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Dry eye syndrome is a common disease of tear film and ocular surface developed in numerous aetiologies. Tear film instability and ocular surface disturbances that subsequently influence the tear film are among the primarily causes of this disease, but many other factors are involved in tear film disorders. Although eye surface is easily reached by classical ocular dosage forms, novel drug delivery systems for ocular administration offer advantages in terms of increased residence time on eye surface and/or controlled release of the drug, with enhanced therapeutic effectiveness. This new book provides an overview on the potential benefits and limitations in dry eye syndrome management and reported successful formulations.
Ocular Therapeutics: Eye on New Discovery focuses on emerging areas in ocular research, from new approaches to dry eye to gene therapy in the management of retinal diseases. This comprehensive book features more than 25 chapters of information that will be vital for ocular investigators and ophthalmologists bringing them new information on promising therapeutics. It is the intent of this book to provide not only information on current approaches to treatment, but also in giving the reader a greater understanding as to what may become available for treating a number of important eye diseases. Each chapter features some new aspect of treatment that holds great promise for the future. The approach has been to concentrate on those areas of ocular diseases that are more prevalent. It also features new insight for drug delivery and for managing devasting diseases, such as macula edema and glaucoma, two of the leading causes of blindness in the United States. This book will serve as an important resource as it contains a number of relevant references highlighted for their importance to the field. New investigators will be able to obtain an historical perspective for each of the topics and to develop an understanding of the new research directions that are underway. Ocular Therapeutics: Eye on New Discovery is more than a reference book, as it also provides an important glimpse into the near future. * Contains information that is vital for ocular investigators and ophthalmologists bringing them new information on promising therapeutics.* Provides not only information on current approaches to treatment, but also gives the reader a greater understanding as to what may become available for treating a number of important eye diseases.* Historical perspective for each of the topics as well as an important glimpse into the near future to develop an understanding of the new research directions underway.* New insight for drug delivery and for managing devastating diseases, such as macula edema and glaucoma, two of the leading causes of blindness in the United States
The eye is a computerized system that has been designed for self-defense, and these defense mechanisms create challenges in administration of medications to the eye. Therefore, ocular drug delivery has been a major challenge to drug delivery researchers. There are on-going studies, in search of treatment especially for the diseases affecting the posterior segment of the eye. This book gives and overview of the background of ocular drug delivery and is unique for pharmacists, medical practitioners, students and drug delivery researchers.
Drug discovery for ocular diseases has taken great strides in the last two decades. From cornea to choroid, new drugs have been formulated to address a great variety of ocular diseases. Yet without good drug delivery systems, these drugs are less effective than they might be or could even cause serious side effects. Ocular Drug Delivery Systems: Barriers and Application of Nanoparticulate Systems presents research on the development of currently marketed devices and recent trends in the topical delivery of drugs to the posterior of the eye. With contributions from leading pharmaceutical researchers and industry experts, eye researchers, surgeons, pharmacologists from academia, the National Eye Institute, and leading ophthalmic companies such as Pfizer, Allergan, and Novartis, the book presents the state of the art in the use of nanoparticles in ocular drug delivery systems and also sets the stage for future developments. This volume provides both a current evaluation and a future roadmap for developments in ocular drug delivery. The subjects range from biological needs to material challenges and finally to clinical applications for improving drug delivery for conditions where treatments already exist. It also explores areas where effective drugs may be currently available but yet need a safe, efficient, and efficacious delivery vehicle.
This invaluable book presents a concise discussion on the most important topics of ophthalmology — mechanism of ophthalmic diseases, imaging techniques used for diagnosis, novel therapies and drug delivery systems. It also covers current knowledge about anti-VEGF therapies that revolutionized neovascular AMD treatment, anti-inflammatory and dry eye treatment, as well as nanoparticles use of drug delivery.Written by experts in ophthalmology, this unique volume provides a comprehensive overview of the latest research in the field. This is an essential reading that will provide up-to-date reference to practicing physicians and current knowledge to residents and students.
Academic Paper from the year 2023 in the subject Medicine - Pharmacology, Pharmacy, course: M.Pharmacy, language: English, abstract: Ocular drug delivery plays a vital role in the treatment of various eye diseases and conditions. The unique anatomical and physiological characteristics of the eye pose significant challenges for effective drug delivery. Over the years, extensive research efforts have been dedicated to developing innovative strategies and formulations to overcome these challenges and improve therapeutic outcomes. This review provides an overview of recent advances in ocular drug delivery, highlighting the key challenges faced and discussing the potential future directions in this field. The first section of the review focuses on the barriers to ocular drug delivery, including the tear film, cornea, conjunctiva, and blood-ocular barriers. These barriers limit the bioavailability and efficacy of drugs administered to the eye. Strategies to bypass or overcome these barriers, such as the use of penetration enhancers, nanoparticles, and prodrug approaches, are discussed. The second section explores various ocular drug delivery systems, including eye drops, ophthalmic gels, ocular inserts, and contact lens-based delivery systems. Each system is examined in terms of its advantages, limitations, and recent advancements. Special attention is given to sustained drug release systems that aim to prolong drug residence time on the ocular surface and improve patient compliance. Next, the review delves into the role of nanotechnology in ocular drug delivery. Nanoparticles, liposomes, and nanomicelles have shown promise in improving drug solubility, stability, and ocular bioavailability. The use of novel nanomaterials and their surface modifications for targeted drug delivery to specific ocular tissues is also discussed. Furthermore, the review highlights emerging techniques in ocular drug delivery, such as microneedles, hydrogels, and gene therapy-based approach
Common eye diseases such as dry eye syndrome affect 15% of the population. Although eye drops are the most common treatment for these diseases, over 95% of the drugs applied through eye drops are quickly cleared away due to blinking and tear turnover. Consequently, patients struggle with the multiple daily applications required and the resulting side effects. Nanoparticle (NP) drug carriers have gained significant traction recently because of several advantages they provide over conventional eye drop delivery methods. NP surfaces can be tuned to achieve specific properties such as binding affinity towards the ocular surface. NPs can also carry a large amount of drugs and release them in a sustained manner over a long period. Due to their small size, NPs do not cause abrasive sensations on the eye upon patient application. With these unique advantages, NP drug carriers may drastically improve patient compliance while reducing side effects. The thesis focuses on developing an ocular drug delivery platform using NPs to improve retention of ocular therapeutics on the precorneal surface. We developed a method to synthesize an amphiphilic block copolymer composed of poly(D,L-lactide) (PLA) and dextran (Dex) that can self-assemble into NP drug carriers. The size of the NPs can be tuned between 15 and 70 nm by adjusting the molecular weights of PLA and/or Dex. The PLA-b-Dex NPs form the foundation of the ocular drug delivery platform developed in this thesis. A targeted delivery system is crucial for ocular drug delivery due to the rapid clearance by tear drainage on the corneal surface. The PLA-b-Dex NPs were surface modified with phenylboronic acid (PBA) molecules, which can undergo covalent binding with the mucous membrane to circumvent the rapid clearance. Due to the abundance of functional groups on the dextran, we were able to tune the density of PBA on the NP surface to optimize the binding affinity between the NPs and the mucin. While maximizing the PBA density on the NP surface improved the covalent interaction between the NPs and the mucin, it also compromised the NP colloidal stability. The PBA modified NPs demonstrated encapsulation of Cyclosporine A (CsA), a dry eye treatment drug, and sustained release for up to 5 days in vitro, showing their potential as a long-term eye drop delivery platform. We then performed biocompatibility and efficacy studies on these NPs using animal models. Biocompatibility is of the utmost importance in developing new drug delivery formulations. During the 12 weeks of study, no physical signs of irritation or discomfort were detected nor was any inflammatory response or ocular tissue damage observed in the eyes administered with NPs. Topical administration of CsA-loaded NPs on dry eye induced mice using once a week dosing demonstrated complete elimination of the inflammatory response as well as full recovery of the integrity of the ocular tissues. In the same study, the commercial eye drop form of CsA, Restasis®, administered thrice daily only eliminated the inflammatory infiltrates without recovering ocular goblet cells. By delivering CsA through PLA-b-Dex-g-PBA NPs, we can significantly reduce the dose and the frequency of eye drop administration without compromising the treatment efficacy. In vitro mucoadhesion as a result of PBA's on NP surfaces was demonstrated. We proceeded to further demonstrate this mucoadhesion using in vivo models. Indocyanine green (ICG), a near-infrared fluorescent dye, was encapsulated in the NPs and administered to rabbit eyes to track its ocular retention. ICG delivered via PBA modified NPs showed ocular retention beyond 24 hours on rabbit eyes, whereas free ICG or ICG delivered via unmodified NPs were mostly cleared within the first 3 hours. When the weekly dosing of CsA loaded PLA-b-Dex-g-PBA NPs was repeated for 4 weeks on dry eye induced mice, we observed the same elimination of inflammatory infiltrates but also the damaged ocular tissue structures. When the concentration of the CsA in the weekly dosing of NPs was further reduced 5 times, the treatment effect was much more pronounced, showing both the elimination of the inflammation and the full recovery of the ocular surface tissues. Overall, by using mucoadhesive nanoparticle drug carriers, we reduced the dosage of CsA at least 50-fold compared with the commercial product, Restasis®, without compromising the dry eye treatment efficacy. Finally, we developed a scalable method to synthesize PLA-b-Dex-g-PBA block copolymers using a semi-solid state reaction chemistry. The previous method of conjugating PBA to the Dex required long reaction hours with multiple reaction and purification steps. In contrast, the new method combines the quickness of a semi-solid state reaction with the simplicity of a Williamson ether chemistry to graft PBA to Dex. The results showed that the new method achieved a similar range of tunability of PBA density onto Dex using reaction times as short as 10 minutes. This thesis demonstrates the development process of a polymeric NP as a topical ocular drug delivery system. The PLA-b-Dex-g-PBA NPs demonstrated delivery of a clinically relevant dosage of dry eye therapeutics, controlled release of therapeutics over prolonged period of time, and mucoadhesive properties resulting in prolonged ocular surface retention of drugs. These mucoadhesive NPs show remarkable promise as a long-term topical ocular drug delivery system that significantly reduces the dose and the administration frequency of the eye drops while minimizing side effects.
The research on ocular pharmacology has increased significantly, over the past decade. More recently, the discovery and approval of eye disease modifying treatments is considered an unbelievable scientific breakthrough. Anti-VEGF molecules, cell therapy and gene therapy for age-related retinal degeneration, autologous corneal cells replacement, and Leber’s congenital amaurosis to name a few as some impressive examples. New drugs have been recently introduced for the treatment of glaucoma focusing on new pharmacological targets, such as Rho kinase inhibitors. For example, such novel treatments have been approved for optic neuromyelitis spectrum disorders. Regarding diseases of the front of the eye, advances have been reached with approval of recombinant Nerve Growth Factor (cenegermin) for treatment of neurotrophic keratitis. New discoveries and treatments recently introduced in ophthalmology should promote new efforts and encourage research in ocular pharmacology. It is noteworthy that several medical unmet needs remain in the field of ocular diseases, particularly for glaucoma, diabetic retinopathy (DR) and age-related macular degeneration (AMD). Early stages of DR or dry AMD need a cure and glaucoma deserves a new therapeutic approach in terms of retinal ganglion cells protection. Furthermore, current pharmacological treatments of glaucoma do not address one major issue underlying the pathology: neuroinflammation. When it comes to dry eye disorders, novel ophthalmic formulations and research findings focusing on immunomodulatory responses are welcomed to provide new insights on these conditions. Finally, one of the most challenging aspects in ocular pharmacology is related to ocular drug delivery. This Research Topic would like to address and discuss important medical unmet needs, and include a tangible contribution to handle sight threatening diseases that have a devastating impact not only for the patients but also for the healthcare system. This Research Topic aims to translate new basic science into clinically breakthrough therapies to help patients faced with debilitating ocular diseases. The Topic welcomes submissions of Original Research, Reviews, Clinical trials, and Case Reports articles that cover the following topics, but not limited to: • Diagnostic and prognostic biomarkers as potential pharmacological target of eye diseases (glaucoma, retinal diseases, ocular surface diseases). • Investigation on novel pharmacological targets for treatment of diabetic retinopathy, age related macular degeneration, glaucoma and dry eye. • New ocular drug delivery systems.