Contents. Preface...xv. Contributors...xvii. 1 Reviewing the Gaps in the Safety and Risk Assessment of Nanoparticles and Nanomaterials...

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1 Preface...xv Contributors...xvii 1 Reviewing the Gaps in the Safety and Risk Assessment of Nanoparticles and Nanomaterials Introduction Risk Assessment and Sustainability Effect of Nanosized Particles Integrated Platforms for Nanoparticle Toxicity Analysis Conclusions... 9 References Lipid Nanoparticles in Cancer Therapy: Past, Present and Future Introduction Concepts and Definitions of Lipid Nanoparticles In Vitro Properties and In Vivo Features of Lipid Nanoparticles Lipid Nanoparticles for Cancer Chemotherapeutics Delivery of Poorly Water-soluble Compounds Delivery of Water-soluble Ionic Salts Delivery of Water-soluble Nonionic Drug Molecules Conclusions References v

2 3 Multifunctional Lipid Nanocarriers for Cancer Prevention and Therapy Introduction Cancer Vaccines and Chemoprevention Cancer Treatment Strategies Delivery Challenges in Cancer Prevention and Therapy Lipid-based Nanotechnology for Cancer Nanotechnology Applications in Medicine Cancer Nanomedicine Passive and Active Targeting Strategies Multifunctional Nanotechnology Illustrative Examples in Cancer Prevention Lipid Nanocarriers for Cancer Vaccines Lipid Nanocarriers for Cancer Prevention Illustrative Examples in Cancer Therapy Multifunctional Liposomal Formulations Multifunctional Nanoemulsion Formulations Illustrative Examples of Lipid Nanocarriers for Nucleic Acid Delivery Conclusions Acknowledgements References Targeting Solid Lipid Nanoparticles for Drug Delivery in Cancer Therapy Introduction Chemotherapy and Its Limitations Need for Targeted Drug Delivery Systems Particulate Carriers for Anti-cancer Drug Delivery Solid Lipid Nanoparticles Encapsulation of Hydrophobic Drugs Encapsulation of Hydrophilic Drugs Modifications to Improve Encapsulation Efficiency and Release Characteristics Modifications to Improve Multidrug Resistance Modifications to Improve Cellular Uptake and Targetability vi

3 4.7 Modifications to Achieve Brain Targeting Toxicity Concerns Conclusions References Targeting Liposomes for Drug Delivery in Cancer Therapy Introduction Types of Liposomal Anti-cancer Drugs and Their Clinical Use Anthracyclines: Liposomal Doxorubicin and Daunorubicin Pyrimidine Analogues: Liposomal Cytarabine and Gemcitabine Vinca Alkaloids: Liposomal Vincristine and Vinorelbine Taxanes: Liposomal Paclitaxel and Docetaxel Platinum Compound: Liposomal Cisplatin and Oxaliplatin Liposomal Camptothecin Analogues Podophyllotoxin Derivatives: Liposomal Etoposide Nitrogen Mustard Analogues: Liposomal Chlorambucil Ligand-mediated Targeting Liposomes Antibody-mediated Targeting Liposomes Peptide-mediated Targeting Liposomes Folate-mediated Targeting Liposomes Transferrin-mediated Targeting Liposomes Future Directions of Liposome-based Anti-cancer Drugs Conclusions Acknowledgements References Cationic Liposomes and Tumour Vasculature Targeting: A Therapeutic Approach that has Potential for Solid Tumours Introduction Tumour Cell Targeting versus Tumour Vasculature Targeting Tumour Angiogenesis Formation of Tumour Vessels Structure and Function of Tumour Vessels vii

4 6.3.3 Lack of Functional Lymphatics Methods for Evaluating Angiogenesis Tumour Vascular Targeting with Cationic Liposomes Development of Cationic Liposomes Homing to Tumour Vasculature Cationic Liposomes and Encapsulated Drug Behaviour Effect of Dosing Schedule on the Anti-tumour Efficacy of Cationic Liposomal Formulations Pharmacokinetics of Cationic Liposomes Dual Targeting Approach of Both Tumour Endothelial Cells and Tumour Cells Effect of Sequential Administration on the Anti-tumour Efficacy of Cationic Liposomal Formulations Clinical Applications of Cationic Liposomes: Promise and Obstacles Safety of Cationic Liposomes in Preclinical and Clinical Use Clinical Applications of Cationic Liposomes in Cancer Therapy Conclusions Acknowledgements References Lipid-based Nanocarriers for Cancer Gene Therapy Introduction Preclinical Studies Testing Lipid-based Nanocarriers for Cancer Gene Therapy Clinical Studies Testing Lipid-based Nanocarriers for Cancer Gene Therapy Conclusions Acknowledgements References Lipid-based Biomimetics: General Perspectives in Drug and Vaccine Delivery Introduction Intermolecular Interactions viii

5 8.3 Carriers in the Biological Milieu Lipid Coating on Particles and Its Applications Conclusions References Acknowledgements Advances in Liposomal Formulations for Targeting Lung Cancer Introduction Targeting Lung Cancer Cells Physical Targeting Biological Targeting Lipid-based Targeted Therapies Ligand-targeted Liposomes Drug Release from Liposomes Therapeutic Agents Delivered by Liposomes Clinical Use of Liposomes for Lung Cancer Liposomal Formulations of Anthracyclines Liposomal Formulations of Topoisomerase I Inhibitors and Taxanes Liposomal Formulations of Cancer Vaccines and Gene Therapy Agents Liposomal Formulations of Cisplatin Conclusions References Nanocarriers Targeting Breast Cancers to Deliver Modulators of Oestrogen Receptor Introduction Oestrogen Receptor in the Mammary Gland Oestrogen Receptors in the Normal Breast Oestrogen Receptor in Breast Cancers Oestrogen Receptor-mediated Signalling Oestradiol-dependent Transcription Oestrogen Receptor Activation through Phosphorylations ix

6 Nongenomic Action of Oestrogen Receptor The Intriguing Role of Oestrogen Receptor β Classical Therapeutics used in Breast Cancer Chemotherapy and Radiotherapy Hormone Therapy Nanocarriers Targeting Oestrogen Receptor-dependent Breast Cancer General Considerations Conventional Nanoparticles Stealth Nanoparticles Active Targeted Nanoparticles Small Molecule-targeted Liposomes Magneto-liposomes Immuno-targeted Liposomes Novel Molecular-targeted Approaches for Liposomal Delivery Silencing Ribonucleic Acids and Antisense Oligonucleotides Heat Shock Protein 90 Inhibitors Histone Deacetylase Inhibitors PI3K/Akt Inhibitors Tyrosine Kinase Inhibitors Inhibitors of the Ras Family Ubiquitin-proteasome Inhibitors Gene Therapy Conclusions Acknowledgements References Lipid Nanocarriers Targeting Adrenocortical Tumour Cells: Genetics, Clinical Implications, Treatment Strategies and Molecular Targets Introduction Aetiology of Adrenocortical Carcinoma Li-Fraumeni Syndrome, the TP53 Gene and the 17p13 Locus x

7 Beckwith-Wiedemann Syndrome, the IGF2 Gene and the 11p15 Locus Multiple Endocrine Neoplasia Type 1, MEN1 Gene and 11q13 Locus Carney s Complex, Protein Kinase A R1A and 17q22 24 Locus Clinical Implications Recognising Familial or Syndromic Adrenocortical Tumours Evaluating the Prognosis of Patients with Adrenocortical Tumours Current Therapies for Adrenocortical Carcinoma Mechanism and Biotransformation of Mitotane Emerging Technologies in the Treatment of Adrenocortical Carcinoma Emerging Molecular Targets in Adrenocortical Carcinoma Challenges in Lipid-based Drug Delivery Systems for Adrenocortical Carcinoma Conclusions References Advances in Microemulsions and Nanoemulsions for Improved Therapy in Brain Cancer Introduction Brain Cancer Primary Brain Tumours Metastatic Brain Tumours Blood-brain Barrier Transport across the Blood-brain Barrier Blood-brain Barrier in Brain Cancer Drug Delivery Strategies Local Delivery Systemic Delivery Nano Drug Delivery Approaches for Brain Cancer Microemulsions and Nanoemulsions Preparation of Microemulsions and Nanoemulsions Components of Microemulsions and Nanoemulsions xi

8 12.7 Microemulsions and Nanoemulsions for Cancer Therapy Functional Microemulsions and Nanoemulsions to Cross the Blood-brain Barrier Functional Oils Functional Surfactants and Cosurfactants Multifunctional Microemulsions and Nanoemulsions Characterisation of Microemulsion and Nanoemulsion Evaluation In Vitro and In Vivo Advantages of Microemulsions and Nanoemulsions as Drug Delivery Systems Conclusions Acknowledgements References Bioavailability Enhancement and Brain Targeting of Curcumin: A Potential Anti-tumour Agent Introduction Chemistry of Curcumin Brain Tumour Blood-brain Barrier Role of Curcumin in Cancer Contribution of Curcumin in the Induction of Apoptotic Mechanism In Vitro Anti-cancer Effects of Curcumin Preclinical Pharmacodynamic Studies Combinatorial Chemoprevention by Curcumin Pharmacokinetic Studies in Animals Pharmacokinetic Studies in Humans Alleviation of Chemotherapy-induced Symptoms Therapeutic Strategies for Bioavailability Enhancement of Curcumin Adjuvants Self-microemulsifying Drug Delivery System Liposomes, Micelles and Phospholipid Complexes Nanoparticulate Delivery System Solid Lipid Nanoparticles xii

9 13.7 Curcumin-loaded Solid Lipid Nanoparticles for Oral Administration Pharmacokinetics of Curcumin-loaded Solid Lipid Nanoparticles Apoptotic Effect of Curcumin-loaded Solid Lipid Nanoparticles on Human Neuroblastoma Cell Lines Curcumin-loaded Solid Lipid Nanoparticles across Blood-brain Barrier Conclusions References Lipid Nanomedicines for Eye Cancer Treatment Anatomy and Physiology of the Eye Neoplastic Diseases of the Eye Treatment of Ophthalmic Cancers Ocular Pharmacokinetics: Challenges and Obstacles New Frontiers in Drug Delivery to the Eye: Lipid Nanomedicines Conclusions Acknowledgements References Lipid Nanocarriers for Topical Anti-cancer Therapy: An Update Introduction Introduction to Skin Anatomy and Physiology The Epidermis The Dermis The Skin Appendages Skin Pathogens, Exotoxins and Cutaneous Cellular Defence Percutaneous Absorption Transepidermal Absorption Transfollicular (Shunt Pathway) Absorption Intercellular Pathway Factors Influencing Percutaneous Absorption xiii

10 15.4 Lipid-based Particulate Carriers Class I - Based Delivery Systems Class II - Based Delivery Systems Class III - Based Delivery Systems Lipid-based Nanocarriers for Herbal Anti-cancers Lipid-based Nanocarriers for Gene Delivery for Cancer Toxicity Considerations of Nanoparticles Conclusions Acknowledgements References Treatment of Skin Cancer Using Sesamol-loaded Solid Lipid Nanoparticles Introduction Antioxidants in Skin Cancer Need of Suitable Delivery Systems for Antioxidant Molecules Open Sesame Pharmacology of Sesamol Preliminary Physicochemical Studies on Sesamol Solid Lipid Nanoparticles Solid Lipid Nanoparticles in Topical Drug Delivery In Vitro Evaluation of Sesamol Anti-cancer Studies in Molt-4 and HL-60 Cancer Cell Lines Deoxyribonucleic Acid Fragmentation Assay (4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium Bromide Assay Development and Characterisation of Sesamol-loaded Solid Lipid Nanoparticles Preparation of Solid Lipid Nanoparticles by Microemulsification-solidification Method Particle Size Analysis Encapsulation Efficiency Differential Scanning Calorimetry xiv

11 16.8 Skin Permeation Studies Pharmacokinetic Studies In Vivo Skin Anti-cancer Studies Animal Model and Treatment Groups Macroscopic Evaluation of Cancer Biochemical Analysis of Skin Homogenates Histopathological Analysis Conclusions References Abbreviations Index xv