Drug Delivery Systems for Metabolic Disorders

Front Cover
Drug Delivery Systems for Metabolic Disorders
Copyright Page
Contents
List of contributors
About the editors
1 Introduction to metabolic disorders
	1.1 Metabolic disorders due to deregulation of protein/amino acid metabolism
		1.1.1 Protein metabolism disorders
			1.1.1.1 Amyloidosis
			1.1.1.2 Kwashiorkor
			1.1.1.3 Porphyria
			1.1.1.4 Erythropoietic uroporphyrin
		1.1.2 Amino acid metabolism disorders
			1.1.2.1 Phenylketonuria
			1.1.2.2 Tyrosinemia type II
			1.1.2.3 Tyrosinemia type III
			1.1.2.4 Alkaptonuria
			1.1.2.5 Tyrosinemia type I
			1.1.2.6 Maple syrup urine disease
	1.2 Metabolic disorders due to deregulation of lipid metabolism
		1.2.1 Atherosclerosis
		1.2.2 Cerebrotendinous xanthomatosis
		1.2.3 Sitosterolemia
		1.2.4 Gaucher disease
		1.2.5 Tay-Sachs disease
		1.2.6 Niemann pick disease
		1.2.7 Letterer-Siwe disease
	1.3 Metabolic disorder due to deregulation in carbohydrate metabolism
		1.3.1 Galactosemia
		1.3.2 Hereditary fructose intolerance
		1.3.3 Fructose 1,6-diphosphatase deficiency
		1.3.4 Glycogen storage disorders
		1.3.5 Hurler and Scheie syndrome
		1.3.6 Hunter syndrome
		1.3.7 Sanfilippo syndrome
	1.4 Metabolic disorder due to disturbance in hormone metabolism
		1.4.1 Hypoglycemia
		1.4.2 Diabetes (hyperglycemia)
		1.4.3 Hypopituitarism and hyperpituitarism
			1.4.3.1 Hypopituitarism (panhypopituitarism)
		1.4.4 Sheehan syndrome
		1.4.5 Pituitary apoplexy
		1.4.6 Hyperpituitarism
		1.4.7 Hypoparathyroidism
		1.4.8 Hyperparathyroidism
		1.4.9 Pseudohypoparathyroidism
		1.4.10 Hyperthyroidism
		1.4.11 Hypothyroidism
	1.5 Metabolic disorder due to deregulation in lysosomal storage disorders
		1.5.1 Schindler disease
		1.5.2 Faber disease
		1.5.3 Sandhoff diseases
		1.5.4 Pycnodysostosis
	1.6 Metabolic disorder due to deregulation in mitochondrial disorders
		1.6.1 Wilson disease
		1.6.2 Pearson marrow syndrome
		1.6.3 Leigh syndrome
		1.6.4 Alpers disease
		1.6.5 Batten disease
	References
	Further reading
2 Cellular and molecular mechanisms involved in metabolic disorders
	2.1 Introduction
	2.2 Alterations in single-minded protein-1: downstream mediator of leptin-melanocortin pathway
	2.3 Link between osteocalcin deficiency and insulin resistance
	2.4 Aberrations in the JAK-STAT pathway
	2.5 Alteration in AMPK activity: insulin resistance and cardiovascular problems
	2.6 Conclusion
	Acknowledgments
	References
3 Current practices in drug delivery for metabolic disorders
	3.1 Introduction
	3.2 Oral drug delivery approaches
	3.3 Site-specific drug delivery approaches
	3.4 Targeted drug delivery
	3.5 Intelligent drug delivery
	3.6 Conclusion
	Acknowledgments
	References
4 Recent developments in the treatment of amyloidosis
	4.1 Introduction
	4.2 The history of amyloidosis
	4.3 Amyloid fibril
		4.3.1 Amyloid fibrillogenesis
		4.3.2 Pathogenicity of amyloid fibril
		4.3.3 Classification of amyloidosis
			4.3.3.1 Localized amyloidosis
			4.3.3.2 Systematic amyloidosis
			4.3.3.3 AL amyloidosis
			4.3.3.4 AA Amyloidosis
			4.3.3.5 Aß2M Amyloidosis
			4.3.3.6 ATTRwt Amyloidosis
		4.3.4 Hereditary systemic amyloidosis
		4.3.5 Methods used for diagnosis of amyloidosis
		4.3.6 Treatment of amyloidosis
			4.3.6.1 AL Amyloidosis
			4.3.6.2 ATTRm amyloidosis
			4.3.6.3 AA Amyloidosis
	4.4 Conclusion
	Acknowledgments
	References
5 Advanced drug delivery systems targeting to improve therapeutic outcomes in porphyria
	5.1 Introduction
	5.2 Prevalence
	5.3 Pathophysiology
		5.3.1 5-ALA- dehydratase-deficient porphyria
		5.3.2 Acute intermittent porphyria
		5.3.3 Congenital erythropoietic porphyria
		5.3.4 Porphyria cutanea tarda and hepatoerythropoietic porphyria
		5.3.5 Hereditary coproporphyria
		5.3.6 Variegate porphyria
		5.3.7 Erythropoietic protoporphyria
		5.3.8 X-linked protoporphyria
	5.4 Symptoms and diagnosis
		5.4.1 5-ALA- dehydratase-deficient porphyria
		5.4.2 Acute intermittent porphyria
		5.4.3 Porphyria cutanea tarda and hepatoerythropoietic porphyria
		5.4.4 Hereditary coproporphyria
		5.4.5 Variegate porphyria
		5.4.6 Congenital erythropoietic porphyria
		5.4.7 Erythropoietic protoporphyria and X-linked protoporphyria
	5.5 Treatment strategies
		5.5.1 Acute intermittent porphyria
		5.5.2 5-ALA- dehydratase-deficient porphyria
		5.5.3 Porphyria cutanea tarda and hepatoerythropoietic porphyria
		5.5.4 Hereditary coproporphyria
		5.5.5 Variegate porphyria
		5.5.6 Congenital erythropoietic porphyria
		5.5.7 Erythropoietic protoporphyria and X-linked protoporphyria
	5.6 Overview of treatment drugs and current treatment problems
		5.6.1 Intravenous hemin (panhematin)
		5.6.2 Chloroquine and hydroxychloroquine
		5.6.3 Afamelanotide
		5.6.4 Beta-carotene
		5.6.5 Givosiran (GIVLAARI)
	5.7 Novel therapies
	5.8 Summary and conclusion
	References
6 Advanced drug delivery systems targeting kwashiorkor involving a disturbance in protein metabolism
	6.1 Introduction
	6.2 Physiological changes associated with kwashiorkor disease
	6.3 Biochemical manifestations and metabolic disorders associated with kwashiorkor disease
	6.4 Signs, symptoms, and clinical manifestations in kwashiorkor
	6.5 Current treatment of kwashiorkor
	6.6 Metabolic disturbances associated with kwashiorkor
	6.7 Role of nanotechnology in drug-delivery
	6.8 Different types of drug delivery vehicles
	6.9 Advanced drug delivery system targeting kwashiorkor
	6.10 Conclusion
	References
7 Advanced drug delivery systems targeting metabolic disorders: erythropoietic protoporphyria
	7.1 Introduction
	7.2 Etiology
	7.3 Clinical features
		7.3.1 Dermatologic involvement
		7.3.2 Hematological involvement
	7.4 Diagnosis
	7.5 Pathophysiology
	7.6 Genotype-phenotype correlations
	7.7 Current and emerging therapies
		7.7.1 Modulation of iron supply
		7.7.2 Antisense oligonucleotide therapy
		7.7.3 Increased light tolerance with antioxidants or stimulators of skin melanin synthesis
		7.7.4 Surgery
		7.7.5 Consultations
	7.8 Conclusion and future perspective
	References
8 Combating atherosclerosis with nanodrug delivery approaches: from bench side to commercialization
	8.1 Introduction
	8.2 Atherosclerosis
		8.2.1 Etiology
		8.2.2 Pathogenesis
		8.2.3 Clinical effects
		8.2.4 Pharma-armamentarium and mechanistic insights
	8.3 Nanoformulations for the treatment of atherosclerosis with implementation of quality by design
		8.3.1 Nanoparticles
			8.3.1.1 Implementation of the concept of quality by design for nanoformulations
		8.3.2 Liposomes
			8.3.2.1 Liposomes in treatment of atherosclerosis
			8.3.2.2 Implementation of the concept of QbD in the formulation of liposomes
	8.4 Dendrimers
		8.4.1 Implementation of concept QbD during the formulation of dendrimer
	8.5 Challenges in translating nanodrug delivery systems from bench to bedside
		8.5.1 Scalability
		8.5.2 Safety
		8.5.3 Process optimization
		8.5.4 Stability of the product
		8.5.5 GRAS status of the material
		8.5.6 Regulatory clearance
		8.5.7 Nanoparticles
		8.5.8 Liposomes
		8.5.9 Dendrimer
	8.6 Conclusion
	References
9 Advanced drug delivery systems in the management of Gaucher disease
	9.1 History
	9.2 Epidemiology
	9.3 Etiology
	9.4 Pathogenesis
	9.5 Clinical classification of Gaucher disease
	9.6 Management of Gaucher disease
		9.6.1 Baseline management
		9.6.2 Disease-specific management
			9.6.2.1 Enzyme replacement therapies
				9.6.2.1.1 Liposome encapsulated GCase
				9.6.2.1.2 RBCs encapsulated GCase
				9.6.2.1.3 Micro-carriers loaded with GCase
			9.6.2.2 Substrate reduction therapies
		9.6.3 Other specific treatments
			9.6.3.1 Pharmacological chaperone therapies
				9.6.3.1.1 Iminosugars
				9.6.3.1.2 Ambroxol
				9.6.3.1.3 Noninhibitory chaperone
			9.6.3.2 Histone deacetylase inhibitors
			9.6.3.3 Gene therapy
			9.6.3.4 Bone marrow transplant and total joint replacement
			9.6.3.5 Splenectomy
	9.7 Conclusion
	References
10 Advanced drug delivery systems focusing the metabolic disorders due to deregulation of lipid metabolism: Niemann Pick Di...
	10.1 Introduction
		10.1.1 Lipid metabolic disorder
	10.2 Neimann’s Pick disease
		10.2.1 Common symptoms of Neimann’s disease
	10.3 Etiology
		10.3.1 The molecular biology underlying NP-C pathophysiology
		10.3.2 Lipid trafficking and NPC1: cholesterol transport
		10.3.3 NPC protein function: NPC1 & NPC2
		10.3.4 Diagnosis
		10.3.5 History taking and clinical examination
		10.3.6 Laboratory findings
		10.3.7 Genetic testing
		10.3.8 Pathophysiology of sphingomyelinase deficiency Niemann’s pick disease
		10.3.9 Niemann’s Pick disease type A
		10.3.10 Niemann’s Pick disease type B
		10.3.11 Niemann’s Pick disease type C
		10.3.12 Regular laboratory testing
		10.3.13 Diagnostic biomarkers
		10.3.14 Plasma oxysterols
		10.3.15 Plasma lysosphingolipids
		10.3.16 Management of NPDs
		10.3.17 Letterer-Siwe disease
		10.3.18 Sign and symptoms
		10.3.19 Pathophysiology of Letterer Siwe disease
	10.4 Stage 1: early lesion’s phase
	10.5 Stage 2: fibrous phase
	10.6 Stage 3: extra lesion phase
	10.7 Diagnosis Letterer Siwe disease
		10.7.1 Physical diagnosis
		10.7.2 Laboratory diagnosis
		10.7.3 Epidemiology
		10.7.4 Treatment
		10.7.5 Novel drug delivery systems for treatment of Niemann’s Pick disease and Letterer-Siwe disease
		10.7.6 Resealed erythrocytes
		10.7.7 Liposomes
		10.7.8 Microcapsules
		10.7.9 Nanocarriers
	10.8 Prospects
	10.9 Conclusion
	References
11 Genetic disease and Niemann-Pick disorders: novel treatments and drug delivery systems
	11.1 Introduction to genetic disorders
	11.2 Classification of inherited metabolic disorders
	11.3 Physiology of lipid metabolism and diseases associated with lipid metabolism
	11.4 Essential aspects of Niemann-Pick disease: prevalence, pathophysiology, diagnosis, and symptoms
	11.5 Current therapeutic strategies to treat Niemann-Pick disease
	11.6 Problems associated with the current therapeutic strategies to treat Niemann-Pick disease
	11.7 Possible novel drug delivery systems to improve therapeutic efficacy in Niemann-Pick disease
	References
12 Novel 3D printing drug delivery system for the prevention and treatment of Atherosclerosis
	12.1 Importance of 3D printing drug delivery systems
	12.2 Pathophysiology of atherosclerosis
	12.3 Drugs used for the prevention and treatment of atherosclerosis
	12.4 Problems with current oral drug delivery
	12.5 Customized 3D printed dosage forms for atherosclerosis and associated diseases
	12.6 Conclusion
	References
13 Advanced drug delivery systems to treat Huntington’s disease: challenges and opportunities
	13.1 Introduction
	13.2 Global prevalence and economic burden
	13.3 Pathophysiology
		13.3.1 Genetic factors
		13.3.2 Mitochondrial dysfunction
		13.3.3 Oxidative stress
		13.3.4 Neurodegeneration
	13.4 Pharmacological management of Huntington’s disease
	13.5 Herbal therapy
	13.6 Challenges associated with conventional therapy and the need for advanced drug delivery systems
		13.6.1 Nanoemulsions
			13.6.1.1 Method of preparation of nanoemulsions
		13.6.2 Self-emulsifying drug delivery system
			13.6.2.1 Advantages of self-emulsifying drug delivery system over other drug delivery systems
			13.6.2.2 Mechanism of self-emulsification, dissolution enhancement, and drug transport by self-emulsifying drug delivery system
		13.6.3 Liposomes
		13.6.4 Polymeric micelles
		13.6.5 Nanostructured lipid carriers
		13.6.6 Solid lipid nanoparticles
	13.7 Conclusion and perspectives
	References
14 Advanced drug delivery systems for targeting obesity
	14.1 Introduction
	14.2 Reason for weight gain
	14.3 Obesity management
	14.4 Conventional anti-obesity treatments
	14.5 Advanced drug delivery systems
		14.5.1 Nanoparticle
		14.5.2 Metallic nanoparticles
		14.5.3 Solid lipid nanoparticles
		14.5.4 Liposomes
		14.5.5 Microneedles
		14.5.6 Nanoemulsion
		14.5.7 Gene-based therapy
		14.5.8 Interleukins
	14.6 Conclusion and future prospectus
	References
15 Advanced drug delivery systems for treatment of diabetes mellitus
	15.1 Introduction
	15.2 Antidiabetic medication-related complications
	15.3 Possibilities provided by the various Novel drug delivery systems
	15.4 Development and designing of various advanced drug delivery systems for diabetes treatment
		15.4.1 Particulate transport system
		15.4.2 Microparticulate systems
		15.4.3 Nanoparticulate systems
		15.4.4 Vesicular system
			15.4.4.1 Liposomes
			15.4.4.2 Niosomes
		15.4.5 Transdermal drug delivery systems
			15.4.5.1 Employment of microneedle in patch
			15.4.5.2 Gelation and hydroxyapatite fabricated bioceramic composite microneedle
			15.4.5.3 Double-layered, bullet-shaped microneedle with swellable tips patch
			15.4.5.4 Biodegradable alginate and hyaluronate polymer microneedle patch
			15.4.5.5 Poly- γ-glutamic acid microneedles with supporting structure
			15.4.5.6 Alginate and maltose microneedle patch
		15.4.6 Transdermal delivery systems incorporated with biosensor
			15.4.6.1 Swellable microneedle patch in interstitial fluid extraction for glucose metabolic analysis
			15.4.6.2 Patch-type 3D stainless steel microneedle array enzyme-free glucose biosensor
			15.4.6.3 A composite nanostructured surface electrochemical glucose sensor
			15.4.6.4 The ultra-miniaturization planar amperometric glucose sensor
			15.4.6.5 Lab-on-chip with triboelectric liquid volume sensor
		15.4.7 Point of care therapy
			15.4.7.1 H2O2-responsive polymeric vesicle with microneedle
			15.4.7.2 Insulin-loaded and H2O2-responsive mesoporous silica nanoparticle integrated microneedle patch
			15.4.7.3 Sweat-based electrochemical patch with thermoresponsive microneedle
			15.4.7.4 Hypoxia and H2O2 dual-sensitive polymersome based vesicle smart insulin patch
		15.4.8 Employment of technologies for carrier, entrapment, penetration, and release
			15.4.8.1 Permeation enhancement via proniosomal gel entrapment
			15.4.8.2 Proniosome carbopol-based transgel system
			15.4.8.3 Transferosomal gel with the chemical “iodophor”
			15.4.8.4 Microemulsion gel
			15.4.8.5 Transdermal nanoemulsion encapsulation
			15.4.8.6 Nanostructured lipid carriers transdermal system
			15.4.8.7 Hyaluronic acid encapsulated CuS gel-mediated near-infrared laser nanosystem
			15.4.8.8 Choline and geranate (CAGE) deep eutectic solvent transdermal delivery vehicle
			15.4.8.9 Amidated pectin hydrogel matrix patch
			15.4.8.10 HPMC and PVA based transdermal patch
	15.5 Prospects and conclusion
	References
16 Advanced drug delivery system in the treatment of hyperglycemia and hypoglycemia
	16.1 Introduction
		16.1.1 Carbohydrate metabolism disorders
		16.1.2 Galactose and fructose metabolism disorders
		16.1.3 Glycogen storage disorders
		16.1.4 Glucose transport disorder
		16.1.5 Congenital disorders of glycosylation
		16.1.6 Glucose metabolism disorders
			16.1.6.1 Type 1 diabetes mellitus
			16.1.6.2 Type 2 diabetes mellitus
			16.1.6.3 Gestational diabetes mellitus
	16.2 Conventional treatment for glucose metabolism disorders
		16.2.1 Insulin therapies
		16.2.2 Herbal treatment for diabetes mellitus
	16.3 Alternative approaches to diabetes
		16.3.1 Dietary fibers
		16.3.2 Minerals used in the treatment of hyperglycemia
	16.4 Nanomaterials for treatment of diabetes
		16.4.1 Oral administration
		16.4.2 Inhalations
		16.4.3 Nano-pumps
		16.4.4 Artificial pancreas
	16.5 Advances in insulin delivery
	16.6 Conclusion and future perspectives
	References
17 Emerging drug delivery in the treatment of hyperpituitarism and hypopituitarism
	17.1 Introduction
		17.1.1 Pituitary gland (hypophysis)
		17.1.2 Hormones of pituitary gland
		17.1.3 Human growth hormone or somatotropin
		17.1.4 Thyroid-stimulating hormone or thyrotropin
		17.1.5 Prolactin or mamotrophin hormone or luteotrophic hormone
		17.1.6 Follicle-stimulating hormone
		17.1.7 Luteinizing hormone
		17.1.8 Adrenocorticotropic hormone
		17.1.9 Melanocyte-stimulating hormone
		17.1.10 Antiduretic hormone or vasopressin or pitressin
		17.1.11 Oxytocin (OT, Pitocin)
	17.2 Treatment of hypopituitarism and hyperpituitarism
		17.2.1 Treatment of hypopituitarism
			17.2.1.1 Adrenocorticotropic hormone replacement therapy
			17.2.1.2 Thyroid-stimulating hormone deficiency replacement therapy
			17.2.1.3 Gonadotropin deficiency treatment
			17.2.1.4 Growth hormone deficiency treatment
		17.2.2 Treatment of hyperpituitarism
	17.3 Conclusion and future perspective
	References
18 Advance drug delivery systems targeting hypoparathyroidism and hyperparathyroidism
	18.1 Introduction
		18.1.1 Parathyroidism
			18.1.1.1 Hyperparathyroidism
			18.1.1.2 Hypoparathyroidism
	18.2 Pathophysiology
		18.2.1 Pathophysiology of hyperparathyroidism
		18.2.2 Pathophysiology of hypoparathyroidism
	18.3 Clinical manifestations
	18.4 Current treatments for hypoparathyroidism and hyperparathyroidism
		18.4.1 Advance drug delivery therapy for hypoparathyroidism
		18.4.2 Advance drug delivery therapy for hyperparathyroidism
	18.5 Conclusion
	References
19 An update on the development of advanced drug delivery systems for the treatment of hyperthyroidism
	19.1 Introduction
	19.2 Epidemiology of hyperthyroidism
	19.3 Common etiology and pathogenesis of hyperthyroidism
		19.3.1 Grave’s disease
		19.3.2 Toxic nodular disease
		19.3.3 Thyroiditis
		19.3.4 Hyperthyroidism due to drug interactions
		19.3.5 Hyperthyroidism due to iodine
	19.4 Diagnosis of hyperthyroidism
	19.5 Advancement in drug delivery systems/techniques for the management of hyperthyroidism
		19.5.1 Methimazole
		19.5.2 Propylthiouracil
		19.5.3 Carbimazole
		19.5.4 Iodine containing compounds
		19.5.5 Potassium perchlorate
		19.5.6 Beta-blockers
		19.5.7 Lithium carbonate
		19.5.8 Glucocorticoids
	19.6 Potential future therapies
		19.6.1 Immunotherapy
		19.6.2 Rituximab
		19.6.3 CFZ533
		19.6.4 ATX-GD-59
		19.6.5 K1–70
		19.6.6 Ultrasound based therapies
		19.6.7 Radiofrequency ablation
	19.7 Nanoparticles: promising auxiliary agents for therapy of hyperthyroidism and associated diseases
		19.7.1 Inorganic nanoparticles: carbon nanoparticles
		19.7.2 Inorganic Nanoparticles: metal-containing nanoparticles
		19.7.3 Inorganic and hydrid nanoparticles: mesoporous silica and organic mesoporous silica nanoparticles
		19.7.4 Organic nanoparticles: lipid nanoparticles
		19.7.5 Nanoparticles in clinical trials
	19.8 Conclusions and future perspectives
	References
20 Advanced drug delivery systems involving lysosomal storage disorders for Schinder disease and other disorders
	20.1 Introduction to lysosomal storage disorders
	20.2 Potential targets for lysosomal disorders
		20.2.1 Targeting the affected genes
		20.2.2 Targeting the lipid storage
		20.2.3 Targeting lysosomes and autophagy
		20.2.4 Targeting mitochondria and oxidative stress
		20.2.5 Targeting calcium imbalance
		20.2.6 Targeting synaptic impairment and neuron excitability
		20.2.7 Targeting inflammation
		20.2.8 Targeting hypomyelination
	20.3 Potential strategies using advanced delivery systems for lysosomal storage diseases
		20.3.1 Enzyme replacement therapy
		20.3.2 Bone marrow transplantation
		20.3.3 Small molecule therapies
			20.3.3.1 Use of molecular chaperones
			20.3.3.2 Proteostasis regulators
			20.3.3.3 Substrate reduction therapy
			20.3.3.4 Small molecules targeting nonsense mutations
		20.3.4 Hematopoietic stem cell therapy
		20.3.5 CSF-delivery of enzyme replacement therapy agents
		20.3.6 Nanocarrier delivery therapies
	20.4 Attempts in treatment of lysosomal storage diseases by utilization of gene therapy
		20.4.1 Concept of gene therapy for lysosomal storage disorder
			20.4.1.1 Viral vectors for gene therapy
				20.4.1.1.1 Retroviruses
				20.4.1.1.2 Lentiviruses
				20.4.1.1.3 Adenoviruses
				20.4.1.1.4 Adeno-associated viruses
		20.4.2 Systemic gene therapy
		20.4.3 CNS—directed gene therapy
		20.4.4 Future-generation gene therapy strategies
	20.5 Current novel lysosomal storage disorder therapies in clinical trials
	Acknowledgments
	References
21 Advanced drug delivery systems involving lysosomal storage disorders for Fabry disease
	21.1 Introduction
	21.2 Classification and clinical manifestations
	21.3 Diagnosis
	21.4 Treatments
		21.4.1 Enzyme replacement therapy
		21.4.2 Pharmacological chaperones
	21.5 New approaches for the treatment of Fabry disease
		21.5.1 Second generation enzyme therapies
			21.5.1.1 Pegunigalsidase-alpha (PRX-120)
			21.5.1.2 Moss-α-GAL A (Moss derived α GAL A)
			21.5.1.3 Modified α-N-Acetylgalactosaminidase (NAGA)
		21.5.2 Substrate reduction therapy
		21.5.3 Gene therapy
			21.5.3.1 Ex-vivo gene therapy
			21.5.3.2 In-vivo gene therapy
		21.5.4 mRNA therapy
			21.5.4.1 Pros and cons of the emerging therapies
	21.6 Advanced drug delivery systems in Fabry disease
		21.6.1 Liposomes
		21.6.2 Polystyrene capsules
		21.6.3 Polyelectrolyte complexes
		21.6.4 Solid-lipid nanoparticles
		21.6.5 Extracellular vesicles
	21.7 Conclusion
	References
22 Drug delivery systems in Krabbe disease—present and prospective approaches
	22.1 Introduction
	22.2 Genetic background
	22.3 Pathophysiology
		22.3.1 Sulfatide insufficiency
		22.3.2 Galactocerebroside β-galactosidase deficiency
		22.3.3 The psychosine hypothesis
		22.3.4 Saposin A deficiency
	22.4 Current approaches and challenges
		22.4.1 Single modality therapies
			22.4.1.1 HSCT with bone marrow transplantation
			22.4.1.2 Oligodendrocyte transplantation
			22.4.1.3 Neuronal and mesenchymal stem cell transplantation
			22.4.1.4 Neural stem cell gene therapy
			22.4.1.5 Virus mediated gene therapy
			22.4.1.6 Enzyme replacement therapy
			22.4.1.7 Substrate reduction therapy
			22.4.1.8 Antiinflammatory approaches
			22.4.1.9 Antioxidant therapy
		22.4.2 Multimodality therapies
			22.4.2.1 Vascular endothelial growth factor+bone marrow transplantation
			22.4.2.2 L-cycloserine+bone marrow transplantation
			22.4.2.3 N-Acetylcysteine+bone marrow transplantation
			22.4.2.4 Enzyme replacement therapy+bone marrow transplantation
			22.4.2.5 Gene therapy+bone marrow transplantation
			22.4.2.6 Gene therapy+substrate reduction therapy+bone marrow transplantation
	22.5 Potential targets and approaches
		22.5.1 Advances in substrate reduction therapy
			22.5.1.1 S2O2, a novel GalCer inhibitor
			22.5.1.2 A chemotherapeutic agent as a potential therapeutic agent
		22.5.2 Enzyme-loaded nanoparticles
		22.5.3 Pharmacological chaperons
			22.5.3.1 α-Lobeline as a potential agent
			22.5.3.2 3′,4′,7-trihydroxyisoflavone
			22.5.3.3 N-octyl-4-epi-β-valienamine
			22.5.3.4 Azasugars and iminosugars as potential candidates
		22.5.4 Quantum dots as nano-vehicle
	22.6 Conclusion
	References
23 Strategies to combat Tay-Sachs disease
	23.1 Introduction
	23.2 Overview of Tay-Sachs disease
		23.2.1 Pathophysiology of gangliosidosis and HexA synthesis
	23.3 Treatment strategies and management
		23.3.1 Substrate reduction therapy
			23.3.1.1 Application of substrate reduction therapy in Tay-Sachs disease
		23.3.2 Bone marrow transplantation
			23.3.2.1 Application of bone marrow transplantation in Tay-Sachs disease
		23.3.3 Enzyme replacement therapy
			23.3.3.1 Application of enzyme replacement therapy for Tay-Sachs disease
		23.3.4 Gene therapy
			23.3.4.1 Application of gene therapy in Tay-Sachs disease
	23.4 Developmental treatment for Tay-Sachs disease
		23.4.1 Genetically modified multipotent cells
	23.5 Conclusion
	References
24 Sandhoff disease: pathology and advanced treatment strategies
	24.1 Lysosomal storage disease
	24.2 Sandhoff disease
		24.2.1 Introduction
	24.3 Etiology and pathogenesis
		24.3.1 Normal function of HEXB gene
		24.3.2 Mutation in the gene HEXB
	24.4 Prevalence and occurrence
	24.5 Clinical characteristics
	24.6 Treatment
		24.6.1 Substrate replacement therapy
		24.6.2 Enhanced gene therapy through complimentary drug therapy
		24.6.3 Suppression through bone marrow transplantation
	24.7 Carriers for lysosomal drug delivery
		24.7.1 Resealed erythrocytes
	24.8 Liposomes
	24.9 Future developments on sandhoff disease
	24.10 Conclusion
	References
25 Nanomaterials-based drug delivery approaches for metabolic disorders
	25.1 Introduction
	25.2 Routes of drug delivery for metabolic disorders
		25.2.1 Drug delivery strategies
			25.2.1.1 Targeted drug delivery strategies
			25.2.1.2 Intelligent stimulus-responsive drug delivery strategies
		25.2.2 Different drug administration routes
			25.2.2.1 Oral route of drug delivery approach
			25.2.2.2 Local drug delivery strategies
			25.2.2.3 Transdermal drug delivery approach
			25.2.2.4 Inhalation/nasal drug delivery route
			25.2.2.5 Intravenous drug delivery route
	25.3 Nanomaterial-based drug delivery approaches
		25.3.1 Nanomaterial based drug delivery systems
			25.3.1.1 Polymeric drug delivery system: micelles
			25.3.1.2 Polymeric drug delivery system: dendrimers
			25.3.1.3 Liposomes mediated drug delivery system
			25.3.1.4 Protein-based drug delivery systems
			25.3.1.5 Metal nanoparticle-based delivery systems
			25.3.1.6 Composite based nanomaterials
		25.3.2 Different drug delivery routes of nanocarriers
			25.3.2.1 Nanomaterial-based oral-drug delivery
			25.3.2.2 Nano-based transdermal drug delivery
			25.3.2.3 Nano-based drug approaches for nasal route
		25.3.3 Nanotoxicity
		25.3.4 Blood-brain barrier and nano-based drug delivery
	25.4 Applications of nano-based drug delivery systems to treat metabolic disorders
		25.4.1 Treatment of diabetes
			25.4.1.1 Liposomes mediated drug delivery
			25.4.1.2 Niosomes-based treatment
		25.4.2 Treatment of pulmonary hypertension
		25.4.3 Treatment of cardiovascular diseases
	25.5 Limitations of using nano-based drug delivery approach
	25.6 Future prospective
	25.7 Conclusion
	References
26 Eye in metabolic disorders: manifestations and drug delivery systems
	26.1 Introduction
	26.2 Diabetic retinopathy (Dr)
		26.2.1 Prevalence of diabetes
		26.2.2 Types and management of Diabetic retinopathy
		26.2.3 Treatment of Diabetic retinopathy
		26.2.4 Drug delivery systems for managing Diabetic retinopathy
			26.2.4.1 Nanotechnology for diagnosis
			26.2.4.2 Nanoparticles
			26.2.4.3 Magnetic nanoparticles
			26.2.4.4 Liposomes
			26.2.4.5 Nanomicelles
			26.2.4.6 Hydrogels
	26.3 Glaucoma
		26.3.1 Types of glaucoma and symptoms
			26.3.1.1 Management of glaucoma
				26.3.1.1.1 Laser treatment aspects for glaucoma
				26.3.1.1.2 Conventional surgical approaches
				26.3.1.1.3 Medication-based delivery system
				26.3.1.1.4 Nanoparticles
				26.3.1.1.5 Polymeric nanoparticles
				26.3.1.1.6 Solid lipid nanoparticles
				26.3.1.1.7 Silica nanoparticles
				26.3.1.1.8 Liposomes
				26.3.1.1.9 Polymeric hydrogels
				26.3.1.1.10 Dendrimers
				26.3.1.1.11 Cubosomes
				26.3.1.1.12 Transfersomes
	26.4 Cataract
		26.4.1 Disease and its prevalence
		26.4.2 Causes of cataract
			26.4.2.1 Metabolic cataract
				26.4.2.1.1 Galactosemic cataract
				26.4.2.1.2 Diabetic cataract
				26.4.2.1.3 Hypocalcemic cataract
				26.4.2.1.4 Cataracts due to error in copper metabolism
		26.4.3 Management of cataract
			26.4.3.1 Oxidative/antioxidative system
			26.4.3.2 Aldose reductase inhibitors
			26.4.3.3 Dissolution of crystalline aggregates
		26.4.4 Current therapies for the treatment of cataract
			26.4.4.1 Cataracts surgery
			26.4.4.2 Drug delivery systems
				26.4.4.2.1 Solution
				26.4.4.2.2 In situ gelling system
				26.4.4.2.3 Colloidal drug delivery systems
				26.4.4.2.4 Liposomes
				26.4.4.2.5 Micro or nano emulsions
	26.5 Conclusion
	References
27 Advanced drug delivery systems involving mitochondrial disorders
	27.1 Introduction
	27.2 Mitochondrial DNA
	27.3 Clinical manifestations of mitochondrial disorders
	27.4 Mitochondrial diseases
		27.4.1 Alpers disease
		27.4.2 Batten disease
		27.4.3 Pearson marrow syndrome
		27.4.4 Luft disease
		27.4.5 Leigh syndrome
		27.4.6 Wilson disease
			27.4.6.1 Drug delivery systems for Wilson disease
				27.4.6.1.1 Nanoparticles
				27.4.6.1.2 Liposomes
	27.5 Delivery systems for mitochondrial diseases
		27.5.1 Liposomes
		27.5.2 Polymeric nanoparticles
		27.5.3 Dendrimers
	27.6 Peptide-based mitochondrial-targeted strategy
	27.7 Mitochondrial targeting sequences
	27.8 Szeto–Schiller peptides
	27.9 Vehicle-based mitochondrial-targeted strategy
	27.10 MITO-Porter
	27.11 Mesoporous silica nanoparticles
	27.12 Conclusions
	References
28 Applications of phytopharmaceuticals in targeting metabolic disorders
	28.1 Introduction
	28.2 Role of polyphenols and terpenoids in the treatment of metabolic disorders
		28.2.1 Effect of polyphenols on hyperglycemia
		28.2.2 Hypertension
		28.2.3 Obesity
		28.2.4 Dyslipidemia
	28.3 Management of metabolic disorders via phytomedicinal therapy
		28.3.1 Panax ginseng
		28.3.2 Rhizoma coptidis
		28.3.3 Momordica charantia
		28.3.4 Ligustrum lucidum Ait
		28.3.5 Glycyrriza uralensis Fisch
		28.3.6 Hoodia gordonii
		28.3.7 Crataegus laevigata
		28.3.8 Vitis vinifera
		28.3.9 Vaccinium angustifolium Aiton
		28.3.10 Artemisia dracunculus L
		28.3.11 Cassia obtusifolia L
		28.3.12 Polygonatum odoratum
		28.3.13 Rehmannia glutinosa
		28.3.14 Cucurbita moschata
		28.3.15 Aloe vera L
	28.4 Future prospective of phytopharmaceuticals for metabolic disorders
	28.5 Conclusion
	References
29 Phytonanoparticles toward the treatment of diabetes
	29.1 What is diabetes?
	29.2 Classification and treatment available for diabetes
		29.2.1 Type 1 diabetes
		29.2.2 Type 2 diabetes
		29.2.3 Genetic defects of beta-cell function
		29.2.4 Gestational diabetes mellitus
	29.3 Treatment available for diabetes
	29.4 Nanoparticles for the treatment of diabetes
	29.5 Advantages of phytoderived nanoparticles
	29.6 List of nanoparticles for the treatment of diabetes
	29.7 List of phytonanoparticles for the treatment of diabetes
		29.7.1 Piperine
			29.7.1.1 Piperine coated gold nanoparticles
				29.7.1.1.1 Synthesis of Piperine coated gold nanoparticles
				29.7.1.1.2 Size of nanoparticles
				29.7.1.1.3 Studies on piperine coated gold nanoparticles and insulin fibrils interaction
				29.7.1.1.4 Mode of action
			29.7.1.2 Pioglitazone loaded Bovine Serum Albumin nanoparticles with piperine
				29.7.1.2.1 Synthesis of Pioglitazone loaded Bovine Serum Albumin nanoparticles with piperine
				29.7.1.2.2 Size of the nanoparticles
				29.7.1.2.3 Studies on Pioglitazone loaded Bovine Serum Albumin nanoparticles with piperine
				29.7.1.2.4 Mode of action
		29.7.2 Lignin
			29.7.2.1 Silver phenolated lignin nanoparticles
				29.7.2.1.1 Synthesis of silver phenolated lignin nanoparticles
				29.7.2.1.2 Size of the nanoparticles
				29.7.2.1.3 Studies on silver phenolated lignin nanoparticles
				29.7.2.1.4 Mode of action
		29.7.3 Quercetin
			29.7.3.1 Quercetin conjugated superparamagnetic iron oxide nanoparticles
				29.7.3.1.1 Synthesis of Quercetin coated iron oxide nanoparticles
				29.7.3.1.2 Size of the nanoparticles
				29.7.3.1.3 Studies on Quercetin conjugated superparamagnetic iron oxide nanoparticles
				29.7.3.1.4 Mode of action
			29.7.3.2 Quercetin enveloped Soluplus/P407 micelles
				29.7.3.2.1 Synthesis of Quercetin-Soluplus/P407 micelles
				29.7.3.2.2 Size of the nanoparticle
				29.7.3.2.3 Studies on Quercetin enveloped Soluplus/P407 micelles
				29.7.3.2.4 Mode of action
		29.7.4 Cellulose
			29.7.4.1 AgNPs embedded in cellulose nanocrystals
				29.7.4.1.1 Synthesis of AgNPs embedded in cellulose nanocrystals
				29.7.4.1.2 Size of the nanoparticles
				29.7.4.1.3 Studies on AgNPs embedded in cellulose nanocrystals
				29.7.4.1.4 Mode of action
		29.7.5 Curcumin
			29.7.5.1 Nanocurcumin
				29.7.5.1.1 Synthesis of nanocurcumin
				29.7.5.1.2 Size of the nanoparticle
				29.7.5.1.3 Studies on nanocurcumin
				29.7.5.1.4 Mode of action
			29.7.5.2 Curcumin-zinc oxide composite nanoparticles
				29.7.5.2.1 Synthesis of Curcumin-zinc oxide composite nanoparticles
				29.7.5.2.2 Size of the nanoparticles
				29.7.5.2.3 Studies on Curcumin-zinc oxide composite nanoparticles
				29.7.5.2.4 Mode of action
		29.7.6 Berberine
			29.7.6.1 O-hexadecyl-dextran entrapped berberine chloride nanoparticles
				29.7.6.1.1 Synthesis of O-hexadecyl-dextran entrapped berberine chloride nanoparticles
				29.7.6.1.2 Size of the nanoparticles
				29.7.6.1.3 Studies on O-hexadecyl-dextran entrapped berberine chloride nanoparticles
				29.7.6.1.4 Mode of action
		29.7.7 Metformin
			29.7.7.1 Metformin loaded chitosan nanoparticles
				29.7.7.1.1 Synthesis of metformin loaded chitosan nanoparticles
				29.7.7.1.2 Size of the nanoparticles
				29.7.7.1.3 Studies on metformin loaded chitosan nanoparticles
				29.7.7.1.4 Mode of action
			29.7.7.2 Metformin-loaded alginate nanoparticles
				29.7.7.2.1 Synthesis of Metformin-loaded alginate nanoparticles
				29.7.7.2.2 Size of the nanoparticle
				29.7.7.2.3 Studies on Metformin-loaded alginate nanoparticles
				29.7.7.2.4 Mode of action
		29.7.8 Lectins
			29.7.8.1 Lectin-modified insulin liposomes
				29.7.8.1.1 Synthesis of lectin liposomes
				29.7.8.1.2 Size of the nanoparticles
				29.7.8.1.3 Studies on lectin-modified insulin liposomes
				29.7.8.1.4 Mode of action
		29.7.9 Inulin
			29.7.9.1 Nanomicelles of inulin D α-tocopherol succinate
				29.7.9.1.1 Synthesis of nanomicelles of inulin D α-tocopherol succinate
				29.7.9.1.2 Size of the nanoparticle
				29.7.9.1.3 Studies on nanomicelles of inulin D α-tocopherol succinate
				29.7.9.1.4 Mode of action
	29.8 Conclusion
	Acknowledgments
	References
30 Role of nutraceuticals in metabolic syndrome
	30.1 Introduction
	30.2 Definition, pathogenesis, and pathophysiology of metabolic syndrome
		30.2.1 Pathogenesis and pathophysiology of Ms
			30.2.1.1 Insulin resistance
			30.2.1.2 Inflammatory condition
				30.2.1.2.1 Hypertension
	30.3 Applications of nutraceuticals in the management of Ms
		30.3.1 Quercetin
		30.3.2 Curcumin
		30.3.3 Cinnamon
		30.3.4 Resveratrol
		30.3.5 Vitamins
		30.3.6 Dietary Fibers
		30.3.7 Omega-3-fatty acid
			30.3.7.1 Macro and trace elements
	30.4 Conclusion
	References
31 Latest advances of phytomedicine in drug delivery systems for targeting metabolic disorders
	31.1 Introduction
	31.2 Significance of phytomedicines as therapeutics
		31.2.1 Phytomedicine: from ancient to modern therapy system
	31.3 Pathophysiology of metabolic syndrome
		31.3.1 Resistance to insulin
		31.3.2 Neurohormonal stimulation
		31.3.3 Inflammatory responses
			31.3.3.1 TNF-alpha: a tumor necrosis factor
			31.3.3.2 C-reactive protein and interleukin 6
	31.4 Phytomedicines in drug delivery system
		31.4.1 Administration of phytomedicines
		31.4.2 Nano-based drug administration
		31.4.3 Nano-based drug delivery to treat metabolic disorders
			31.4.3.1 Diabetes
			31.4.3.2 Obesity
			31.4.3.3 Dyslipidemia
			31.4.3.4 Pulmonary arterial hypertension
	31.5 Future perspective
	31.6 Conclusion
	References
32 Clinical trials, future prospects and challenges of drug delivery in combating metabolic disorders
	32.1 Challenges faced by advanced delivery systems
	32.2 Future prospects
	32.3 Conclusion
	References
Index
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