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Lipid Nanocarriers in Cancer Diagnosis and Therapy
Description:
This book introduces fundamental principles of lipid nanocarriers science relevant to cancer therapy. The first in this field, it fills a need for an accurate, coherent and authoritative introduction to lipid nanocarriers focusing in cancer therapy; both because of the growing popularity of these modern drug delivery systems and also because of the emergent need of dealing with cancer treatment.
Active drug delivery and targeting using nanobiotechnologies has become one of the most successful strategies to approach chemotherapy. This book deals with lipid nanocarriers for targeted delivery to tumours of various organs and combination of these with other methods of treatment of cancer such as radiotherapy, diagnostic and imaging analysis. Lipid nanocarriers are also used for gene therapy for cancer.
Also addressed is how diagnostic strategies with lipid nanocarriers can be combined with therapeutics, which will be important for the personalized management of cancer.
Cancer chemotherapeutic drugs are also being used as immunosuppressive agents in the chronic treatment of non-neoplastic diseases. The scientific research in this field has been focused on the development of strategies to target and deliver several cancer chemotherapeutic drugs to decrease citotoxicity. These include both carrier- and receptor-mediated nanocarriers. Being biodegradable and biocompatible systems, lipid nanocarriers have been extensively explored to increase its therapeutic index, reducing adverse side effects to ultimately extend life-span of patients.
Furthermore, a familiarity with lipid materials science will enable scientists to conduct rational performulation studies, to understand and optimize formulations, drug delivery systems and their manufacturing processes as well as associated process analytical technologies and quality by design.
Active drug delivery and targeting using nanobiotechnologies has become one of the most successful strategies to approach chemotherapy. This book deals with lipid nanocarriers for targeted delivery to tumours of various organs and combination of these with other methods of treatment of cancer such as radiotherapy, diagnostic and imaging analysis. Lipid nanocarriers are also used for gene therapy for cancer.
Also addressed is how diagnostic strategies with lipid nanocarriers can be combined with therapeutics, which will be important for the personalized management of cancer.
Cancer chemotherapeutic drugs are also being used as immunosuppressive agents in the chronic treatment of non-neoplastic diseases. The scientific research in this field has been focused on the development of strategies to target and deliver several cancer chemotherapeutic drugs to decrease citotoxicity. These include both carrier- and receptor-mediated nanocarriers. Being biodegradable and biocompatible systems, lipid nanocarriers have been extensively explored to increase its therapeutic index, reducing adverse side effects to ultimately extend life-span of patients.
Furthermore, a familiarity with lipid materials science will enable scientists to conduct rational performulation studies, to understand and optimize formulations, drug delivery systems and their manufacturing processes as well as associated process analytical technologies and quality by design.
Contents:
Preface
Contributors
1. Reviewing the Gaps in the Safety and Risk Assessment of Nanoparticles and Nanomaterials
1.1 Introduction
1.2 Risk Assessment and Sustainability
1.2.1 Effect of Nanosized Particles
1.2.2 Integrated Platforms for Nanoparticle Toxicity Analysis
1.3 Conclusions
References
2. Lipid Nanoparticles in Cancer Therapy: Past, Present and Future
2.1 Introduction
2.2 Concepts and Definitions of Lipid Nanoparticles
2.3 In Vitro Properties and In Vivo Features of Lipid Nanoparticles
2.4 Lipid Nanoparticles for Cancer Chemotherapeutics
2.4.1 Delivery of Poorly Water-soluble Compounds
2.4.2 Delivery of Water-soluble Ionic Salts
2.4.3 Delivery of Water-soluble Nonionic Drug Molecules
2.5 Conclusions
References
3. Multifunctional Lipid Nanocarriers for Cancer Prevention and Therapy
3.1 Introduction
3.1.1 Cancer Vaccines and Chemoprevention
3.1.2 Cancer Treatment Strategies
3.1.3 Delivery Challenges in Cancer Prevention and Therapy
3.2 Lipid-based Nanotechnology for Cancer
3.2.1 Nanotechnology Applications in Medicine
3.2.2 Cancer Nanomedicine
3.2.3 Passive and Active Targeting Strategies
3.2.4 Multifunctional Nanotechnology
3.3 Illustrative Examples in Cancer Prevention
3.3.1 Lipid Nanocarriers for Cancer Vaccines
3.3.2 Lipid Nanocarriers for Cancer Prevention
3.4 Illustrative Examples in Cancer Therapy
3.4.1 Multifunctional Liposomal Formulations
3.4.2 Multifunctional Nanoemulsion Formulations
3.5 Illustrative Examples of Lipid Nanocarriers for Nucleic Acid Delivery
3.6 Conclusions
Acknowledgements
References
4. Targeting Solid Lipid Nanoparticles for Drug Delivery in Cancer Therapy
4.1 Introduction
4.2 Chemotherapy and Its Limitations
4.2.1 Need for Targeted Drug Delivery Systems
4.2.2 Particulate Carriers for Anti-cancer Drug Delivery
4.3 Solid Lipid Nanoparticles
4.3.1 Encapsulation of Hydrophobic Drugs
4.3.2 Encapsulation of Hydrophilic Drugs
4.4 Modifications to Improve Encapsulation Efficiency and Release Characteristics
4.5 Modifications to Improve Multidrug Resistance
4.6 Modifications to Improve Cellular Uptake and Targetability
4.7 Modifications to Achieve Brain Targeting
4.8 Toxicity Concerns
4.9 Conclusions
References
5. Targeting Liposomes for Drug Delivery in Cancer Therapy
5.1 Introduction
5.2 Types of Liposomal Anti-cancer Drugs and Their Clinical Use
5.2.1 Anthracyclines: Liposomal Doxorubicin and Daunorubicin
5.2.2 Pyrimidine Analogues: Liposomal Cytarabine and Gemcitabine
5.2.3 Vinca Alkaloids: Liposomal Vincristine and Vinorelbine
5.2.4 Taxanes: Liposomal Paclitaxel and Docetaxel
5.2.5 Platinum Compound: Liposomal Cisplatin and Oxaliplatin
5.2.6 Liposomal Camptothecin Analogues
5.2.7 Podophyllotoxin Derivatives: Liposomal Etoposide
5.2.8 Nitrogen Mustard Analogues: Liposomal Chlorambucil
5.3 Ligand-mediated Targeting Liposomes
5.3.1 Antibody-mediated Targeting Liposomes
5.3.2 Peptide-mediated Targeting Liposomes
5.3.3 Folate-mediated Targeting Liposomes
5.3.4 Transferrin-mediated Targeting Liposomes
5.4 Future Directions of Liposome-based Anti-cancer Drugs
5.5 Conclusions
Acknowledgements
References
6. Cationic Liposomes and Tumour Vasculature Targeting: A Therapeutic Approach that has Potential for Solid Tumours
6.1 Introduction
6.2 Tumour Cell Targeting versus Tumour Vasculature Targeting
6.3 Tumour Angiogenesis
6.3.1 Formation of Tumour Vessels
6.3.2 Structure and Function of Tumour Vessels
6.3.3 Lack of Functional Lymphatics
6.3.4 Methods for Evaluating Angiogenesis
6.4 Tumour Vascular Targeting with Cationic Liposomes
6.4.1 Development of Cationic Liposomes Homing to Tumour Vasculature
6.4.2 Cationic Liposomes and Encapsulated Drug Behaviour
6.4.3 Effect of Dosing Schedule on the Anti-tumour Efficacy of Cationic Liposomal Formulations
6.4.4 Pharmacokinetics of Cationic Liposomes
6.5 Dual Targeting Approach of Both Tumour Endothelial Cells and Tumour Cells
6.6 Effect of Sequential Administration on the Anti-tumour Efficacy of Cationic Liposomal Formulations
6.7 Clinical Applications of Cationic Liposomes: Promise and Obstacles
6.7.1 Safety of Cationic Liposomes in Preclinical and Clinical Use
6.7.2 Clinical Applications of Cationic Liposomes in Cancer Therapy
6.8 Conclusions
Acknowledgements
References
7. Lipid-based Nanocarriers for Cancer Gene Therapy
7.1 Introduction
7.2 Preclinical Studies Testing Lipid-based Nanocarriers for Cancer Gene Therapy
7.3 Clinical Studies Testing Lipid-based Nanocarriers for Cancer Gene Therapy
7.4 Conclusions
Acknowledgements
References
8. Lipid-based Biomimetics: General Perspectives in Drug and Vaccine Delivery
8.1 Introduction
8.2 Intermolecular Interactions
8.3 Carriers in the Biological Milieu
8.4 Lipid Coating on Particles and Its Applications
8.5 Conclusions
References
Acknowledgements
9. Advances in Liposomal Formulations for Targeting Lung Cancer
9.1 Introduction
9.2 Targeting Lung Cancer Cells
9.2.1 Physical Targeting
9.2.2 Biological Targeting
9.3 Lipid-based Targeted Therapies
9.3.1 Ligand-targeted Liposomes
9.3.2 Drug Release from Liposomes
9.4 Therapeutic Agents Delivered by Liposomes
9.5 Clinical Use of Liposomes for Lung Cancer
9.5.1 Liposomal Formulations of Anthracyclines
9.5.2 Liposomal Formulations of Topoisomerase I Inhibitors and Taxanes
9.5.3 Liposomal Formulations of Cancer Vaccines and Gene Therapy Agents
9.5.4 Liposomal Formulations of Cisplatin
9.6 Conclusions
References
10 Nanocarriers Targeting Breast Cancers to Deliver Modulators of Oestrogen Receptor
10.1 Introduction
10.2 Oestrogen Receptor in the Mammary Gland
10.2.1 Oestrogen Receptors in the Normal Breast
10.2.2 Oestrogen Receptor in Breast Cancers
10.3 Oestrogen Receptor-mediated Signalling
10.3.1 Oestradiol-dependent Transcription
10.3.2 Oestrogen Receptor Activation through Phosphorylations
10.3.3 Nongenomic Action of Oestrogen Receptor
10.3.4 The Intriguing Role of Oestrogen Receptor ß
10.4 Classical Therapeutics used in Breast Cancer
10.4.1 Chemotherapy and Radiotherapy
10.4.2 Hormone Therapy
10.5 Nanocarriers Targeting Oestrogen Receptor-dependent Breast Cancer
10.5.1 General Considerations
10.5.2 Conventional Nanoparticles
10.5.3 Stealth® Nanoparticles
10.6 Active Targeted Nanoparticles
10.6.1 Small Molecule-targeted Liposomes
10.6.2 Magneto-liposomes
10.6.3 Immuno-targeted Liposomes
10.7 Novel Molecular-targeted Approaches for Liposomal Delivery
10.7.1 Silencing Ribonucleic Acids and Antisense Oligonucleotides
10.7.2 Heat Shock Protein 90 Inhibitors
10.7.3 Histone Deacetylase Inhibitors
10.7.4 PI3K/Akt Inhibitors
10.7.5 Tyrosine Kinase Inhibitors
10.7.6 Inhibitors of the Ras Family
10.7.7 Ubiquitin-proteasome Inhibitors
10.7.8 Gene Therapy
10.8 Conclusions
Acknowledgements
References
11. Lipid Nanocarriers Targeting Adrenocortical Tumour Cells: Genetics, Clinical Implications, Treatment Strategies and Molecular Targets
11. 1 Introduction
11.2 Aetiology of Adrenocortical Carcinoma
11.2.1 Li-Fraumeni Syndrome, the TP53 Gene and the 17p13 Locus
11.2.2 Beckwith-Wiedemann Syndrome, the IGF2 Gene and the 11p15 Locus
11.2.3 Multiple Endocrine Neoplasia Type 1, MEN1 Gene and 11q13 Locus
11.2.4 Carney’s Complex, Protein Kinase A R1A and 17q22–24 Locus
11.3 Clinical Implications
11.3.1 Recognising Familial or Syndromic Adrenocortical Tumours
11.3.2 Evaluating the Prognosis of Patients with Adrenocortical Tumours
11.4 Current Therapies for Adrenocortical Carcinoma
11.4.1 Mechanism and Biotransformation of Mitotane
11.4.2 Emerging Technologies in the Treatment of Adrenocortical Carcinoma
11.5 Emerging Molecular Targets in Adrenocortical Carcinoma
11.6 Challenges in Lipid-based Drug Delivery Systems for Adrenocortical Carcinoma
11.7 Conclusions
References
12. Advances in Microemulsions and Nanoemulsions for Improved
Therapy in Brain Cancer
12.1 Introduction
12.2 Brain Cancer
12.2.1 Primary Brain Tumours
12.2.2 Metastatic Brain Tumours
12.3 Blood-brain Barrier
12.3.1 Transport across the Blood-brain Barrier
12.4 Blood-brain Barrier in Brain Cancer
12.5 Drug Delivery Strategies
12.5.1 Local Delivery
12.5.2 Systemic Delivery
12.5.3 Nano Drug Delivery Approaches for Brain Cancer
12.6 Microemulsions and Nanoemulsions
12.6.1 Preparation of Microemulsions and Nanoemulsions
12.6.2 Components of Microemulsions and Nanoemulsions
12.7 Microemulsions and Nanoemulsions for Cancer Therapy
12.8 Functional Microemulsions and Nanoemulsions to Cross the Blood-brain Barrier
12.8.1 Functional Oils
12.8.2 Functional Surfactants and Cosurfactants
12.9 Multifunctional Microemulsions and Nanoemulsions
12.10 Characterisation of Microemulsion and Nanoemulsion
12.11 Evaluation In Vitro and In Vivo
12.12 Advantages of Microemulsions and Nanoemulsions as Drug Delivery Systems
12.13 Conclusions
Acknowledgements
References
13. Bioavailability Enhancement and Brain Targeting of Curcumin: A Potential Anti-tumour Agent
13.1 Introduction
13.2 Chemistry of Curcumin
13.3 Brain Tumour
13.4 Blood-brain Barrier
13.5 Role of Curcumin in Cancer
13.5.1 Contribution of Curcumin in the Induction of Apoptotic Mechanism
13.5.2 In Vitro Anti-cancer Effects of Curcumin
13.5.3 Preclinical Pharmacodynamic Studies
13.5.4 Combinatorial Chemoprevention by Curcumin
13.5.5 Pharmacokinetic Studies in Animals
13.5.6 Pharmacokinetic Studies in Humans
13.5.7 Alleviation of Chemotherapy-induced Symptoms
13.6 Therapeutic Strategies for Bioavailability Enhancement of Curcumin
13.6.1 Adjuvants
13.6.2 Self-microemulsifying Drug Delivery System
13.6.3 Liposomes, Micelles and Phospholipid Complexes
13.6.4 Nanoparticulate Delivery System
13.6.5 Solid Lipid Nanoparticles
13.7 Curcumin-loaded Solid Lipid Nanoparticles for Oral Administration
13.7.1 Pharmacokinetics of Curcumin-loaded Solid Lipid Nanoparticles
13.7.2 Apoptotic Effect of Curcumin-loaded Solid Lipid Nanoparticles on Human Neuroblastoma Cell Lines
13.7.3 Curcumin-loaded Solid Lipid Nanoparticles across Blood-brain Barrier
13.8 Conclusions
References
14. Lipid Nanomedicines for Eye Cancer Treatment
14.1 Anatomy and Physiology of the Eye
14.2 Neoplastic Diseases of the Eye
14.3 Treatment of Ophthalmic Cancers
14.4 Ocular Pharmacokinetics: Challenges and Obstacles
14.5 New Frontiers in Drug Delivery to the Eye: Lipid Nanomedicines
14.6 Conclusions
Acknowledgements
References
15. Lipid Nanocarriers for Topical Anti-cancer Therapy: An Update
15.1 Introduction
15.2 Introduction to Skin Anatomy and Physiology
15.2.1 The Epidermis
15.2.2 The Dermis
15.2.3 The Skin Appendages
15.2.4 Skin Pathogens, Exotoxins and Cutaneous Cellular Defence
15.3 Percutaneous Absorption
15.3.1 Transepidermal Absorption
15.3.2 Transfollicular (Shunt Pathway) Absorption
15.3.3 Intercellular Pathway
15.3.4 Factors Influencing Percutaneous Absorption
15.4 Lipid-based Particulate Carriers
15.4.1 Class I - Based Delivery Systems
15.4.2 Class II - Based Delivery Systems
15.4.3 Class III - Based Delivery Systems
15.5 Lipid-based Nanocarriers for Herbal Anti-cancers
15.6 Lipid-based Nanocarriers for Gene Delivery for Cancer
15.7 Toxicity Considerations of Nanoparticles
15.8 Conclusions
Acknowledgements
References
16. Treatment of Skin Cancer Using Sesamol-loaded Solid Lipid Nanoparticles
16.1 Introduction
16.2 Antioxidants in Skin Cancer
16.3 Need of Suitable Delivery Systems for Antioxidant Molecules
16.4 ‘Open Sesame’
16.4.1 Pharmacology of Sesamol
16.4.2 Preliminary Physicochemical Studies on Sesamol
16.5 Solid Lipid Nanoparticles
16.5.1 Solid Lipid Nanoparticles in Topical Drug Delivery
16.6 In Vitro Evaluation of Sesamol
16.6.1 Anti-cancer Studies in Molt-4 and HL-60 Cancer Cell Lines
16.6.2 Deoxyribonucleic Acid Fragmentation Assay
16.6.3 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium Bromide Assay
16.7 Development and Characterisation of Sesamol-loaded Solid Lipid Nanoparticles
16.7.1 Preparation of Solid Lipid Nanoparticles by Microemulsification- solidification Method
16.7.2 Particle Size Analysis
16.7.3 Encapsulation Efficiency
16.7.4 Differential Scanning Calorimetry
16.8 Skin Permeation Studies
16.9 Pharmacokinetic Studies
16.10 In Vivo Skin Anti-cancer Studies
16.10.1 Animal Model and Treatment Groups
16.10.2 Macroscopic Evaluation of Cancer
16.10.3 Biochemical Analysis of Skin Homogenates
16.10.4 Histopathological Analysis
16.11 Conclusions
References
Abbreviations
Index
Contributors
1. Reviewing the Gaps in the Safety and Risk Assessment of Nanoparticles and Nanomaterials
1.1 Introduction
1.2 Risk Assessment and Sustainability
1.2.1 Effect of Nanosized Particles
1.2.2 Integrated Platforms for Nanoparticle Toxicity Analysis
1.3 Conclusions
References
2. Lipid Nanoparticles in Cancer Therapy: Past, Present and Future
2.1 Introduction
2.2 Concepts and Definitions of Lipid Nanoparticles
2.3 In Vitro Properties and In Vivo Features of Lipid Nanoparticles
2.4 Lipid Nanoparticles for Cancer Chemotherapeutics
2.4.1 Delivery of Poorly Water-soluble Compounds
2.4.2 Delivery of Water-soluble Ionic Salts
2.4.3 Delivery of Water-soluble Nonionic Drug Molecules
2.5 Conclusions
References
3. Multifunctional Lipid Nanocarriers for Cancer Prevention and Therapy
3.1 Introduction
3.1.1 Cancer Vaccines and Chemoprevention
3.1.2 Cancer Treatment Strategies
3.1.3 Delivery Challenges in Cancer Prevention and Therapy
3.2 Lipid-based Nanotechnology for Cancer
3.2.1 Nanotechnology Applications in Medicine
3.2.2 Cancer Nanomedicine
3.2.3 Passive and Active Targeting Strategies
3.2.4 Multifunctional Nanotechnology
3.3 Illustrative Examples in Cancer Prevention
3.3.1 Lipid Nanocarriers for Cancer Vaccines
3.3.2 Lipid Nanocarriers for Cancer Prevention
3.4 Illustrative Examples in Cancer Therapy
3.4.1 Multifunctional Liposomal Formulations
3.4.2 Multifunctional Nanoemulsion Formulations
3.5 Illustrative Examples of Lipid Nanocarriers for Nucleic Acid Delivery
3.6 Conclusions
Acknowledgements
References
4. Targeting Solid Lipid Nanoparticles for Drug Delivery in Cancer Therapy
4.1 Introduction
4.2 Chemotherapy and Its Limitations
4.2.1 Need for Targeted Drug Delivery Systems
4.2.2 Particulate Carriers for Anti-cancer Drug Delivery
4.3 Solid Lipid Nanoparticles
4.3.1 Encapsulation of Hydrophobic Drugs
4.3.2 Encapsulation of Hydrophilic Drugs
4.4 Modifications to Improve Encapsulation Efficiency and Release Characteristics
4.5 Modifications to Improve Multidrug Resistance
4.6 Modifications to Improve Cellular Uptake and Targetability
4.7 Modifications to Achieve Brain Targeting
4.8 Toxicity Concerns
4.9 Conclusions
References
5. Targeting Liposomes for Drug Delivery in Cancer Therapy
5.1 Introduction
5.2 Types of Liposomal Anti-cancer Drugs and Their Clinical Use
5.2.1 Anthracyclines: Liposomal Doxorubicin and Daunorubicin
5.2.2 Pyrimidine Analogues: Liposomal Cytarabine and Gemcitabine
5.2.3 Vinca Alkaloids: Liposomal Vincristine and Vinorelbine
5.2.4 Taxanes: Liposomal Paclitaxel and Docetaxel
5.2.5 Platinum Compound: Liposomal Cisplatin and Oxaliplatin
5.2.6 Liposomal Camptothecin Analogues
5.2.7 Podophyllotoxin Derivatives: Liposomal Etoposide
5.2.8 Nitrogen Mustard Analogues: Liposomal Chlorambucil
5.3 Ligand-mediated Targeting Liposomes
5.3.1 Antibody-mediated Targeting Liposomes
5.3.2 Peptide-mediated Targeting Liposomes
5.3.3 Folate-mediated Targeting Liposomes
5.3.4 Transferrin-mediated Targeting Liposomes
5.4 Future Directions of Liposome-based Anti-cancer Drugs
5.5 Conclusions
Acknowledgements
References
6. Cationic Liposomes and Tumour Vasculature Targeting: A Therapeutic Approach that has Potential for Solid Tumours
6.1 Introduction
6.2 Tumour Cell Targeting versus Tumour Vasculature Targeting
6.3 Tumour Angiogenesis
6.3.1 Formation of Tumour Vessels
6.3.2 Structure and Function of Tumour Vessels
6.3.3 Lack of Functional Lymphatics
6.3.4 Methods for Evaluating Angiogenesis
6.4 Tumour Vascular Targeting with Cationic Liposomes
6.4.1 Development of Cationic Liposomes Homing to Tumour Vasculature
6.4.2 Cationic Liposomes and Encapsulated Drug Behaviour
6.4.3 Effect of Dosing Schedule on the Anti-tumour Efficacy of Cationic Liposomal Formulations
6.4.4 Pharmacokinetics of Cationic Liposomes
6.5 Dual Targeting Approach of Both Tumour Endothelial Cells and Tumour Cells
6.6 Effect of Sequential Administration on the Anti-tumour Efficacy of Cationic Liposomal Formulations
6.7 Clinical Applications of Cationic Liposomes: Promise and Obstacles
6.7.1 Safety of Cationic Liposomes in Preclinical and Clinical Use
6.7.2 Clinical Applications of Cationic Liposomes in Cancer Therapy
6.8 Conclusions
Acknowledgements
References
7. Lipid-based Nanocarriers for Cancer Gene Therapy
7.1 Introduction
7.2 Preclinical Studies Testing Lipid-based Nanocarriers for Cancer Gene Therapy
7.3 Clinical Studies Testing Lipid-based Nanocarriers for Cancer Gene Therapy
7.4 Conclusions
Acknowledgements
References
8. Lipid-based Biomimetics: General Perspectives in Drug and Vaccine Delivery
8.1 Introduction
8.2 Intermolecular Interactions
8.3 Carriers in the Biological Milieu
8.4 Lipid Coating on Particles and Its Applications
8.5 Conclusions
References
Acknowledgements
9. Advances in Liposomal Formulations for Targeting Lung Cancer
9.1 Introduction
9.2 Targeting Lung Cancer Cells
9.2.1 Physical Targeting
9.2.2 Biological Targeting
9.3 Lipid-based Targeted Therapies
9.3.1 Ligand-targeted Liposomes
9.3.2 Drug Release from Liposomes
9.4 Therapeutic Agents Delivered by Liposomes
9.5 Clinical Use of Liposomes for Lung Cancer
9.5.1 Liposomal Formulations of Anthracyclines
9.5.2 Liposomal Formulations of Topoisomerase I Inhibitors and Taxanes
9.5.3 Liposomal Formulations of Cancer Vaccines and Gene Therapy Agents
9.5.4 Liposomal Formulations of Cisplatin
9.6 Conclusions
References
10 Nanocarriers Targeting Breast Cancers to Deliver Modulators of Oestrogen Receptor
10.1 Introduction
10.2 Oestrogen Receptor in the Mammary Gland
10.2.1 Oestrogen Receptors in the Normal Breast
10.2.2 Oestrogen Receptor in Breast Cancers
10.3 Oestrogen Receptor-mediated Signalling
10.3.1 Oestradiol-dependent Transcription
10.3.2 Oestrogen Receptor Activation through Phosphorylations
10.3.3 Nongenomic Action of Oestrogen Receptor
10.3.4 The Intriguing Role of Oestrogen Receptor ß
10.4 Classical Therapeutics used in Breast Cancer
10.4.1 Chemotherapy and Radiotherapy
10.4.2 Hormone Therapy
10.5 Nanocarriers Targeting Oestrogen Receptor-dependent Breast Cancer
10.5.1 General Considerations
10.5.2 Conventional Nanoparticles
10.5.3 Stealth® Nanoparticles
10.6 Active Targeted Nanoparticles
10.6.1 Small Molecule-targeted Liposomes
10.6.2 Magneto-liposomes
10.6.3 Immuno-targeted Liposomes
10.7 Novel Molecular-targeted Approaches for Liposomal Delivery
10.7.1 Silencing Ribonucleic Acids and Antisense Oligonucleotides
10.7.2 Heat Shock Protein 90 Inhibitors
10.7.3 Histone Deacetylase Inhibitors
10.7.4 PI3K/Akt Inhibitors
10.7.5 Tyrosine Kinase Inhibitors
10.7.6 Inhibitors of the Ras Family
10.7.7 Ubiquitin-proteasome Inhibitors
10.7.8 Gene Therapy
10.8 Conclusions
Acknowledgements
References
11. Lipid Nanocarriers Targeting Adrenocortical Tumour Cells: Genetics, Clinical Implications, Treatment Strategies and Molecular Targets
11. 1 Introduction
11.2 Aetiology of Adrenocortical Carcinoma
11.2.1 Li-Fraumeni Syndrome, the TP53 Gene and the 17p13 Locus
11.2.2 Beckwith-Wiedemann Syndrome, the IGF2 Gene and the 11p15 Locus
11.2.3 Multiple Endocrine Neoplasia Type 1, MEN1 Gene and 11q13 Locus
11.2.4 Carney’s Complex, Protein Kinase A R1A and 17q22–24 Locus
11.3 Clinical Implications
11.3.1 Recognising Familial or Syndromic Adrenocortical Tumours
11.3.2 Evaluating the Prognosis of Patients with Adrenocortical Tumours
11.4 Current Therapies for Adrenocortical Carcinoma
11.4.1 Mechanism and Biotransformation of Mitotane
11.4.2 Emerging Technologies in the Treatment of Adrenocortical Carcinoma
11.5 Emerging Molecular Targets in Adrenocortical Carcinoma
11.6 Challenges in Lipid-based Drug Delivery Systems for Adrenocortical Carcinoma
11.7 Conclusions
References
12. Advances in Microemulsions and Nanoemulsions for Improved
Therapy in Brain Cancer
12.1 Introduction
12.2 Brain Cancer
12.2.1 Primary Brain Tumours
12.2.2 Metastatic Brain Tumours
12.3 Blood-brain Barrier
12.3.1 Transport across the Blood-brain Barrier
12.4 Blood-brain Barrier in Brain Cancer
12.5 Drug Delivery Strategies
12.5.1 Local Delivery
12.5.2 Systemic Delivery
12.5.3 Nano Drug Delivery Approaches for Brain Cancer
12.6 Microemulsions and Nanoemulsions
12.6.1 Preparation of Microemulsions and Nanoemulsions
12.6.2 Components of Microemulsions and Nanoemulsions
12.7 Microemulsions and Nanoemulsions for Cancer Therapy
12.8 Functional Microemulsions and Nanoemulsions to Cross the Blood-brain Barrier
12.8.1 Functional Oils
12.8.2 Functional Surfactants and Cosurfactants
12.9 Multifunctional Microemulsions and Nanoemulsions
12.10 Characterisation of Microemulsion and Nanoemulsion
12.11 Evaluation In Vitro and In Vivo
12.12 Advantages of Microemulsions and Nanoemulsions as Drug Delivery Systems
12.13 Conclusions
Acknowledgements
References
13. Bioavailability Enhancement and Brain Targeting of Curcumin: A Potential Anti-tumour Agent
13.1 Introduction
13.2 Chemistry of Curcumin
13.3 Brain Tumour
13.4 Blood-brain Barrier
13.5 Role of Curcumin in Cancer
13.5.1 Contribution of Curcumin in the Induction of Apoptotic Mechanism
13.5.2 In Vitro Anti-cancer Effects of Curcumin
13.5.3 Preclinical Pharmacodynamic Studies
13.5.4 Combinatorial Chemoprevention by Curcumin
13.5.5 Pharmacokinetic Studies in Animals
13.5.6 Pharmacokinetic Studies in Humans
13.5.7 Alleviation of Chemotherapy-induced Symptoms
13.6 Therapeutic Strategies for Bioavailability Enhancement of Curcumin
13.6.1 Adjuvants
13.6.2 Self-microemulsifying Drug Delivery System
13.6.3 Liposomes, Micelles and Phospholipid Complexes
13.6.4 Nanoparticulate Delivery System
13.6.5 Solid Lipid Nanoparticles
13.7 Curcumin-loaded Solid Lipid Nanoparticles for Oral Administration
13.7.1 Pharmacokinetics of Curcumin-loaded Solid Lipid Nanoparticles
13.7.2 Apoptotic Effect of Curcumin-loaded Solid Lipid Nanoparticles on Human Neuroblastoma Cell Lines
13.7.3 Curcumin-loaded Solid Lipid Nanoparticles across Blood-brain Barrier
13.8 Conclusions
References
14. Lipid Nanomedicines for Eye Cancer Treatment
14.1 Anatomy and Physiology of the Eye
14.2 Neoplastic Diseases of the Eye
14.3 Treatment of Ophthalmic Cancers
14.4 Ocular Pharmacokinetics: Challenges and Obstacles
14.5 New Frontiers in Drug Delivery to the Eye: Lipid Nanomedicines
14.6 Conclusions
Acknowledgements
References
15. Lipid Nanocarriers for Topical Anti-cancer Therapy: An Update
15.1 Introduction
15.2 Introduction to Skin Anatomy and Physiology
15.2.1 The Epidermis
15.2.2 The Dermis
15.2.3 The Skin Appendages
15.2.4 Skin Pathogens, Exotoxins and Cutaneous Cellular Defence
15.3 Percutaneous Absorption
15.3.1 Transepidermal Absorption
15.3.2 Transfollicular (Shunt Pathway) Absorption
15.3.3 Intercellular Pathway
15.3.4 Factors Influencing Percutaneous Absorption
15.4 Lipid-based Particulate Carriers
15.4.1 Class I - Based Delivery Systems
15.4.2 Class II - Based Delivery Systems
15.4.3 Class III - Based Delivery Systems
15.5 Lipid-based Nanocarriers for Herbal Anti-cancers
15.6 Lipid-based Nanocarriers for Gene Delivery for Cancer
15.7 Toxicity Considerations of Nanoparticles
15.8 Conclusions
Acknowledgements
References
16. Treatment of Skin Cancer Using Sesamol-loaded Solid Lipid Nanoparticles
16.1 Introduction
16.2 Antioxidants in Skin Cancer
16.3 Need of Suitable Delivery Systems for Antioxidant Molecules
16.4 ‘Open Sesame’
16.4.1 Pharmacology of Sesamol
16.4.2 Preliminary Physicochemical Studies on Sesamol
16.5 Solid Lipid Nanoparticles
16.5.1 Solid Lipid Nanoparticles in Topical Drug Delivery
16.6 In Vitro Evaluation of Sesamol
16.6.1 Anti-cancer Studies in Molt-4 and HL-60 Cancer Cell Lines
16.6.2 Deoxyribonucleic Acid Fragmentation Assay
16.6.3 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium Bromide Assay
16.7 Development and Characterisation of Sesamol-loaded Solid Lipid Nanoparticles
16.7.1 Preparation of Solid Lipid Nanoparticles by Microemulsification- solidification Method
16.7.2 Particle Size Analysis
16.7.3 Encapsulation Efficiency
16.7.4 Differential Scanning Calorimetry
16.8 Skin Permeation Studies
16.9 Pharmacokinetic Studies
16.10 In Vivo Skin Anti-cancer Studies
16.10.1 Animal Model and Treatment Groups
16.10.2 Macroscopic Evaluation of Cancer
16.10.3 Biochemical Analysis of Skin Homogenates
16.10.4 Histopathological Analysis
16.11 Conclusions
References
Abbreviations
Index
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