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      Fibrosis quística: tratamiento actual y avances con la nanotecnología Translated title: Cystic fibrosis: actual treatment and future perspectives with nanotechnology

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          Abstract

          Resumen Introducción: Actualmente, los tratamientos existentes para tratar la fibrosis quística (FQ) están diseñados para controlar sus síntomas, consistentes principalmente en retención de moco e infección crónica. Se propone la vía pulmonar como alternativa para la administración de los fármacos, principalmente antimicrobianos. Sin embargo, su rápido aclaramiento, que conduce a niveles bajos de fármaco e incremento de los regímenes posológicos, así como la aparición de efectos adversos, hacen de la nanotecnología una estrategia interesante para esta enfermedad. Objetivo: estudiar y analizar los diferentes sistemas nanoparticulares existentes para su uso por vía pulmonar, concretando en el uso de sistemas lipídicos para el tratamiento de la FQ. Método: se realizó una búsqueda no sistemática de artículos en diferentes bases de datos, en los últimos 10 años principalmente, siguiendo pautas establecidas de palabras clave. Resultados: Los progresos que se han conseguido en los últimos años hacen que la FQ pase a ser una enfermedad de adultos. Los tratamientos que se están usando en la actualidad están siendo cada vez más desplazados por otras alternativas, como los sistemas nanoparticulares, siendo idóneos para la administración pulmonar debido a su pequeño tamaño, su liberación sostenida y su elevada biocompatibilidad. Entre éstos, destacan los liposomas por su similitud estructural con el surfactante pulmonar, así como por su capacidad de destruir las biopelículas bacterianas. La mayoría de las formulaciones encontradas contenían un solo fármaco. Conclusión: Existen evidencias científicas que indican que la investigación debe dirigirse hacia el desarrollo de formulaciones que sean capaces de destruir la biopelícula.

          Translated abstract

          Abstract Introduction: Currently, the management of treatments in cystic fibrosis (CF) is mainly focused to control symptoms, which consist of mucus retention and chronic infection. The pulmonary route is proposed as an interesting alternative for administering drugs, especially antimicrobials. However, the rapid clearance of these, which leads to low drug levels and increased dosage regimens, as well as the appearance of adverse effects, make nanotechnology an interesting strategy for this disease. Objective: to study and analyze the different nanoparticulate systems available for use via the lung, specifying the use of lipid systems for the treatment of CF. Method: a non-systematic search of articles in different databases was carried out, mainly in the last 10 years, following established guidelines for selecting keywords. Results: The progress in recent years makes CF become an adult disease. Current treatments are increasingly being displaced by other alternatives, such as nanoparticular systems, being suitable for pulmonary administration due to their small size, sustained release and high biocompatibility. Among these, liposomes stand out for their structural similarity to lung surfactant, as well as for their ability to destroy bacterial biofilms. Most of the formulations contained a single drug. Conclusion: Scientific literature evidenced that research studies should be directed towards the development of formulations that are intended to destroy the biofilm.

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          Most cited references61

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          Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for pulmonary application: a review of the state of the art.

          Drug delivery by inhalation is a noninvasive means of administration that has following advantages for local treatment for airway diseases: reaching the epithelium directly, circumventing first pass metabolism and avoiding systemic toxicity. Moreover, from the physiological point of view, the lung provides advantages for systemic delivery of drugs including its large surface area, a thin alveolar epithelium and extensive vasculature which allow rapid and effective drug absorption. Therefore, pulmonary application is considered frequently for both, the local and the systemic delivery of drugs. Lipid nanoparticles - Solid Lipid Nanoparticles and Nanostructured Lipid Carriers - are nanosized carrier systems in which solid particles consisting of a lipid matrix are stabilized by surfactants in an aqueous phase. Advantages of lipid nanoparticles for the pulmonary application are the possibility of a deep lung deposition as they can be incorporated into respirables carriers due to their small size, prolonged release and low toxicity. This paper will give an overview of the existing literature about lipid nanoparticles for pulmonary application. Moreover, it will provide the reader with some background information for pulmonary drug delivery, i.e., anatomy and physiology of the respiratory system, formulation requirements, application forms, clearance from the lung, pharmacological benefits and nanotoxicity.
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            Current perspectives in pulmonary surfactant--inhibition, enhancement and evaluation.

            Pulmonary surfactant (PS) is a complicated mixture of approximately 90% lipids and 10% proteins. It plays an important role in maintaining normal respiratory mechanics by reducing alveolar surface tension to near-zero values. Supplementing exogenous surfactant to newborns suffering from respiratory distress syndrome (RDS), a leading cause of perinatal mortality, has completely altered neonatal care in industrialized countries. Surfactant therapy has also been applied to the acute respiratory distress syndrome (ARDS) but with only limited success. Biophysical studies suggest that surfactant inhibition is partially responsible for this unsatisfactory performance. This paper reviews the biophysical properties of functional and dysfunctional PS. The biophysical properties of PS are further limited to surface activity, i.e., properties related to highly dynamic and very low surface tensions. Three main perspectives are reviewed. (1) How does PS permit both rapid adsorption and the ability to reach very low surface tensions? (2) How is PS inactivated by different inhibitory substances and how can this inhibition be counteracted? A recent research focus of using water-soluble polymers as additives to enhance the surface activity of clinical PS and to overcome inhibition is extensively discussed. (3) Which in vivo, in situ, and in vitro methods are available for evaluating the surface activity of PS and what are their relative merits? A better understanding of the biophysical properties of functional and dysfunctional PS is important for the further development of surfactant therapy, especially for its potential application in ARDS.
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              Inhalation drug delivery devices: technology update

              The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided.
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                Author and article information

                Journal
                ars
                Ars Pharmaceutica (Internet)
                Ars Pharm
                Universidad de Granada (Granada, Granada, Spain )
                2340-9894
                June 2020
                : 61
                : 2
                : 81-96
                Affiliations
                [1] Andalucía orgnameUniversidad de Sevilla orgdiv1Facultad de Farmacia orgdiv2Departamento de Farmacia y Tecnología Farmacéutica Spain
                Article
                S2340-98942020000200081 S2340-9894(20)06100200081
                10.30827/ars.v61i2.11358
                ed8ac551-6587-4705-85a2-2c684ce4fd89

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

                History
                : 06 April 2020
                : 19 October 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 65, Pages: 16
                Product

                SciELO Spain

                Categories
                Artículos de Revisión

                liposomas,Cystic fibrosis,liposomes,biopelícula,CFTR,biofilm,CTFR,fibrosis quística

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