RESUMO
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that replicates inside human alveolar macrophages. This disease causes significant morbidity and mortality throughout the world. According to the World Health Organization 1.4 million people died of this disease in 2021. This indicates that despite the progress of modern medicine, improvements in diagnostics, and the development of drug susceptibility tests, TB remains a global threat to public health. In this sense, host-directed therapy may provide a new approach to the cure of TB, and the expression of miRNAs has been correlated with a change in the concentration of various inflammatory mediators whose concentrations are responsible for the pathophysiology of M. tuberculosis infection. Thus, the administration of miRNAs may help to modulate the immune response of organisms. However, direct administration of miRNAs, without adequate encapsulation, exposes nucleic acids to the activity of cytosolic nucleases, limiting their application. Dendrimers are a family of highly branched molecules with a well-defined architecture and a branched conformation which gives rise to cavities that facilitate physical immobilization, and functional groups that allow chemical interaction with molecules of interest. Additionally, dendrimers can be easily functionalized to target different cells, macrophages among them. In this sense, various studies have proposed the use of different cell receptors as target molecules to aim dendrimers at macrophages and thus release drugs or nucleic acids in the cell of interest. Based on the considerations, the primary objective of this review is to comprehensively explore the potential of functionalized dendrimers as delivery vectors for miRNAs and other therapeutic agents into macrophages. This work aims to provide insights into the use of functionalized dendrimers as an innovative approach for TB treatment, focusing on their ability to target and deliver therapeutic cargo to macrophages.
RESUMO
A novel co-encapsulation system called bicosomes (bicelles within liposomes) has been developed to overcome the limitations associated with the topical application of curcumin (cur) and α-tocopherol (α-toc). The physicochemical properties and biological activity in vitro of bicosome systems were evaluated. Bicelles were prepared with DPPC, DHPC, cur, and α-toc (cur/α-toc-bicelles). Liposomal vesicles loading cur/α-toc-bicelles were prepared with Lipoid P-100 and cholesterol-forming cur/α-toc-bicosomes. Three cur/α-toc-bicosomes were evaluated using different total lipid percentages (12, 16, and 20% w/v). The results indicated that formulations manage to solubilize cur and α-toc in homogeneous bicelles < 20 nm, while the bicosomes reaches 303-420 nm depending on the total lipid percentage in the systems. Bicosomes demonstrated high-encapsulation efficiency (EE) for cur (56-77%) and α-toc (51-65%). The loading capacity (LC) for both antioxidant compounds was 52-67%. In addition, cur/α-toc-bicosomes decreased the lipid oxidation by 52% and increased the antioxidant activity by 60% compared to unloaded bicosomes. The cell viability of these cur/α-toc-bicosomes was >85% in fibroblasts (3T3L1/CL-173™) and ≥65% in keratinocytes (Ha-CaT) and proved to be hematologically compatible. The cur/α-toc-bicelles and cur/α-toc-bicosomes inhibited the growth of C. albicans in a range between 33 and 76%. Our results propose bicosome systems as a novel carrier able to co-encapsulate, solubilize, protect, and improve the delivery performance of antioxidant molecules. The relevance of these findings is based on the synergistic antioxidant effect of its components, its biocompatibility, and its efficacy for dermal tissue treatment damaged by oxidative stress or by the presence of C. albicans. However, further studies are needed to assess the efficacy and safety of cur/α-toc bicosomes in vitro and in vivo.
RESUMO
La participación comunitaria ha sido uno de los aspectos fundamentales en las políticas sanitarias en Chile desde 1990. Sin embargo, aun reconociéndose la importancia de la participación comunitaria en el trabajo de los equipos de salud, esta estrategia ha presentado dificultades en su implementación, derivadas tanto de aspectos prácticos como de problemas teóricos. La ausencia de definiciones conceptuales claras y compartidas acerca de la participación resulta en tensiones ideológicas y políticas que se expresan a su vez en una interpretación, aplicación y evaluación distinta de las actividades de participación. Así, se hace necesario desarrollar herramientas de evaluación de la participación que, utilizándose transversalmente, fortalezcan el trabajo de los equipos de salud, al mismo tiempo que promuevan el desarrollo teórico del área. Un instrumento de evaluación de la participación comunitaria, diseñado especialmente para ser utilizado en atención primaria de salud, lo constituye el Spidergram, o mapa en tela de araña, que incorpora la evaluación de cinco dimensiones del proceso participativo. El presente estudio tiene por objetivo adaptar y validar este instrumento en un contexto urbano en Chile. Se evaluó la validez del cuestionario grupal traducido al español basado en la revisión de la literatura, la aplicación del instrumento piloto y las discusiones sostenidas por parte del equipo de investigación. Este instrumento alcanzó un adecuado nivel de consistencia interna y de concordancia interobservador en la mayoría de las variables al ser aplicado por moderadores externos, permitiéndose su recomendación como herramienta de trabajo para los equipos de atención primaria de salud.
Community participation has been one of the fundamental aspects of Chilean health care policies since 1990. Though the importance of health care teams' community participation should be recognized, this strategy has nevertheless faced a number of obstacles during its implementation, due to practical and theoretical problems. The absence of a clear and common conceptual definition of community participation results in ideological and political tensions that are, in turn, expressed in different interpretations, applications, and assessments of participatory activities. Thus, it is necessary to develop methods for the assessment of community participation that can be used across the board, and which may allow health care workers to strengthen their work with local communities, while promoting theoretical advances in the area. One instrument for measuring community participation, especially designed to be used in primary health care settings, is the Spidergram, which includes the evaluation of 5 variables related to the participatory process. This study aims to adapt and validate this assessment method in an urban context in Chile. The validity of the instrument was assessed through a literature review, a pilot application of a version translated into Spanish, and multiple discussions within the multidisciplinary research team. This instrument achieved adequate internal consistency and inter-observer concordance in most variables when applied by external observers, supporting its recommendation as a valuable tool for primary health care workers.