should be considered in order to produce and propose a real and applicable nanomedicine for the cure of neurodegenerative disorders and neurological diseases.

With critical behavior and with deep knowledge, scientists of high experience and skills in their field of research or clinical settings analyzed different aspects of nanomedicine for brain delivery and targeting of drugs.

From the bases of neurodegenerative diseases as anatomy and pathology of brain disorders, this book opens to wide overview of the applications of nanosystem to brain disorders, addressed by means of application of nanomedicines to neuronopathic lysosomal storage disorders, or by the application of nanoparticles to target mitochondria in neurodegenerative diseases. Drug delivery to the brain by liposomal systems along with nanotopography sensing are also approached, together with the targeting of nanomedicine in mucopolysaccharidoses and brain compromission, along with the validation of drug nanoconjugates in vivo. Finally, safety aspects and benefit/risk focus is given by means of analysis of protein corona affecting the in vivo efficiency of polymeric NPs and neuroendocrine aspects of nanoparticles into neurodegeneration.

Giovanni Tosi
Associate Professor, Department of Life Sciences,
University of Modena and Reggio Emilia,
Via Campi 103, 41124 Modena,
Italy

List of Contributors

Author(s):
Giovanni Tosi
Department of Life Sciences
University of Modena and Reggio Emilia
Modena
Italy




Contributor(s):
Tasnuva Sarowar
Neurology Dept., Neurocenter of Ulm University
WG Molecular Analysis of Synaptopathies
Ulm
Germany


Andreas M. Grabrucker
Neurology Dept., Neurocenter of Ulm University
WG Molecular Analysis of Synaptopathies
Ulm
Germany
/
Ulm University
Institute for Anatomy and Cell Biology
Ulm
Germany


Michal Cagalinec
Estonia Centre of Biosciences (former Institute of Molecular Physiology and Genetics), Slovak Academy of Sciences
Department of Pharmacology, Faculty of Medicine, University of Tartu, Tartu, Estonia Centre of Biosciences
Bratislava
Slovakia


Tonazzini Ilaria
Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12
NEST
56127 Pisa
Italy


Cecchini Marco
Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12
NEST
56127 Pisa
Italy
/
Piazza Velasca 5
Fondazione Umberto Veronesi
20122 Milano
Italy


Anne Mahringer
Institute of Pharmacy and Molecular Biotechnology, Im Neuenheimer Feld 329
Ruprecht-Karls University
69120 Heidelberg
Germany


Gert Fricker
Institute of Pharmacy and Molecular Biotechnology, Im Neuenheimer Feld 329
Ruprecht-Karls University
69120 Heidelberg
Germany


Cinzia M. Bellettato
Department of Women and Children Health, Via Giustiniani 3
Brains for Brains Foundation
35128 Padova
Italy


David J. Begley
Department of Women and Children Health, Via Giustiniani 3
Brains for Brains Foundation
35128 Padova
Italy
/
Institute of Pharmaceutical Science, Franklin-Wilkins Building, 150 Stamford Street
Kings College London
London, SE1 9NH
UK


Christina Lampe
Institute of Pharmaceutical Science, Franklin-Wilkins Building, 150 Stamford Street
Kings College London
London, SE1 9NH
UK
/
Department of Child and Adolescent Medicine
Center for Rare Diseases Helios Horst Schmidt Kliniken
Ludwig-Erhard-Straße 100 65199 Wiesbaden
Germany


Maurizio Scarpa
Institute of Pharmaceutical Science, Franklin-Wilkins Building, 150 Stamford Street
Kings College London
London, SE1 9NH
UK
/
Department of Child and Adolescent Medicine
Center for Rare Diseases Helios Horst Schmidt Kliniken
Ludwig-Erhard-Straße 100 65199 Wiesbaden
Germany
/
Department of Women and Children Health, Via Giustiniani 3
University of Padova
35128 Padova
Italy


Marika Salvalaio
Department of Women’s and Children’s Health, University of Padova
Laboratory of Diagnosis and Therapy of Lysosomal Disorders
Padova
Italy
/
Institute “Città della Speranza”
Pediatric Research
Padova
Italy


Laura Rigon
Department of Women’s and Children’s Health, University of Padova
Laboratory of Diagnosis and Therapy of Lysosomal Disorders
Padova
Italy


Francesca D’Avanzo
Department of Women’s and Children’s Health, University of Padova
Laboratory of Diagnosis and Therapy of Lysosomal Disorders
Padova
Italy
/
Foundation Onlus
Brains for Brain
Padova
Italy


Elisa Legnini
Department of Women’s and Children’s Health, University of Padova
Laboratory of Diagnosis and Therapy of Lysosomal Disorders
Padova
Italy


Valeria Balmaceda Valdez
Department of Women’s and Children’s Health, University of Padova
Laboratory of Diagnosis and Therapy of Lysosomal Disorders
Padova
Italy


Alessandra Zanetti
Department of Women’s and Children’s Health, University of Padova
Laboratory of Diagnosis and Therapy of Lysosomal Disorders
Padova
Italy


Rosella Tomanin
Department of Women’s and Children’s Health, University of Padova
Laboratory of Diagnosis and Therapy of Lysosomal Disorders
Padova
Italy


Ibane Abasolo
Vall d’Hebron Institut de Recerca (VHIR). Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN)
Functional Validation & Preclinical Research (FVPR). Drug Delivery & Targeting. CIBBIM-Nanomedicine
Barcelona
Spain


Yolanda Fernández
Vall d’Hebron Institut de Recerca (VHIR). Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN)
Functional Validation & Preclinical Research (FVPR). Drug Delivery & Targeting. CIBBIM-Nanomedicine
Barcelona
Spain


Simó Schwartz Jr.
Vall d’Hebron Institut de Recerca (VHIR). Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN)
Functional Validation & Preclinical Research (FVPR). Drug Delivery & Targeting. CIBBIM-Nanomedicine
Barcelona
Spain


Francesca Pederzoli
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103
Te.Far.T.I
41124 Modena
Italy


Marianna Galliani
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103
Te.Far.T.I
41124 Modena
Italy


Flavio Forni
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103
Te.Far.T.I
41124 Modena
Italy


Maria Angela Vandelli
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103
Te.Far.T.I
41124 Modena
Italy


Daniela Belletti
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103
Te.Far.T.I
41124 Modena
Italy


Giovanni Tosi
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103
Te.Far.T.I
41124 Modena
Italy


Barbara Ruozi
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103
Te.Far.T.I
41124 Modena
Italy


Eva Rollerova
Faculty of Public Health, Department of Toxicology and Faculty of Medicine, Laboratory of Immunotoxicology
Slovak Medical University
Bratislava
Slovak Republic


Alzbeta Bujnakova Mlynarcikova
Institute of Experimental Endocrinology
Biomedical Research Center Slovak Academy of Sciences
Bratislava
Slovak Republic


Jana Tulinska
Faculty of Public Health, Department of Toxicology and Faculty of Medicine, Laboratory of Immunotoxicology
Slovak Medical University
Bratislava
Slovak Republic


Jevgenij Kovriznych
Faculty of Public Health, Department of Toxicology and Faculty of Medicine, Laboratory of Immunotoxicology
Slovak Medical University
Bratislava
Slovak Republic


Alexander Kiss
Institute of Experimental Endocrinology
Biomedical Research Center Slovak Academy of Sciences
Bratislava
Slovak Republic


Sona Scsukova
Institute of Experimental Endocrinology
Biomedical Research Center Slovak Academy of Sciences
Bratislava
Slovak Republic




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