Copper release by MOF-74(Cu): a novel pharmacological alternative to diseases with deficiency of a vital oligoelement.

Copper deficiency can trigger various diseases such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and even compromise the development of living beings, as manifested in Menkes disease (MS). Thus, the regulated administration (controlled release) of copper represents an alternative to reduce neuronal deterioration and prevent disease progression. Therefore, we present, to the best of our knowledge, the first experimental in vitro investigation for the kinetics of copper release from MOF-74(Cu) and its distribution in vivo after oral administration in male Wistar rats. Taking advantage of the abundance and high periodicity of copper within the crystalline-nanostructured metal-organic framework material (MOF-74(Cu)), it was possible to control the release of copper due to the partial degradation of the material. Thus, we simultaneously corroborated a low accumulation of copper in the liver (the main detoxification organ) and a slight increase of copper in the brain (striatum and midbrain), demonstrating that MOF-74(Cu) is a promising pharmacological alternative (controlled copper source) to these diseases.

Copper(II)-MOFs for bio-applications.

The recent development and implementation of copper-based metal-organic frameworks in biological applications are reviewed. The advantages of the presence of copper in MOFs for relevant applications such as drug delivery, cancer treatment, sensing, and antimicrobial are highlighted. Advanced composites such as MOF-polymers are playing critical roles in developing materials for specific applications.

Armonización Curricular Farmacéutica en Iberoamérica. Documento de trabajo de la Conferencia Iberoamericana de Facultades de Farmacia (COIFFA) / Pharmaceutical Curriculum Harmonization in Ibero-America. Working document of the Ibero-American Conference of Faculties of Pharmacy (COIFFA)

La Conferencia Iberoamericana de Facultades de Farmacia (COIFFA) viene desarrollando desde su fundación como Conferencia Hispanoamericana (COHIFFA) en 1992, en la Universidad de los Andes (Mérida, Venezuela) una amplia labor en el ámbito de la formación y educación farmacéutica. Esta labor se ha traducido en declaraciones sucesivas desde la efectuada en Santiago (Chile) hasta la más reciente de Xochimilco (México). El grado de avance que han experimentado las ciencias y la práctica farmacéutica en las últimas décadas ha sido espectacular. Así se refleja en documentos de organismos y foros nacionales e internacionales. A esto se une las facilidades que en el ámbito de la movilidad internacional procuran tanto las Universidades a través de sus convenios bilaterales, como los organismos nacionales e internacionales de América Latina y de la Unión Europea, a través de los proyectos y convocatorias pertinentes. Todo ello hace aconsejable la elaboración por parte de COIFFA de un documento marco de consenso, en donde se recoja la problemática que el trascendental tema de la armonización de los estudios de farmacia conlleva. Los esfuerzos que ha venido realizando COIFFA se han traducido en la elaboración durante el Simposio Biregional Unión Europea-América Latina celebrado en junio de 2018 Xochimilco (México), de un documento de trabajo. Tres mesas de discusión coordinadas han tenido por objeto: I) el análisis y definición de perfil de egreso y de los mínimos curriculares; II) el análisis de los términos utilizados en la denominación de programas académicos títulos universitarios y distintas actividades; y III) el análisis y propuestas de mecanismos de colaboración y cofinanciación interinstitucionales Universidad-Gobierno-Empresa. (AU)

The Ibero-American Conference of Faculties of Pharmacy (COIFFA) has been developing a wide-ranging task in the field of pharmaceutical training and education since its foundation as Hispanic-American Conference (COHIFFA) in 1992, at the Universidad de los Andes (Mérida, Venezuela). This work has been materialized into successive statements from the one made in Santiago (Chile) to the most recent one in Xochimilco (Mexico). The degree of progress that the sciences and pharmaceutical practice have experienced in recent decades has been spectacular. This is reflected in documents from national and international organizations and forums. To this is added the facilities that, in the field of international mobility, universities get through their bilateral agreements, as well as with national and international organizations in Latin America and the European Union, through the relevant projects and calls. All this makes advisable the elaboration on the part of COIFFA of a framework document of consensus, where the problematic that the transcendental subject of the harmonization of the pharmacy studies entails be covered. The efforts that COIFFA has been carrying out have resulted in the elaboration of a working document at the Biregional European Union-Latin America Symposium held in June 2018 in Xochimilco (Mexico). Three coordinated working groups were there devoted to: I) the analysis and definition of the graduate profile, as well as the common minimum topics to be included in the “pensum”; II) the analysis of the terms to be used in the denomination of academic programs, university degrees and various related activities; III) the analysis and proposals for cooperation mechanisms and properly ways of University-Government-Company co-financing. (AU)

Linezolid@MOF-74 as a host-guest system with antimicrobial activity.

Linezolid (LNZ) is a new-generation synthetic molecule for the antibacterial treatment of severe infections, particularly in infective cases where the bacterial resistance to first-choice drugs is caused by Gram-positive pathogens. In this context, since 2009, some strains resistant to LNZ in patients with long-term treatments have been reported. Therefore, there is a need to use not only new drug molecules with antibacterial activities in the dosage form but also a different approach to pharmacotherapeutic strategies for skin infections, which lead to a reduction in the concentration of biocides. This work explores LNZ hosted at two isostructural MOFs, MOF-74(Zn) and MOF-74(Cu), as promising antimicrobial systems for gradual biocide release within 6 h. These systems reach a lower minimum inhibitory concentration (MIC) in comparison to free LNZ. Even a decreased MIC value is also observed, which is an encouraging result regarding the efficiency of the systems to control concentration-dependent antimicrobial resistance.

Caracterización fisicoquímica y evaluación in vitro de sistemas autoemulsionables de liberación de indometacina

Objetivo: incorporar la indometacina en sistemas autoemulsionables de liberación con la finalidad de aumentar su solubilidad en medio acuoso, la velocidad de disolución y permeación in vitro. Metodología: se llevaron a cabo ensayos de solubilidad al equilibrio para preparar formulaciones con los excipientes, en los cuales la indome-tacina presentó mayor incremento de solubilidad; los sistemas fueron caracterizados por medio del tiempo de autoemulsificación, estabilidad física, tamaño de partícula, potencial zeta, perfiles de disolución y permeación a través de membrana sintética. Resultados: el diseño experimental de los sistemas autoemulsionables de liberación permitió crear formulaciones que aumentaron la solubilidad de la indometacina en un orden de 105 veces con respecto a la solubilidad acuosa. Las formulaciones que resultaron viables presentaron tiempos de autoemulsificación menores que 60 segundos, además, las distribuciones de tamaño de partícula de las dispersiones fueron inferiores a los 300 nm, presentó índices de polidispersión inferiores a 0,3 y valores de potencial zeta menores de -25 mV. Los perfiles de disolución mostraron que las formulaciones cumplen con un valor de factor de similitud mayor que 50, además, la permeabilidad a través de membrana sintética es mayor para las formulaciones autoemulsionables que el producto de referencia. Conclusiones: la formulación de indometacina en sistemas autoemulsionables de liberación incrementa la solubilidad en medio acuoso, aumenta la disolución y liberación. Estos resultados sugieren que la administración oral de indometacina incorporada en sistemas autoe-mulsionables puede acelerar el inicio del efecto farmacológico.

SUMMARY Aim: To load indomethacin into self-emulsifying delivery systems in order to increase, water-solubility, rate dissolution and in vitro permeation. Methodology: Equilibrium solubility tests were carried out to prepare formulations with the excipients, in which indomethacin presented a greater increase in solubility; the systems were characterized by self-emulsification time, physical stability, particle size, zeta potential, dissolution profiles and permeation through synthetic membrane. Results: The experimental design of self-emulsifying delivery systems allowed to create formulations that increase the solubility of indomethacin in an order of 105 times with respect to the aqueous solubility. The feasible formulations presented autoemulsification times less than 60 seconds, in addition, the particle size distributions of the dispersions were less than 300 nm, with polydispersity index smaller than 0.3, and zeta potential values lower than -25 mV. The dissolution profiles showed that the formulations comply with a similarity factor value greater than 50, in addition, the permeability through a synthetic membrane is higher for the self-emulsifying formulations than the reference product. Conclusion: The formulation of indomethacin into self-emulsifying delivery systems enhances the solubility in aqueous medium, increases dissolution and accelerate release. These results suggest that the oral administration of indomethacin incorporated into self-emulsifying delivery systems can accelerate the onset of the pharmacological effect.

Objetivo: incorporar a indometacina em sistemas de liberação autoemulsificantes a fim de aumentar sua solubilidade em meio aquoso, a taxa de dissolução e permeação in vitro. Metodologia: foram realizados testes de solubilidade de equilíbrio para preparar formulações com os excipientes, nas quais a indometacina apresentou maior aumento na solubilidade; os sistemas foram caracterizados quanto ao tempo de autoemulsificação, estabilidade física, tamanho de partícula, potencial zeta, perfis de dissolução e permeação através de membrana sintética. Resultados: o desenho experimental dos sistemas de liberação autoemulsificantes permitiu a criação de formulações que aumentaram a solubilidade da indometacina na ordem de 105 vezes em relação à solubilidade aquosa. As formulações que se mostraram viáveis apresentaram tempos de autoemulsificação inferiores a 60 segundos, além disso, as distribuições granulométricas das dispersões foram inferiores a 300 nm, apresentaram índices de polidispersidade inferiores a 0,3 e valores de potencial zeta inferiores a -25 mV. Os perfis de dissolução mostraram que as formulações atendem a um valor de fator de similaridade maior que 50, além disso, a permeabilidade através da membrana sintética é maior para as formulações autoemulsionantes do que para o produto de referência. Conclusões: a formulação de indometacina em sistemas de liberação autoemulsificantes aumenta a solubilidade em meio aquoso, aumenta a dissolução e a liberação. Esses resultados sugerem que a administração oral de indometacina incorporada em sistemas autoemulsificantes pode acelerar o início do efeito farmacológico.

The COPHELA (Cooperation in Quality Assurance for Pharmacy Education and Training between Europe and Latin America) Project.

COPHELA (Cooperation in Quality Assurance for Pharmacy Education and Training between Europe and Latin America), a collaborative project between the European Union (EU) and Latin America, will produce on-line courses for the master degree in pharmacy. The program runs from 2019 through 2021. It is funded by the Erasmus+ program of the Education, Audio-visual and Culture Executive Agency (EACEA) of the European Commission. The partners are EU and Latin American universities. These are accompanied by associated partners from EU and Latin American universities, as well as from governmental and non-governmental organizations, such as pharmacy chambers and educational associations. The project is coordinated by the University of Granada, Spain (first author of this paper). It will produce distance learning master degree courses in a dozen fields of specialized pharmaceutical science education and practice, ranging from patient care to industrial pharmacy. This paper describes the design of the project and is intended to evoke constructive comments. It also represents a call for the recruitment of additional associated partners.

Armonización Curricular Farmacéutica en Iberoamérica. Documento de trabajo de la Conferencia Iberoamericana de Facultades de Farmacia (COIFFA) / Pharmaceutical Curriculum Harmonization in Ibero-America. Working document of the Ibero-American Conference of Faculties of Pharmacy (COIFFA)

La Conferencia Iberoamericana de Facultades de Farmacia (COIFFA) viene desarrollando desde su fundación como Conferencia Hispanoamericana (COHIFFA) en 1992, en la Universidad de los Andes (Mérida, Venezuela) una amplia labor en el ámbito de la formación y educación farmacéutica. Esta labor se ha traducido en declaraciones sucesivas desde la efectuada en Santiago (Chile) hasta la más reciente de Xochimilco (México). El grado de avance que han experimentado las ciencias y la práctica farmacéutica en las últimas décadas ha sido espectacular. Así se refleja en documentos de organismos y foros nacionales e internacionales. A esto se une las facilidades que en el ámbito de la movilidad internacional procuran tanto las Universidades a través de sus convenios bilaterales, como los organismos nacionales e internacionales de América Latina y de la Unión Europea, a través de los proyectos y convocatorias pertinentes. Todo ello hace aconsejable la elaboración por parte de COIFFA de un documento marco de consenso, en donde se recoja la problemática que el trascendental tema de la armonización de los estudios de farmacia conlleva. Los esfuerzos que ha venido realizando COIFFA se han traducido en la elaboración durante el Simposio Biregional Unión Europea-América Latina celebrado en junio de 2018 Xochimilco (México), de un documento de trabajo. Tres mesas de discusión coordinadas han tenido por objeto: I) el análisis y definición de perfil de egreso y de los mínimos curriculares; II) el análisis de los términos utilizados en la denominación de programas académicos títulos universitarios y distintas actividades; y III) el análisis y propuestas de mecanismos de colaboración y cofinanciación interinstitucionales Universidad-Gobierno-Empresa. La revisión y actualización de algunos aspectos contemplados en el citado documento se han llevado a cabo en el seno del First World Congress of Faculties of Pharmacy (IPAP18), celebrado en Salamanca en September de 2018. Este documento es provisional y está sujeto a los elementos de mejora que se irán introduciendo de forma paulatina en las sucesivas reuniones que COHIFFA seguirá llevando a cabo

The Ibero-American Conference of Faculties of Pharmacy (COIFFA) has been developing a wide-ranging task in the field of pharmaceutical training and education since its foundation as Hispanic-American Conference (COHIFFA) in 1992, at the Universidad de los Andes (Mérida, Venezuela). This work has been materialized into successive statements from the one made in Santiago (Chile) to the most recent one in Xochimilco (Mexico). The degree of progress that the sciences and pharmaceutical practice have experienced in recent decades has been spectacular. This is reflected in documents from national and international organizations and forums. To this is added the facilities that, in the field of international mobility, universities get through their bilateral agreements, as well as with national and international organizations in Latin America and the european Union, through the relevant projects and calls. All this makes advisable the elaboration on the part of COIFFA of a framework document of consensus, where the problematic that the transcendental subject of the harmonization of the pharmacy studies entails be covered. The efforts that COIFFA has been carrying out have resulted in the elaboration of a working document at the Biregional European Union-Latin America Symposium held in June 2018 in Xochimilco (Mexico). Three coordinated working groups were there devoted to: I) the analysis and definition of the graduate profile, as well as the common minimum topics to be included in the "pensum"; II) the analysis of the terms to be used in the denomination of academic programs, university degrees and various related activities; III) the analysis and proposals for cooperation mechanisms and properly ways of University-Government-Company co-financing. The review and updating of some of the topics approached in the aforementioned document have been carried out by COIFFA within the First World Congress of Faculties of Pharmacy (IPAP 18), held in Salamanca (September, 2018). This document is provisional and subject to the elements of improvement that will be gradually introduced in future COIFFA meetings

Physicochemical characterization and thermal behavior of hexosomes containing ketoconazole as potential topical antifungal delivery system.

OBJECTIVE: The main purpose of this article is to show the valuable characteristics that liotropic liquid crystal systems possess to be employed as new drug delivery systems. SIGNIFICANCE: Colloidal aqueous dispersions of lyotropic liquid crystal mesophases such as the identified as cubosomes and hexosomes, and so on, have received considerable attention due to their unique nanostructures and their thermodynamic properties, which provide the potential as a sustained drug release matrix. Additionally, their large surface area and similarity with the liquid crystal structures of intercellular lipids of stratum corneum enhances the interaction with the skin and mucous, increasing the potential for topical drug delivery efficiency of biopharmaceutical class II drugs as the antifungal ketoconazole. METHODS: This article presents the results in morphological characteristics, particle size, ζ potential, flow, thermal behavior and drug release studies of hexosomes containing ketoconazole (LHLC-K) obtained with glycerol monooleate, propylene glycol monolaurate, poloxamer, and water mixtures. RESULTS: This colloidal system exhibits a Newtonian-type flow and a hexagonal nanostructure with a median particle size of 107 ± 20 nm and ζ potential of +4.45 ± 0.50 mV. Through differential scanning calorimetry studies, the LHLC-K demonstrated physical and chemical stability for more than six months and mesophasic thermal reversibility between 10 and 50 °C. Finally, LHLC-K releases ketoconazole following a kinetics described by the first order model. CONCLUSIONS: Physicochemical properties of the hexosomes containing ketoconazole are important for topical mycosis treatment administration, conditions of storage, and for its incorporation into the formulation of semi-solid dosage forms.

Tratamiento periodontal no quirúrgico en pacientes con gingivitis y periodontitis moderada. Respuesta bioquímica y microbiológica / Non surgical periodontal treatment in patients with gingivitis and moderate periodontitis. Biochemical and microbiological response

Objetivo: Conocer la respuesta inflamatoria a través de la presencia de interleucina 1β e identificar microorganismos patógenos como posibles marcadores inmunológicos y microbiológicos en el diagnóstico y tratamiento periodontal no quirúrgico en sujetos con gingivitis y periodontitis crónica moderada en población mexicana. Material y métodos: En este estudio prospectivo de cohortes, se seleccionaron 18 pacientes con signos clínicos de gingivitis y 17 pacientes con periodontitis crónica moderada, se recolectaron las muestras de biopelícula subgingival y de fluido gingival crevicular. Se cuantificó la interleucina 1β durante las fases pretratamiento, postratamiento y de mantenimiento del tratamiento periodontal no quirúrgico. Resultados: Las variables de respuesta microbiológica mostraron que Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans disminuyeron significativamente en individuos con gingivitis. Así como Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans y Actinomyces sp. en periodontitis crónica moderada. Las variables de respuesta bioquímica mostraron una disminución significativa en la concentración y cuenta total de interleucina 1β en los individuos con periodontitis crónica moderada en la fase de mantenimiento del tratamiento así como de las variables de respuesta clínica. Conclusión: Hay reducción de los niveles de interleucina 1β con la disminución de la microflora. Los niveles de interleucina 1β son marcadores sensibles para el diagnóstico y severidad de la enfermedad periodontal.

Objective: To ascertain inflammatory response through interleucina 1β presence and identify pathogenic microorganisms as possible immunological and microbiological markers in diagnosis and treatment non-surgical periodontal in patients with gingivitis and moderate chronic periodontitis in a sample of Mexican population. Material and methods: In the present prospective cohort study, 18 patients with signs of gingivitis and 17 patients with moderate chronic periodontitis were selected. Samples of subgingival biofilm and of crevicular gingival fluid were collected. Interleukine 1β was quantified during the pre-treatment, post-treatment and maintenance phases of the nonsurgical periodontal treatment. Continuous variables were analyzed with the Student test, as well as categorical variables which were analyzed with the TurkeyKramer test. For independent groups the Pearson test was used. Results: Microbiological response variables showed that Porphyromonas gingivalis, Prevotella intermedia , Fusobacterium nucleatum , Aggregatibacter actinomycetemcomitans significantly decreased in subjects with gingivitis. Porphyromonas gingivalis , Tannerella forsythia , Fusobacterium nucleatum , Aggregatibacter actinomycetemcomitans and Actinomyces ssp . decreased in cases. Biochemical response variables showed significant decrease in IL-1β concentration and total count in individuals with moderate chronic periodontitis in treatment maintenance phase. The same result applied to clinical response variables. Conclusions: There is a decrease in Interleukin 1β levels with decrease in microflora. Interleukin 1β are sensitive markers for diagnosis of periodontal disease and assessment of its severity.

Elaboration and structural analysis of aquasomes loaded with indomethacin.

The aim of this study was to prepare nanoparticles in form of aquasomes with Indomethacin as a low solubility drug mode. Aquasomes charged with Indomethacin were obtained through the formation of an inorganic core of calcium phosphate covered with a Lactose film and further adsorption of the Indomethacin. Structural analyses, particle size, and morphology were evaluated by X-ray powder diffractometry, transmission electron microscopy, and scanning electron microscopy. The X-ray analysis of the samples and their observation through electronic microscopy allowed us to identify the inorganic calcium phosphate nucleus formation, as well as the layers of Lactose and Indomethacin. The particle size analysis of the aquasomes obtained with the Lactose layer and charged with the drug indicated an average particle size in the range of 60-120 nm, with a media of 90 nm. Standard deviation was 18.0234 and the standard error of the media 4.1348. The method was reproducible under the conditions used to prepare the aquasomes, such as ultrasound frequency and the moment of sonication for the formation of inorganic cores.