Nanotechnology in Drug Delivery
Fundamentals, Design, and Applications

Saurabh Bhatia, PhD

Nanotechnology in Drug Delivery

Published. Now available.
Pub Date: June 2016
Hardback Price: $149.95 US
Hard ISBN: 9781771883603
E-Book ISBN: 9781771883610
Pages: 390pp w/ index
Binding Type: hardback
Notes: 7 color and 21 b/w illustrations

This important new book provides the fundamental understanding of the peptide and protein drug delivery systems with a special focus on their nanotechnology applications. Addressing an increasing interest in peptide and protein drug delivery systems in both academic and industrial circles worldwide, this book fills the need for a comprehensive review and assessment of conventional and nonconventional routes of administration.

The book provides fundamental and comprehensive information regarding the synthesis, stability, degradation, and physicochemical aspects of proteins and peptides. It also addresses barriers to peptide and protein delivery and examines formulation and delivery strategies. The book goes on to discuss pharmacokinetic considerations; methods of preparation, design and synthesis of peptides; structure-function relationships; peptide-polymer conjugates; peptide-encapsulating nanoparticles; biomedical applications of peptide-polymer conjugates; and nonpeptide targeting.

This book creates interest in the area of peptide and protein drug delivery and provides a framework for the pharmaceutical or biotechnological scientist to formulate a strategy to deliver peptide and protein drugs to their site of action. This book is the first book to discuss these three key features that are current in demand simultaneously: peptides, nanoparticles, and drug delivery. The book introduces some novel classes of peptides and classifies according to their DD applications.

According to the author’s survey, more than 30% of highly reputed biomedical science articles published today explore peptide-mediated nanotechnology. This is the first book to provide a clear overview, which will be of interest and value to students, researchers, biologists, pharmacists, chemists, chemical engineers, and in particular protein biochemists, chemical biologists, molecular biologists, microbiologists, geneticists, bioinformaticians, biotechnologist, NDDS, and other professionals who are interested in associated areas.

1.1 Introduction
1.2 Structures of proteins
1.2.1 Levels of protein structure
1.3 Chemical synthesis of protein and peptides
1.3.1 Protein synthesis
1.3.2 Peptide synthesis Solid phase peptide synthesis
1.3.3 Protein synthesis by peptide ligation
1.3.4 Peptide ligation with sulfur
1.3.5 Peptide ligation with selenium
1.3.6 General strategies for peptide ligation
1.4 Degradation pathways indicating instability of proteins and peptides
1.4.1 Structural and functional stabilization of protein
1.4.2 General stability issues
1.4.3 Physical instability
1.4.4 Chemical instability
1.5 Factors affecting delivery of protein based drugs
1.6 Physicochemical properties of peptides and proteins
1.7 Barriers to peptide and protein delivery
1.8 Various routes of administration for protein or peptide drugs
1.9 Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications
1.10 Peptide targeting
1.11 Development of delivery system for peptide based pharmaceuticals
1.12 Delivery of proteins and nucleic acids using a non-covalent peptide-based strategy
1.13 Protein transduction technology
1.14 Peptide and protein drugs—brief overview and delivery problems
1.15 Intracellular targets and intracellular drug delivery – pharmaceutical carriers

2.1 Introduction
2.2 Pharmacokinetic consideration for peptide mediated drug delivery
2.3 Peptide-based drug delivery: Methods of preparation
2,3.1 Design and synthesis of peptide
2.3.2 Rational design
2.3.3 Structure-function relationship
2.3.4 Computer-aided drug designing
2.3.5 Combinatorial library design
2.3.6 Biological peptide library
2.3.7 Peptide phage library
2.3.8 Synthetic peptide library requiring deconvolution
2.3.9 One bead one compound library
2.3.10 Spatially addressed parallel library
2.3.11 Synthetic library method using affinity chromatography selection
2.4 Peptide/polymer nanoparticle
2.4.1 Ion gelation method
2.4.2 Emulsion solvent evaporation technique
2.4.3 Layer by layer assembly
2.4.4 Nanolithography
2.4.5 Stober method
2.4.6 Nanoprecipitation
2.4.7 Chemical coprecipitation
2.4.8 Emulsion diffusion
2.4.9 Coarcervation technique
2.4.10 Salting out
2.4.11 Tayor cone jet methods
2.4.12 Surface functionalization of gold NPs
2.4.13 Solvent evaporation
2.4.14 Interfacial polymerization
2.5 Peptide polymer conjugate
2.5.1 Criteria for designing peptide polymer conjugate
2.5.2 Coupling of peptide on the surface of nanoparticle Direct interaction Electrostatic interaction Covlent coupling Non covalent coupling Bioconjugation of peptide and protein on nanoparticles
• Maleimide reactions
• EDC–NHS bioconjugation
• Affinity interactions
• Click chemistry
• Streptavidin–biotin reaction
2.6 Peptide mediated targeting
2.6.1 Peptide encapsulating nanoparticle
2.6.2 Nanocarriers of peptide and protein encapsulants Metallic nanocarriers Polymeric nanocarriers Natural nanocarriers Synthetic nanocarriers Protein itself as nanoparticles
2.7 Biomedical application of peptide polymer conjugate
2.7.1 Cancer
2.7.2 Immune system
2.7.3 Respiratory disease
2.7.4 Liver and pancreas
2.7.5 Skin
2.7.6 Neurological disorder
2.7.7 Vasculature
2.7.8 Opthalmic disease
2.7.9 Other
2.8 Nonpeptide targeting
2.8.1 Protein as targeting agent
2.8.2 Vitamin as targeting ligands
2.8.3 Nucleic acid (aptamers) as ligand
2.9 Nanoencapsulation improves the therapeutic importance of proteins and peptides
2.10 The stability of nanoencapsulated peptide and protein
2.11 Therapeutic use of the nanoprotein molecules
2.12 Conclusion
2.13 References

3. Introduction
3.1 Cell-penetrating peptides
3.1.1 Clinical development of CPPs
3.1.2 Problems and limitations of CPPS for drug delivery in vivo
3.1.3 Toxicity of cationic CPPs
3.1.4 Local CPP-mediated delivery
3.1.5 Some ways to home CPPs
• Exploiting matrix metalloproteases
• Exploiting the peritumoral acidic pH
• Exploiting the biological state of targeted cells
3.1.6 CPP-loaded devices and local release
• Thermal sensitive polymers
• Ultrasound sensitive particles
3.1.7 Types of cell-penetrating peptides Protein-derived cell-penetrating peptides
• Tat-derived peptides
• Signal-sequence-based peptides Synthetic and/or chimeric cell-penetrating peptides
• Transportan
• Protein-derived cell-penetrating peptides
• Synthetic and/or chimeric cell-penetrating peptides
• Model amphipathic peptides
• Herpes simplex virus type 1 (HSV-1) protein VP22
• Trans-activating transcriptional activator (TAT)
• Homeodomain of Antennapedia (Antp)
• Other transducing peptides
3.1.8 Penetration of CPPs in vitro and in vivo Mechanism of penetration
3.1.9 Cellular uptake of CPPs: new insights into the route of entry Delivery of proteins Delivery of DNA Delivery of antibodies Delivery of imaging agents
3.1.10 Applications of cell-penetrating peptides Intracellular delivery Delivery of oligonucleotides Delivery of large particles and DNA Cargo Delivering quantum dots across the blood–brain barrier CPPs for the intracellular delivery of antibodies Visualizing viral infection in real time with CPPs Harnessing CPPs to deliver intracellular biosensors horses
3.1.11 Cellular trojan Small molecule delivery Harnessing CPPs for delivery of peptides, peptoids and proteins Delivery of nucleic acids and siRNA Increasing absorption with CPPs CPPs in cancer therapy
3.2 Cell-targeting peptides (CTPS)
3.2.1 Identification of CTPs
3.2.2 Structure–activity relationship of ligands
3.2.3 Phage display
3.2.4 Chemical strategies (one bead one compound, ligand mimetics…)
3.2.5 Improving CTPs
3.2.6 The RGD peptide: a “scholar study”
3.2.7 Cyclization
3.2.8 Multimerization

About the Authors / Editors:
Saurabh Bhatia, PhD
Assistant Professor, PDM College of Pharmacy,Bahadurgarh, Haryana, India

Saurabh Bhatia, PhD, is currently an Assistant Professor at the PDM College of Pharmacy in Bahadurgarh, Haryana, India. He has several years of academic experience, teaching such specialized subjects as pharmacognosy, traditional concepts of medicinal plants, plant tissue culture, modern extraction and isolation methodologies, natural polymers, parasitology (Leismania), medicinal and pharmaceutical values of marine and fresh water algae, and nanoparticles and peptide-mediated drug delivery systems. He has investigated several marine algae and their derived polymers throughout India. He has written more than 30 international publications in these areas and has been an active participant of more than 35 national and international conferences. His published books include Modern Applications of Plant Biotechnology in Pharmaceutical Science and Practical Applications of Plant Biotechnology (in press).

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