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      New ophthalmic drug delivery systems Translated title: Nuevos sistemas de liberación de fármacos a nivel ocular

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          Abstract

          Abstract For decades, topical ophthalmic drug administration through the use of eye drops has been the most widely used technique for the treatment of eye diseases. The development of galenic formulation has led to the use and commercialization of new formulations, such as suspensions, emulsions, and ophthalmic ointments that increase residence time in the site of action. Recently, new administration systems have been developed, such as devices and inserts that provide the sustained release of active substance. Some of these systems are already available on the market, whereas others are still undergoing clinical trials, such as promising systems based on nanostructures (nanocapsules, cyclodextrins, nanoemulsions, etc.). Similarly, various formulations and devices have been developed in the field of intravitreal administration, with different implants available on the European market for the treatment of age-related macular degeneration (AMD), diabetic macular edema, or infections that affect the posterior segment. This review includes current developments in ophthalmic topical and intravitreal drug administration routes as well as those under investigation.

          Translated abstract

          Resumen Desde hace décadas, la administración tópica oftálmica de fármacos mediante el empleo de colirios ha sido la técnica más empleada para el tratamiento de patologías oculares. El desarrollo de la galénica ha permitido el uso y comercialización de nuevas formulaciones que incrementan el tiempo de residencia en el lugar de acción, como es el caso de las suspensiones, emulsiones y pomadas oftálmicas. Recientemente se han desarrollado nuevos sistemas de administración, como es el caso de dispositivos e insertos que proporcionan una cesión sostenida de principio activo. Algunos de estos sistemas ya se encuentran disponibles en el mercado, mientras que otros todavía están en fase de ensayo clínico, como es el caso también de los prometedores sistemas basados en nanoestructuras (nanocápsulas, ciclodextrinas, nanoemulsiones, etc.). De la misma forma, diversas formulaciones y dispositivos han sido desarrollados en el campo de la administración intravítrea, estando disponibles en el mercado europeo diversos implantes para el tratamiento de la degeneración macular asociada a la edad (DMAE), el edema macular diabético o infecciones que afectan al segmento posterior. En esta revisión se recogen los desarrollos actualmente implementados y en fase de investigación asociados a las vías de administración oftálmica de fármacos tópicos e intravítreos.

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          Most cited references83

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          From bacterial killing to immune modulation: Recent insights into the functions of lysozyme

          Lysozyme is a cornerstone of innate immunity. The canonical mechanism for bacterial killing by lysozyme occurs through the hydrolysis of cell wall peptidoglycan (PG). Conventional type (c-type) lysozymes are also highly cationic and can kill certain bacteria independently of PG hydrolytic activity. Reflecting the ongoing arms race between host and invading microorganisms, both gram-positive and gram-negative bacteria have evolved mechanisms to thwart killing by lysozyme. In addition to its direct antimicrobial role, more recent evidence has shown that lysozyme modulates the host immune response to infection. The degradation and lysis of bacteria by lysozyme enhance the release of bacterial products, including PG, that activate pattern recognition receptors in host cells. Yet paradoxically, lysozyme is important for the resolution of inflammation at mucosal sites. This review will highlight recent advances in our understanding of the diverse mechanisms that bacteria use to protect themselves against lysozyme, the intriguing immunomodulatory function of lysozyme, and the relationship between these features in the context of infection.
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            Pharmacokinetic aspects of retinal drug delivery

            Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.
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              Aqueous Humor Dynamics: A Review

              Glaucoma is a family of optic neuropathies which cause irreversible but potentially preventable vision loss. Vision loss in most forms of glaucoma is related to elevated IOP with subsequent injury to the optic nerve. Secretion of aqueous humor and regulation of its outflow are physiologically important processes for maintaining IOP in the normal range. Thus, understanding the complex mechanisms that regulate aqueous humor circulation is essential for management of glaucoma. The two main structures related to aqueous humor dynamics are the ciliary body and the trabecular meshwork (TM). Three mechanisms are involved in aqueous humor formation: diffusion, ultrafiltration and active secretion. Active secretion is the major contributor to aqueous humor formation. The aqueous humor flow in humans follows a circadian rhythm, being higher in the morning than at night. The aqueous humor leaves the eye by passive flow via two pathways - the trabecular meshwork and the uveoscleral pathway. In humans, 75% of the resistance to aqueous humor outflow is localized within the TM with the juxtacanalicular portion of the TM being the main site of outflow resistance. Glycosaminoglycan deposition in the TM extracellular matrix (ECM) has been suggested to be responsible for increased outflow resistance at this specific site whereas others have suggested deposition of proteins, such as cochlin, obstruct the aqueous humor outflow through the TM. The uveoscleral outflow pathway is relatively independent of the intraocular pressure and the proportion of aqueous humor exiting the eye via the uveoscleral pathway decreases with age.
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                Author and article information

                Journal
                fh
                Farmacia Hospitalaria
                Farm Hosp.
                Grupo Aula Médica (Toledo, Toledo, Spain )
                1130-6343
                2171-8695
                August 2020
                : 44
                : 4
                : 149-157
                Affiliations
                [2] Santiago de Compostela orgnameInstituto de Investigación Sanitaria Santiago de Compostela (IDIS) orgdiv1Grupo de Farmacología Clínica Spain
                [3] Santiago de Compostela Galicia orgnameUniversidad de Santiago de Compostela orgdiv1Departamento de Farmacología, Farmacia y Tecnología Farmacéutica orgdiv2Facultad de Farmacia Spain
                [1] Santiago de Compostela orgnameServicio Galego de Saúde (SERGAS) orgdiv1Área Sanitaria de Santiago de Compostela e Barbanza orgdiv2Servicio de Farmacia Spain
                Article
                S1130-63432020000400006 S1130-6343(20)04400400006
                10.7399/fh.11388
                03c289ea-a280-480c-9038-3f67a1e7647b

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 13 December 2019
                : 12 March 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 84, Pages: 9
                Product

                SciELO Spain

                Categories
                Reviews

                Inyecciones intravítreas,Intravitreal injections,Ophthalmic solutions,Sistemas de liberación oftálmica,Drug delivery systems,Soluciones oftálmicas,Insertos oculares,Ocular inserts

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