Pharmaceutical Applications of Dendrimers

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Pharmaceutical Applications
of Dendrimers
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Contributors
Preface
Section A: Dendrimers and their properties
1
Engineering critical nanoscale design parameters (CNDPs): A strategy for developing effective nanomedicine the ...
	Introduction
	Historical
		Dendrimer-based nanoscale atom mimicry: A window to nanoperiodicity
		Dendrimer-based protein mimicry
		Dendrimer-based dendritic effects as a window to nanoperiodic property patterns
	Application of nanoperiodic property patterns and CNDP engineering principles to nanomedicine
		Developing an optimum nanotherapeutic platform based on intrinsic structure controlled, tunable nanoparticle CNDPs
	Unique dendrimer features that facilitate systematic CNDP engineering for optimized nanomedicine applications
	Nanoparticle structural control and engineering CNDPs: Implications for nanomedicine
		Size
	Recent progress in dendrimer based CNDP-engineering
		Size/shape
		Surface/interior chemistry
		Flexibility/Rigidity
	Optimizing dendrimer properties for nanomedicine applications
		Early examples of engineering dendrimer CNDPs for nanomedicine applications
		An early example of engineering dendrimer CNDPs related to targeted therapy for cancer
		Quality assurance of dendrimer quality/CNDP engineering for clinical trials
		Quality assurance of dendrimers for experimental literature: Minimum information reporting in bio-nano experimental  ...
	Progress in dendrimer-based CNDP engineering related to quantitative nanostructure-activity relationships (QNSARs) and ...
		Quantitative nanostructure-activity relationships (QNSARs)
		CNDP-based QNSARs to determine most effective antiviral dendrimers against influenza A (H1N1)
	Conclusions
	Acknowledgment
	References
	Further reading
2
Dendrimers in drug delivery and the role of ``critical nanoscale design parameters´´ (CNDPs)
	Introduction
		Formulation approach
		Nanoconstruct approach
	Dendrimer as drug delivery?
	Critical nanoscale design parameters (CNDPs) in dendrimers for drug delivery
	References
Section B: Dendrimers for pharmaceutical applications
3
Dendrimers for drug solubilization, dissolution and bioavailability
	Introduction
	Molecular features of dendrimers
	Concept of solubility enhancement with dendrimer
		Non-covalent interaction
		Covalent interaction
	Dendrimer-based solubility enhancement of various classes of drugs
		NSAIDs
		Anticancer drug
		Anti-microbial drugs
		Antihyperlipidemic/hypolipidemic drugs
		Anti-hypertensive drugs
		Diuretics
		Antipsychotic drug
		Anti-glaucoma drug
		Phytoconstituents
		Anthelmintic/benzimidazole carbamate albendazole (ABZ)
		Miscellaneous
	Dendrimer-based drug-delivery through various routes
		Intravenous delivery
		Intranasal delivery
		Oral delivery
		Ocular delivery
		Pulmonary delivery
		Transdermal delivery
	Conclusion
	Acknowledgments
	References
4
Pharmacokinetic considerations in design of dendrimer-based nanomedicines
	Introduction
	Effect of size, molecular weight, hydrophobicity and charge on pharmacokinetic profile of dendrimers
	Effect of surface functionalization on pharmacokinetic profile of dendrimers
	Conclusion
	Acknowledgment
	References
5
Dendrimer-based targeted drug delivery
	Introduction
	Designing of dendrimers for drug targeting
	Types of surface modification of dendrimers
		PEGylation
			For cancer
			For bone diseases
		Folic acid conjugation
			For cancer
			For rheumatoid arthritis
		Amino acids/peptides/proteins conjugation
			For cancer
			For human immunodeficiency virus HIV
			For dental applications
		N-acetyl-cysteine (NAC) conjugation
			For cerebral palsy (CP)
			For Rett syndrome (RTT)
		Carbohydrate functionalization
			For cancer
			For infections
			For human immunodeficiency virus (HIV)
			For scar prevention
			For antimalarial drug delivery
			For lung disorders
		Biotinylation
			For cancer
		Lauroyl chain conjugation
			For cancer
		Tuftsin grafting
			For HIV
		Antibody grafting
			For cancer
		Phosphonate derivatization
		Sulfate derivatization
			For human immunodeficiency virus (HIV) and herpes simplex virus (HSV)
		P-hydroxyl benzoic acid (pHBA) functionalization
		Hyaluronic acid functionalization
	Conclusion
	References
6
Dendrimers for anticancer drug delivery
	Introduction
	Brief about dendrimers and application for cancer drug delivery
	PAMAM dendrimer for cancer therapy
	PPI dendrimers for cancer therapy
	PPL dendrimers for cancer therapy
	Conclusion
	Acknowledgment
	References
7
Cancer-targeted chemotherapy: Emerging role of the folate anchored dendrimer as drug delivery nanocarrier
	Cancer world ``the making of modern disease´´
		What is cancer?
		Causes of cancer
		Origin of the word cancer
			The oldest description of cancer
		Biology of cancer
		Tumor vasculature
		Physiology of tumor structure
		Stages of tumor development
		Classification of cancer
		Prevention of cancer
			Tobacco
			Alcohol
			Physical inactivity, dietary factors, and obesity
			Infections
			Environmental pollution
			Occupational carcinogens
			Radiation
		World cancer day
		Diagnosis of cancer
		How cancer is treated?
			Surgery
			Radiation therapy
			Immunotherapy
			Hormone therapy
			Gene therapy
			Chemotherapy
		Current approaches to cancer therapy
		Barriers in cancer therapy
			Physiological barriers
			Cellular barriers
			Pharmacokinetic barriers
		Limitations of conventional cancer therapy
		Tumor targeting via a novel drug delivery system
			Passive targeting
			Active targeting
	Nanotechnology
		Properties of carrier systems used for drug delivery
		Nanovision for targeting of cancer
			Carbon nanotubes (CNTs)
			Gold nanocarriers
			Mesoporous silica nanoparticles (MSNs)
			Quantum dots
			Liposomes
			Polymeric micelles
			Dendrimers
	Dendrimer in nanotechnology
		What are dendrimers
		Properties of dendrimeric domain
		Potential applications of dendrimers
			Inkjet inks and toners
			In vitro diagnostics
			In vitro gene transfection
			Controlled drug delivery
			Solubilization of drug
			Drug delivery units
			Catalyst support
			Delivery agents for vaccines
			Protein mimicry
			Patterning and templating
		A tribute to dendrimer workers
		The rationale for selecting dendrimers as drug delivery carrier
		The rationale for opting dendrimer-based drug targeting
		Cancer and dendrimer
			Drug-loaded dendrimers as nano-vehicles
			Target specific dendritic scaffolds
			The rationale for selecting folic acid as a ligand
				Folate-targeted dendritic nanocarriers
				Folate-PEG dendrimer in cancer targeting
				DNA assembled dendrimer-folate conjugate
				Folate-DTPA dendrimer in cancer targeting
			Multimodality dendrimers based diagnostic agents
	Conclusion
	References
	Further reading
8
Design of dendrimer based prodrugs
	Introduction
	Advantages of dendrimer over other polymers for prodrug preparation
	Advantages of dendrimer prodrugs
	Requirements for dendrimer prodrugs
	Strategies for design and synthesis of dendrimer prodrugs
	Dendrimer prodrugs without spacer
		Dicyclohexylcarbodiimide (DCC)
		1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC, EDCI)
		Coupling reactions involving N-hydroxysuccinimide (NHS) ester derivative
	Dendrimer-prodrugs with spacers
	Conclusion
	References
9
Dendrimers in gene delivery
	Introduction
	Mechanism of gene delivery using dendriplexes
		Synthesis of dendriplexes
		Targeted dendriplexes
		Intracellular trafficking
		Endolysosomal escape
			Proton-sponge hypothesis
		Transport across the cytoplasm
		Nuclear localization
		Release of genetic material from dendriplexes
	Factors affecting dendrimer-based gene delivery
		Structure of dendrimers
		Size and molecular weight
		Surface charge and charge density
		Polyvalency
		Hydrophilicity
		Polymer-DNA charge ratio
	Design criteria for formulating dendrimer vectors for gene delivery
	Problems in dendrimer-based gene delivery
	Surface modification in dendrimer for efficient gene delivery
		Amino acid-modified dendrimers
		Protein- or peptide-modified dendrimers
		Carbohydrate-modified dendrimers
		Polymer- or lipid-modified dendrimers
		Other ligand-modified dendrimers
	Modification of dendrimer core for efficient gene delivery
		For flexibility of dendrimers
		For hydrophobicity of dendrimers
		For functional versatility of dendrimers
	Conclusion
	Acknowledgments
	References
	Further reading
10
Dendrimers in immunotherapy and hormone therapy
	Dendrimers in immunotherapy
		Effect of dendrimers on innate immune system
		Effect of dendrimers on adaptive immune system
		Role of dendrimers as vaccine delivery systems
	Dendrimers in hormone therapy
	Limitations of dendrimers
	Future prospects
	Acknowledgments
	References
11
Toxicity and biocompatibility aspects of dendrimers
	Introduction
	Dendrimer architecture
	Dendrimer types
		Polyether dendrimers
		Polyester dendrimers
		Tecto/core-shell dendrimers
		Triazine dendrimers
		Citric acid dendrimers
		Phosphate dendrimers
		Melamine dendrimers
		Polyether imine (PEI) dendrimers
		Polyether-polyester (PPE) dendrimers
		Other dendrimers
		PAMAM dendrimers
		PPI dendrimers
		Glycodendrimers
		Chiral dendrimers
		Poly-l-lysine dendrimers
		Hybrid dendrimers
		PAMAM-organosilicon (PAMAMOS) dendrimers
		Liquid crystalline (LC) dendrimers
		Polyurea dendrimers
		Peptide dendrimers
	Mechanism of dendrimer biocompatibility and toxicity
	Why are dendrimers toxic?
		Cationic charge
		Core associated toxicity
		Free amine toxicity
	Dendrimer toxicity and biocompatible strategies
		Cytotoxicity
		Hematological toxicity
		Hemolytic toxicity
		Immunogenic toxicity
		In-vivo toxicity
	Surface modified dendrimer for compatibility
		PEGylation
		Folic acid surface tagging
		Amino acid/peptide surface modification
		Antibody tagging
	Miscellaneous
	Future prospectus
	References
12
Therapeutic dendrimers
	Introduction
	Classification of therapeutic dendrimer
		Antimicrobial therapy
		Anti-inflammatory/inflammation
		Tumors
		Angiogenesis inhibitor
		Antiviral
	Conclusion
	Acknowledgments
	References
Section C: Dendrimers for non-pharmaceutical applications
13
Dendrimers for diagnostic applications
	Introduction
	Problem with carrier free in-vivo delivery of diagnostic agents
	Advantage of dendrimer-based imaging systems
	Design criteria for formulating dendrimer vectors as contrasting agents
		Low polydispersity index
		Enhanced permeability and retention effect
		High permeability
		Sustained/extended effect
		Higher solubilization potential
		High uniformity and purity
		Multifunctional platform
		High loading capacity
		High stability
		Low toxicity
		Low immunogenicity
		Dendrimers can be modified as stimuli responsive to release drug
		Dendrimers microvascular extravasation properties
	Dendrimer for encapsulating contrasting agents within the cavity
		Dendrimer-based magnetic resonance imaging agents
		Dendrimer-based positron emission tomography agents
		Dendrimers-based computed tomography agents
		Dendrimer-based fluorescence imaging agents
		Dendrimer-based PDT, PTT and neutron capture therapy agents
	Dendrimer for conjugating contrasting agents on the surface
		Dendrimer-based magnetic resonance imaging agents
		Dendrimer-based positron emission tomography (PET) agents
		Dendrimer-conjugated computed tomography agents
		Dendrimer-conjugated florescence imaging agents
		Dendrimer-conjugated PDT, PTT and neutron capture therapy agents
	Major challenges of dendrimer-based diagnostic systems
		Toxicity
		Immunogenicity
	Conclusion
	References
14
Dendrimer-based marketed formulations and miscellaneous applications in cosmetics, veterinary, and agriculture
	Current scenario: Translation of dendrimer-based product from research to market
		VivaGel
		Alert ticket
		Stratus CS
		SuperFect
		Priofect
		Gadomer-17
	Dendrimer-based formulations under clinical trial
	Miscellaneous applications of dendrimers
		Dendrimers in cosmetics
		Dendrimers in veterinary
		Dendrimers in agricultural application
	Conclusion
	References
Author Index
Subject Index
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