Nanotherapeutics From Laboratory to Clinic

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 designAdministration of small-molecule drugs: Traffic routes toward the bloodstreamFates of the small-molecule drugs in bloodMajor problems associated with traditional formulations of small-molecule drugsAlteration of pharmacokinetics of small-molecule drugs with macromoleculesProtein-based macromolecular drugsDNA/RNA-based macromolecular drugsMacromolecules for prodrug therapyMacromolecules for vaccine deliveryNanoparticles for photodynamic therapyMacromolecules for image-guided drug deliveryThe ultimate destinations for delivery and release of nanotherapeuticsSustained-release formulationsIntracellular delivery and releaseFactors involved in drug release from nanoparticlesDiversity of bioactive nanoparticles from biological, chemical, and physical perspectivesViral vectorsNonviral vectorsHybrid particlesGenetically-engineered drug carriersBioconjugation schemes for functionalization of and ligand attachment to nanoparticle surfaceFabrication strategies for biofunctional nanoparticlesChemical synthesis and engineeringRecombinant DNA, hybridoma, and phage display techniquesInteractions and orientation of therapeutic drugs in the vicinity of nanoparticlesDendrimer-drug interactionsAmphiphilic block copolymer-drug interactionsLiposome-drug interactionsInorganic nanoparticle-drug interactionsVariable interactions of nanoparticles with blood, lymph, and extracellular and intracellular componentsSerum proteins with affinity to nanoparticlesFates of the serum protein-coated nanoparticlesInteractions of nanoparticles with interstitial fluid and lymphExtracellular matrix-nanoparticle interactionsInteractions between nanoparticles and cell componentsPharmacokinetics and biodistribution of nanoparticlesInfluence of particle sizeInfluence of plasticity of nanoparticlesInfluence of protein corona formed around nanoparticlesInfluence of charge and hydrophilicityInfluence of endogenous membrane coatingInfluence of ligand coatingInfluence of coating of CD47 as a "self" markerExtravasation from blood through vascular endotheliumTransport across the interstitiumCellular uptake, metabolism, and excretionSpecific roles of nanoparticles in various steps of drug transportProtection of nucleic acid- and protein-based drugs against degradationPassive targeting to facilitate endothelial escapeDrug delivery via the lymphatic systemTargeting cell surface receptors and facilitated uptakeEndosomal escapeNuclear targetingNanotechnology approaches to modulate transport, release, and bioavailability of classical and emerging therapeuticsControlled release and bioavailability of oral nanoformulationsSustained release and bioavailability of ocular drugsSustained release and bioavailability of dermal drugsSustained release and bioavailability of pulmonary drugsIntracellular and extracellular transport vehiclesNanotechnology in the development of innovative treatment strategiesGene therapyProtein- and DNA-based prophylactic vaccinesImmunotherapyPhotodynamic therapyImage-guided therapyNanoparticles for therapeutic delivery in animal models of different cancersBrain cancerBreast cancerColon cancerLung cancerOvarian cancerPancreatic cancerSkin cancerNanoparticles for therapeutic delivery in animal models of other critical human diseasesArthritisCardiovascular diseasesDiabetesNeurodegenerative diseasesDegenerative retinal diseasesInflammatory bowel diseasesObstructive respiratory diseasesHepatic fibrosis and infectionsMalariaRegeneration of tissuesNanomedicine in clinical trialsDifferent phases of clinical trialsNanoparticulate drug delivery systems in clinical trialsMonoclonal antibodies as therapeutics in clinical trials (selected)Approved and commercialized nanomedicineCurrent safety issues: Biodegradability, reactivity, and clearanceNanoparticle interaction with blood cellsDeformation of cellular membraneLysosomal rupture and release of contentsDisruption of cytoskeletonDamage to nuclear DNA and proteinsReferences

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.