Injectable Emulsion Research Articles

A Novel Etanercept-loaded Nano-emulsion for Targeted Treatment of Inflammatory Arthritis via Draining Lymph Node.

Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune response and inflammatory cytokine production. The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions (NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2. A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were investigated by using a laser particle size analyzer and transmission electron microscopy, respectively. The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation. In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development of the mouse arthritis model. Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA) mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as, anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN. NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work provides an experimental foundation for expanding the clinical application of EN.

Pharmaceutical Considerations and Metabolic Fate of Parenteral Lipid Nanoparticle Dosage Forms

The physical stability of parenteral dispersions for delivery of drugs to patients is of particular clinical importance, given their general overall superior bioavailability compared to other routes of administration. Although official pharmacopeial methods for lipid injectable emulsions have been established for triglyceride oil-in-water dispersions (i.e., “mini-emulsions”) through USP Chapter <729>, no pharmaceopeial guidance exists for lipid nanoparticle (LNP)-based “micro-emulsions”. At present, there are several LNP-based drugs approved for clinical use, including mRNA vaccines. Moreover, the increased interest in using mRNA as a platform technology for an array of potential therapeutic drug candidates increases the importance of developing appropriate methods to ensure their physical stability, safety and efficacy. For all dispersions and by various detection mechanisms (e.g., electrical, mechanical, mathematical), the fusion or growth of droplets/particles in the large-diameter tails of the particle size distribution (PSD) signals the onset of instability. Consequently, the measurement for LNP dispersions will require the use of a modified optical detection design in order to extend the lower particle detection limit into the “relative” large-diameter tail of the PSD for both light extinction and light-scattering methods based on single-particle optical sensing techniques. Fortunately, the technology is currently available and capable of providing the requisite quantitative analysis.

Association between two different lipid injectable emulsions and parenteral nutrition-associated cholestasis in very low birth weight infants: A retrospective cohort study.

Using soybean oil-based lipid emulsions (Intralipid), which contain higher amounts of ω-6 fatty acids and phytosterols in parenteral nutrition, is a risk factor for cholestasis (parenteral nutrition-associated cholestasis [PNAC]). An alternative form of a mixed lipid emulsion (SMOFlipid) has been developed to reduce the risk of PNAC, but significant benefits over Intralipid in very low birth weight (VLBW) infants have yet to be demonstrated. The aim of this study was to compare the differences in PNAC incidence in VLBW infants receiving SMOFlipid vs Intralipid. The study was conducted in Sir Run Run Shaw Hospital of the Zhejiang University School of Medicine, Hangzhou, China, from January 2016 to March 2022. In total, 235 VLBW infants were administered SMOFlipid or Intralipid for ≥21 days and were included in the study. The primary outcome was the incidence of PNAC. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, length of stay, weight 28 days after birth, severity of PNAC, and the time to reversal of PNAC. Forty-four VLBW infants (35.5%) in the SMOFlipid group vs 41 (36.9%) in the Intralipid group achieved PNAC (P = 0.817). The subgroup analysis showed that the peak direct bilirubin level was lower (median [interquartile range] 55.6 [36.4] vs 118.4 [77.2] μmol/L; P < 0.001), and the time to reversal of PNAC was shorter (44 [49] vs 96 [61]; P < 0.001) in the SMOFlipid group than in the Intralipid group. SMOFlipid may represent a better alternative for VLBW infants who require prolonged parenteral nutrition.

Pediatric all-in-one parenteral nutrition stability with 100% fish oil and composite lipid injectable emulsions containing fish oil

Pediatric all-in-one parenteral nutrition stability with 100% fish oil and composite lipid injectable emulsions containing fish oil

All-in-one parenteral nutrition stability with fish oil-containing lipid injectable emulsions

All-in-one parenteral nutrition stability with fish oil-containing lipid injectable emulsions

Guidelines for parenteral nutrition in preterm infants: The American Society for Parenteral and Enteral Nutrition.

Parenteral nutrition (PN) is prescribed for preterm infants until nutrition needs are met via the enteral route, but unanswered questions remain regarding PN best practices in this population. An interdisciplinary committee was assembled to answer 12 questions concerning the provision of PN to preterm infants. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used. Questions addressed parenteral macronutrient doses, lipid injectable emulsion (ILE) composition, and clinically relevant outcomes, including PNALD, early childhood growth, and neurodevelopment. Preterm infants with congenital gastrointestinal disorders or infants already diagnosed with necrotizing enterocolitis or PN-associated liver disease (PNALD) at study entry were excluded. The committee reviewed 2460 citations published between 2001 and 2023 and evaluated 57 clinical trials. For most questions, quality of evidence was very low. Most analyses yielded no significant differences between comparison groups. A multicomponent oil ILE was associated with a reduction in stage 3 or higher retinopathy of prematurity (ROP) compared to an ILE containing 100% soybean oil. For all other questions, expert opinion was provided. Most clinical outcomes were not significantly different between comparison groups when evaluating timing of PN initiation, amino acid dose, and ILE composition. Future clinical trials should standardize outcome definitions to permit statistical conflation of data, thereby permitting more evidence based recommendations in future guidelines. This guideline has been approved by the ASPEN 2022-2023 Board of Directors.

SO,MCT,OO,FO-ILE Is Associated With Better Side Effect Profile Than SO-ILE in Critically Ill Children Receiving Parenteral Nutrition.

This study aimed to evaluate the side effect profile of soybean oil lipid injectable emulsion -(SO-ILE) and soybean oil, medium-chain triglyceride, olive oil, fish oil lipid injectable emulsion (SO,MCT,OO,FO-ILE) in critically ill children requiring parenteral nutrition (PN). This is an observational study of children admitted to our pediatric intensive care unit requiring PN for ≥7 days. Patients were divided into 2 cohorts: SO,MCT,OO,FO-ILE (n = 34) and SO-ILE (n = 111). Outcomes included development of hypertriglyceridemia (HTG), intestinal failure-associated liver disease (IFALD), length of stay, and mortality. Logistic regression was performed after controlling for duration and maximum dose of lipids. The median maximum lipid dose was significantly higher in the SO,MCT,OO,FO-ILE cohort (2.7 vs 3 g/kg; p = 0.01). Prevalence of baseline HTG was similar in both cohorts. After excluding patients with baseline HTG, incidence of HTG upon PN introduction was higher in the SO-ILE cohort (51.2% vs 26.7%; p = 0.02). The SO-ILE cohort also had significantly higher triglyceride concentrations at peak and upon discontinuation of PN (p < 0.05). Direct bilirubin and C-reactive protein were significantly higher in the SO-ILE cohort after stopping PN. Five patients (3.4%) developed IFALD, 4 of whom were in the SO-ILE cohort (p = 0.85). Upon logistic regression, mortality rate and incidence of HTG remained significantly higher in the SO-ILE cohort (adjusted odds ratio, 2.3 [95% CI, 1.1-5.3]; p = 0.04; and adjusted odds ratio, 2.0 [95% CI, 1.3-5.1]; p = 0.03, respectively). In critically ill children requiring PN, SO-ILE was associated with a higher risk of HTG, -elevated direct bilirubin, inflammatory markers and mortality compared with SO,MCT,OO,FO-ILE.

Drug-drug interaction of ciprofol injectable emulsion with mefenamic acid capsules in healthy subjects.

To investigate the drug-drug interaction (DDI) of ciprofol injectable emulsion and mefenamic acid capsules in healthy subjects. Twenty healthy subjects were enrolled in this single-centre, open-label, two-period DDI study. Ciprofol (0.4mg kg-1 ) was administered as a single dose on days 1 and 5. A 500-mg oral loading dose of mefenamic acid was given on day 4 followed by a 250-mg maintenance dose every 6h (a total of eight doses). Blood samples for pharmacokinetic analyses were collected. Depth of anaesthesia was monitored using the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale and Bispectral Index scores (BISs). Compared with administration of ciprofol alone, administration with mefenamic acid showed no significant difference in exposure. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) for maximum plasma concentration (Cmax ), area under the plasma concentration-time curve calculated from 0 to the last measurement point (AUC0-last ) and AUC to infinity (AUC0-inf ) were 91.6% (86.5-96.9%), 103.3% (100.3-106.4%) and 107.0% (101.2-113.2%), respectively. The MOAA/S and BIS curves for the two treatment periods essentially coincided, indicating that the anaesthesia effect of ciprofol was not affected by mefenamic acid. Seven subjects (35%) reported eight adverse events (AEs) when ciprorol was administered alone and 12 subjects (60%) reported 18 AEs when ciprofol was administered in combination with mefenamic acid. All AEs were mild. Mefenamic acid, a UGT1A9 inhibitor, had no significant effect on the pharmacokinetics and pharmacodynamics of ciprofol in healthy subjects. Ciprofol was safe and well tolerated when administered with mefenamic acid.

Proinflammatory mediators in lipid emulsions and parenteral-nutrition associated liver disease: Review of leading factors.

Lipid injectable emulsions have been in clinical use for over 60 years. The first product launched was Intralipid, which consisted of an emulsion of soybean oil in water for intravenous administration. It was a key source of essential fatty acids and an alternative source of energy for patients with gastrointestinal dysfunction requiring long-term parenteral nutrition. With clinical experience, a condition known as parenteral nutrition-associated liver disease (PNALD), or intestinal failure-associated liver disease (IFALD), was observed, with a focus on carbohydrate and fat energy. Modifying the daily doses and infusion rates had some salutary effects, but PNALD persisted. Subsequently, on closer inspection of the fatty acids profile and phytosterol concentrations, degradation products arising from chemical and physical stability issues of the available lipid injectable emulsions were implicated. Recently, the US Food and Drug Administration convened an online workshop entitled "The Role of Phytosterols in PNALD/IFALD," with an emphasis on (1) the multifactorial pathophysiology of PNALD/IFALD, (2) risk associated with phytosterols, and (3) regulatory history. The scope of this review includes the multifactorial pathophysiology of PNALD/IFALD as it relates to the pharmaceutical aspects of the various lipid injectable emulsions on the market, with respect to potential proinflammatory components, as well as physical and chemical stability issues that may also affect products' safe intravenous administration to patients.

SIMULTANEOUS DETERMINATION OF PHYTONADIONE AND ITS DEGRADANTS BY HPLC IN INJECTABLE EMULSION FORMULATION USED TO TREAT VKDB IN NEWBORNS

Phytonadione, also known as Phytomenadione or Vitamin K1 is used as an Injectable emulsion is used to Newborns for the precautionary treatment for Vitamin K Deficiency Bleeding (VKDB) during birth. In the current study, A Gradient, Sensitive &amp; Cost effective HPLC method has been developed to determine and quantify the degradants of Phytonadione and Benzyl Alcohol into Phytonadione Injectable Emulsion. The chromatographic separation was performed by GL Sciences Inert sustain HP™ C18 (250 × 4.6 mm, 3.0 μ) column. The degradants were well separated by a gradient program started with the mixture of 25 mM Ammonium Acetate in water as buffer, pH 3.5 and Methanol in the ratio of 40: 60 V/V at the flow rate of 1.0 mL min­­‑1 and UV detection was performed at 254 nm. The degradation products from Phytonadione and Benzyl Alcohol were well resolved from the main peaks and its other impurities by the developed method. The method was validated by complying specificity/selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy and precision following ICH Q2 (R1). The developed method in this study could be applied for the analysis of routine quality control related substances of Phytonadione Injectable Emulsion, since there is no official monograph. KEYWORDS: Phytomenadione, Vitamin K, Method validation, Impurities, Degradants.

Comparison of in vivo pharmacokinetic behaviors of R- and S-flurbiprofen after intravenous injection of flurbiprofen axetil.

Flurbiprofen axetil (FA) is a prodrug of flurbiprofen (FP), and it is hydrolyzed to the active FP by carboxylesterase in plasma after intravenous injection. The pharmacological action of FP is closely related to its chirality, and S-FP shows better analgesic effects than R-FP. Therefore, it is of great significance to compare the in vivo pharmacokinetic behaviors of R-FP and S-FP. In this study, we designed a sensitive high performance liquid chromatography-tandem mass spectrometry method and used CHIRALPAK-IG3 column for chiral separation to quantify the concentrations of R-FP and S-FP in rat plasma. The results show that this method can accurately and effectively analyze the contents of R-FP and S-FP in plasma. In addition, the systemic exposure was approximately 3.09-folds for the S-FP compared with the R-FP following intravenous administration of the FA to rats at a single dose of 4.5mg/kg. More importantly, the clearance rate of S-FP is significantly smaller than that of R-FP. Therefore, the development of S-FA injectable emulsion for clinical treatment of postoperative pain is very necessary.

METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF CLASS-I ELEMENTAL IMPURITIES IN PROPOFOL EMULSION USING ICP-MS

Elemental impurities are the traces of metals that can be found in finished drug products which may enter through various sources like excipients, and active pharmaceutical ingredients etc., their toxicity is to be estimated as they may pose serious toxicological effects to patients. The aim of this work is to estimate Class-I elements (Cd, Pb, As, Hg) simultaneously in Propofol 10 mg/mL Emulsion for Injection or Infusion using modern technique Inductively coupled plasma mass spectrometry, employing microwave-assisted digestion of sample. The developed method was validated for various parameters according to ICHQ2(R1) to prove that the developed method is fit for the required purpose and can be adaptable regularly. Validation results showed that the method was linear over the range of LOQ to 250%, with a good linearity correlation factor of R≥0.99, the method was found to be robust against the deliberate changes in sample preparation and uptake speed.

Clinical impact of lipid injectable emulsion in internal medicine inpatients exclusively receiving parenteral nutrition: a propensity score matching analysis from a Japanese medical claims database

BackgroundAlthough guidelines recommend lipid injectable emulsions (ILEs) be used as a part of parenteral nutrition, many patients in Japan receive lipid-free parenteral nutrition. Furthermore, little is known about the effect of ILEs on clinical outcomes in medical inpatients managed with parenteral nutrition. The aim of this study was to investigate the clinical impact of ILEs on internal medicine inpatients receiving parenteral nutrition.MethodsA propensity score matching (PSM) analysis was performed using a medical claims database covering 451 hospitals in Japan. Participants included the following internal medicine inpatients, ages ≥ 18 years, fasting > 10 days, and receiving exclusively parenteral nutrition, between 2011 and 2020. Participants were divided into 2 groups: those who did and did not receive ILEs. The primary endpoint was in-hospital mortality. The secondary endpoints included intravenous catheter infection, activities of daily living (ADL), hospital length of stay (LOS), and total medical costs. To adjust for energy doses, logistic or multiple regression analyses were performed using energy dose as an additional explanatory variable.ResultsAfter PSM, 19,602 matched pairs were formed out of 61,437 patients. The ILE group had significantly lower incidences than the non-ILE group of in-hospital mortality (20.3% vs. 26.9%; odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66–0.72; p < 0.001), deteriorated ADL (10.8% vs. 12.5%; OR, 0.85; 95% CI, 0.79–0.92; p < 0.001), and shorter LOS (regression coefficient, − 0.8; 95% CI, − 1.6–0.0; p = 0.045). After adjusting for energy dose, these ORs or regression coefficients demonstrated the same tendencies and statistical significance. The mean total medical costs were $21,009 in the ILE group and $21,402 in the non-ILE group (p = 0.08), and the adjusted regression coefficient for the ILE vs. the non-ILE group was − $860 (95% CI, − $1252 to − $47).ConclusionsILE use was associated with improved clinical outcomes, including lower in-hospital mortality, in internal medicine inpatients receiving parenteral nutrition.

Syringe-dispensed omega-3 lipid injectable emulsions should be stored under airtight refrigeration: A proposal for the efficient supply of unapproved precious lipid resources.

Both fish-oil lipid injectable emulsion (FO-ILE) and mixed-oil lipid injectable emulsion (MO-ILE) are key components of parenteral nutrition and require importation into Japan, and they are easily oxidized after opening. Given the small daily volumes of these lipids dispensed in infants and children with intestinal failure (IF), the purpose of the study was to identify the optimal storage method. Lipids were prepared in polypropylene syringes in the following manner: air-sealing and photoprotection, air-sealing only, photoprotection only, and uncovered. Samples were stored for 14 days at 4°C or 26°C. The degree of oxidative degradation was evaluated by measuring malondialdehyde (MDA) concentration and pH and comparing them to the values measured immediately after opening. For FO-ILE, the increase in MDA concentration for 14 days was insignificant in air-sealed samples, regardless of photoprotection (+0.45 μM, P = 1.0) or no photoprotection (+0.52 μM, P = 1.0). This trend was more pronounced at 4°C than at 26°C (P < 0.01). The maximum pH decrease was 0.08 at 4°C. MO-ILE exhibited an insignificant increase in MDA concentration for 14 days with air-sealed samples, regardless of photoprotection (+0.36 μM, P = 0.11) or no photoprotection (+0.33 μM, P = 0.76). This trend was more pronounced at 4°C than at 26°C (P < 0.01). The maximum pH decrease was 0.12 at 4°C. For soybean-oil lipid injectable emulsion, the trend was similar with no considerable deterioration. Syringe-dispensed FO-ILE and MO-ILE stored under airtight refrigeration remained undeteriorated for 14 days. Our results are considered clinically valuable when supplying these expensive resources for infants with IF.

The impact of a lipid injectable emulsion (SMOF) on conjugated bilirubin levels in children receiving prolonged parenteral nutrition: A large single center experience

The SMOFlipid is a composite emulsion that has showed benefits, but limited data is available on children receiving prolonged parenteral nutrition (PN). This study aimed to compare conjugated bilirubin (CB) levels at the end of ILE administration in this population. Medical charts of all infants treated with Intralipid (Jan 2012-Sep 2013) or SMOFlipid (Oct 2013-Dec 2016) were reviewed. Only infants that received PN for ≥28 consecutive days were included. Laboratory data were extracted from the closest day of initiation and discontinuation of the ILE (±7 days). For the primary objective, an analysis of covariance was employed, adjusting for initial CB values and total days of ILE administration. CB values were log-transformed to normalize distribution. Statistical tests were two-sided and performed at the significance level <0.05. A total of 150 infants were included: 72 used Intralipid for 82 times and 88 received SMOFlipid in 92 occasions. The incidence of cholestasis was 20% (Intralipid) and 4.5% (SMOFlipid). Infants treated with SMOFlipid had significantly lower CB levels at the end of ILE administration with geometric mean ratio between groups of 1.7 (95% CI:1.0, 2.8; p<0.05). In a large and heterogenous group of infants receiving PN for ≥28 consecutive days the final levels of CB were significantly lower with SMOFlipid when compared to Intralipid suggesting a protective role of this type of ILE in this high-risk population. SMOFlipid is an emulsion that has showed benefits, but limited data is available on children receiving prolonged parenteral nutrition (PN). This study compared conjugated bilirubin (CB) levels at the end of ILE administration in infants that received PN for ≥28 consecutive days with either SMOFlipid or Intralipid. In a large number of patients with several gastrointestinal diseases lower CB levels were observed with the use of SMOFlipid with geometric mean ratio between groups of 1.7 (95% CI:1.0, 2.8; p<0.05). Our results demonstrate a protective role of this type of ILE in this high-risk population.

Propofol Augments Paclitaxel-Induced Cervical Cancer Cell Ferroptosis In Vitro.

Introduction: Cervical cancer is common in women. The present standardized therapies including surgery, chemotherapy, and radiotherapy are still not enough for treatment. Propofol is the most commonly used intravenous anesthetic agent for induction and maintenance of anesthesia and has been shown to exert anti-malignancy effects on cancer cells, inducing oxidative stress and apoptosis. However, the biological effects of propofol have not yet been systematically assessed. In this study, we examined the ferroptosis-related changes caused by propofol and the chemotherapeutic agent paclitaxel besides apoptosis in vitro. Methods: Cervical cancer cell lines (C-33A and HeLa) were treated with propofol alone (1, 2, 5, 10, and 20 μg/ml) or in combination with paclitaxel (0.5, 1, and 5 μg/ml). The viability was assessed using cell counting kit-8 (CCK8), apoptosis was detected by flow cytometry, morphological changes of mitochondria were examined using transmission electron microscope (TEM), cellular reactive oxygen species (ROS), and intracellular ferrous ions were determined by fluorescence microscope or confocal microscopy. The expression and cellular localization of apoptosis and ferroptosis-related molecules were detected by Western blot and multiplex immunohistochemistry (mIHC), respectively. Calcusyn software was used to determine whether propofol has a synergistic effect with paclitaxel. Results: Propofol and paclitaxel inhibited C-33A and HeLa cell viability. There were also synergistic effects when propofol and paclitaxel were used in combination at certain concentrations. In addition, propofol promoted paclitaxel-induced cervical cancer cell death via apoptosis. ROS level and Fe2+ concentrations were also influenced by different drug treatments. Furthermore, propofol, propofol injectable emulsion, and paclitaxel induced ferroptosis-related morphological changes of mitochondria in C-33A and HeLa cells. Ferroptosis-related signaling pathways including SLC7A11/GPX4, ubiquinol/CoQ10/FSP1, and YAP/ACSL4/TFRC were found to be changed under drug treatments. Conclusion: Propofol showed synergistic anticancer effects with paclitaxel in cervical cancer cells. Propofol and paclitaxel may induce ferroptosis of cervical cancer cells besides apoptosis.

Propofol Inhibits Proliferation and Augments the Anti-Tumor Effect of Doxorubicin and Paclitaxel Partly Through Promoting Ferroptosis in Triple-Negative Breast Cancer Cells.

BackgroundTriple-negative breast cancer (TNBC) is relatively common in women and is associated with a poor prognosis after surgery and adjuvant chemotherapy. Currently, the mechanism underlying the relationship between propofol and breast cancer is controversial and limited to cell apoptosis. Moreover, there are only a few studies on the effect of propofol on the chemotherapeutic sensitivity of TNBC cells. Therefore, this study explored whether propofol and its commonly used clinical formulations affect the proliferation and chemotherapeutic effects on TNBC cells by regulating cell ferroptosis.MethodsWe selected MDA-MB-231 cells, and the effects of propofol, propofol injectable emulsion (PIE), or fospropofol disodium, alone or combined with doxorubicin or paclitaxel on cell viability, apoptosis, intracellular reactive oxygen species (ROS) accumulation, ferroptosis-related morphological changes, intracellular Fe2+ levels, and the expression and localization of ferroptosis-related proteins were investigated.ResultsWe found that propofol significantly inhibited MDA-MB-231 cell proliferation, and all three propofol formulations augmented the anti-tumor effects of doxorubicin and paclitaxel. The results from the ROS assay, transmission electron microscopy, intracellular Fe2+ assay, western blotting, and multiplex immunohistochemistry revealed that propofol not only induced apoptosis but also triggered ferroptosis-related changes, including morphological changes of mitochondria, increased intracellular ROS levels, and intracellular iron accumulation in MDA-MB-231 cells. The ferroptosis-related p53-SLC7A11-GPX4 pathway was also altered under different treatment propofol, doxorubicin, or paclitaxel regimens.ConclusionPropofol showed anti-proliferation effects on TNBC cells and could be a potential adjuvant to enhance the chemotherapeutic sensitivity of TNBC cells partly by promoting cell ferroptosis.

Exploring the long-term risk factors associated with intestinal failure-associated liver disease in pediatric and adult patients: The role of lipid injectable emulsions in the development of liver disease.

Despite parenteral nutrition (PN) being life sustaining, one of the risk factors associated with its long-term use is intestinal failure-associated liver disease (IFALD), which increases the risk for morbidity and mortality. This review examines some of the risk factors associated with IFALD. A literature review using the databases PubMed, EMBASE, and CINAHL between 2010 and 2020 was performed using search terms, including long-term total PN and liver failure, serum plant sterols and liver failure, and complications and PN. Articles in English using both human and animal participants were included. The pathophysiology associated with PN and liver disease is multifactorial and influenced by the remaining small-bowel length, presence of the ileal cecal valve, lack of enteral stimulation, type of lipid injectable emulsion (ILE), plant sterol content, and excessive calories. The type of ILE plays a major role because of the phytosterol (PS) content, affecting the microbiome composition and inhibiting key gut signals. The PS content is highest in soy oil (SO)-based ILE, which increases inflammation and impairs biliary flow. Serum PS correlates with liver biomarker abnormalities and is highest in SO-based ILE use compared with mixed-oil emulsions. Selection of a low-PS content ILE is recommended to reduce the risk of biliary cholestasis. Stimulation of the gut, if possible, is recommended to maintain gut integrity and reduce bacterial overgrowth. Fish oil (FO) shows promise in IFALD reversal however, large randomized controlled trials are needed to further establish support for the use of FO in adults.

Guidelines for the provision of nutrition support therapy in the adult critically ill patient: The American Society for Parenteral and Enteral Nutrition.

This guideline updates recommendations from the 2016 American Society for Parenteral and Enteral Nutrition (ASPEN)/Society of Critical Care Medicine (SCCM) critical care nutrition guideline for five foundational questions central to critical care nutrition support. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process was used to develop and summarize evidence for clinical practice recommendations. Clinical outcomes were assessed for (1) higher vs lower energy dose, (2) higher vs lower protein dose, (3) exclusive isocaloric parenteral nutrition (PN) vs enteral nutrition (EN), (4) supplemental PN (SPN) plus EN vs EN alone, (5A) mixed-oil lipid injectable emulsions (ILEs) vs soybean oil, and (5B) fish oil (FO)-containing ILE vs non-FO ILE. To assess safety, weight-based energy intake and protein were plotted against hospital mortality. Between January 1, 2001, and July 15, 2020, 2320 citations were identified and data were abstracted from 36 trials including 20,578 participants. Patients receiving FO had decreased pneumonia rates of uncertain clinical significance. Otherwise, there were no differences for any outcome in any question. Owing to a lack of certainty regarding harm, the energy prescription recommendation was decreased to 12-25 kcal/kg/day. No differences in clinical outcomes were identified among numerous nutrition interventions, including higher energy or protein intake, isocaloric PN or EN, SPN, or different ILEs. As more consistent critical care nutrition support data become available, more precise recommendations will be possible. In the meantime, clinical judgment and close monitoring are needed. This paper was approved by the ASPEN Board of Directors.

Simultaneous Determination of Phytonadione and its Degradants by High Performance Liquid Chromatography in Injectable Emulsion Formulation Used to Treat Vkdb in Newborns

Simultaneous Determination of Phytonadione and its Degradants by High Performance Liquid Chromatography in Injectable Emulsion Formulation Used to Treat Vkdb in Newborns