Nanotechnology in Ophthalmology

Table of Contents

List of contributors Foreword Preface Section I General introduction 1. Nanotechnology in the diagnosis of ocular diseases, drug delivery, and therapy: challenges and opportunities Lokanath Mishra, Sushama Talegaonkar, Mahendra Rai, Marcelo L. Occhiutto and Monalisa Mishra 1. Introduction 2. Nanotechnology for early diagnosis of ocular diseases 3. Conventional treatment modalities 3.1 Eye drops 3.2 Emulsions 3.3 Suspensions 3.4 Ointments 3.5 Injection 3.6 Systemic method for delivery of the drug 4. Advantages and disadvantages of the conventional treatment 5. Challenges in ocular drug delivery 5.1 Inadvertent drug washout from the eye's surface 5.2 Corneal epithelium 5.3 The bloodeOcular barrier 5.4 Tear turnover 5.5 Nasolacrimal drainage 5.6 Drug binding to tear proteins 5.7 Melanin binding 5.8 Drug metabolism 6. Ocular drug delivery and the role of nanotechnology 6.1 Nanoemulsion 6.2 Nanosuspension 6.3 Nanoparticles 6.4 Liposomes 6.5 Dendrimers 6.6 Nanomicelles 6.7 Niosomes 7. Different types of eye disease and how nanotechnology can counter them 7.1 Ocular infections 7.2 Eye inflammation 7.3 Dry eye syndrome 7.4 Glaucoma 7.5 Drug administration into the posterior segment 8. Different types of nanoformulations are used as a carrier to treat various diseases 9. Role of phytoconstituents in the drug delivery system 10. Conclusion and future perspectives Acknowledgments References Section II Perspectives of nanotechnology in ocular drug delivery 2. An overview of ocular drug delivery systems--conventional and novel drug delivery systems Tarun Virmani, Girish Kumar, Ashwani Sharma and Kamla Pathak 1. Introduction 2. Ocular barriers to drug delivery 2.1 Anatomical barriers 2.2 Physiological barriers 3. Conventional dosage forms 3.1 Eye drops 3.2 Eye ointment 3.3 Ophthalmic gels 3.4 Ocular emulsions 3.5 Ocular suspensions 3.6 Ocular injections 4. Nanotechnology-based approaches 4.1 Liposomes 4.2 Solid lipid nanoparticles 4.3 Nanostructured lipid carriers 4.4 Polymeric nanoparticles 4.5 Nanoemulsions 4.6 Niosomes 4.7 Dendrimers 4.8 Hydrogels 4.9 Polymeric micelles 5. Recent advancements in ocular drug delivery 6. Clinical status of nanotechnology-based ocular delivery systems 7. Patents on various ophthalmic preparations and devices 8. Commercialized conventional and novel ophthalmic formulations 9. Conclusion and future prospective References 3. Fathoming biopharmaceutical tenets and characterization techniques for the plausible ophthalmic drug delivery performance Nitu Dogra, Richu Singla, Sushama Talegaonkar and Honey Goel 1. Introduction 2. Topical drug delivery 2.1 Biopharmaceutics and its pharmacokinetic aspects 2.2 Considerations for optimal ophthalmic design 2.3 Subconjunctival drug administration 3. Considerations for the optimal design 3.1 Subconjunctival injection 4. Nanotechnology-based drug delivery carriers 5. Characterization of ophthalmic drug forms 5.1 In Vitro characterization 5.2 Evaluation and assessment of drug parameters in the dosage form 5.3 In vivo Assessment 6. Conclusions References Section III Biomedical applications of nanocarriers in ocular diseases, and toxicity 4. Newer nanoformulated peptides in ocular therapeutics: issues and approaches Bakr Ahmed, Pratibha Sharma, Ujjesha Mudgill and Indu Pal Kaur 1. Introduction 2. Challenges related to peptide ocular delivery 3. Ocular bioavailability and peptide transport systems 4. Newer peptide therapeutics and their nanocarriers trending in ophthalmology 4.1 Human amniotic membrane in ocular therapeutics 4.2 Cell-penetrating peptide 4.3 Vasoactive intestinal peptide 5. Conclusion and future perspective References 5. An overview of nanocarriers used in corneal disease Priti Singh, Smita Patel, Nikhila C. Jain, Vidhya Verma and Bhavana Sharma 1. Introduction 2. Corneal anatomical and physiological factors 3. Effect of the tear film on drug permeability 4. Benefits and limitations of common ocular delivery routes 4.1 Systemic administration 4.2 Topical administration 4.3 Intrastromal and intracameral routes of administration 5. Nanomedicine 5.1 Idea of theranostics 5.2 Nanoparticles 5.3 Nanofiber scaffold 5.4 Nanodevices 5.5 Nanoadhesives, nanosponges, and carbon nanotubes 5.6 Nanodelivery 6. Future challenges and perspectives 7. Conclusion Acknowledgments References Further reading 6. Nanomedicine-based solutions: nanoemulsions and nanosuspension for ocular diseases Marco Vinicius Chaud and Thais Francine Ribeiro Alves 1. Introduction 2. Nanomedicines for the management of ocular disease 2.1 Nanoemulsion 2.2 Nanosuspension 3. Conclusion References 7. Nanotechnology for surgical glaucoma treatment Carolina P.B. Gracitelli, Marcelo Lui�s Occhiutto and Vital Paulino Costa 1. Introduction 2. The goal of glaucoma treatment 3. Nanoparticle-based formulations and wound-healing modulation 4. Glaucoma drainage devices and nanodevices 5. Nanotechnology-ocular devices for glaucoma treatment 6. Nanotechnology for optic nerve regeneration 7. Limitations of nanomaterials 8. Future perspectives and conclusions Disclosure References 8. Nanotechnology in glaucomad conceptual and clinical treatment aspects Qi Xun Lim, Kelvin Cheng Kah Wai and Pankaj Kumar Agarwal 1. Introduction 2. Limitations in current management of glaucoma 2.1 Poor treatment adherence 2.2 Limited bioavailability of drugs 3. Nanotechnology and nanomedicine 4. Nanomedicine and drug delivery 5. Liposomes 6. Polymeric nanoparticles 6.1 Chitosan nanoparticles 6.2 Eudragit nanoparticles 7. Lipid nanoparticles 7.1 Solid lipid nanoparticles 7.2 Nanostructured lipid carriers 8. Dendrimers 9. Niosomes 10. Cyclodextrin 11. Challenges and looking ahead 12. Conclusion References Further reading 9. Polymeric and lipid nanocarriers in glaucoma Manisha S. Lalan, Pranav Shah, Kalyani Barve, Rahul Jha and Jyoti Jha 1. Introduction 2. Current treatment options for glaucoma 3. Ocular barriers and challenges in treatment with conventional dosage forms 4. Nanotechnology in glaucoma management 5. Polymeric nanocarriers in the management of glaucoma 5.1 Polymeric nanoparticles 5.2 Polymeric micelles 5.3 Dendrimers 6. Lipidic nanocarriers 6.1 Liposomes 6.2 Cubosomes 6.3 Lipid nanoparticlesdsolid lipid nanoparticles and nanostructured lipid carriers 6.4 Microemulsions 6.5 Lipid nanoemulsions 7. Toxicity concerns 8. Regulatory aspects of nanoformulations 9. Conclusion References 10. Lipid-based nanotherapeutic interventions for the treatment of ocular diseases: current status and future perspectives Jasjeet Kaur Narang, Kiranjeet Kaur, Gurpreet Kaur, Anmol Dogra and Deepti Pandita 1. Introduction 2. Lipid-based nanotherapeutic interventions for the treatment of ocular diseases 2.1 Liposomes 2.2 Transferosomes 2.3 Niosomes 2.4 Nanomicelles 2.5 Phytosomes 2.6 Lipid nanocapsules 2.7 Solid lipid nanoparticles 2.8 Nanostructured lipid carriers 2.9 Microemulsion 2.10 Nanoemulsions 2.11 Cubosomes 2.12 Transethosomes 2.13 Olaminosomes 2.14 SMEDDSs (self-microemulsifying drug delivery systems) 2.15 SNEDDSs (self-nanoemulsifying drug delivery systems) 2.16 SEDDS (self-emulsifying drug delivery system) 2.17 Mixed micelles 3. Patented nanolipid carriers for ocular disorders 4. Marketed formulations of lipid-based nanotherapeutic interventions for the treatment of ocular diseases 5. Conclusion and perspectives References Further reading 11. Nanotechnology in retinal drug delivery Himanshu Shekhar, Priyanka Panigrahi and Harekrushna Sahoo 1. Introduction 2. Human eyeball and different barriers in drug delivery 3. Eye diseases 4. Traditional routes in retinal drug delivery 5. Nanotechnology in ocular drug delivery 5.1 Liposome 5.2 Dendrimers 5.3 Hydrogel 5.4 Polymeric micelles 5.5 Cyclodextrin 5.6 Albumin nanoparticles 5.7 Inorganic nanoparticles 6. Conclusion 7. Limitations and future perspectives References 12. Advances in nanotherapies in the management of microbial keratitis Nagendra Bhuwane, Ishwari Choudhary, Ravi Parashar, Narayan Hemnani and Preeti K. Suresh 1. Introduction 2. Classification of microbial keratitis 2.1 Bacterial keratitis 2.2 Fungal keratitis 2.3 Parasitic keratitis 2.4 Viral keratitis 3. Nanotechnology in microbial keratitis 3.1 Nanoparticles 3.2 Liposomes 3.3 Solid lipid nanoparticles 3.4 Nanostructured lipid carriers 3.5 Niosomes 3.6 Nanosuspension 3.7 Nanomicelles 3.8 Emulgel 3.9 Nanoemulsion 3.10 Nanogels 3.11 Dendrimers 4. Conclusion and future prospects References 13. Polymeric micelles: a novel treatment option for mycotic keratitis Mrunali R. Patel, Mayank N. Jain and Rashmin B. Patel 1. Introduction 2. Novel drug delivery systems for delivering drugs to the eyes with a special focus on polymeric micelles 3. Fundamental considerations of polymeric micelles for ocular delivery 4. Opportunities and challenges of using polymeric micelles to treat fungus keratitis 5. Conclusion References 14. Use of nanotechnology in dry eye syndrome Surbhi Sharma, Konika Tyagi and Shweta Dang 1. Introduction 2. Pathophysiology, causes, and diagnosis 2.1 Tear volume 2.2 Tear osmolarity 3. Immune-based inflammation mechanisms in DED 3.1 Immune-mediated changes 3.2 Factors responsible for the inflammation in DED 4. Medical management of dry eye syndrome 4.1 Artificial tears 4.2 Nonsteroidal antiinflammatory drugs 4.3 Antibiotics 4.4 Corticosteroids 4.5 Cyclosporine A 4.6 Punctal plugs 4.7 Health supplements 4.8 Omega-3 fatty acid 4.9 Colloidal systems for management of DES 5. Limitations in current treatment methods of dry eye syndrome 5.1 Limitations due to ocular anatomical and physiological barriers 5.2 Limitations due to ocular drug delivery routes 6. Nanotechnology in the management of dry eye syndrome 6.1 Introduction to nanotechnology in ophthalmic conditions 6.2 Current strategies for dry eye syndrome based on nanotechnology 6.3 Nanotechnology-based treatment of dry eye syndrome 7. Current challenges and future prospects References 15. Advances in nanotechnology-based anti-VEGF agents for the management of ocular angiogenesis Hamoudi Ghassan Awde Alfonso, Mari�a Constanza Paz, Santiago Daniel Palma and Mari�a Lina Formica 1. Introduction 2. Neovascular disorders of the posterior segment of the eye 3. Available anti-VEGF drugs: features and challenges 4. Nanotechnological systems for anti-VEGF delivery for the treatment of ocular angiogenesis 4.1 Polymeric nanoparticles 4.2 Lipid nanoparticles 5. Conclusion Acknowledgments References 16. Application of nanotechnology towards reduction of oxidative stress-induced ocular diseases Nabamita Haldar and Monalisa Mishra 1. Introduction 2. Oxidative stress and ocular diseases 2.1 Oxidative stress and diabetic retinopathy 2.2 Oxidative stress and Glaucoma 2.3 Oxidative stress and age-related macular degeneration 2.4 Oxidative stress in other ocular diseases 3. Barriers to ocular drug deliverydanatomical and physiological 3.1 Tear film 3.2 Cornea 3.3 Conjunctiva 3.4 Aqueous humor 3.5 Sclera 3.6 Choroid 4. Synthetic and natural antioxidants targeting ROS in ocular diseases 4.1 Disadvantages of synthetic and natural antioxidants 5. Nanotechnology: a novel ocular drug delivery approach 5.1 Metallic/inorganic nanoparticles 5.2 Nanoemulsions 5.3 Solid lipid nanoparticles 5.4 Nanoliposomes 5.5 Nanopolymersomes (NPSs) 5.6 Nanocrystals 6. Toxicity of nanodelivery system 6.1 Toxicity of neurons 6.2 Nanotoxicity in the eye 7. Future perspectives 8. Conclusion References Further reading 17. Nanotechnology in age-related macular degeneration Julio Zaki Abucham Neto, Cristina Nery Carbajo and Leonardo Amarante Pereira 1. Introduction 2. Treatment evolution and present-day options 3. Current challenges in AMD treatment 3.1 Short time of drug action with frequent injections 3.2 Exclusive intra-vitreal delivery 3.3 No treatment for geographic atrophy 4. Nanotechnology in AMD 4.1 Extending drug action time 4.2 Alternative methods for drug delivery 4.3 Geographic atrophy treatment 5. Conclusion and future perspectives References 18. Nanotechnological strategies for the treatment of diabetic retinopathy: progress and limitations Mari�a Constanza Paz, Cristian Alan Rossetti, Mari�a Lina Formica and Santiago Daniel Palma Abbreviations 1. Introduction 2. Diabetic retinopathy 2.1 Retina 2.2 Pathophysiology and classification of diabetic retinopathy 2.3 Pathogenesis of diabetic retinopathy 2.4 Current pharmacotherapies for diabetic retinopathy 3. Nanocarriers for the ocular drug delivery: focusing on diabetic retinopathy 3.1 Nanocarriers based on polymers 3.2 Nanocarriers based on lipids 3.3 Nanocarriers based on inorganic compounds 4. Conclusion References 19. Advanced hydrogel-based platform for ocular drug delivery Sopan N. Nangare, Jidnyasa R. Pantwalawalkar, Namdeo R. Jadhav, Petra O. Nnamani, Zamir G. Khan, Pravin O. Patil and Sanjaykumar B. Bari 1. Introduction 1.1 Nanotechnology in ocular drug delivery system 2. Hydrogels 2.1 Stimuli-responsive polymeric hydrogel 2.2 Biocompatibility of ocular hydrogel 3. Hydrogel-based ocular drug delivery system 3.1 Stimuli-responsive hydrogels 3.2 Nonstimuli-responsive hydrogels 4. Current challenges and future prospects 5. Conclusion Acknowledgments References 20. Nanotoxicity in ocular drug delivery Triveni Shelke and Monalisa Mishra 1. Introduction 2. Barriers to eye 2.1 Anterior segment barrier 2.2 Posterior segment barrier 2.3 Other factors 3. Conventional methods to treat ophthalmic diseases 3.1 Topical administrations 3.2 Eye drops 3.3 Suspensions 3.4 Eye injections 3.5 Systemic injections 3.6 Oral administration 4. Advantages of nanomaterials in drug delivery 4.1 Microemulsion 4.2 Nanosuspensions 4.3 Nanoparticles 4.4 Liposomes 4.5 Niosomes 4.6 Cyclodextrins 4.7 Nanowafers 5. Nanotoxicity 5.1 Toxic effects of nanoparticles 5.2 Assessment of nanotoxicity 6. Conclusion References Index

Authors

Mahendra Rai Visiting Scientist, Nicolaus Copernicus University, Torun, Poland.

Professor Mahendra Rai is a UGC-Basic Science Research Faculty Fellow and former head of the Department of Biotechnology, Sant Gadge Baba Amravati University, India. Presently, he is a visiting Scientist at the Department of Microbiology, Nicolaus Copernicus University, Poland. His areas of expertise include microbial biotechnology and nanobiotechnology. Currently, his group's main research interest is green synthesis of metal nanoparticles particularly using fungi and their applications as nanoantimicrobials against pathogenic microbes. Prof. Rai has received several prestigious awards, including the Medini Award by the Government of India. He has been featured in Stanford's list of the top 2% of scientists in nanoscience.

Marcelo Luis Occhiutto Physician, Department of Anterior Segment and Refractive Surgery, Tadeu Cvintal Institute of Ophthalmology, S�o Paulo, Brazil Researcher, University of Campinas, S�o Paulo, Brazil. Marcelo Occhiutto, MD, is a Physician in the Department of Anterior Segment and Refractive Surgery of the Tadeu Cvintal Institute of Ophthalmology, Brazil. He is also a Researcher at the Department of Ophthalmology and Human Genetics in the University of Campinas. His most recent research focuses on the use of nanotechnology for antiproliferative drugs in glaucoma surgeries and the identification of genetic polymorphisms that participate in the etiology of this serious eye disease. Sushama Talegaonkar Associate Professor, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, India. Dr. Sushama Talegaonkar is an Associate Professor at the Department of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, India. She has approximately 21 years of experience, and has published more than 220 research papers in high impact international journals. Besides this, she has coauthored 6 books and authored 15 chapters in international reference books. Recently, she received the Professor C. J. Shishoo Award for Best Research. Her research paper titled "Development and bioavailability assessment of ramipril nanoemulsion formulation� has received the most cited research paper award on behalf of Elsevier and the board of European Journal of Pharmaceutics and Biopharmaceutics. She was awarded the prestigious Motan Devi Dandiya Biennial Prize for best publication in Pharmaceutical Sciences for the period 2010-11. Dr. Talegaonkar is actively involved in developing a wide variety of smart and functionalized nanodrug delivery systems for targeted anticancer drug delivery.