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Common eye diseases such as conjunctivitis affect around 6 million people annually. Although eye drops are the most common treatment for these diseases, topical administration is limited by low ocular bioavailability due to lachrymal drainage, low drug permeability across the corneal epithelium, and low drug stability as a result of tear dilution and turnover. This results in over 95% of the drugs applied through eye drops to be quickly cleared away. Consequently, patients struggle with the multiple daily applications required and the resulting side effects. In order to overcome these barriers and to increase contact time of drugs on the surface of the eye, several nanoparticle (NP) technologies have been developed for the delivery of drugs to our systems like liposomes, hydrogels, microparticles, micelles, implants...etc. 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. There is no one technology that is suitable for any drug to any site, however biodegradable colloidal systems appear to be the most advantageous. Their popularity stems from their biocompatibility with ocular tissues, high encapsulation efficiency, sustained release, and ability to degrade into non-toxic by-products that are safely cleared from ocular tissues. With these unique advantages, NP drug carriers may drastically improve patient compliance while reducing side effects. Research conducted in the Frank Gu Research Group suggests that NP drug carriers are capable of circumventing corneal clearance mechanisms by manipulating the surface functionalization of polymeric nanoparticles (NPs) such that they can interact with the ocular mucosa. In view of this background, this thesis was aimed at exploring the potential of mucoadhesive NPs (MNPs) to encapsulate hydrophilic drugs in the core of the NP, while maintaining mucoadhesive functionality in the shell of the NP. We developed a novel approach to formulate a double emulsion mucoadhesive nanoparticle (DE MNP) system to deliver hydrophilic molecules. Double emulsions allow us to generate a vesicle-like structure of hydrophilic interior and hydrophilic exterior and have been successful as nanoparticle drug carriers in the past. Most double emulsions utilize PLGA to make up the primary emulsion because it is a biodegradable and biocompatible polymer that has the ability to degrade into non-toxic by-products (lactic acid and glycolic acid) that are metabolized by the human body. The novelty in the DE MNP method involves using PLA-Dex-PBA in the outer emulsion, rather than common stabilizers such as PVA and Tween. The amphiphilic characteristics of PLA-Dex-PBA will arrange on the surface of PLGA emulsions with PLA facing the oil phase and Dex-PBA facing the exterior of the particle, making up the surface of DE MNPs. The PBA moieties on the surface of DE MNPs can covalently target the sialic acid moieties that are abundant on the ocular mucous membrane and avoid rapid clearance. DE MNPs form the foundation of the ocular drug delivery platform developed in this thesis, using fluorescein isothiocyanate dextran (FITC-Dex), a commercially used fluorescent dye, as the model drug to determine the capability of DE MNPs to encapsulate and release hydrophilic molecules. DE MNPs were first evaluated for size and morphology. They demonstrated sizes in the sub-200 nm range, nearly double the size of PLA-Dex-PBA MNP micelles. Their spherical shell/vesicle conformation was confirmed by static light scattering and TEM, and remained stable and unchanged with the addition of model FITC-Dex. DE MNPs demonstrated encapsulation of FITC-Dex up to 87 wt%, and sustained release for up to 7 days in vitro, showing their potential as a long-term eye drop delivery platform. In vitro mucoadhesion study as a proof of concept demonstration of PBA on DE MNPs' surfaces was demonstrated by studying the binding kinetics of PBA to sialic acid through the Stern-Volmer equation. The KA value for DE MNPs with sialic acid was determined to be 107.83 M-1, which is far higher than the literature values for PBA-SA. This gave confidence to the presence of PBA on the surface of DE MNPs. Next, we proceeded to attempt to demonstrate this mucoadhesion using in vivo models. FITC-Dex was encapsulated in the NPs and administered to rabbit eyes to track its ocular retention. FITC-Dex delivered DE MNPs showed ocular retention for no longer than 3 hours on rabbit eyes; this trend was also seen for free FITC-Dex. Povidone-Iodine (PVP-I), an inexpensive and commercially available drug commonly used to treat ocular bacterial infections, was encapsulated and evaluated for bactericidal activity upon release from DE MNPs. DE MNPs revealed that that encapsulation of the drug did not change the properties of the drug, and also confirmed that the amount of drug being encapsulated (1% w/v) in DE MNPs, is a sufficient concentration to elicit antimicrobial activity, and better than current formulations such as Betadine® which uses 5%w/v PVP-I for treatment of ocular infection. This thesis demonstrates the development process of DE MNPs as topical ocular drug delivery systems for hydrophilic drugs. DE MNPs demonstrated delivery of a clinically relevant dosage of PVP-I, controlled release of therapeutics over prolonged period of time, and mucoadhesive properties in vitro. These DE mucoadhesive NPs show significant promise as a long-term topical ocular hydrophilic drug delivery system that significantly reduces the dose and the administration frequency of the eye drops while minimizing side effects.
The second edition of this text assembles significant ophthalmic advances and encompasses breakthroughs in gene therapy, ocular microdialysis, vitreous drug disposition modelling, and receptor/transporter targeted drug delivery.
Nanoemulsions: Formulation, Applications, and Characterization provides detailed information on the production, application and characterization of food nanoemulsion as presented by experts who share a wealth of experience. Those involved in the nutraceutical, pharmaceutical and cosmetic industries will find this a useful reference as it addresses findings related to different preparation and formulation methods of nanoemulsions and their application in different fields and products. As the last decade has seen a major shift from conventional emulsification processes towards nanoemulsions that both increase the efficiency and stability of emulsions and improve targeted drug and nutraceutical delivery, this book is a timely resource. Summarizes general aspects of food nanoemulsions and their formulation Provides detailed information on the production, application, and characterization of food nanoemulsion Reveals the potential of nanoemulsions, as well as their novel applications in functional foods, nutraceutical products, delivery systems, and cosmetic formulations Explains preparation of nanoemulsions by both low- and high-energy methods
Diabetes Mellitus, a syndrome of disordered metabolism, characterised by abnormal elevation in blood glucose level, has become a life-threatening condition for many people. Current means of therapy for Diabetes Mellitus do not mimic the normal physiological pattern of insulin release. Oral delivery is the preferred route of administration due to its non-invasive nature. Oral delivery of insulin presents an overview of Diabetes Mellitus, and discusses the strategies and techniques adopted for oral delivery of insulin. This title begins with an introductory chapter on symptoms, complications and therapy for Diabetes Mellitus. Subsequent chapters cover the various routes for administering insulin; the challenges and strategies of oral delivery; experimental techniques in the development of an oral insulin carrier; lipids; inorganic nanoparticles and polymers in oral insulin delivery; and a summary and presentation of future perspectives on oral delivery of insulin. Presents an overview of Diabetes Mellitus Includes a discussion of various strategies and techniques adopted for oral delivery of insulin Presents an update of research in the field
The thoroughly revised Sixth Edition of this classic reference on ocular disease is the perfect guide for all clinicians who treat eye disorders. Written in a concise outline format, this quick reference is perfect for diagnosis and management of hundreds of ocular conditions. This pocket-size manual covers - from symptoms to treatment - all ocular disorders likely to be encountered in the office, emergency room, or hospital setting.
Offers a comprehensive guide to the isolation, properties and applications of chitin and chitosan Chitin and Chitosan: Properties and Applications presents a comprehensive review of the isolation, properties and applications of chitin and chitosan. These promising biomaterials have the potential to be broadly applied and there is a growing market for these biopolymers in areas such as medical and pharmaceutical, packaging, agricultural, textile, cosmetics, nanoparticles and more. The authors – noted experts in the field – explore the isolation, characterization and the physical and chemical properties of chitin and chitosan. They also examine their properties such as hydrogels, immunomodulation and biotechnology, antimicrobial activity and chemical enzymatic modifications. The book offers an analysis of the myriad medical and pharmaceutical applications as well as a review of applications in other areas. In addition, the authors discuss regulations, markets and perspectives for the use of chitin and chitosan. This important book: Offers a thorough review of the isolation, properties and applications of chitin and chitosan. Contains information on the wide-ranging applications and growing market demand for chitin and chitosan Includes a discussion of current regulations and the outlook for the future Written for Researchers in academia and industry who are working in the fields of chitin and chitosan, Chitin and Chitosan: Properties and Applications offers a review of these promising biomaterials that have great potential due to their material properties and biological functionalities.
Colloid and Interface Science in Pharmaceutical Research and Development describes the role of colloid and surface chemistry in the pharmaceutical sciences. It gives a detailed account of colloid theory, and explains physicochemical properties of the colloidal-pharmaceutical systems, and the methods for their measurement. The book starts with fundamentals in Part I, covering fundamental aspects of colloid and interface sciences as applied to pharmaceutical sciences and thus should be suitable for teaching. Parts II and III treat applications and measurements, and they explains the application of these properties and their influence and use for the development of new drugs. Provides a clear description of the fundamentals of colloid and interface science relevant to drug research and development Explains the physicochemical/colloidal basis of pharmaceutical science Lists modern experimental characterization techniques, provides analytical equations and explanations on analyzing the experimental data Describes the most advanced techniques, AFM (Atomic Force Microscopy), SFA (Surface Force Apparatus) in detail
This contribution book collects reviews and original articles from eminent experts working in the interdisciplinary arena of novel drug delivery systems and their uses. From their direct and recent experience, the readers can achieve a wide vision on the new and ongoing potentialities of different drug delivery systems. Since the advent of analytical techniques and capabilities to measure particle sizes in nanometer ranges, there has been tremendous interest in the use of nanoparticles for more efficient methods of drug delivery. On the other hand, this reference discusses advances in the design, optimization, and adaptation of gene delivery systems for the treatment of cancer, cardiovascular, pulmonary, genetic, and infectious diseases, and considers assessment and review procedures involved in the development of gene-based pharmaceuticals.
Emerging Nanotechnologies for Diagnostics, Drug Delivery and Medical Devices covers the modern micro and nanotechnologies used for diagnosis, drug delivery, and theranostics using micro, nano, and implantable systems. In-depth coverage of all aspects of disease treatment is included. In addition, the book covers cutting-edge research and technology that will help readers gain knowledge of novel approaches and their applications to improve drug/agent specificity for diagnosis and efficient disease treatment. It is a comprehensive guide for medical specialists, the pharmaceutical-industry, and academic researchers discussing the impact of nanotechnology on diagnosis, drug delivery, and theranostics. Gives readers working in immunology, drug delivery, and medicine a greater awareness on how novel nanotechnology orientated methods can help improve treatment Provides readers with backgrounds in nanotechnology, chemistry, and materials science an understanding on how nanotechnology is used in immunology and drug delivery Includes focused coverage of the use of nanodevices in diagnostics, therapeutics, and theranostics not offered by other books
This book combines emulsion knowledge into a single, comprehensive volume, ideal for professionals and students involved in the areas of pharmaceutical science who are looking to learn about this emergent research concept. Compiles the step-by-step investigations made concerning the potential of nanosized emulsions on both drug delivery and drug targeting areas by different group of scientists in various laboratories across the world Inverts the common nano-emulsions coverage trend of focusing on focused on the particulate system itself, instead exploring the way to turn nanosized emulsions as biomedical tool, as well as, treating the in vitro and in vivo aspects after administration Provides an overview of the current state-of-the art regarding the development of tocol emulsions, emulsion adjuvants in immunization research, oxygen-carrying emulsions (called as fluorocarbon emulsion) and emulsions for delivering drugs to nasal and topical (ocular and transdermal) routes