1st Edition

Nanotherapeutics From Laboratory to Clinic

By Ezharul Hoque Chowdhury Copyright 2016
    356 Pages 72 Color Illustrations
    by CRC Press

    354 Pages 72 Color Illustrations
    by CRC Press

    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
    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
    Cardiovascular diseases
    Neurodegenerative diseases
    Degenerative retinal diseases
    Inflammatory bowel diseases
    Obstructive respiratory diseases
    Hepatic fibrosis and infections
    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



    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.