Patient-reported preferences for subcutaneous or intravenous administration of parenteral drug treatments in adults with immune disorders: a systematic review and meta-analysis.

Aim: Several studies have found subcutaneous (SC) and intravenous (IV) administration of similar drugs for long-lasting immunological and autoimmune diseases to have similar clinical effectiveness, meaning that what patients report they prefer is, or should be, a major factor in treatment choices. Therefore, it is important to systematically compile evidence regarding patient preferences, treatment satisfaction and health-related quality of life (HRQL) using SC or IV administration of the same drug. Materials & methods: PubMed database searches were run on 15 October 2021. Studies involving patients with experience of both home-based SC and hospital-based IV administration of immunoglobulins or biological therapies for the treatment of any autoimmune disease or primary immunodeficiencies (PIDs) were included. The outcomes assessed were patient preferences, treatment satisfaction and HRQL. Preference data were meta-analyzed using a random-effects model. Results: In total, 3504 citations were screened, and 46 publications describing 37 studies were included in the review. There was a strong overall preference for SC over IV administration, with similar results seen for PIDs and autoimmune diseases: PID, 80% (95% confidence interval [CI], 64-94%) preferred SC; autoimmune diseases, 83% (95% CI: 73-92%); overall, 82% (95% CI: 75-89%). The meta-analysis also found that 84% (95% CI: 75-92%) of patients preferred administration at home to treatment in hospital. Analysis of treatment satisfaction using the life quality index found consistently better treatment interference and treatment setting scores with SC administration than with IV administration. Conclusion: Compared with IV infusions in hospital, patients tend to prefer, to be more satisfied with and to report better HRQL with SC administration of the same drug at home, primarily due to the greater convenience. This study contributes to evidence-based care of patients with autoimmune diseases or PIDs.

[Translated article] Safe administration of noradrenaline by the peripheral route: A systematic review.

PURPOSE: To review and analyse the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety. METHODS: Systematic review on the databases PubMed, ISI Web of Science, SCOPUS, and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included. RESULTS: NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischaemia, and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA. CONCLUSIONS: Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.

Controversies in the management of community-acquired pneumonia in adults.

Community-acquired pneumonia (CAP) is a common infectious syndrome in Australia and a leading global cause of morbidity and mortality. It drives a significant amount of antimicrobial prescribing in Australia. Accurate assessment and stratification of CAP severity is important. However, adequate evaluation is challenging and controversy remains about the optimal method. Streptococcus pneumoniae is the most commonly identified bacterial pathogen causing CAP. As such, oral amoxicillin monotherapy is the mainstay of empirical therapy for low-severity CAP. The need to start empirical therapy for pathogens such as Mycoplasma pneumoniae and Legionella species in low-severity CAP remains controversial; evaluating the causative pathogen on clinical grounds alone is difficult. Oral antibiotics recommended for CAP (e.g. amoxicillin, doxycycline) have excellent bioavailability and may be used instead of intravenous therapy in some hospitalised patients. A duration of 5 days of antibiotic therapy is recommended in clinical practice guidelines for patients with uncomplicated CAP who meet stability criteria at follow-up.

Emerging delivery strategy for oncolytic virotherapy.

Oncolytic virotherapy represents a promising approach in cancer immunotherapy. The primary delivery method for oncolytic viruses (OVs) is intratumoral injection, which apparently limits their clinical application. For patients with advanced cancer with disseminated metastasis, systemic administration is considered the optimal approach. However, the direct delivery of naked viruses through intravenous injection presents challenges, including rapid clearance by the immune system, inadequate accumulation in tumors, and significant side effects. Consequently, the development of drug delivery strategies has led to the emergence of various bio-materials serving as viral vectors, thereby improving the anti-tumor efficacy of oncolytic virotherapy. This review provides an overview of innovative strategies for delivering OVs, with a focus on nanoparticle-based or cell-based delivery systems. Recent pre-clinical and clinical studies are examined to highlight the enhanced efficacy of systemic delivery using these novel platforms. In addition, prevalent challenges in current research are briefly discussed, and potential solutions are proposed.

Safe administration of noradrenaline by the peripheral route: A systematic review. / Administración segura de noradrenalina por vía periférica: una revisión sistemática.

PURPOSE: To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety. METHODS: Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included. RESULTS: NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA. CONCLUSIONS: Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.

Unmet Needs and Treatment Preference of Systemic Treatments for Moderate-to-Severe Psoriasis from the Perspectives of Patients and Dermatologists in China.

INTRODUCTION: The treatment options for moderate to severe psoriasis (msPsO) in China have been greatly increased with the approvals of biologics. However, the unmet needs and treatment preferences of systemic treatments for msPsO in China remain unclarified. METHODS: Fifty dermatologists and 300 patients with msPsO (41% with severe psoriasis) were surveyed for effectiveness, safety, treatment convenience, and treatment preferences (using a choice-based conjoint questionnaire). Descriptive statistics and conjoint simulation analyses were employed to summarize survey information and assess treatment preferences. RESULTS: Both patients and dermatologists reported shorter treatment duration for oral drugs (2.7-6.2 months) than that for biologics (9.5-17.0 months). The most frequently reported treatment discontinuation reasons by the surveyed patients and dermatologists were unsatisfactory effectiveness (average 84.5%) for oral drugs and loss of efficacy over time (average 68.5%) for biologics. Commonly reported treatment inconveniences included regular lab tests for traditional oral drugs (average 71.5%) and administration assistance for biologics (average 58.0%). Injection site reactions (average 51.5%) and needle fear (average 35.5%) were frequently reported for biologics among the surveyed patients and dermatologists. Once-daily oral treatment was preferred over biweekly subcutaneous injection treatment when the two had comparable attributes (average in patients 87.1% vs. 12.9%; average in dermatologists 93.4% vs. 6.6%). CONCLUSIONS: Unmet needs of systemic treatments remain for msPsO in China. Once-daily oral treatment is preferred over biweekly subcutaneous injections to treat msPsO when other treatment attributes are comparable.

Perception of the impact of intravenous biological treatment on the work and professional environment in patients with inflammatory bowel disease. / Percepción del impacto del tratamiento biológico endovenoso sobre el ámbito laboral y personal en pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: In the treatment of inflammatory bowel disease (IBD), we have biologic therapies administered intravenously and subcutaneously. Recently, some drugs can be administered by either of these routes. The real impact that intravenous administration has on the perception of the disease and the personal and work life of the patient is unknown. METHODS: All IBD patients receiving intravenous infliximab treatment for at least 6 months were anonymously invited to participate. They were provided with a specific structured questionnaire with visual analogue scales (0-10) at two reference centers in the Barcelona area. RESULTS: A total of 90 patients with a median age of 45 years (36-56) and a median infliximab treatment duration of 48 months (24-84) were included. The visit and therapy with infliximab in the day hospital were globally well evaluated (9, IQR 7-10). 78% of patients combined day hospital stays with other activities (26% employment). The personal impact was generally low (4, IQR 0-5.8), but the patient's job was threatened in 43% of patients on intensified treatment. CONCLUSIONS: The intravenous administration of biologic drugs on an outpatient basis is highly satisfactory among IBD patients. The impact on the work sphere appears to be more pronounced than on the personal sphere, an aspect that should be considered in shared decision-making with the patient.

Mucosal adjuvanticity and mucosal booster effect of colibactin-depleted probiotic Escherichia coli membrane vesicles.

There is a growing interest in development of novel vaccines against respiratory tract infections, due to COVID-19 pandemic. Here, we examined mucosal adjuvanticity and the mucosal booster effect of membrane vesicles (MVs) of a novel probiotic E. coli derivative lacking both flagella and potentially carcinogenic colibactin (ΔflhDΔclbP). ΔflhDΔclbP-derived MVs showed rather strong mucosal adjuvanticity as compared to those of a single flagellar mutant strain (ΔflhD-MVs). In addition, glycoengineered ΔflhDΔclbP-MVs displaying serotype-14 pneumococcal capsular polysaccharide (CPS14+MVs) were well-characterized based on biological and physicochemical parameters. Subcutaneous (SC) and intranasal (IN) booster effects of CPS14+MVs on systemic and mucosal immunity were evaluated in mice that have already been subcutaneously prime-immunized with the same MVs. With a two-dose regimen, an IN boost (SC-IN) elicited stronger IgA responses than homologous prime-boost immunization (SC-SC). With a three-dose regimen, serum IgG levels were comparable among all tested regimens. Homologous immunization (SC-SC-SC) elicited the highest IgM responses among all regimens tested, whereas SC-SC-SC failed to elicit IgA responses in blood and saliva. Furthermore, serum IgA and salivary SIgA levels were increased with an increased number of IN doses administrated. Notably, SC-IN-IN induced not only robust IgG response, but also the highest IgA response in both serum and saliva among the groups. The present findings suggest the potential of a heterologous three-dose administration for building both systemic and mucosal immunity, e.g. an SC-IN-IN vaccine regimen could be beneficial. Another important observation was abundant packaging of colibactin in MVs, suggesting increased applicability of ΔflhDΔclbP-MVs in the context of vaccine safety.

Pharmacokinetics of intranasal drugs, still a missed opportunity?

The intranasal (IN) route of administration is important for topical drugs and drugs intended to act systemically. More recently, direct nose-to-brain input was considered to bypass the blood-brain barrier.Processes related to IN absorption and nose-to-brain distribution are complex and depend, sometimes in contrasting ways, on chemico-physical and structural parameters of the compounds, and on formulation options.Due to the intricacies of these processes and despite the large number of articles published on many different IN compounds, it appears that absorption after IN dosing is not yet fully understood. In particular, at variance of the understanding and modelling approaches that are available for predicting the pharmacokinetics (PK) following oral administration of xenobiotics, it appears that there is not a similar understanding of the chemico-physical and structural determinants influencing drug absorption and disposition of compounds after IN administration, which represents a missed opportunity for this research field. This is even more true regarding the understanding of the direct nose-to-brain input. Due to this, IN administrations may represent an interesting and open research field for scientists aiming to develop PK property predictions tools, mechanistic PK models describing rate and extent of IN absorption, and translational tools to anticipate the clinical PK following IN dosing based on in vitro and in vivo non clinical experiments.This review intends to provide: i) some basic knowledge related to the physiology of PK after IN dosing, ii) a non-exhaustive list of preclinical and clinical examples related to compounds explored for the potential nose-to-blood and nose-to-brain passage, and iii) the identification of some areas requiring improvements, the understanding of which may facilitate the development of IN drug candidates.

The Biodistribution of Replication-Defective Simian Adenovirus 1 Vector in a Mouse Model.

The administration route affects the biodistribution of a gene transfer vector and the expression of a transgene. A simian adenovirus 1 vector carrying firefly luciferase and GFP reporter genes (SAdV1-GFluc) were constructed, and its biodistribution was investigated in a mouse model by bioluminescence imaging and virus DNA tracking with real-time PCR. Luciferase activity and virus DNA were mainly found in the liver and spleen after the intravenous administration of SAdV1-GFluc. The results of flow cytometry illustrated that macrophages in the liver and spleen as well as hepatocytes were the target cells. Repeated inoculation was noneffective because of the stimulated serum neutralizing antibodies (NAbs) against SAdV-1. A transient, local expression of low-level luciferase was detected after intragastric administration, and the administration could be repeated without compromising the expression of the reporter gene. Intranasal administration led to a moderate, constant expression of a transgene in the whole respiratory tract and could be repeated one more time without a significant increase in the NAb titer. An immunohistochemistry assay showed that respiratory epithelial cells and macrophages in the lungs were transduced. High luciferase activity was restricted at the injection site and sustained for a week after intramuscular administration. A compromised transgene expression was observed after a repeated injection. When these mice were intramuscularly injected for a third time with the human adenovirus 5 (HAdV-5) vector carrying a luciferase gene, the luciferase activity recovered and reached the initial level, suggesting that the sequential use of SAdV-1 and HAdV-5 vectors was practicable. In short, the intranasal inoculation or intramuscular injection may be the preferred administration routes for the novel SAdV-1 vector in vaccine development.

Systematic review on microbiome-related nutritional interventions interfering with the colonization of foodborne pathogens in broiler gut to prevent contamination of poultry meat.

This systematic review aimed to compile the available body of knowledge about microbiome-related nutritional interventions contributing to improve the chicken health and having an impact on the reduction of colonization by foodborne pathogens in the gut. Original research articles published between 2012 and 2022 were systematically searched in Scopus and PubMed. A total of 1,948 articles were retrieved and 140 fulfilled the inclusion criteria. Overall, 73 papers described 99 interventions against colonization by Escherichia coli and related organisms; 10 papers described 15 interventions against Campylobacter spp.; 36 papers described 54 interventions against Salmonella; 40 papers described 54 interventions against Clostridium perfringens. A total of 197 microbiome-related interventions were identified as effective against one or more of the listed pathogens and included probiotics (n = 80), prebiotics (n = 23), phytobiotics (n = 25), synbiotics (n = 12), organic acids (n = 12), enzymes (n = 4), essential oils (n = 14) and combination of these (n = 27). The identified interventions were mostly administered in the feed (173/197) or through oral gavage (11/197), in the drinking water (7/197), in ovo (2/197), intra amniotic (2/197), in fresh or reused litter (1/197) or both in the feed and water (1/197). The interventions enhanced the beneficial microbial communities in the broiler gut as Lactic acid bacteria, mostly Lactobacillus spp., or modulated multiple microbial populations. The mechanisms promoting the fighting against colonization by foodborne pathogens included competitive exclusion, production of short chain fatty acids, decrease of gut pH, restoration of the microbiome after dysbiosis events, promotion of a more stable microbial ecology, expression of genes improving the integrity of intestinal mucosa, enhancing of mucin production and improvement of host immune response. All the studies extracted from the literature described in vivo trials but performed on a limited number of animals under experimental settings. Moreover, they detailed the effect of the intervention on the chicken gut without details on further impact on poultry meat safety.

A sensitive and specific LC-MS/MS method for determination of a novel antihypertensive peptide FR-6 in rat plasma and pharmacokinetic study.

The investigation of peptide drugs has become essential in the development of innovative medications for hypertension. In this study, a sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the plasma concentration and stability of the antihypertensive peptide FR-6 in rats. An isotopically labeled peptide (with an unchanged sequence) was utilized as an internal standard (IS) for validation purposes. Subsequently, this assay was employed to examine the pharmacokinetics of different administration methods (tail vein and gavage) in Sprague Dawley (SD) rats. Extracted plasma samples underwent sample preparation through methanol protein precipitation, followed by elution of FR-6 on Wondasil C18 Superb column (4.6 × 150 mm, 5 µm), using a mobile phase consisting of formic acid (0.1%) in water (A) and formic acid (0.125%)-ammonium formate (2 mM) in methanol (B). Ion pairs corresponding to FR-6 and IS were monitored via multiple reaction monitoring (MRM) under positive ion mode: m/z 400.7 â†’ 285.1 for FR-6 and m/z 406.1 â†’ 295.1 for IS detection respectively. The method exhibited excellent linearity with respect to FR-6 concentrations. In addition, the inter-day and intra-day precision were 0.61-6.85% and 1.76-11.75%; the inter-day and intra-day accuracy were -7.28-0.13% and -7.20-2.28%, respectively. In conclusion, the matrix effect, extraction recovery, and stability data were validated according to FDA recommended acceptance criteria for bioanalytical methods. This validated method serves as a reliable tool for determining the concentration of antihypertensive peptide FR-6, and has been successfully applied in pharmacokinetic studies involving rats.

Novel technologies for applying immune checkpoint blockers.

Cancer cells develop several ways to subdue the immune system among others via upregulation of inhibitory immune checkpoint (ICP) proteins. These ICPs paralyze immune effector cells and thereby enable unfettered tumor growth. Monoclonal antibodies (mAbs) that block ICPs can prevent immune exhaustion. Due to their outstanding effects, mAbs revolutionized the field of cancer immunotherapy. However, current ICP therapy regimens suffer from issues related to systemic administration of mAbs, including the onset of immune related adverse events, poor pharmacokinetics, limited tumor accessibility and immunogenicity. These drawbacks and new insights on spatiality prompted the exploration of novel administration routes for mAbs for instance peritumoral delivery. Moreover, novel ICP drug classes that are adept to novel delivery technologies were developed to circumvent the drawbacks of mAbs. We therefore review the state-of-the-art and novel delivery strategies of ICP drugs.

Relative bioavailability of fedratinib through various alternative oral administration methods in healthy adults.

Fedratinib is an oral Janus kinase 2-selective inhibitor for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis; however, some patients have difficulty with oral dosing. This randomized, phase 1, open-label, 2-part crossover study evaluated the relative bioavailability, safety, tolerability, taste, and palatability of fedratinib resulting from various alternative oral administration methods in healthy adults. Participants could receive fedratinib 400 mg orally as intact capsules along with a nutritional supplement; as contents of capsules dispersed in a nutritional supplement, delivered via nasogastric tube; or as a divided dose of 200 mg orally twice daily as intact capsules with a nutritional supplement. Fifty-eight participants received treatment. Total exposure to fedratinib was similar after oral administration of intact capsules or when dispersed in a nutritional supplement (area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration geometric mean ratio [AUC0-t GMR] [90% CI], 1.007 [0.929-1.092]). Total exposure to fedratinib was slightly reduced following nasogastric administration (AUC0-t GMR 0.850 [0.802-0.901]) and as a divided dose (AUC0-t GMR 0.836 [0.789-0.886]). No new safety signals were identified for fedratinib, and most participants found the taste and palatability acceptable when dispersed in a nutritional supplement. Overall, results suggest no clinically meaningful differences in total exposure to fedratinib between the tested oral administration methods. These findings may facilitate administration of fedratinib to patients who are intolerant of swallowing the capsule dosage form. (ClinicalTrials.gov: NCT05051553).

Impact of In-Feed versus In-Water Chlortetracycline and Tiamulin Administrations on Fecal Prevalence and Antimicrobial Susceptibilities of Campylobacter in a Population of Nursery Pigs.

Antimicrobial resistance (AMR) in bacteria is a major public health concern in the US and around the world. Campylobacter is an important foodborne pathogen that resides in the gut of pigs and is shed in feces, with the potential to be transmitted to humans. In pigs, the oral route, either in-feed or in-water, is by far the most common route of administration of antimicrobials. Because the distribution of the antibiotic in the gut and the dosages are different, the impact of in-feed vs. in-water administration of antibiotics on the development of AMR is likely to be different. Therefore, a study was conducted to compare in-feed vs. in-water administrations of chlortetracycline (CTC) and/or tiamulin on fecal prevalence and AMR profiles of Campylobacter among weaned nursery piglets. A total of 1,296 weaned piglets, allocated into 48 pens (27 piglets per pen), were assigned randomly to six treatment groups: Control (no antibiotic), in-feed CTC, in-water CTC, in-feed tiamulin, in-water tiamulin, or in-feed CTC and tiamulin. Fecal samples were collected randomly from 5 piglets from each pen during the pre-treatment (days 0, 7), treatment (days 14, 21), and post-treatment (days 28, 35) phases. Bacterial isolations and species identifications were conducted by culture and PCR, respectively. The microbroth dilution method with SensititreTM plates was used to determine the antimicrobial susceptibility and resistance of Campylobacter isolates. The results on resistance were interpreted based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) epidemiological cutoff values for Campylobacter. The overall prevalence of Campylobacter was 18.2% (262/1440). Speciation of Campylobacter isolates by PCR indicated the prevalence of only two species: Campylobacter hyointestinalis (17.9%; 258/1440) and C. coli (0.3%; 4/1440). Campylobacter isolates were resistant to tetracycline (98.5%), ciprofloxacin (89.3%), and nalidixic acid (60.3%). Neither the antibiotic nor the route of administration had an effect (p > 0.05) on the prevalence of AMR Campylobacter in the feces of piglets.

Effects of Antimicrobial Administration Route on Growth and Antimicrobial Resistance in Weaned Piglets.

This study aimed to determine how the route of antimicrobial administration affected the growth performance of weaned piglets. Additionally, we aimed to investigate potential differences between antimicrobial resistance developed by antimicrobials administered orally through drinking water, and those administered through feed, in weaned piglets. The research was undertaken on a farm housing 500 sows and involved 150 weaned piglets at 21 days of age. These piglets were evenly distributed into three groups of equal size: water, feed, and control. Antimicrobials were administered through drinking water and feed in the water and feed groups, respectively, while the control group received no antimicrobial treatment. The observation of piglets continued until they reached 70 days of age. The feed conversion ratio in the water group (1.7 ± 0.78) was significantly higher than in the control (2.4 ± 1.77) and feed (2.7 ± 1.68) groups. Additionally, the route of administration did not affect antimicrobial resistance rates. Based on these results, it can be inferred that administering antimicrobials through drinking water is advantageous for pig farming.

mRNA Cancer Vaccines: Construction and Boosting Strategies.

In late 2020, the U.S. Food and Drug Administration (FDA) approved a lipid-based mRNA vaccine for the prevention of COVID-19, which has pushed this field to be more closely studied and motivated researchers to delve deeper into mRNA therapeutics. To date, the research on mRNA cancer vaccines has been developed rapidly, and substantial hopeful therapeutic results have been achieved against various solid tumors in clinical trials. In this review, we first introduce three main components of mRNA cancer vaccines, including mRNA antigens, adjuvants, and delivery vectors. Engineering these components can optimize the therapeutic effects of mRNA cancer vaccines. For instance, appropriate modification of mRNA structure can alleviate the poor stability and innate immunogenicity of mRNA, and the use of mRNA delivery vectors can address the issues of low delivery efficiency in vivo. Second, we emphatically discuss some strategies to further improve the efficacy of mRNA cancer vaccines, namely modulating the immunosuppressive tumor environment, optimizing administration routes, achieving targeting delivery to intended tissues or organs, and employing combination therapy. These strategies can strengthen the tumor inhibitory ability of mRNA cancer vaccines and increase the possibility of tumor elimination. Finally, we point out some challenges in the clinical practice of mRNA cancer vaccines and offer our perspectives on future developments in this rapidly evolving field. It is anticipated that mRNA cancer vaccines will be rapidly developed for clinical cancer therapy in the near future.

Emerging drug delivery systems with traditional routes - A roadmap to chronic inflammatory diseases.

Inflammation is prevalent and inevitable in daily life but can generally be accommodated by the immune systems. However, incapable self-healing and persistent inflammation can progress to chronic inflammation, leading to prevalent or fatal chronic diseases. This review comprehensively covers the topic of emerging drug delivery systems (DDSs) for the treatment of chronic inflammatory diseases (CIDs). First, we introduce the basic biology of the chronic inflammatory process and provide an overview of the main CIDs of the major organs. Next, up-to-date information on various DDSs and the associated strategies for ensuring targeted delivery and stimuli-responsiveness applied to CIDs are discussed extensively. The implementation of traditional routes of drug administration to maximize their therapeutic effects against CIDs is then summarized. Finally, perspectives on future DDSs against CIDs are presented.

Evaluation of a self-amplifying mRNA reporter vaccine in explant models of broiler chickens.

In order to minimize animal loss and economical loss, industrial poultry is heavily vaccinated against infectious agents. mRNA vaccination is an effective vaccination platform, yet little to no comprehensive, comparative studies in avians can be found. Nevertheless, poultry mRNA vaccination could prove to be very interesting due to the relatively low production cost, especially true when using self-amplifying mRNA (saRNA), and their extreme adaptability to new pathogens. The latter could be particularly useful when new pathogens join the stage or new variants arise. As a first step toward the investigation of saRNA vaccines in poultry, this study evaluates a luciferase-encoding saRNA in avian tracheal explants, conjunctival explants, primary chicken cecal cells and 18-day embryonated eggs. Naked saRNA in combination with RNase inhibitor and 2 different lipid-based formulations, that is, ionizable lipid nanoparticles (LNPs) and Lipofectamine Messenger Max, were evaluated. The saRNA-LNP formulation led to the highest bioluminescent signal in the tracheal explants, conjunctival explants and cecal cell cultures. A dose-response experiment with these saRNA-LNPs (33-900 ng/well) in these avian organoids and cells showed a nonlinear dose-response relationship. After in ovo administration, the highest dose of the saRNA-LNPs (5 µg) resulted in a visual expression as a weak bioluminescence signal could be seen. The other delivery approaches did not lead to a visual saRNA expression in the embryos. In conclusion, effective entry of saRNA encapsulated in LNPs followed by successful saRNA translation in poultry was established. Hence, mRNA vaccination in poultry could be possible, but further in vivo testing is needed.

[Translated article] Deglufarm: Mobile application with recommendations for the safe administration of drugs in patients with dysphagia or swallowing disorders.

OBJECTIVE: Develop an App to use in healthcare practice, with updated and accurate information on the handling of medications in patients with dysphagia or deglution disorders, as well as their compatibility with food and thickeners. METHODS: The development of the Deglufarm® App was based on the CRONOS, Nutrition and Techno working groups of the Sociedad Española de Farmacia Hospitalaria. A group of specialist pharmacists was created from different care areas for patients with dysphagia. The creation of Deglufarm® consisted of several stages: selection of active drugs, literature review, content development, design (an expert company in App design was contacted), testing, launch, content update and follow-up. RESULTS: Deglufarm® is available for Android and IOS free of charge from July 2022. It has been tested among the members of the research group and collaborators, Currently, 540 monographs of active drugs have been reviewed and registered in Deglufarm. The first version is aimed at healthcare professionals. CONCLUSIONS: Deglufarm® is an easy tool to consult, with the most current evidence on handling the medicines it contains.