Pharmaceutical Applications of Dendrimers

✍ Scribed by Abhay Singh Chauhan (editor), Hitesh Kulhari (editor)

• Publisher: Elsevier
• Year: 2019
• Tongue: English
• Leaves: 385
• Series: Micro and Nano Technologies
• Edition: 1
• Category: Library

✦ Synopsis

Pharmaceutical Applications of Dendrimers explores the applications of dendrimers in the solubilization of hydrophobic active ingredients, drug delivery, gene delivery, imaging, diagnosis and photodynamic therapy. The book discusses the diagnostic applications of dendrimers, including their use as MRI contrast agents and in the imaging of diseased areas. In addition, the anti-inflammatory, antimicrobial and antiviral properties of PPI and PAMAM are also covered, along with a discussion on photosensitizers, such as rose Bengal and protoporphyrin IX that have been delivered using PAMAM and PPI dendrimers for the treatment of cancer.

This book is an important research reference for those who want to learn more about the development of dendrimer-based solutions for drug delivery.

✦ Table of Contents

Cover
Pharmaceutical Applications
of Dendrimers
Copyright
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 worldthe 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
Back Cover