Dendrimer-Based Drug Delivery Systems: From Theory to Practice

533 Pages·2012·7.766 MB·English

by  Binghe Wang(eds.)

DENDRIMER-BASED
DRUG DELIVERY
SYSTEMS
Wiley Seriesin Drug Discovery and Development
BingheWang,SeriesEditor
Acompletelistofthetitlesinthisseriesappearsattheendofthisvolume.
DENDRIMER-BASED
DRUG DELIVERY
SYSTEMS
From Theory to Practice
Edited by
YIYUN CHENG
East China NormalUniversity
Shanghai,P.R. China
Copyright(cid:2)2012byJohnWiley&Sons,Inc.Allrightsreserved
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LibraryofCongressCataloging-in-PublicationData:
Dendrimer-baseddrugdeliverysystems:fromtheorytopractice/editedby
YiyunCheng.
p.;cm.–(Wileyseriesindrugdiscoveryanddevelopment)
Includesbibliographicalreferencesandindex.
ISBN978-0-470-46005-4(cloth)
I.Cheng,Yiyun.II.Series:Wileyseriesindrugdiscoveryanddevelopment.
[DNLM:1.Dendrimers–chemistry.2.DrugDeliverySystems.3.
Nanotechnology.QV785]
615.1’9–dc23
2011043341
PrintedintheUnitedStatesofAmerica
ISBN:9780470460054
10 9 8 7 6 5 4 3 2 1
CONTENTS
Foreword vii
DonaldA.Tomalia
Preface ix
Acknowledgments xi
Contributors xiii
About the Editor xvii
1 Dendrimer Chemistry: Supramolecular Perspectives and
Applications 1
CharlesN.Moorefield,SujithPerera,andGeorgeR.Newkome
2 Physicochemical Propertiesof Dendrimers and Dendrimer
Complexes 55
ToyokoImae
3 The Use ofDendrimers to Optimizethe Physicochemical
and Therapeutic Properties ofDrugs 93
NicoleStieger,WilnaLiebenberg,MariqueE.Aucamp,and
MelgardtM.deVilliers
4 Biological Propertiesof PhosphorusDendrimers 139
Anne-MarieCaminadeandJean-PierreMajoral
v
vi CONTENTS
5 Dendrimer-Based Prodrugs: Synthesis and Biological Evaluation 157
MohammadNajlah,ZhengyuanZhou,andAntonyD’Emanuele
6 Improving the Biocompatibility ofDendrimers in Drug Delivery 207
YiwenLi,LiboZhao,andYiyunCheng
7 Degradable Dendrimers for Drug Delivery 239
MarcGingrasandMyriamRoy
8 Design ofStimuli-Responsive Dendrimers for Biomedical Purposes 307
ChieKojima
9 Dendrimer-Based Gene Delivery Systems: Administration Routes
and In Vivo Evaluation 329
Santander-OrtegaM.J.,UchegbuI.F.,andScha¨tzleinA.G.
10 Triazine Dendrimers for DNAand siRNA Delivery: Progress,
Challenges, andOpportunities 355
MeredithA.Mintzer,OliviaM.Merkel,ThomasKissel,andEricE.Simanek
11 Dendrimer-Coated Carbohydrate Residuesas Drug Delivery
Trojan Horses inGlycoscience 407
YoannM.ChabreandRene´ Roy
12 Nuclear Magnetic Resonance Techniquesin the Analysis of
Pamam Dendrimer-Based Drug Delivery Systems 439
XueyanFeng,KunYang,JingjingHu,TongwenXu,andYiyunCheng
13 Dendrimer-BasedMedical Nanodevices for Magnetic
ResonanceImagingApplications 463
HongdongCai,MingwuShen,andXiangyangShi
14 Dendrimer-Related Nanoparticle System for Computed
Tomography Imaging 479
ChenPengandXiangyangShi
Index 501
FOREWORD
History has shown that seminal discoveries of the first three major traditional
polymer architectures; namely: (I) linear, (II) cross-linked, and (III) branched
architectures were in all cases followed by predictable patterns of intense inter-
nationalscientificandcommercialactivity.Unarguably,theseactivitieswerefueled
by the emergence of unprecedented new architecturally derived properties and
possibilities. Many of these architecturally driven properties have provided the
basis for new scientific principles, applications, and commercial products which
have served to enrich the human condition. Meanwhile, the past three decades
since the discovery of the fourth major polymeric architecture; namely: “dendritic
polymers/dendrimers”hasproventobenoexception.Consistentwithpastpatterns,
a fivefold increase in literature publications (i.e., H15,000) has been documented
for the past decade (2000–2011) compared to the first two decades since the
discovery of this new architectural class. Furthermore, a recent survey has
predicted extraordinary demand for nanomedicine derived products to grow over
17% per year through 2014 to an estimated market size of $75.1 billion, with
subsequent growth to exceed $149 billion by 2019.1
Presently, dendrimers are viewed as one of the most preeminent and actively
researched platforms in this rapidly emerging field of nanomedicine. More specif-
ically, these precise nanostructures are presently receiving intense attention in the
rapidlygrowingareaof“dendrimer-baseddrugdelivery.”Thisexplosiveactivityis
largely attributed to a growing list of unique architecturally driven properties
manifested by dendrimers, which includes the following:
1B.Martineau,GeneticEngineering&BiotechnologyNews,October15,2010,14–15.
vii
viii FOREWORD
. Precise synthetic control over: size, shape, and surface chemistry to produce
nanostructures that scale closely to proteins, yet do not exhibit immunogenic
responses.
. Well defined, versatile surface/interior chemistry that may be engineered to
delivertherapeuticlevelsofconjugatedpro-drugs,nanocontainer,drugencap-
sulationfeatures,targetinggroup/selectedbiodistributionpropertiesinconcert
with designed surface moieties that exhibit acceptable toxicity properties and
safety margins.
. Precise size calibrated nanostructures that may be suitably decorated with
appropriate imaging or stimuli responsive moieties for in vivo “theranostic”
applications.
. Well-definednanostructuresizesandfeatures(i.e.,self-immolative/biodegrad-
able) suitable for engineeringdesirable excretionmodes.
Professor Yiyun Cheng from East China Normal University has assembled an
internationalteamofesteemeddendrimerpioneersandresearchersforthepurposeof
sharingtheirvaluedperspectivesonallfacetsofDendrimer-BasedDrugDelivery—
FromTheorytoPractice.Inthiscomprehensivesurvey,anumberofcriticalissuesare
analyzedthatbridgethecriticalpathfromfundamentalconcepts,design,synthesis,
analyticalmethodologies,biologicalassessmenttothepracticaluseofdendrimersfor
drug delivery applications. More specifically, major points of emphasis may be
categorized andsummarized asfollows:
. Introductiontodendrimer-baseddrugdeliverysystems,synthesisofdendrimers,
physicochemical/biologicalpropertiesofdendrimersanddendrimercomplexes,
synthesisandbiologicalevaluationsofdendrimer-basedprodrugs,andtheeffect
of dendrimersonthe therapeutic properties ofdrugs:Chapters 1–5;
. Theimportanceofbiocompatibilitytodendrimer-baseddrugdeliverysystems,
and strategies used to improve the biocompatibility of dendrimers including
stimuli-responsive,degradable,andself-immolativedendrimers:Chapters6–8;
. Applications of dendrimers in the delivery of DNA and siRNA, including
complex structures, in vitro and in vivo transfection efficiency, and potential
administration routes, and the synthesis and pharmaceutical applications of
glycodendrimers: Chapters 9–11;
. Nuclearmagneticresonancetechniquesintheanalysisofdendrimer-baseddrug
delivery systems, and the applications of dendrimers in magnetic resonance
imagingand computed tomography: Chapters12–14.
Insummary,basedontheexperience/qualityofauthorshipandtherangeofcritical
issues reviewed, this book represents a unique collection of know-how for under-
standingandpracticingunprecedentednewdrugdeliverystrategiesinthecontextof
nanomedicine.Thisbookshouldserveasavaluableresourceforbothacademicand
commercialinvestigatorswhoareseekingpromisingnewstrategiesforthesafeand
effectivedeliveryofin vivo therapies,imaging anddiagnostics.
DONALDA.TOMALIA
PREFACE
Dendrimers are hot research points and have been widely used in supramolecular
chemistry,host–guestchemistry,electrochemistry,photochemistry,astemplatesfor
nanoparticle synthesis, as scaffolds for catalysts, and in drug and gene delivery.
Among these applications, biomedical applications of dendrimers have attracted
increasing interest during the past decade. Because of the unique opportunities,
issues,andchallengesinvolvedwithexploitingdendrimersfordrugdelivery,thereisa
needforabooktohelppharmacistsandrelatedscientistsunderstandandworkwith
thisnewclass ofpromising biomaterials. Thistimelybookcovers topicsincluding
dendrimerhistory,synthesis,physicochemicalproperties,principlesindrugdelivery,
andapplicationsinmiscellaneousbiomedicalfields,andprovidespracticalsugges-
tionsfor the design andoptimization ofdendrimer-based drugdelivery systems.
Thisbookincludes14chapters.Chapter1presentsahistoricalviewondendrimer
chemistryandgivessupramolecularperspectivesondendrimers.Chapter2focuseson
the physicochemical properties of dendrimers and dendrimer complexes.Chapter 3
discusses the use of dendrimers to tailor the physicochemical and therapeutic
properties of loaded drugs. In Chapter 4, Caminade and Majoral summarize the
biologicalpropertiesofphosphorusdendrimersthatweredevelopedintheirlaboratory.
Chapter 5 reports the synthesis and biological applications of dendrimer-based
prodrugs.Chapter6aimsatthesafetyofdendrimersandproposesseveralstrategies
toimprovethebiocompatibilityofdendrimers.Chapter7emphasizestheimportance
of dendrimer degradability for drug delivery. Chapter 8 focuses on the design of
stimuli-responsivedendrimersforbiomedicalpurpose.Chapter9presentsdendrimer-
based gene delivery systems. The administration routes and in vivo evaluations of
dendrimer/DNAscomplexesarealsodiscussed.Chapter10alsointroducesdendrimer
applicationsingenedeliverybutemphasizestriazinedendrimersthatweredeveloped
ix
x PREFACE
inSimanek’sresearchgroup.InChapter11,Royandcoworkersintroducetheuseof
carbohydrate-functionalized dendrimers as drug delivery Trojan horses. Chapter 12
relatestheapplicationsofNMRtechniquesintheanalysisofdendrimer-baseddrug
formulations.InChapters13and14,Shietal.introducetheapplicationsofdendrimers
inmagneticresonanceimagingandcomputedtomographyimaging.
Thisbookisdirectedprimarilyatthepharmaceuticalsciences,andaimstobethe
definitivereferencebookforscientistsinthefieldofbiomaterials,nanomedicine,drug
delivery systems, pharmacy, and dendrimer chemistry. It is my hope that it can
stimulate the interest ofresearchers fromthesefields.
YIYUN CHENG