Nanotechnology in Ophthalmology

Prof. Mahendra Rai is a UGC Basic Science Research Faculty Fellow and former Head of the Department of Biotechnology at Sant Gadge Baba Amravati University, India. He is currently a senior visiting professor in the Department of Chemistry at the Federal University of Piaui (UFPI), Brazil.His areas of expertise include microbial biotechnology and nanobiotechnology, focusing on the green synthesis of metal nanoparticles using fungi and their applications as nanoantimicrobials against pathogenic microbes. His research is interdisciplinary, integrating microbial biotechnology with nanotechnology.Professor Rai has received several prestigious awards, including the Father T.A. Mathias Award from the All India Association for Christian Higher Education and the Medini Award from the Government of India. He has participated in multiple international collaborations and has held visiting positions at various institutions, including the University of Geneva (Switzerland), Debrecen University (Hungary), and Nicolaus Copernicus University (Poland).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. 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.

• List of contributors Foreword Preface Section IGeneral introduction1. Nanotechnology in the diagnosis of ocular diseases, drug delivery, and therapy: challenges and opportunitiesLokanath Mishra, Sushama Talegaonkar, Mahendra Rai, Marcelo L. Occhiutto and Monalisa Mishra1. Introduction2. Nanotechnology for early diagnosis of ocular diseases3. Conventional treatment modalities3.1 Eye drops3.2 Emulsions3.3 Suspensions3.4 Ointments3.5 Injection3.6 Systemic method for delivery of the drug4. Advantages and disadvantages of the conventional treatment5. Challenges in ocular drug delivery5.1 Inadvertent drug washout from the eye’s surface5.2 Corneal epithelium5.3 The bloodeOcular barrier5.4 Tear turnover5.5 Nasolacrimal drainage5.6 Drug binding to tear proteins5.7 Melanin binding5.8 Drug metabolism6. Ocular drug delivery and the role of nanotechnology6.1 Nanoemulsion6.2 Nanosuspension6.3 Nanoparticles6.4 Liposomes6.5 Dendrimers6.6 Nanomicelles6.7 Niosomes7. 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 IIPerspectives of nanotechnology in ocular drug delivery2. An overview of ocular drug delivery systems--conventional and novel drug delivery systemsTarun Virmani, Girish Kumar, Ashwani Sharma and Kamla Pathak1. 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 performanceNitu Dogra, Richu Singla, Sushama Talegaonkar and Honey Goel1. 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 IIIBiomedical applications of nanocarriers in ocular diseases, and toxicity4. Newer nanoformulated peptides in ocular therapeutics: issues and approachesBakr Ahmed, Pratibha Sharma, Ujjesha Mudgill and Indu Pal Kaur1. 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 diseasePriti Singh, Smita Patel, Nikhila C. Jain, Vidhya Verma and Bhavana Sharma1. 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 diseasesMarco Vinicius Chaud and Thais Francine Ribeiro Alves1. Introduction 2. Nanomedicines for the management of ocular disease 2.1 Nanoemulsion 2.2 Nanosuspension 3. Conclusion References7. Nanotechnology for surgical glaucoma treatmentCarolina P.B. Gracitelli, Marcelo Luı´s Occhiutto and Vital Paulino Costa1. 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 aspectsQi Xun Lim, Kelvin Cheng Kah Wai and Pankaj Kumar Agarwal1. 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 glaucomaManisha S. Lalan, Pranav Shah, Kalyani Barve, Rahul Jha and Jyoti Jha1. 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 perspectivesJasjeet Kaur Narang, Kiranjeet Kaur, Gurpreet Kaur, Anmol Dogra and Deepti Pandita1. 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 deliveryHimanshu Shekhar, Priyanka Panigrahi and Harekrushna Sahoo1. 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 keratitisNagendra Bhuwane, Ishwari Choudhary, Ravi Parashar, Narayan Hemnani and Preeti K. Suresh1. 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 keratitisMrunali R. Patel, Mayank N. Jain and Rashmin B. Patel1. 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 syndromeSurbhi Sharma, Konika Tyagi and Shweta Dang1. 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 angiogenesisHamoudi Ghassan Awde Alfonso, Marı´a Constanza Paz, Santiago Daniel Palma and Marı´a Lina Formica1. 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 diseasesNabamita Haldar and Monalisa Mishra1. 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 degenerationJulio Zaki Abucham Neto, Cristina Nery Carbajo and Leonardo Amarante Pereira1. 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 limitationsMarı´a Constanza Paz, Cristian Alan Rossetti, Marı´a Lina Formica and Santiago Daniel PalmaAbbreviations 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 deliverySopan N. Nangare, Jidnyasa R. Pantwalawalkar, Namdeo R. Jadhav, Petra O. Nnamani, Zamir G. Khan, Pravin O. Patil and Sanjaykumar B. Bari1. 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 References20. Nanotoxicity in ocular drug deliveryTriveni Shelke and Monalisa Mishra1. 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