Biocompatibility and stability of polysaccharide polyelectrolyte complexes aimed at respiratory delivery

Chitosan (CS) and chondroitin sulfate (CHS) are natural polymers with demonstrated applicability in drug delivery, while nanoparticles are one of the most explored carriers for transmucosal delivery of biopharmaceuticals. In this work we have prepared CS/CHS nanoparticles and associated for the first time the therapeutic protein insulin. Fluorescein isothiocyanate bovine serum albumin (FITC-BSA) was also used to enable comparison of behaviors regarding differences in molecular weight (5.7 kDa versus 67 kDa). Nanoparticles of approximately 200 nm and positive zeta potential around +20 mV were obtained. These parameters remained stable for up to 1 month at 4 C. Proteins were associated with efficiencies of more than 50%. The release of FITC-BSA in PBS pH 7.4 was more sustained (50% in 24 h) than that of insulin (85% in 24 h). The biocompatibility of nanoparticles was tested in Calu-3 and A549 cells by means of three different assays. The metabolic assay MTT, the determination of lactate dehydrogenase release, and the quantification of the inflammatory response generated by cell exposure to nanoparticles have indicated an absence of overt toxicity. Overall, the results suggest good indications on the application of CS/CHS nanoparticles in respiratory transmucosal protein delivery, but the set of assays should be widened to clarify obtained results

Riesgos asociados a la utilización de antimicrobianos en personas mayores

Objetivos: Describir los cambios fisiológicos más relevantes asociados al envejecimiento, las características de las infecciones en estos pacientes así como los efectos adversos más frecuentes e interacciones farmacológicas graves de los antimicrobianos en los mayores. Material y Métodos: Se realizó una revisión bibliográfica sobre los riesgos asociados al uso de antibióticos en ancianos. La información se apoyó en la actualización de la evidencia científica y la información de las Fichas Técnicas de los medicamentos. La búsqueda se limitó a los últimos 11 años, seleccionándose documentos publicados en español, inglés o francés. Se realizó una búsqueda electrónica de fuentes secundarias (revisiones sistemáticas) y una búsqueda manual “ad hoc”, partiendo de la bibliografía recuperada, estudios primarios, informes de agencias de evaluación de medicamentos, guías de práctica clínica y documentos de Sociedades Científicas. Se utilizaron como fuentes de información: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®. Resultados: Se localizaron 321 resultados, tras eliminar los que no cumplían criterios de inclusión 52 documentos, además de las fichas técnicas de todos los antibióticos citados, se incluyeron en la revisión bibliográfica. Conclusiones: Los pacientes mayores adquieren con mayor frecuencia infecciones por patógenos multi-resistentes y sufren más complicaciones graves de las infecciones. Los antibióticos son un grupo de fármacos especialmente sensibles a los cambios fisiológicos producidos por la edad, lo que puede condicionar la respuesta a los estos y exige en muchas ocasiones modificaciones posológicas con el fin de evitar intoxicaciones y/o fracasos terapéuticos. Este trabajo aporta información sobre estos cambios fisiológicos y los riesgos de los antibióticos en las personas mayores, aspectos necesarios para elegir un tratamiento adecuado.Aim: Describe the most important physiological changes associated with aging, the characteristics of infections in these patients and the most common side effects and severe interactions with antimicrobials in older people. Material and methods: We conducted a literature review on the risks associated with the use of antibiotics in the elderly. The information was based on the update of the scientific evidence and information from the drug Sheets. The search was limited to the past 11 years, selected papers published in English, Spanish or French. We performed an electronic search of secondary sources (systematic reviews) and a manual search “ad hoc” basis of the literature retrieved, primary studies, reports of drug evaluation agencies, clinical practice guidelines and documents of Scientific Societies. Information sources: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®. Results: We identified 321 results, after eliminating those who did not meet inclusion criteria 52 papers in addition to the technical specifications of all mentioned antibiotics were included in the literature review. Conclusion: Older patients can acquire infections more frequently multi-resistant pathogens and suffer more serious complications of infections. The antibiotics is a group of drugs sensitive to the physiological changes induced by aging, which may influence the response to these and often requires dosage modifications to avoid poisoning and / or therapeutic failures. This paper provides information on these physiological changes and risks of antibiotics in the elderly, aspects necessary to choose a proper treatment.Este trabajo ha sido realizado con la co- financiación de sendos proyectos de investigación: FISS PI/10/01152 y Consejería de Salud de la Junta de Andalucía PI-0160-2010

Risks associated with the use of antimicrobials in elderly

Objetivos: Describir los cambios fisiológicos más relevantes asociados al envejecimiento, las características de las infecciones en estos pacientes así como los efectos adversos más frecuentes e interacciones farmacológicas graves de los antimicrobianos en los mayores.Material y Métodos: Se realizó una revisión bibliográfica sobre los riesgos asociados al uso de antibióticos en ancianos. La información se apoyó en la actualización de la evidencia científica y la información de las Fichas Técnicas de los medicamentos. La búsqueda se limitó a los últimos 11 años, seleccionándose documentos publicados en español, inglés o francés. Se realizó una búsqueda electrónica de fuentes secundarias (revisiones sistemáticas) y una búsqueda manual “ad hoc”, partiendo de la bibliografía recuperada, estudios primarios, informes de agencias de evaluación de medicamentos, guías de práctica clínica y documentos de Sociedades Científicas. Se utilizaron como fuentes de información: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®.Resultados: Se localizaron 321 resultados, tras eliminar los que no cumplían criterios de inclusión 52 documentos, además de las fichas técnicas de todos los antibióticos citados, se incluyeron en la revisión bibliográfica.Conclusiones: Los pacientes mayores adquieren con mayor frecuencia infecciones por patógenos multi-resistentes y sufren más complicaciones graves de las infecciones. Los antibióticos son un grupo de fármacos especialmente sensibles a los cambios fisiológicos producidos por la edad, lo que puede condicionar la respuesta a los estos y exige en muchas ocasiones modificaciones posológicas con el fin de evitar intoxicaciones y/o fracasos terapéuticos. Este trabajo aporta información sobre estos cambios fisiológicos y los riesgos de los antibióticos en las personas mayores, aspectos necesarios para elegir un tratamiento adecuado.Aim: Describe the most important physiological changes associated with aging, the characteristics of infections in these patients and the most common side effects and severe interactions with antimicrobials in older people.Material and methods: We conducted a literature review on the risks associated with the use of antibiotics in the elderly. The information was based on the update of the scientific evidence and information from the drug Sheets. The search was limited to the past 11 years, selected papers published in English, Spanish or French. We performed an electronic search of secondary sources (systematic reviews) and a manual search “ad hoc” basis of the literature retrieved, primary studies, reports of drug evaluation agencies, clinical practice guidelines and documents of Scientific Societies. Information sources: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®.Results: We identified 321 results, after eliminating those who did not meet inclusion criteria 52 papers in addition to the technical specifications of all mentioned antibiotics were included in the literature review.Conclusion: Older patients can acquire infections more frequently multi-resistant pathogens and suffer more serious complications of infections. The antibiotics is a group of drugs sensitive to the physiological changes induced by aging, which may influence the response to these and often requires dosage modifications to avoid poisoning and / or therapeutic failures. This paper provides information on these physiological changes and risks of antibiotics in the elderly, aspects necessary to choose a proper treatment

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

Polymeric nanoparticles have revealed very effective in transmucosal delivery of proteins. Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability. In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up. In this work we propose the production of pullulan-based nanoparticles by a mild method of polyelectrolyte complexation. As pullulan is a neutral polysaccharide, sulfated and aminated derivatives of the polymer were synthesized to provide pullulan with a charge. These derivatives were then complexed with chitosan and carrageenan, respectively, to produce the nanocarriers. Positively charged nanoparticles of 180-270 nm were obtained, evidencing ability to associate bovine serum albumin, which was selected as model protein. In PBS pH 7.4, pullulan-based nanoparticles were found to have a burst release of 30% of the protein, which maintained up to 24h. Nanoparticle size and zeta potential were preserved upon freeze-drying in the presence of appropriate cryoprotectants. A factorial design was approached to assess the cytotoxicity of raw materials and nanoparticles by the metabolic test MTT. Nanoparticles demonstrated to not cause overt toxicity in a respiratory cell model (Calu-3). Pullulan has, thus, demonstrated to hold potential for the production of nanoparticles with an application in protein delivery

Patients receiving a high burden of antibiotics in the community in Spain: a cross-sectional study

Some patients in the community receive a high burden of antibiotics. We aimed at describing the characteristics of these patients, antibiotics used, and conditions for which they received antibiotics. We carried out a cross-sectional study. Setting: Thirty Health Primary Care Areas from 12 regions in Spain, covering 5, 960, 191 inhabitants. Patients having at least 30 packages of antibacterials for systemic use dispensed in 2017 were considered. Main outcome measures: Prevalence of antibiotic use, conditions for which antibiotics were prescribed, clinical characteristics of patients, comorbidities, concomitant treatments, and microbiological isolates. Patient''s average age was 70 years; 52% were men; 60% smokers/ex-smokers; 54% obese. Overall, 93% of patients had, at least, one chronic condition, and four comorbidities on average. Most common comorbidities were cardiovascular and/or hypertension (67%), respiratory diseases (62%), neurological/mental conditions (32%), diabetes (23%), and urological diseases (21%); 29% were immunosuppressed, 10% were dead at the time of data collection. Patients received three antibiotic treatments per year, mainly fluoroquinolones (28%), macrolides (21%), penicillins (19%), or cephalosporins (12%). Most frequently treated conditions were lower respiratory tract (infections or prophylaxis) (48%), urinary (27%), and skin/soft tissue infections (11%). Thirty-five percent have been guided by a microbiological diagnosis, being Pseudomonas aeruginosa (30%) and Escherichia coli (16%) the most frequent isolates. In conclusion, high antibiotic consumers in the community were basically elder, with multimorbidity and polymedication. They frequently received broad-spectrum antibiotics for long periods of time. The approach to infections in high consumers should be differentiated from healthy patients receiving antibiotics occasionally

A systematic review of clinical decision support systems for antimicrobial management: are we failing to investigate these interventions appropriately?

Objectives Clinical decision support systems (CDSS) for antimicrobial management can support clinicians to optimize antimicrobial therapy. We reviewed all original literature (qualitative and quantitative) to understand the current scope of CDSS for antimicrobial management and analyse existing methods used to evaluate and report such systems. Method PRISMA guidelines were followed. Medline, EMBASE, HMIC Health and Management and Global Health databases were searched from 1 January 1980 to 31 October 2015. All primary research studies describing CDSS for antimicrobial management in adults in primary or secondary care were included. For qualitative studies, thematic synthesis was performed. Quality was assessed using Integrated quality Criteria for the Review Of Multiple Study designs (ICROMS) criteria. CDSS reporting was assessed against a reporting framework for behaviour change intervention implementation. Results Fifty-eight original articles were included describing 38 independent CDSS. The majority of systems target antimicrobial prescribing (29/38;76%), are platforms integrated with electronic medical records (28/38;74%), and have a rules-based infrastructure providing decision support (29/38;76%). On evaluation against the intervention reporting framework, CDSS studies fail to report consideration of the non-expert, end-user workflow. They have narrow focus, such as antimicrobial selection, and use proxy outcome measures. Engagement with CDSS by clinicians was poor. Conclusion Greater consideration of the factors that drive non-expert decision making must be considered when designing CDSS interventions. Future work must aim to expand CDSS beyond simply selecting appropriate antimicrobials with clear and systematic reporting frameworks for CDSS interventions developed to address current gaps identified in the reporting of evidence

Nanoencapsulated capsaicin changes migration behavior and morphology of madin darby canine kidney cell monolayers

We have developed a drug delivery nanosystem based on chitosan and capsaicin. Both substances have a wide range of biological activities. We investigated the nanosystem’s influence on migration and morphology of Madin Darby canine kidney (MDCK-C7) epithelial cells in comparison to the capsaicin-free nanoformulation, free capsaicin, and control cells. For minimally-invasive quantification of cell migration, we applied label-free digital holographic microscopy (DHM) and single-cell tracking. Moreover, quantitative DHM phase images were used as novel stain-free assay to quantify the temporal course of global cellular morphology changes in confluent cell layers. Cytoskeleton alterations and tight junction protein redistributions were complementary analyzed by fluorescence microscopy. Calcium influx measurements were conducted to characterize the influence of the nanoformulations and capsaicin on ion channel activities. We found that both, capsaicin-loaded and unloaded chitosan nanocapsules, and also free capsaicin, have a significant impact on directed cell migration and cellular motility. Increase of velocity and directionality of cell migration correlates with changes in the cell layer surface roughness, tight junction integrity and cytoskeleton alterations. Calcium influx into cells occurred only after nanoformulation treatment but not upon addition of free capsaicin. Our results pave the way for further studies on the biological significance of these findings and potential biomedical applications, e.g. as drug and gene carriers

Patients receiving a high burden of antibiotics in the community in Spain: a cross-sectional study.

Some patients in the community receive a high burden of antibiotics. We aimed at describing the characteristics of these patients, antibiotics used, and conditions for which they received antibiotics. We carried out a cross-sectional study. Setting: Thirty Health Primary Care Areas from 12 regions in Spain, covering 5,960,191 inhabitants. Patients having at least 30 packages of antibacterials for systemic use dispensed in 2017 were considered. Main outcome measures: Prevalence of antibiotic use, conditions for which antibiotics were prescribed, clinical characteristics of patients, comorbidities, concomitant treatments, and microbiological isolates. Patient's average age was 70 years; 52% were men; 60% smokers/ex-smokers; 54% obese. Overall, 93% of patients had, at least, one chronic condition, and four comorbidities on average. Most common comorbidities were cardiovascular and/or hypertension (67%), respiratory diseases (62%), neurological/mental conditions (32%), diabetes (23%), and urological diseases (21%); 29% were immunosuppressed, 10% were dead at the time of data collection. Patients received three antibiotic treatments per year, mainly fluoroquinolones (28%), macrolides (21%), penicillins (19%), or cephalosporins (12%). Most frequently treated conditions were lower respiratory tract (infections or prophylaxis) (48%), urinary (27%), and skin/soft tissue infections (11%). Thirty-five percent have been guided by a microbiological diagnosis, being Pseudomonas aeruginosa (30%) and Escherichia coli (16%) the most frequent isolates. In conclusion, high antibiotic consumers in the community were basically elder, with multimorbidity and polymedication. They frequently received broad-spectrum antibiotics for long periods of time. The approach to infections in high consumers should be differentiated from healthy patients receiving antibiotics occasionally