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The encapsulation of nanoparticles within microparticles designed for specific delivery to the colon is a relevant strategy to avoid premature degradation or release of nanoparticles during their passage through the stomach and upper gastrointestinal tract (GIT), allowing the targeted delivery of chemotherapeutics to the colon after oral administration. Here, we designed an oral multiparticulate system to achieve targeted release in the colon. In this sense, chitosan nanoparticles (CS NPs) encapsulated with 5-fluorouracil (5-FU) and incorporated into retrograded starch and pectin (RS/P) microparticles were developed and their in vivo distribution along the mouse GIT after oral administration was monitored using multispectral optical imaging. In vitro release studies revealed that the encapsulation of CS NPs into RS/P microparticles promoted greater control of 5-FU release rates, with a significant reduction (53%) in acid media that might replicate that found in the stomach following oral administration. The evaluation of the in vivo biodistribution of the CS NPs in mice showed a faster clearance in the distribution pattern along the mouse GIT, i.e., a shorter transit time of CS NPs compared to CS NPs-loaded RS/P microparticles. Additionally, CS NPs alone showed non-specific absorption into the blood-stream with associated kidney accumulation, while for the CS NPs-loaded RS/P microparticles no significant accumulation was observed in blood or major clearance organs. This suggests the specific degradability of RS/P by the colon microbiota appears to have been decisive in the higher protection of the CS NPs along the GIT until release in the colon, preventing unwanted absorption into the bloodstream and major organs following oral administration. Our findings represent a proof of concept for the use of RS/P microparticles as potential carriers for delivering drug-loaded nanoparticles to the colon and this work will contribute to the development of oral-systems for colorectal cancer therapy.Interaction of conventional drug delivery systems such as polymeric or lipid based nano- and microparticles with the in vivo milieu has garnered significant interest, primarily to orchestrate immune escape and/or improve targeting. Surface modification with targeting ligands has been heavily relied upon for the mentioned purpose in the recent years. However, the surface modified particles can also activate the immune system. Large-scale manufacturing can also be a challenge, as surface modification needs to be reproducible. Furthermore, in vivo, the targeting is dependent on the receptor expression density and number of target sites, which adds to the pharmacokinetic variability of the constructs. An evolving paradigm to overcome complications of surface functionalization is the incorporation of bio-inspired topographies into these conventional delivery systems to enable them to better interact with biological systems. Biomimetic delivery systems combine the unique surface composition of cells or cell membranes, and versatility of synthetic nanoparticles. In this review, we focus on one such delivery system, silica particles, and explore their interaction with different biological membranes.Current therapy of tuberculosis (TB) has several limitations, such as risk of liver injury and intestinal dysbiosis due to frequent oral administration of antibiotics. Transdermal administration could be used to improve antibiotic delivery for treatment of Mycobacterium tuberculosis infection. Therefore, we developed a novel approach, using hydrogel-forming microneedle (MN) arrays to transdermally deliver TB drugs, namely rifampicin, isoniazid, pyrazinamide and ethambutol, which have different physicochemical properties. These drugs were individually prepared into three types of drug reservoirs, including lyophilised tablets, directly compressed tablets and poly(ethylene glycol) tablets. Formulations of each drug reservoir type were optimised to achieve a rapidly dissolving tablet, and further integrated with hydrogel-forming MN arrays for in vitro permeation studies. Three types of hydrogel formulation were manufactured using different type of polymers and crosslinking processes. These MN arrays were then evtantly, the results of this work have demonstrated the versatility of hydrogel formulations to deliver a TB drug regime using MN arrays. Accordingly, this is a promising approach to deliver high dose of TB drugs.
Despite nurses' responsibilities in recognition and treatment of sepsis, little evidence documents whether patient-to-nurse staffing ratios are associated with clinical outcomes for patients with sepsis.
Using linked data sources from 2017 including MEDPAR patient claims, Hospital Compare, American Hospital Association, and a large survey of nurses, we estimate the effect of hospital patient-to-nurse staffing ratios and adherence to the Early Management Bundle for patients with Severe Sepsis/Septic Shock SEP-1 sepsis bundles on patients' odds of in-hospital and 60-day mortality, readmission, and length of stay. Logistic regression is used to estimate mortality and readmission, while zero-truncated negative binomial models are used for length of stay.
Each additional patient per nurse is associated with 12% higher odds of in-hospital mortality, 7% higher odds of 60-day mortality, 7% higher odds of 60-day readmission, and longer lengths of stay, even after accounting for patient and hospital covariates including hospital adherence to SEP-1 bundles. Adherence to SEP-1 bundles is associated with lower in-hospital mortality and shorter lengths of stay; however, the effects are markedly smaller than those observed for staffing.
Improving hospital nurse staffing over and above implementing sepsis bundles holds promise for significant improvements in sepsis patient outcomes.
Improving hospital nurse staffing over and above implementing sepsis bundles holds promise for significant improvements in sepsis patient outcomes.
Health care associated infections (HAIs) are a major health concern associated with significant morbidity and mortality. read more The relationship between frailty, a syndrome often associated with older individuals, and HAIs has not been investigated.
To determine if frailty scoring systems can assist in predicting the risk of developing HAIs in health care settings.
A directed search was conducted across 4 databases (MEDLINE, Cochrane, Scopus, and CINAHL) for articles published between 1 January 1990 and 31 December 2019. All articles were screened for relevance to the research aims. The Newcastle-Ottawa Scale was utilised to assess the study quality and risk of bias.
The literature search yielded 290 results, with 14 articles meeting the inclusion criteria. Significant heterogeneity was present across the studies with regards to the frailty index employed and HAI definitions. Most studies were conducted in an acute health care setting (n = 12), while 2 studies were conducted in nursing homes. Eight studies demonstrated that frail individuals were at an increased risk of developing HAIs, in both surgical (n = 5) and medical patient populations (n = 2).
Website: https://www.selleckchem.com/products/az628.html
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