Intravenous Route Of Administration Research Articles

Nanoemulsion: Importance in Pharmaceutical Nanotechnology

Nanoemulsions are transparent system mostly covering droplet size in nanometric scale because of their small droplet sizes. This review aims on the method of formulation, evaluation Methods, advantages and disadvantages and the different route of drug delivery of Nanoemulsion. Nanoemulsion is utilized as transdermal drug delivery and characterized as required component, which optimal isotropic and thermodynamically settled aqueous solute with droplet size generally in the size range from 10 to 200 nm. To improves the soluble and permeability of slightly water dissoluble drug. The in-vitro skin penetration profile of optimized manufacturing were compared with general drug formulation. The factors determines the transdermal penetration of medications are the movement of medication in solvent, discharge the medication solvent, also penetration of drug within skin These are enhancing the rate of absorption discharge volatility in absorption and enhance bioavailability. The methods used for the preparation of Nanoemulsions include high pressure homogenization, Microfluidization, ultrasonication, and spontaneous emulsification. The prepared Nanoemulsions are Characertized by in vitro drug release, Thermodynamical stability studies, Nanoemulsion Droplet size. The future direction on Nanoemulsion is to study the drug delivery of topical, parenteral, intravenous and other route of administration. In this review, the discussion is intended to give a basic knowledge about its preparation, evaluation, mechanism and its application.

Pharmacokinetic profiles of levofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits (Oryctolagus cuniculus).

Levofloxacin pharmacokinetic profiles were evaluated in 6 healthy female rabbits after intravenous (I/V), intramuscular (I/M), or subcutaneous (S/C) administration routes at a single dose of 5 mg/kg in a 3 × 3 cross-over study. Plasma levofloxacin concentrations were detected using a validated Ultra Performance Liquid Chromatography method with a fluorescence detector. Levofloxacin was quantifiable up to 10 h post-drug administration. Mean AUC0-last values of 9.03 ± 2.66, 9.07 ± 1.80, and 9.28 ± 1.56 mg/h*L were obtained via I/V, I/M, and S/C, respectively. Plasma clearance was 0.6 mL/g*h after I/V administration. Peak plasma concentrations using the I/M and S/C routes were 3.33 ± 0.39 and 2.91 ± 0.56 µg/mL. Bioavailability values, after extravascular administration were complete, - 105% ± 27% (I/M) and 118% ± 40% (S/C). Average extraction ratio of levofloxacin after I/V administration was 7%. Additionally, levofloxacin administration effects on tear production and osmolarity were evaluated. Tear osmolarity decreased within 48 h post-drug administration. All 3 levofloxacin administration routes produced similar pharmacokinetic profiles. The studied dose is unlikely to be effective in rabbits; however, it was calculated that a daily dose of 29 mg/kg appears effective for I/V administration for pathogens with MIC < 0.5 µg/mL.

Biologic Therapies in Polyarticular Juvenile Idiopathic Arthritis. Comparison of Long‐Term Safety Data from the German BIKER Registry

ObjectiveBiologics have an important role in the treatment of juvenile idiopathic arthritis (JIA). Long‐term safety data are limited. Direct comparison of different agents regarding occurrence of adverse events (AEs), especially of rare events, requires large quantities of patient years. In this analysis, long‐term safety with regard to AE of special interest (AESI) was compared between different biologics.MethodsPatients with nonsystemic JIA were selected from the German BIKER registry. Safety assessments were based on AE reports. Number of AEs, serious AEs, and 25 predefined AESIs, including medically important infection, uveitis, inflammatory bowel disease, cytopenia, hepatic events, anaphylaxis, depression, pregnancy, malignancy, and death, were analyzed. Event rates and relative risks were calculated using AEs reported after first dose through 70 days after last dose.ResultsA total of 3873 patients entered the analysis with 7467 years of exposure to biologics. The most common AESIs were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequent with tocilizumab (risk ratio [RR] 8.0, 95% confidence interval [CI] 4.2‐15, and RR 4.7, 95% CI 1.8‐12.2, respectively). Anaphylactic events were associated with intravenous route of administration. In patients ever exposed to biologics, eight malignancies were reported. Six pregnancies have been documented in patients with tumor necrosis factor inhibitors. No death occurred in this patient cohort during observation.ConclusionSurveillance of pharmacotherapy as provided by the BIKER registry is an import approach, especially for long‐term treatment of children. Overall, tolerance was acceptable. Differences between biologics were noted and should be considered in daily patient care.

Evaluation of Marine Diindolinonepyrane in Vitro and in Vivo: Permeability Characterization in Caco-2 Cells Monolayer and Pharmacokinetic Properties in Beagle Dogs.

A marine fibrinolytic compound was studied for use in thrombolytic therapy. Firstly, the absorption and transportation characteristics of 2,5-BHPA (2,5-BHPA:2,5-Bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-tertahydro-6H-pyran[a]isoindol-2-yl]-pentanoic acid, a novel pyran-isoindolone derivative with bioactivity isolated from a rare marine microorganism in our laboratory) in the human Caco-2 cells monolayer model were investigated. We collected 2,5-BHPA in the cells to calculate the total recovery, and its concentration was analyzed by LC/MS/MS (Liquid Chromatography/Mass Spectrum/Mass Spectrum). The results showed that 2,5-BHPA has low permeability and low total recoveries in the Caco-2 cells membrane. Pharmacokinetics and tissue distribution of 2,5-BHPA were investigated in beagle dogs using HPLC (High Performance Liquid Chromatography) after intravenous administration of three different doses (7.5, 5.0, 2.5 mg·kg−1). Pharmacokinetic data indicated that 2,5-BHPA fitted well to a two-compartment model. Elimination half-lives (T1/2) were 49 ± 2, 48 ± 2, and 49 ± 2 min, respectively; the peak concentrations (Cmax) were 56.48 ± 6.23, 48.63 ± 5.53, and 13.64 ± 2.76 μg·mL−1, respectively; clearance rates (CL) were 0.0062 ± 0.0004, 0.0071 ± 0.0008, and 0.0092 ±0.0006 L·min−1·kg−1, respectively; mean retention times (MRT) were 28.17 ± 1.16, 26.23 ± 0.35, and 28.66 ± 0.84 min, respectively. The low penetrability of 2,5-BHPA indicated that the intravenous route of administration is more appropriate than the oral route. Meanwhile, 2,5-BHPA showed a good pharmacokinetic profile in beagle dogs. The tissue distribution showed that 2,5-BHPA could quickly distribute into the heart, intestines, liver, stomach, spleen, lungs, testicles, urine, intestine, kidneys, brain, and feces. The concentration of 2,5-BHPA was higher in the liver and bile. Interestingly, 2,5-BHPA was detected in the brain. Taken together, the above results suggested that our work might be beneficial in the development of agents for thrombolytic treatment.

Versatile Impact of Serum Proteins on Ruthenium(II) Polypyridyl Complexes Properties - Opportunities and Obstacles.

Ruthenium(II) polypyridyl complexes have been extensively studied for the past few decades as promising anticancer agents. Despite the expected intravenous route of administration, the interaction between Ru(II) polypyridyl compounds and serum proteins is not well characterized and vast majority of the available literature data concerns determination of the binding constant. Ru-protein adducts can modify the biological effects of the Ru complexes influencing their cytotoxic and antimicrobial activity as well as introduce significant changes in their photophysical properties. More extensive research on the interaction between serum proteins and Ru(II) polypyridyl complexes is important for further development of Ru(II) polypyridyl compounds towards their application in anticancer therapy and diagnostics and can open new opportunities for already developed complexes.

Cerium Aminoclay-A Potential Hybrid Biomaterial for Anticancer Therapy.

In this study, novel biomedical properties of Ce-aminoclay (CeAC) were investigated through in vitro and in vivo assays. CeAC (≥500 μg/mL) can selectively kill cancer cells (A549, Huh-1, AGS, C33A, HCT116, and MCF-7 cells) while leaving most normal cells unharmed (WI-38 and CCD-18Co cells). Notably, it displayed a high contrast of simultaneous imaging in HeLa cells by blue photoluminescence without any fluorescence dye. Its anticancer mechanism has been fully demonstrated through apoptosis assays; herein CeAC induced high-level apoptosis (16%), which promoted the expression of proapoptotic proteins (Bax, p53, and caspase 9) in tumor cells. Besides, its biological behavior was determined through antitumor effects using intravenous and intratumoral administration routes in mice implanted with HCT116 cells. During a 40 day trial, the tumor volume and tumor weight were reduced by a maximum of 92.24 and 86.11%, respectively. The results indicate that CeAC exhibits high bioavailability and therapeutic potential based on its unique characteristics, including high antioxidant capacity and electrostatic interaction between its amino functional groups and the mucosal surface of cells. In summary, it is suggested that CeAC, with its high bioimaging contrast, can be a promising anticancer agent for future biomedical applications.

Preemptive Effect of Two Different (Intracuff and Intravenous) Routes of Dexamethasone Administration on Postoperative Sore Throat and Cough

Introduction: The most common complications following anesthesia intubation include postoperative sore throat, post-extubation cough, and hoarse voice. Currently, the use of preoperative Dexamethasone has been effective in controlling these complications. Therefore, the present study aimed to compare the preemptive effect of intracuff and intravenous routes of Dexamethasone administration for postoperative sore throat and cough. Materials and Methods: In the present clinical trial, 96 patients who underwent general anesthesia intubation were randomly assigned to three groups. The first group received 4 mg intracuff Dexamethasone, the second group received 4 mg intravenous Dexamethasone, and the third group was administered a placebo. Cough frequency and severity of a sore throat after extubation were investigated in the three groups. Results: Any significant difference was not observed among the three groups regarding hemodynamic variables (P&gt;0.01); however, the incidence of cough was significantly lower in all the three groups (P&lt;0.01). Also, the average severity of a sore throat in PAR and 1 h after surgery in the three groups was significantly lower (P&lt;0.05). Moreover, no difference was detected in the groups regarding the severity of a sore throat within 24 h post-surgery (P&gt;0.01). Conclusion: The use of two methods of intravenous and intracuff Dexamethasone administration before surgery reduced the incidence of postoperative cough and the severity of sore throat in patients.

The duration of fetal antenatal steroid exposure determines the durability of preterm ovine lung maturation

Antenatal corticosteroids (ACS) are the standard of care for maturing the fetal lung and improving outcomes for preterm infants. Antenatal corticosteroid dosing remains nonoptimized, and there is little understanding of how different treatment-to-delivery intervals may affect treatment efficacy. The durability of a lung maturational response is important because the majority of women treated with antenatal corticosteroids do not deliver within the widely accepted 1- to 7-day window of treatment efficacy. We used a sheep model to test the duration of fetal exposures for efficacy at delivery intervals from 1 to 10 days. For infusion studies, ewes with single fetuses were randomized to receive an intravenous bolus and maintenance infusion of betamethasone phosphate to target 1-4 ng/mL fetal plasma betamethasone for 36 hours, with delivery at 2, 4 ,or 7 days posttreatment or sterile saline solution as control. Animals receiving the clinical treatment were randomised to receive either a single injection of 0.25 mg/kg with a 1:1 mixture of betamethasone phosphate+ betamethasone acetate with delivery at either 1 or 7 days posttreatment, or 2 treatments of 0.25 mg/kg betamethasone phosphate+ betamethasone acetate spaced at 24 hours (giving ∼48 hours of fetal steroid exposure) with delivery at 2, 5, 7, or 10 days posttreatment. Negative control animals were treated with saline solution. All lambs were delivered at 121 ± 3 days gestational age and ventilated for 30 minutes to assess lung function. Preterm lambs delivered at 1 or 2 days post-antenatal corticosteroid treatment had significant improvements in lung maturation for both intravenous and single-dose intramuscular treatments. After 2 days, the efficacy of 36-hour betamethasone phosphate infusions was lost. The single dose of 1:1 betamethasone phosphate+ betamethasone acetate also was ineffective at 7 days. In contrast, animals treated with 2 doses had significant improvements in lung maturation at 2, 5, and 7 days, with treatment efficacy reduced by 10 days. In preterm lambs, the durability of antenatal corticosteroids treatment depends on the duration of fetal exposure and is independent of the intravenous or intramuscular maternal route of administration. For acute 24- to 48-hour posttreatment deliveries, a 24-hour fetal antenatal corticosteroids exposure was sufficient for lung maturation. A fetal exposure duration of at least 48 hours was necessary to maintain long-term treatment durability. A single-dose ACS treatment should be sufficient for women delivering within <48 hours of antenatal corticosteroids treatment.

A dialysis-based in vitro drug release assay to study dynamics of the drug-protein transfer of temoporfin liposomes

Today, a growing number of nanotherapeutics is utilized to deliver poorly soluble compounds using the intravenous route of administration. The drug release and the direct transfer of the active pharmaceutical ingredient to serum proteins plays an important role in bioavailability and accumulation of the drug at the target site. It is closely related to the formation of a protein corona as well as the plasma protein binding of the compound. In the present study, two in vitro drug release methods, the flow-through cell and the dispersion releaser technology, were evaluated with regards to their capability to measure a time-resolved profile of the serum protein binding. In this context, the photosensitizer temoporfin and temoporfin-loaded liposomes were tested. While in the fine capillaries of the flow-through cell a rapid agglomeration of proteins occurred, the dispersion releaser technology in combination with the four-step model enabled the measurement of the transfer of drugs from liposomes to proteins. In presence of 10% of fetal calf serum approximately 20% of the model compound temoporfin were bound to serum proteins within the first 3 h. At higher serum concentration this binding remained stable for approximately 10 h.

Effect of ethnicity on vinorelbine pharmacokinetics: a population pharmacokinetics analysis

BackgroundPharmacokinetics of vinorelbine is mainly known from studies conducted in European patients. Interethnic differences in drug disposition may, however, induce interethnic variation in drug exposure. This paper aimed to evaluate the effect of ethnicity on the bioavailability and clearance of oral and intravenous vinorelbine.MethodsOral and intravenous vinorelbine pharmacokinetics data in Asian patients were pooled from two-phase II studies of patients with non-small-cell lung cancer or advanced breast cancer in China. Blood vinorelbine and its active metabolite, 4′-O-deacetylvinorelbine, were quantified using liquid chromatography–tandem mass spectrometry. Bayesian pharmacokinetic parameters were calculated and vinorelbine monotherapy results (intravenous 25 mg/m2; oral 60 mg/m2) of the Asian data set were compared to a reference European data set (intravenous 30 mg/m2; oral 80 mg/m2). Subsequently, a population pharmacokinetics analysis was conducted in a combined cohort (Asian data set + historical vinorelbine pharmacokinetics database) to investigate for a potential effect of ethnicity.ResultsPharmacokinetics data from the Asian data set (oral: n = 47; intravenous: n = 34) was compared to the European reference data set (oral: n = 48; intravenous: n = 48). Mean apparent clearance of oral vinorelbine and mean absolute clearance of intravenous vinorelbine was comparable between the Asian and reference European data set. A population pharmacokinetic analysis (oral: n = 222; intravenous: n = 111) demonstrated no influence of ethnicity on oral and intravenous vinorelbine bioavailability and clearance.ConclusionVinorelbine pharmacokinetics were found to be comparable between Asian and European patients. No relevant influence of ethnicity on vinorelbine bioavailability and clearance for oral and intravenous routes of administration was observed.

Preventing Radiation-Induced Injury by Topical Application of an Amifostine Metabolite-Loaded Thermogel

Despite the development of high-precision radiation therapy, ionizing radiation inevitably damages healthy tissues. Radiodermatitis and radioinduced oral mucositis are frequent and significant side effects among patients with breast and head and neck cancer, respectively. These radiation-related injuries negatively affect patient quality of life and can lead to unplanned therapeutic breaks and compromise treatment outcomes. Currently, no preventive or mitigating agent has emerged to address these issues. Although amifostine, a well-known free radical scavenger, has proven efficacy against specific radio- and chemo-induced toxicities, severe adverse side effects (reversible hypotension, nausea, emesis, etc) combined with logistical hurdles are associated with its recommended intravenous route of administration, limiting its use. We developed a thermogel containing the active thiol metabolite of amifostine (CPh-1014) that polymerizes at body temperature and serves as a matrix for topical application onto the skin or mucosa. Applied before irradiation, CPh-1014 greatly reduced the severity of oral mucositis and dermatitis induced byeither a single dose or fractionated irradiation regimens in invivo mouse models. The cytoprotective effect of CPh-1014 was confirmed by the decrease in DNA double-strand breaks in the irradiated epithelium. Noticeably, CPh-1014 did not affect radiation therapy efficacy against tumors grafted at submucosal and subcutaneous sites. Incontrast to the intravenous administration of amifostine, CPh-1014 oral application did not induce hypotension indogs. CPh-1014 confers radioprotective effects in healthy tissues with reduced systemic side effects without compromising radiation therapy efficacy. We propose CPh-1014 as an easy-to-implement therapeutic approach to alleviate radiation therapy toxicity in patients with breast and head and neck cancer.

Evidence-Based Guidelines for EMS Administration of Naloxone

The opioid crisis is a growing concern for Americans, and it has become the leading cause of injury-related death in the United States. An adjunct to respiratory support that can reduce this high mortality rate is the administration of naloxone by Emergency Medical Services (EMS) practitioners for patients with suspected opioid overdose. However, clear evidence-based guidelines to direct EMS use of naloxone for opioid overdose have not been developed. Leveraging the recent Agency for Healthcare Research and Quality (AHRQ) systematic review on the EMS administration of naloxone for opioid poisonings, federal partners determined the need for a clinical practice guideline for EMS practitioners faced with suspected opioid poisoning. Project funding was provided by the National Highway Traffic Safety Administration, Office of EMS, (NHTSA OEMS), and the Health Resources and Services Administration, Maternal and Child Health Bureau’s EMS for Children Program (EMSC). The objectives of this project were to develop and disseminate an evidence-based guideline and model protocol for administration of naloxone by EMS practitioners to persons with suspected opioid overdose. We have four recommendations relating to route of administration, all conditional, and all supported by low or very low certainty of evidence. We recommend the intravenous route of administration to facilitate titration of dose, and disfavor the intramuscular route due to difficulty with titration, slower time to clinical effect, and potential exposure to needles. We equally recommend the intranasal and intravenous routes of administration, while noting there are variables which will determine which route is best for each patient. Where we are unable to make recommendations due to evidence limitations (dosing, titration, timing, and transport) we offer technical remarks. Limitations of our work include the introduction of novel synthetic opioids after many of the reviewed papers were produced, which may affect the dose of naloxone required for effect, high risk of bias and imprecision in the reviewed papers, and the introduction of new naloxone administration devices since many of the reviewed papers were published. Future research should be conducted to evaluate new devices and address the introduction of synthetic opioids.

Five Years of Successful Inducible Transgene Expression Following Locoregional Adeno-Associated Virus Delivery in Nonhuman Primates with No Detectable Immunity.

Anti-transgene immune responses elicited after intramuscular (i.m.) delivery of recombinant adeno-associated virus (rAAV) have been shown to hamper long-term transgene expression in large-animal models of rAAV-mediated gene transfer. To overcome this hurdle, an alternative mode of delivery of rAAV vectors in nonhuman primate muscles has been described: the locoregional (LR) intravenous route of administration. Using this injection mode, persistent inducible transgene expression for at least 1 year under the control of the tetracycline-inducible Tet-On system was previously reported in cynomolgus monkeys, with no immunity against the rtTA transgene product. The present study shows the long-term follow-up of these animals. It is reported that LR delivery of a rAAV2/1 vector allows long-term inducible expression up to at least 5 years post gene transfer, with no any detectable host immune response against the transactivator rtTA, despite its immunogenicity following i.m. gene transfer. This study shows for the first time a long-term regulation of muscle gene expression using a Tet-On-inducible system in a large-animal model. Moreover, these findings further confirm that the rAAV LR delivery route is efficient and immunologically safe, allowing long-term skeletal muscle gene transfer.

The Bioavailability, Biodistribution, and Toxic Effects of Silica-Coated Upconversion Nanoparticles in vivo.

Lanthanide-doped upconversion nanoparticles can convert long wavelength excitation radiation to short wavelength emission. They have great potential in biomedical applications, such as bioimaging, biodetection, drug delivery, and theranostics. However, there is little information available on their bioavailability and biological effects after oral administration. In this study, we systematically investigated the bioavailability, biodistribution, and toxicity of silica-coated upconversion nanoparticles administrated by gavage. Our results demonstrate that these nanoparticles can permeate intestinal barrier and enter blood circulation by microstructure observation of Peyer's patch in the intestine. Comparing the bioavailability and the biodistribution of silica-coated upconversion nanoparticles with oral and intravenous administration routes, we found that the bioavailability and biodistribution are particularly dependent on the administration routes. After consecutive gavage for 14 days, the body weight, pathology, Zn and Cu level, serum biochemical analysis, oxidative stress, and inflammatory cytokines were studied to further evaluate the potential toxicity of the silica-coated upconversion nanoparticles. The results suggest that these nanoparticles do not show overt toxicity in mice even at a high dose of 100 mg/kg body weight.

Post-Contrast acute kidney injury. Recommendations for updated of the European Society of Urogenital Radiology Contrast Medium Safety Committee guidelines (2018). Part 1

The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (European Society of Urogenital Radiology (ESUR)) updated its 2011 guidelines for the prevention of post-contrast acute kidney injury (PC-AKI). The recommendations are based on literature review data. The updated guidelines will be presented in two parts: Part 1 are discussed clarification of terminology (in particular differences between PC-AKI and contrast-induced nephropathy), the best ways to estimate glomerular filtration rate (eGFR). There were refined risk factors of PC-AKI, including by intravenous and intra-arterial routes of administration of the contrast agent. The key points of the updated recommendations are: 1. PC-AKI is the preferred term to characterize the impairment of renal function after the administration of a contrast agent; 2. PC-AKI has many causes for development; 3.Risk of development of AKI with intravascular injection of a contrast agent, overestimated; 4. Important risk factors for PC-AKI are chronic kidney disease and dehydration.

Bactericidal and Cytotoxic Properties of Silver Nanoparticles.

Silver nanoparticles (AgNPs) can be synthesized from a variety of techniques including physical, chemical and biological routes. They have been widely used as nanomaterials for manufacturing cosmetic and healthcare products, antimicrobial textiles, wound dressings, antitumor drug carriers, etc. due to their excellent antimicrobial properties. Accordingly, AgNPs have gained access into our daily life, and the inevitable human exposure to these nanoparticles has raised concerns about their potential hazards to the environment, health, and safety in recent years. From in vitro cell cultivation tests, AgNPs have been reported to be toxic to several human cell lines including human bronchial epithelial cells, human umbilical vein endothelial cells, red blood cells, human peripheral blood mononuclear cells, immortal human keratinocytes, liver cells, etc. AgNPs induce a dose-, size- and time-dependent cytotoxicity, particularly for those with sizes ≤10 nm. Furthermore, AgNPs can cross the brain blood barrier of mice through the circulation system on the basis of in vivo animal tests. AgNPs tend to accumulate in mice organs such as liver, spleen, kidney and brain following intravenous, intraperitoneal, and intratracheal routes of administration. In this respect, AgNPs are considered a double-edged sword that can eliminate microorganisms but induce cytotoxicity in mammalian cells. This article provides a state-of-the-art review on the synthesis of AgNPs, and their applications in antimicrobial textile fabrics, food packaging films, and wound dressings. Particular attention is paid to the bactericidal activity and cytotoxic effect in mammalian cells.

Comparison of intravenous, topical or combined routes of tranexamic acid administration in patients undergoing total knee and hip arthroplasty: a meta-analysis of randomised controlled trials

ObjectiveThis study aimed to compare the effects of intravenous, topical and combined routes of tranexamic acid (TXA) administration on blood loss and transfusion requirements in patients undergoing total knee arthroplasty...

Patients beliefs on intravenous and subcutaneous routes of administration of biologics for severe asthma treatment: A cross-sectional observational survey study

BackgroundUnderstanding how patients generate preferences for administration route alternatives may improve health-care delivery and clinical outcomes. Recently, novel biological therapies with subcutaneous (SC) and intravenous (IV) administration routes have been approved for severe uncontrolled asthma. The aim of our study was to assess the preferred route of biologic therapy administration and related beliefs among patients with severe uncontrolled asthma. MethodsWe conducted a cross-sectional observational survey study. Patients answered an anonymous, self-administered questionnaire after an outpatient visit in pulmonary disease clinics located throughout Italy. Socio-demographic and clinical information together with the 12-Item Short Form Survey (SF-12), Work Productivity Impairment Scale and the medical resources utilization module of the Health & Work Survey were collected. Patients beliefs and preference towards SC and IV administration were investigated by means of an ad hoc 13 item questionnaire. Results: the main findings150 patients fulfilled the inclusion criteria and completed the questionnaire (47.3% males). Preference for IV and SC administration was 18.7% and 81.3%, respectively. Compared with patients preferring SC formulation, patients that favored IV were older (p ​= ​0.04), less likely to escalate corticosteroid dose (p ​= ​0.03) and had emergency room (ER) access (p ​= ​0.009) during asthma exacerbations. Patients felt that SC was more convenient than IV, but this belief was not associated with higher likelihood of preferring SC administration. IV formulations were more likely associated with quicker and more effective drug action (p ​= ​0.0001), procedural safety and medical oversight (p ​= ​0.0002) and social support (p ​= ​0.007). Predictors of IV preference were represented by the association of worse asthma control and increased use of ER services, and by beliefs toward formulation effectiveness/efficiency in reducing symptoms (p ​= ​0.04 and p ​< ​0.0001, respectively). The model achieved excellent discrimination of administration route preference (area under the curve ​= ​0.87). ConclusionsPreference is guided by partially misleading beliefs, which may generate wrong expectations that in turn can affect treatment satisfaction and adherence. Convenience and efficacy beliefs for drugs with different routes of administration always should be discussed with patients to achieve informed shared-decision making. Trial registrationNot applicable.

Translocation, biotransformation-related degradation, and toxicity assessment of polyvinylpyrrolidone-modified 2H-phase nano-MoS2.

Nano-MoS2 has been extensively investigated in materials science and biomedicine. However, the effects of different methods of exposure on their translocation, biosafety, and biotransformation-related degradability remain unclear. In this study, we combined the advantages of synchrotron radiation (SR) X-ray absorption near-edge structure (XANES) and high-resolution single-cell SR transmission X-ray microscopy (SR-TXM) with traditional analytical techniques to investigate translocation, precise degraded species/ratio, and correlation between the degradation and toxicity levels of polyvinylpyrrolidone-modified 2H-phase MoS2 nanosheets (MoS2-PVP NSs). These NSs demonstrated different biodegradability levels in biomicroenvironments with H2O2, catalase, and human myeloperoxidase (hMPO) (H2O2 < catalase < hMPO). The effects of NSs and their biodegraded byproducts on cell viability and 3D translocation at the single-cell level were also assessed. Toxicity and translocation in mice via intravenous (i.v.), intraperitoneal (i.p.), and intragastric (i.g.) administration routes guided by fluorescence (FL) imaging were investigated within the tested dosage. After i.g. administration, NSs accumulated in the gastrointestinal organs and were excreted from feces within 48 h. After i.v. injection, NSs showed noticeable clearance due to their decreased accumulation in the liver and spleen within 30 days when compared with that in the i.p. group, which exhibited slight accumulation in the spleen. This work paves the way for understanding the biological behaviors of nano-MoS2 using SR techniques that provide more opportunities for future applications.

Cell therapy for ARDS: efficacy of endobronchial versus intravenous administration and biodistribution of MAPCs in a large animal model

IntroductionBone marrow-derived multipotent adult progenitor cells (MAPCs) are adult allogeneic adherent stem cells currently investigated clinically for use in acute respiratory distress syndrome (ARDS). To date, there is no agreement...