Nanomedicines for Brain Drug Delivery

283 Pages·2021·6.03 MB·English

by  Javier O. Morales, Pieter J. Gaillard

Neuromethods 157
Javier O. Morales
Pieter J. Gaillard Editor
Nanomedicines
for Brain Drug
Delivery
N
EUROMETHODS
SeriesEditor
Wolfgang Walz
University ofSaskatchewan
Saskatoon, SK,Canada
Forfurther volumes:
http://www.springer.com/series/7657
Neuromethodspublishescutting-edgemethodsandprotocolsinallareasofneuroscienceas
wellastranslationalneurologicalandmentalresearch.Eachvolumeintheseriesofferstested
laboratoryprotocols,step-by-stepmethodsforreproduciblelabexperimentsandaddresses
methodologicalcontroversiesandpitfallsinordertoaidneuroscientistsinexperimentation.
Neuromethodsfocusesontraditionalandemergingtopicswithwide-rangingimplicationsto
brain function, such as electrophysiology, neuroimaging, behavioral analysis, genomics,
neurodegeneration,translationalresearchandclinicaltrials.Neuromethodsprovidesinvesti-
gators and trainees with highly useful compendiums of key strategies and approaches for
successful research in animal and human brain function including translational “bench to
bedside”approachestomentalandneurologicaldiseases.
Nanomedicines for Brain Drug
Delivery
Edited by
Javier O. Morales
Department of Pharmaceutical Science and Technology, University of Chile, Santiago, Chile
Pieter J. Gaillard
2-BBB Medicines BV, Leiden, The Netherlands
Editors
JavierO.Morales PieterJ.Gaillard
DepartmentofPharmaceuticalScience 2-BBBMedicinesBV
andTechnology Leiden,TheNetherlands
UniversityofChile
Santiago,Chile
ISSN0893-2336 ISSN1940-6045 (electronic)
Neuromethods
ISBN978-1-0716-0837-1 ISBN978-1-0716-0838-8 (eBook)
https://doi.org/10.1007/978-1-0716-0838-8
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Preface to the Series
Experimental life sciences have two basic foundations: concepts and tools. The Neuro-
methodsseriesfocusesonthetoolsandtechniquesuniquetotheinvestigationofthenervous
system and excitable cells. It will not, however, shortchange the concept side of things as
carehasbeentakentointegratethesetoolswithinthecontextoftheconceptsandquestions
underinvestigation.Inthisway,theseriesisuniqueinthatitnotonlycollectsprotocolsbut
also includes theoretical background information and critiques which led to the methods
andtheirdevelopment.Thusitgivesthereaderabetter understandingoftheoriginofthe
techniquesandtheirpotentialfuturedevelopment.TheNeuromethodspublishingprogram
strikes a balance between recent and exciting developments like those concerning new
animal models of disease, imaging, in vivo methods, and more established techniques,
including, for example, immunocytochemistry and electrophysiological technologies. New
traineesinneurosciencesstillneedasoundfootingintheseoldermethodsinordertoapply
acriticalapproachtotheir results.
Under the guidance of its founders, Alan Boulton and Glen Baker, the Neuromethods
serieshasbeenasuccesssinceitsfirstvolumepublishedthroughHumanaPressin1985.The
seriescontinuestoflourishthroughmanychangesovertheyears.Itisnowpublishedunder
theumbrellaofSpringerProtocols.Whilemethodsinvolvingbrainresearchhavechangeda
lot since theseriesstarted, thepublishingenvironmentand technologyhavechanged even
more radically. Neuromethods has the distinct layout and style of the Springer Protocols
program,designedspecificallyfor readabilityandeaseofreferenceinalaboratorysetting.
Thecarefulapplicationofmethodsispotentiallythemostimportantstepintheprocess
of scientific inquiry. In the past, new methodologies led the way in developing new dis-
ciplines in the biological and medical sciences. For example, Physiology emerged out of
Anatomyinthenineteenthcenturybyharnessingnewmethodsbasedonthenewlydiscov-
eredphenomenonofelectricity.Nowadays,therelationshipsbetweendisciplinesandmeth-
ods are more complex. Methods are now widely shared between disciplines and research
areas. New developments in electronic publishing make it possible for scientists that
encounter new methods to quickly find sources of information electronically. The design
of individual volumes and chapters in this series takes this new access technology into
account. Springer Protocols makes it possible to download single protocols separately. In
addition, Springer makes its print-on-demand technology available globally. A print copy
canthereforebeacquiredquicklyandforacompetitivepriceanywhereintheworld.
Saskatoon,SK,Canada WolfgangWalz
v
Preface
Nanomedicines have revolutionized research on drug delivery in multiple diseases, and
leading strategies have achieved clinical success. Moreover, a significant number of clinical
trials are conducted to continue expanding the reach of nanomedicines to new, more
effectiveandwithlesssideeffectstherapies.Thecentralnervoussystem(CNS)hassimilarly
been the focus of extended research in the design and evaluation of novel nanocarriers for
braindrugdelivery.Asatargetsite,theCNSrepresentsauniquechallengegivenitsanatomy
and physiology. The blood brain barrier (BBB) is not only a restrictive limitation for
systemically administered drugs but also continues to be a largely restrictive barrier to
achieve significant CNS nanocarrier bioavailability. While the BBB represents one of the
mainlimitationsforsignificantCNSbiodistribution,overcomingitisnotthesolereasonfor
limited bioavailability and targeting effects. Successfully targeting the brain microvascula-
ture,distributionthroughtheCNS(afterpassagethroughtheBBB),andinternalizationin
target brain cells become important challenges once there is a BBB penetration strategy in
place.
As such, this book will be a source for finding the latest research in CNS-targeted
nanocarriers,methodsfortheirsynthesisandthoroughcharacterization.Moreover,achap-
ter addressing toxicity aspects to be considered in the design and use of brain-targeted
nanocarrierswillbeofinteresttothereader.Thefirsttwochaptersofthebookdelveintothe
most widely investigated nanocarriers as brain-targeted delivery systems, i.e., polymeric
nanoparticles and liposomes. With a thorough description of the state of the art as well as
key aspects of their characterization, the first two chapters also highlight physiological
properties relevant to particle design. Chapter 4 depicts the use of self-assembled peptide-
basedscaffoldsforlesionsofthenervoussystem,whileChapter5describesnotonlytheuse
of peptides as CNS drugs but also as potential carriers to optimize brain-targeted delivery.
Chapters6and7describeinorganicandmagneticnanoparticlesusedfortargetingdrugsto
theCNSaswellastheirpotentialinthedesignoftriggerableandaimedsystems.Chapter8
inspects the long-researched nose-to-brain delivery route, highlighting its potential and
how the limitations this route presents could be addressed to harness its clinical potential.
Chapter9isanexcellentcompilationofcharacterizationmethodstomodelandassessBBB
absorptionofdrugsanddrugdeliverysystems,andassuch,thischapter willbeofgreatuse
toscientistsdesigningbrain-targeteddeliverysystemstopredictbraindistribution.Finally,
Chapter10presentstheconcernsthattheuseofnanomaterialsraisesinthecontextofbrain-
targetedsystems.Assuch,thelastchapterwillbeagoodsourcetounderstandthepotential
neurotoxiceffectsandthepotentialroleofnanomaterialsinneurodegenerationprogress.
The editors are immensely grateful to all the individual contributions and authors for
sharingtheirtime,effort,andknowledgetocreatethisbook.Theiroutstandingworkinthe
fieldscoveredinthisbookwehopewillbeofgreatinteresttothereaderandwillhelpguide
andmoveforwardthefieldofnanomedicinestotargetthebrainandthenervoussystem.
Santiago,Chile JavierO.Morales
Leiden,TheNetherlands PieterJ.Gaillard
vii
Contents
PrefacetotheSeries ........................................................... v
Preface ..................................................................... vii
Contributors................................................................. xi
1 BiodegradablePolymericNanoparticlesforBrain-Targeted
DrugDelivery.......................................................... 1
KristianKempeandJosephA.Nicolazzo
2 LiposomesasBrainTargetedDeliverySystems ............................. 29
FrancescoLai,MicheleSchlich,ChiaraSinico,
andAnnaMariaFadda
3 NanofibersandNanostructuredScaffoldsforNervousSystemLesions ........ 61
JoseL.GerardoNava,JonasC.Rose,HaktanAltinova,
PaulD.Dalton,LauraDeLaporte,andGaryA.Brook
4 Self-AssemblingPeptideNanofibrousScaffoldsinCentralNervous
SystemLesions ......................................................... 103
NaZhang,LiuminHe,andWutianWu
5 TheUseofPeptideandProteinVectorstoCrossthe
Blood-BrainBarrier for theDeliveryofTherapeuticConcentration
ofBiologics ............................................................ 119
MeiMeiTianandReinhardGabathuler
6 InorganicNanoparticlesandTheirStrategiestoEnhanceBrain
DrugDelivery.......................................................... 149
EduardoGallardo-Toledo,CarolinaVelasco-Aguirre,
andMarceloJavierKogan
7 MagneticNanoparticlesasDeliverySystemstoPenetratethe
Blood-BrainBarrier ..................................................... 173
JoanEstelrichandMariaAnto`niaBusquets
8 Nose-to-BrainDrugDeliveryEnabledbyNanocarriers...................... 209
ZacharyWarnken,YangLu,HughD.C.Smyth,
andRobertO.WilliamsIII
9 InVitroModelsofCentralNervousSystemBarriersfor
Blood-BrainBarrierPermeationStudies ................................... 235
SounakBagchi,BehnazLahooti,TanyaChhibber,Sree-pooja
Varahachalam,RahulMittal,AbhijeetJoshi,andRahulDevJayant
10 SafetyandNanotoxicityAspectsofNanomedicinesfor
Brain-TargetedDrugDelivery............................................ 255
JohannaCatalan-FigueroaandJavierO.Morales
Index ...................................................................... 279
ix
Contributors
HAKTANALTINOVA (cid:129) DepartmentofNeurosurgery,UniversityHospitalRWTHAachen,
Aachen,Germany
SOUNAKBAGCHI (cid:129) DepartmentofPharmaceuticalSciences,SchoolofPharmacy,TexasTech
UniversityHealthSciencesCenter(TTUHSC),Amarillo,TX,USA
GARYA.BROOK (cid:129) InstituteofNeuropathology,UniversityHospitalRWTHAachen,Aachen,
Germany
MARIAANTO`NIABUSQUETS (cid:129) PharmacyandPharmaceuticalTechnologyandPhysical
ChemistryDepartment,FacultyofPharmacyandFoodSciences,UniversityofBarcelona,
Barcelona,Catalonia,Spain;InstituteofNanoscienceandNanotechnology,IN2UB,
Barcelona,Catalonia,Spain
JOHANNACATALAN-FIGUEROA (cid:129) DepartmentofPharmaceuticalScienceandTechnology,
SchoolofChemicalandPharmaceuticalSciences,UniversityofChile,Santiago,Chile;
DepartmentofBiochemistry,SchoolofChemicalandPharmaceuticalSciences,University
ofChile,Santiago,Chile;ExperimentalPharmacologyInstitute,CONICET,National
UniversityofCordoba,Cordoba,Argentina;AdvancedCenter forChronicDiseases
(ACCDiS),Santiago,Chile
TANYACHHIBBER (cid:129) DepartmentofPharmaceuticalSciences,SchoolofPharmacy,TexasTech
UniversityHealthSciencesCenter(TTUHSC),Amarillo,TX,USA
PAULD.DALTON (cid:129) DepartmentforFunctionalMaterialsinMedicineandDentistryand
BavarianPolymerInstitute,UniversityofWu¨rzburg,Wu¨rzburg,Germany
LAURADELAPORTE (cid:129) DWI—Leibniz-InstituteforInteractiveMaterials,Aachen,Germany;
InsituteofAppliedMedicalEngineering,RWTHAachenUniversity,Aachen,Germany;
InsituteofTechnicalandMacromolecularChemistryRWTHAachenUniversity,Aachen,
Germany
JOANESTELRICH (cid:129) PharmacyandPharmaceuticalTechnologyandPhysicalChemistry
Department,FacultyofPharmacyandFoodSciences,UniversityofBarcelona,Barcelona,
Catalonia,Spain;InstituteofNanoscienceandNanotechnology,IN2UB,Barcelona,
Catalonia,Spain
ANNAMARIA FADDA (cid:129) DepartmentofLifeandEnvironmentalSciences,Universityof
Cagliari,Cagliari,Italy
REINHARDGABATHULER (cid:129) FacultyofLifeSciencesandMedicine,Blood-BrainBarrierGroup,
KingsCollegeLondon,London,UK
EDUARDOGALLARDO-TOLEDO (cid:129) DepartamentodeQuı´micaFarmacol(cid:1)ogicayToxicol(cid:1)ogica,
FacultaddeCienciasQuı´micasyFarmace´uticas,UniversidaddeChile,Santiago,Chile;
AdvancedCenter forChronicDiseases(ACCDiS),Santiago,Chile
JOSEL.GERARDONAVA (cid:129) InstituteofNeuropathology,UniversityHospitalRWTHAachen,
Aachen,Germany;DWI—Leibniz-InstituteforInteractiveMaterials,Aachen,Germany
LIUMINHE (cid:129) Guangdong-HongKong-MacauInstituteofCNSRegeneration,Jinan
University,Guangzhou,People’sRepublicofChina
RAHULDEVJAYANT (cid:129) DepartmentofPharmaceuticalSciences,SchoolofPharmacy,Texas
TechUniversityHealthSciencesCenter(TTUHSC),Amarillo,TX,USA
ABHIJEETJOSHI (cid:129) CentreforBiosciencesandBio-medicalEngineering,IndianInstituteof
TechnologyIndore(IIT-I),Indore,MadhyaPradesh,India
xi
xii Contributors
KRISTIANKEMPE (cid:129) ARCCentreofExcellenceinConvergentBio-NanoScience&Technology,
andDrugDelivery,DispositionandDynamics,MonashInstituteofPharmaceutical
Sciences,MonashUniversity,Parkville,VIC,Australia
MARCELOJAVIER KOGAN (cid:129) DepartamentodeQuı´micaFarmacol(cid:1)ogicayToxicol(cid:1)ogica,
FacultaddeCienciasQuı´micasyFarmace´uticas,UniversidaddeChile,Santiago,Chile;
AdvancedCenter forChronicDiseases(ACCDiS),Santiago,Chile
BEHNAZLAHOOTI (cid:129) DepartmentofPharmaceuticalSciences,SchoolofPharmacy,TexasTech
UniversityHealthSciencesCenter(TTUHSC),Amarillo,TX,USA
FRANCESCOLAI (cid:129) DepartmentofLifeandEnvironmentalSciences,UniversityofCagliari,
Cagliari,Italy
YANGLU (cid:129) DepartmentofTCMPharmaceutical,SchoolofChineseMaterialMecica,Beijing
UniversityofChineseMedicine,Beijing,People’sRepublicofChina
RAHULMITTAL (cid:129) LaboratoryofHumanMolecularGenetics,DepartmentofOtolaryngology,
MillerSchoolofMedicine,UniversityofMiami(UM),Miami,FL,USA
JAVIERO.MORALES (cid:129) DepartmentofPharmaceuticalScienceandTechnology,Schoolof
ChemicalandPharmaceuticalSciences,UniversityofChile,Santiago,Chile;Advanced
Center forChronicDiseases(ACCDiS),Santiago,Chile;CenterofNewDrugsfor
Hypertension(CENDHY),Santiago,Chile;PharmaceuticalandBiomaterialResearch
Group,DepartmentofHealthSciences,Lulea˚ UniversityofTechnology,Lulea˚,Sweden
JOSEPH A.NICOLAZZO (cid:129) DrugDelivery,DispositionandDynamics,MonashInstituteof
PharmaceuticalSciences,MonashUniversity,Parkville,VIC,Australia
JONAS C.ROSE (cid:129) DWI—Leibniz-InstituteforInteractiveMaterials,Aachen,Germany
MICHELESCHLICH (cid:129) DepartmentofLifeandEnvironmentalSciences,UniversityofCagliari,
Cagliari,Italy
CHIARASINICO (cid:129) DepartmentofLifeandEnvironmentalSciences,UniversityofCagliari,
Cagliari,Italy
HUGHD.C.SMYTH (cid:129) MolecularPharmaceuticsandDrugDeliveryDivision,Collegeof
Pharmacy,TheUniversityofTexasatAustin,Austin,TX,USA
MEIMEITIAN (cid:129) BioasisTechnologiesInc.,Guilford,CT,USA
SREE-POOJAVARAHACHALAM (cid:129) DepartmentofPharmaceuticalSciences,SchoolofPharmacy,
TexasTechUniversityHealthSciencesCenter(TTUHSC),Amarillo,TX,USA
CAROLINAVELASCO-AGUIRRE (cid:129) DepartamentodeQuı´micaFarmacol(cid:1)ogicayToxicol(cid:1)ogica,
FacultaddeCienciasQuı´micasyFarmace´uticas,UniversidaddeChile,Santiago,Chile;
AdvancedCenter forChronicDiseases(ACCDiS),Santiago,Chile
ZACHARYWARNKEN (cid:129) MolecularPharmaceuticsandDrugDeliveryDivision,Collegeof
Pharmacy,TheUniversityofTexasatAustin,Austin,TX,USA
ROBERTO.WILLIAMSIII (cid:129) MolecularPharmaceuticsandDrugDeliveryDivision,College
ofPharmacy,TheUniversityofTexasatAustin,Austin,TX,USA
WUTIAN WU (cid:129) Guangdong-HongKong-MacauInstituteofCNSRegeneration,Jinan
University,Guangzhou,People’sRepublicofChina;Re-StemBiotech,Suzhou,People’s
RepublicofChina
NAZHANG (cid:129) Guangdong-HongKong-MacauInstituteofCNSRegeneration,Jinan
University,Guangzhou,People’sRepublicofChina