The emergence of nanotherapeutics is attributable to the integration of nanotechnology, recombinant DNA technology, and synthetic organic chemistry with medicine for treating critical human diseases in a more efficient and specific molecular approach than therapy with conventionally-designed and formulated drugs. Nanotherapeutics: From Laboratory to Clinic comprehensively discusses the current shortcomings for delivery of classical (small) drugs, macromolecular therapeutics, and recombinant vaccine via the common intravascular and extravascular routes.
The book describes the synthetic/chemical engineering methods as well as recombinant, hybridoma, and phage display technologies to fabricate different types of nanoparticulate carriers and drugs. It also reveals the diversified approaches undertaken by harnessing nanotechnology to overcome the multistep extracellular and intracellular barriers and to facilitate the development of novel strategies for therapeutic delivery and imaging. The author elaborates on the preclinical and clinical trials of potential nanoparticle-based products in animal models and patients and the approval/commercialization of nanotherapeutics, addressing all relevant human diseases.
A focus on the above issues in a concise but illustrative manner fills the gap between the laboratory findings originating from the research on identification of cellular and systemic barriers of classical and macromolecular drugs along with development of strategies for fabrication and testing of nanotherapeutics, and the clinical outcomes emanating from the testing of the selected potential nanotherapeutics on patients of particular diseases. The book also fills a gap in the existing literature between the design and development of diversified nanotherapeutics for various purposes and the investigation and evaluation of potential barriers and resultant therapeutic efficacy of those nano-medicine formulations.
Emergence of nanotherapeutics: Challenges in classical drug transport versus macromolecular drug design
Administration of small-molecule drugs: Traffic routes toward the bloodstream
Fates of the small-molecule drugs in blood
Major problems associated with traditional formulations of small-molecule drugs
Alteration of pharmacokinetics of small-molecule drugs with macromolecules
Protein-based macromolecular drugs
DNA/RNA-based macromolecular drugs
Macromolecules for prodrug therapy
Macromolecules for vaccine delivery
Nanoparticles for photodynamic therapy
Macromolecules for image-guided drug delivery
The ultimate destinations for delivery and release of nanotherapeutics
Sustained-release formulations
Intracellular delivery and release
Factors involved in drug release from nanoparticles
Diversity of bioactive nanoparticles from biological, chemical, and physical perspectives
Viral vectors
Nonviral vectors
Hybrid particles
Genetically-engineered drug carriers
Bioconjugation schemes for functionalization of and ligand attachment to nanoparticle surface
Fabrication strategies for biofunctional nanoparticles
Chemical synthesis and engineering
Recombinant DNA, hybridoma, and phage display techniques
Interactions and orientation of therapeutic drugs in the vicinity of nanoparticles
Dendrimer-drug interactions
Amphiphilic block copolymer-drug interactions
Liposome-drug interactions
Inorganic nanoparticle-drug interactions
Variable interactions of nanoparticles with blood, lymph, and extracellular and intracellular components
Serum proteins with affinity to nanoparticles
Fates of the serum protein-coated nanoparticles
Interactions of nanoparticles with interstitial fluid and lymph
Extracellular matrix-nanoparticle interactions
Interactions between nanoparticles and cell components
Pharmacokinetics and biodistribution of nanoparticles
Influence of particle size
Influence of plasticity of nanoparticles
Influence of protein corona formed around nanoparticles
Influence of charge and hydrophilicity
Influence of endogenous membrane coating
Influence of ligand coating
Influence of coating of CD47 as a "self" marker
Extravasation from blood through vascular endothelium
Transport across the interstitium
Cellular uptake, metabolism, and excretion
Specific roles of nanoparticles in various steps of drug transport
Protection of nucleic acid- and protein-based drugs against degradation
Passive targeting to facilitate endothelial escape
Drug delivery via the lymphatic system
Targeting cell surface receptors and facilitated uptake
Endosomal escape
Nuclear targeting
Nanotechnology approaches to modulate transport, release, and bioavailability of classical and emerging therapeutics
Controlled release and bioavailability of oral nanoformulations
Sustained release and bioavailability of ocular drugs
Sustained release and bioavailability of dermal drugs
Sustained release and bioavailability of pulmonary drugs
Intracellular and extracellular transport vehicles
Nanotechnology in the development of innovative treatment strategies
Gene therapy
Protein- and DNA-based prophylactic vaccines
Immunotherapy
Photodynamic therapy
Image-guided therapy
Nanoparticles for therapeutic delivery in animal models of different cancers
Brain cancer
Breast cancer
Colon cancer
Lung cancer
Ovarian cancer
Pancreatic cancer
Skin cancer
Nanoparticles for therapeutic delivery in animal models of other critical human diseases
Arthritis
Cardiovascular diseases
Diabetes
Neurodegenerative diseases
Degenerative retinal diseases
Inflammatory bowel diseases
Obstructive respiratory diseases
Hepatic fibrosis and infections
Malaria
Regeneration of tissues
Nanomedicine in clinical trials
Different phases of clinical trials
Nanoparticulate drug delivery systems in clinical trials
Monoclonal antibodies as therapeutics in clinical trials (selected)
Approved and commercialized nanomedicine
Current safety issues: Biodegradability, reactivity, and clearance
Nanoparticle interaction with blood cells
Deformation of cellular membrane
Lysosomal rupture and release of contents
Disruption of cytoskeleton
Damage to nuclear DNA and proteins
References
Biography
Dr. Ezharul Hoque Chowdhury is an associate professor and cluster leader of biomedical engineering under the Advanced Engineering Platform at Monash University (Sunway Campus). He obtained his Doctor of Engineering degree in 2003 at Tokyo Tech. Dr. Chowdhury has pioneered the development of pH-sensitive inorganic nanoparticles as smart tools for efficient and targeted intracellular delivery of genetic materials, gene-silencing elements, proteins, and classical anticancer drugs. He is currently applying this smart nanotechnology for the treatment of cancer, particularly breast carcinoma, and cardiovascular diseases, such as diabetes. Dr. Chowdhury holds six Japanese and US patents.
