Nanotechnology for Oral Drug Delivery: From Concept to Applications

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NANOTECHNOLOGY
FOR ORAL DRUG
DELIVERY
From Concept to Applications
Copyright
Contributors
Foreword
Part I: Biological aspects and properties of nanomaterials for oral drug delivery
Oral drug delivery: Overview
	Introduction
	References
Organization of the intestinal mucosa and barriers to oral drug delivery
	Introduction
	Structure of the small intestine
		Cellular compositions
		Tight junctions or zonula occludens
		Adherens junctions or zonula adherens
		Desmosomes or macula adherens
	Metabolizing enzymes
	Efflux pumps
	Transporters for transcytosis
	Mechanism of crossing the intestinal mucosal barrier
		Passive diffusion through transcellular pathways
		Passive diffusion through paracellular pathways
	Models to study intestinal absorption
		In vitro models
		In vivo models
	Conclusions
	References
Nanomaterials for oral drug administration
	Introduction
	The rational design of nanocarriers for oral drug formulation
	Types of nanomaterials
		Nanocrystals and nanosuspensions
		Polymeric-based nanocarriers
			Nanospheres and nanocapsules
			Polymeric micelles
			Nanogels
			Dendrimers
			Polymer-drug conjugates
		Lipid-based nanocarriers
			Liposomes
			Nanoemulsions
			Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC)
		Inorganic based-nanocarriers
			Carbon nanotubes
			Nonporous nanomaterials
			Mesoporous nanomaterials
	Emerging trends in oral nanoformulation: Hybrid, protein and stimuli-responsive nanocarriers
		Hybrid nanocarriers
		Protein nanocarriers
		Stimuli-responsive nanocarriers
	Nanomaterials for the targeting of specific GIT regions
		Targeting the stomach
		Targeting the small intestine
		Colon targeting
	Conclusions and future perspectives
	References
Mucoadhesive and mucus-penetrating polymers for drug delivery
	Introduction
	Definitions and fundamentals
		Bio- and mucoadhesion
		Oral mucosa as route for drug administration
		Reasons for developing oral mucosal drug delivery systems
		Desired physicochemical and biopharmaceutical characteristics of drugs
		Desired physicochemical characteristics of materials
	Mucoadhesive and mucus-penetrating materials
		Mucoadhesive polymers
			Natural mucoadhesive polymers
			Semisynthetic mucoadhesive polymers
			Synthetic mucoadhesive polymers
			New generation of mucoadhesive polymers
		Mucus-penetrating polymers
	Oral mucosal drug delivery systems
		Strategies
		Technology
		Types of systems or pharmaceutical dosage forms
	Safety and toxicity
		In-vitro evaluation
		In-vivo evaluation
	Regulatory status
	Patenting and market
	Conclusions and future perspectives
	References
Size, shape and surface charge considerations of orally delivered nanomedicines
	Introduction to nanomedicine for oral drug delivery
	Challenges associated with oral nDDS
	Size, shape and surface chemistry considerations for orally delivered nanomedicine
		Particle size and shape
		Surface properties of nanoparticles
		Drug loading and release profile
	Summary
	References
Modified drug release: Current strategies and novel technologies for oral drug delivery
	Part 1: Evolution of oral modified release dosage forms
	Part 2: Current oral formulation strategies for modified release
		Extended release formulations
			Dissolution-controlled formulations
			Diffusion-controlled formulations
			Osmosis-based formulations
			Ion exchange-based formulations
		Delayed release formulations
		Targeted release formulations
			Gastroretentive (GR) devices
			Colon-targeted drug delivery systems
	Novel technologies for modified drug release
		Microneedle pills for oral drug delivery
		Three-dimensional (3D) printing medicines
	Conclusions and future perspectives
	References
Delivery platforms for oral drug administration
	Introduction
	Delivery platforms for oral administration of (bio)pharmaceuticals
		Effect of the size and shape of the drug delivery system
		Effect of the surface of the drug delivery system
		Effect of the composition and the preparation method of the drug delivery system
		Targeted drug delivery systems
	Conclusions
	References
	Further reading
(Trans)buccal drug delivery
	Introduction
	Oral cavity: Anatomic and physiologic features
	Buccal mucosa as barrier for drug penetration/permeation
	Strategies to target the buccal mucosa
		Penetration enhancers
		Mucoadhesion
		Enzyme inhibitors
	The advantages of nanoparticles for buccal delivery
		Polymeric nanoparticles
		Polymeric micelles
		Lipid-based nanoparticles
		Liposomes
	Dosage forms for the buccal delivery of nanoparticles
		Films
		Solid matrices
		Gels
	Final remarks
	References
Part II: Advanced technologies for oral delivery applications
Spray-drying for the formulation of oral drug delivery systems
	Introduction
	Spray-drying
		Principle, equipment configurations, main advantages and challenges
		Parameters and variables affecting particle formulation
			Factors affecting particle formation mechanisms
			Feed solution properties
			Process parameters
		Scale-up considerations
	Formulation of drugs/drug delivery systems for oral administration using the spray-drying technology
		Conventional methods versus spray-drying of micro- and nano-particle formulations
		Common excipients used in the preparation of drug formulations prepared by spray-drying
		Preparation of particulate systems with spray-drying and applications in oral drug delivery
			Microparticles
			Nanoparticles
			Pure drug particles
	Conclusions and future perspectives
	References
Microdevices to successfully deliver orally administered drugs
	Introduction
	Design of microdevices
	Materials for the fabrication of microdevices
		Non-biodegradable materials
		Biodegradable materials
	Methods for microfabrication of oral drug delivery devices
		Lithography
			Photolithography
			Soft lithography
			Imprint lithography
		Embossing and punching
		Additive manufacturing
		Other methods
	Loading techniques for drug formulations
		Loading of liquids
			Inkjet printing
		Loading of hydrogels
		Loading of powders into the microdevices
			Manual loading of the microdevices
			Hot embossing
			CO2 impregnation
	Lid formation on the cavity of microdevices
		pH-sensitive lids
		Mucoadhesive lid formation
	In vitro and ex vivo studies
		Characterization techniques of microdevices and their loading
		Bioadhesion of microdevices
		In vitro drug release from microdevices
		In vitro drug transport and toxicity
	In vivo testing and applications
	Future perspectives
	Conclusion
	References
Batch and microfluidic reactors in the synthesis of enteric drug carriers
	Introduction
	Nanotechnology in oral drug delivery
		Nanotechnology approaches for drug delivery carriers to cross the intestinal lining
		Nanotechnology approaches for attaching drug delivery carriers to the intestinal mucosa
	Delivery to the systemic circulation-Passage through the intestinal barrier
	pH-dependent and pH-independent targeted delivery to specific sites of the intestine
		pH-dependent drug delivery
			Copolymers of methyl acrylate, methyl methacrylate and methacrylic acid
			Polymers based on cellulose derivatives
			Polymers based on polyvinyl derivatives
		pH-independent drug delivery
	Microfluidics for the synthesis of micro and nanocarriers in oral delivery
	Conclusions
	References
3D printing in oral drug delivery
	Oral delivery
		Strategies to overcome physiological limitations of the gastrointestinal (GI) tract
		Introduction to the different release mechanisms
		Fixed dose combination drug therapy (FDCDT)
	Personalized medicine
		Motivation for the patient-tailored medicine
		Prerequisites for the production of personalized medicine
		Where do we need the 3D printing?
		Patient perception and preferences of the medicine regarding shape, color, embossing, flavor, and acceptability of p ...
	Introduction to additive manufacturing
		Fused deposition modeling
		Semi-solid extrusion
		Powder-bed printing
	Regulatory challenges
		The first 3D printed drug product on the market
		Requirements for raw materials, printers and manufacturing procedures
		Supply chain
		Data management from the regulatory perspective
	Future perspective
		Robotic devices
		Digital technology and Internet of Things: Fabrication, identification, anti-counterfeiting
		Personalized medicine for veterinary purposes
	Concluding remarks
	References
	Further reading
Part III: Methods for the evaluation of oral drug delivery systems
3D intestinal models towards a more realistic permeability screening
	Introduction
	3D intestinal models
		Multilayered models
		Organoids
		Gut-on-a-chip models
	Limitations and future perspectives
	Conclusion
	References
In vitro relevant information for the assessment of nanoparticles for oral drug administration
	General considerations of oral drug delivery
	Barriers to oral drug delivery
		Gastrointestinal juices and microbiota
		Mucus
		Cellular barriers
	Understanding the biological-material interface
		Electrolytes and pH
		Enzymes and active surface molecules
		Mucus
		Intestinal epithelium
	Nanoparticles for oral drug delivery: In vitro characterization techniques
		Stability in gastrointestinal fluids
		Mucoadhesion and mucodiffusion
			Handmade techniques
				Analysis of muco-interaction
				Analysis of mucodiffusion
			Specialized-equipment techniques
		Interaction with the intestinal epithelium
			Conventional 2D cell culture
				Enterocyte-like model
				Mucus enterocyte model
				Follicle associated epithelium model
			3D cell culture
				Engineered intestinal tissues
				Microfluidic-based approaches
	Conclusions and future perspectives
	References
In vivo testing of orally delivered nanoparticles
	Introduction
	Selection of animal models
	Administration technique
		Oral gavage
		Intragastric infusion
		Intestinal instillation
		Syringe-feeding technique
	Experimental techniques
		Pharmacodynamics study
		Pharmacokinetic profiling
		Organ/tissue analysis
		Imaging systems
			Radioactive labeling
			Optical imaging
		Histological analysis
	In vitro-In vivo correlation
	Ethical considerations
	Conclusion
	References
Part IV: Pharmaceutical industry perspective
Industrial perspectives and future of oral drug delivery
	Introduction: Oral nano-drug delivery
	Current market status
	Challenges
		Gap analyses from benchtop to good manufacturing practice (GMP) production
		Understanding bench top methods and their limitations for up scaling
			Top-down methods
			Bottom-up methods
		Scale-up of nanoparticle production methods
		Scale-up of nanoparticle downstream methods
	Regulatory aspects: Regulations and guidelines
	Conclusions and future perspectives
	Annex I. Existing guidance documents expected to be applied for nano-enabled pharmaceutical products
		ICH guidelines
	Quality
	Safety
	FDA guidance for industryeehttps://www.fda.gov/animal-veterinary/guidance-regulations/guidance-industry.
	FDA nanotechnology guidance documentsffhttps://www.fda.gov/science-research/nanotechnology-programs-fda/nanotechno
	References
Index
	A
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	D
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	M
	N
	O
	P
	Q
	R
	S
	T
	U
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	W
	X
	Z
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