Activation of Nrf2 and FXR via Natural Compounds in Liver Inflammatory Disease.

Liver inflammation is frequently linked to oxidative stress and dysregulation of bile acid and fatty acid metabolism. This review focuses on the farnesoid X receptor (FXR), a critical regulator of bile acid homeostasis, and its interaction with the nuclear factor erythroid 2-related factor 2 (Nrf2), a key modulator of cellular defense against oxidative stress. The review explores the interplay between FXR and Nrf2 in liver inflammatory diseases, highlighting the potential therapeutic effects of natural FXR agonists. Specifically, compounds such as auraptene, cafestol, curcumin, fargesone A, hesperidin, lycopene, oleanolic acid, resveratrol, rutin, ursolic acid, and withaferin A are reviewed for their ability to modulate both the FXR and Nrf2 pathways. This article discusses their potential to alleviate liver inflammation, oxidative stress, and damage in diseases such as metabolic-associated fatty liver disease (MAFLD), cholestatic liver injury, and viral hepatitis. In addition, we address the molecular mechanisms driving liver inflammation, including oxidative stress, immune responses, and bile acid accumulation, while also summarizing relevant experimental models. This review emphasizes the promising therapeutic potential of targeting both the Nrf2 and FXR pathways using natural compounds, paving the way for future treatments for liver diseases. Finally, the limitations of the clinical application were indicated, and further research directions were proposed.

Honokiol Is More Potent than Magnolol in Reducing Head and Neck Cancer Cell Growth.

The efficacy of treatment of head and neck squamous cell carcinoma (HNSCC) patients is still unsatisfactory, and there is an ongoing search for novel therapies. Locoregionally advanced HNSCC cases, which frequently require combined surgery and chemoradiotherapy, are especially difficult to treat. Natural compounds, like Magnolia-derived lignans-honokiol (HON) and magnolol (MAG)-can reduce cancer cell growth but retain a good safety profile and thus may show benefit as adjuvant therapeutics. The aim of this study was to evaluate the anti-cancer effects of HON and MAG in HNSCC cell lines and compare their effects between cisplatin-sensitive and cisplatin-tolerant cells. Cell viability was evaluated in FaDu and SCC-040 cells growing as monolayers and as spheroids. The effect of HON and MAG on the cell cycle, apoptosis, and gene expression was compared between wild-type FaDu cells and cisplatin persister FaDu cells. We observed that HON and MAG were more potent in reducing cell viability in cisplatin persister FaDu cells, although this effect was not directly followed by increased rates of apoptosis. Thus, HON's and MAG's capacity to affect cisplatin persister cells needs further studies. In general, we observed that HON exerted stronger cytotoxic effects than MAG in HNSCC cells, and the difference in their anti-cancer activity was especially pronounced in cells cultured in 3D.

Molecular Mechanisms Underlying Hepatoprotective Activity of Lutein in the Context of Intestinal Failure-Associated Liver Disease.

Intestinal failure-associated liver disease (IFALD) is a spectrum of liver diseases occurring in patients not exposed to liver-damaging factors other than those linked to intestinal dysfunction. The pathogenesis of this disease is multifactorial. It is estimated that up to 90% of people taking long-term parenteral nutrition may develop IFALD, with particular risk for premature neonates and infants due to their immature antioxidant protection and bile acid metabolism. The lack of effective prevention and treatment methods for IFALD encourages scientists to search for new therapeutic solutions. The use of lutein as a substance with antioxidant and anti-inflammatory effects seems to be of great potential in such indication, especially since patients on parenteral nutrition are at risk of deficits in various plant-based nutrients, including lutein. In this review, we explain the pathogenesis of IFALD and summarize knowledge of the hepatoprotective properties of lutein, underscoring its potential as a treatment option. The hepatoprotective effects of lutein and their proposed mechanisms of action are supported by studies on cells and animals exposed to various liver-damaging factors, such as lipopolysaccharide, high-fat diet, alcohol, and more. Finally, we provide perspectives on the future application of lutein in therapy.

Natural bioactive compounds-The promising candidates for the treatment of intestinal failure-associated liver disease.

Parenteral nutrition (PN) is a life-saving procedure conducted to maintain a proper nutritional state in patients with severe intestinal failure who cannot be fed orally. A serious complication of PN therapy is liver failure, known as intestinal failure-associated liver disease (IFALD). The pathogenesis of IFALD is multifactorial and includes inhibition of the farnesoid X receptor (FXR) by PN components, bacteria translocation from impaired intestines, and intravenous line-associated bloodstream infection. Currently, the most frequently researched therapeutic option for IFALD is using lipid emulsions based on soy or fish oil and, therefore, free from phytosterols known as FXR antagonists. Nevertheless, the potential side effects of the lack of soybean oil delivery seem to outweigh the benefits, especially in the pediatric population. PN admixture provides all the necessary nutrients; however, it is deprived of exogenous natural bioactive compounds (NBCs) of plant origin, such as polyphenols, characterized by health-promoting properties. Among them, many substances have already been known to demonstrate the hepatoprotective effect in various liver diseases. Therefore, searching for new therapeutic options for IFALD among NBCs seems reasonable and potentially successful. This review summarizes the recent research on polyphenols and their use in treating various liver diseases, especially metabolic dysfunction-associated steatotic liver diseases (MASLD). Furthermore, based on scientific reports, we have described the molecular mechanism of action of selected NBCs that exert hepatoprotective properties. We also summarized the current knowledge on IFALD pathogenesis, described therapeutic options undergoing clinical trials, and presented the future perspective of the potential use of NBCs in PN therapy.

The Anticancer Application of Delivery Systems for Honokiol and Magnolol.

Cancer is a leading cause of death worldwide, and the effectiveness of treatment is consistently not at a satisfactory level. This review thoroughly examines the present knowledge and perspectives of honokiol (HON) in cancer therapeutics. The paper synthesizes critical insights into the molecular mechanisms underlying the observed anticancer effects, emphasizing both in vitro and in vivo studies. The effects of HON application, primarily in the common types of cancers, are presented. Because the therapeutic potential of HON may be limited by its physicochemical properties, appropriate delivery systems are sought to overcome this problem. This review discusses the effect of different nanotechnology-based delivery systems on the efficiency of HON. The data presented show that HON exhibits anticancer effects and can be successfully administered to the site of action. Honokiol exerts its anticancer activity through several mechanisms. Moreover, some authors used the combinations of classical anticancer drugs with HON. Such an approach is very interesting and worth further investigation. Understanding HON's multiple molecular mechanisms would provide valuable insights into how HON might be developed as an effective therapeutic. Therefore, further research is needed to explore its specific applications and optimize its efficacy in diverse cancer types.

Fisetin modulates the gut microbiota alongside biomarkers of senescence and inflammation in a DSS-induced murine model of colitis.

Colitis, a subtype of inflammatory bowel disease (IBD), is a multifactorial disorder characterized by chronic inflammation of the colon. Among various experimental models used in the study of IBD, the chemical colitogenic dextran sulfate sodium (DSS) is most commonly employed to induce colitis in vivo. In the search for new therapeutic strategies, Fisetin, a flavonoid found in many fruits and vegetables, has recently garnered attention for its senolytic properties. Female mice were administered 2.5% DSS in sterile drinking water and were subsequently treated with Fisetin or vehicle by oral gavage. DSS significantly upregulated beta-galactosidase activity in colonic proteins, while Fisetin remarkably inhibited its activity to baseline levels. Particularly, qPCR revealed that the senescence and inflammation markers Vimentin and Ptgs2 were elevated by DSS exposure with Fisetin treatment inhibiting the expression of p53, Bcl2, Cxcl1, and Mcp1, indicating that the treatment reduced senescent cell burden in the DSS targeted intestine. Alongside, senescence and inflammation associated miRNAs miR-149-5p, miR-96-5p, miR-34a-5p, and miR-30e-5p were significantly inhibited by DSS exposure and restored by Fisetin treatment, revealing novel targets for the treatment of IBDs. Metagenomics was implemented to assess impacts on the microbiota, with DSS increasing the prevalence of bacteria in the phyla Bacteroidetes. Meanwhile, Fisetin restored gut health through increased abundance of Akkermansia muciniphila, which is negatively correlated with senescence and inflammation. Our study suggests that Fisetin mitigates DSS-induced colitis by targeting senescence and inflammation and restoring beneficial bacteria in the gut indicating its potential as a therapeutic intervention for IBDs.

Tea-break with epigallocatechin gallate derivatives - Powerful polyphenols of great potential for medicine.

Epigallocatechin gallate (EGCG) is a polyphenol present in green tea (Camellia sinensis), which has revealed anti-cancer effects toward a variety of cancer cells in vitro and protective potential against neurodegenerative diseases such as Alzheimer's and Parkinson's. Unfortunately, EGCG presents disappointing bioavailability after oral administration, primarily due to its chemical instability and poor absorption. Due to these limitations, EGCG is currently not used in medication, but only as a dietary supplement in the form of green tea extract. Therefore, it needs further modifications before being considered suitable for extensive medical applications. In this article, we review the scientific literature about EGCG derivatives focusing on their biological properties and potential medical applications. The most common chemical modifications of epigallocatechin gallate rely on introducing fatty acid chains or sugar molecules to its chemical structure to modify solubility. Another frequently employed procedure is based on blocking EGCG's hydroxyl groups with various substituents. Novel derivatives reveal interesting properties, of which, antioxidant, anti-inflammatory, antitumor and antimicrobial, are especially important. It is worth noting that the most promising EGCG derivatives present higher stability and activity than base EGCG.

The Development of Magnolol-Loaded Intravenous Emulsion with Low Hepatotoxic Potential.

Intestinal failure-associated liver disease (IFALD) is a severe liver injury occurring due to factors related to intestinal failure and parenteral nutrition administration. Different approaches are studied to reduce the risk or ameliorate the course of IFALD, including providing omega-3 fatty acids instead of soybean oil-based lipid emulsion or administering active compounds that exert a hepatoprotective effect. This study aimed to develop, optimize, and characterize magnolol-loaded intravenous lipid emulsion for parenteral nutrition. The preformulation studies allowed for chosen oils mixture of the highest capacity of magnolol solubilization. Then, magnolol-loaded SMOFlipid was developed using the passive incorporation method. The Box-Behnken design and response surface methodology were used to optimize the entrapment efficiency. The optimal formulation was subjected to short-term stress tests, and its effect on normal human liver cells and erythrocytes was determined using the MTT and hemolysis tests, respectively. The optimized magnolol-loaded SMOFlipid was characterized by the mean droplet diameter of 327.6 ± 2.9 nm with a polydispersity index of 0.12 ± 0.02 and zeta potential of -32.8 ± 1.2 mV. The entrapment efficiency of magnolol was above 98%, and pH and osmolality were sufficient for intravenous administration. The magnolol-loaded SMOFlipid samples showed a significantly lower toxic effect than bare SMOFlipid in the same concentration on THLE-2 cells, and revealed an acceptable hemolytic effect of 8.3%. The developed formulation was characterized by satisfactory stability. The in vitro studies showed the reduced cytotoxic effect of MAG-SMOF applied in high concentrations compared to bare SMOFlipid and the non-hemolytic effect on human blood cells. The magnolol-loaded SMOFlipid is promising for further development of hepatoprotective lipid emulsion for parenteral nutrition.

A critical review of the novelties in the development of intravenous nanoemulsions.

Nanoemulsions have gained increasing attention in recent years as a drug delivery system due to their ability to improve the solubility and bioavailability of poorly water-soluble drugs. This systematic review aimed to collect and critically analyze recent novelties in developing, designing, and optimizing intravenous nanoemulsions appearing in articles published between 2017 and 2022. The applied methodology involved searching two electronic databases PubMed and Scopus, using the keyword "nanoemulsion" in combination with "intravenous" or "parenteral". The resulting original articles were classified by the method of preparation into different categories. An overview of the current methods used for the preparation of such formulations, including high- and low-energy emulsification, was provided. The advantages and disadvantages of these methods were discussed, as well as their potential impact on the properties of the developed intravenous nanoemulsions. The problem of inconsistency in intravenous nanoemulsion terminology may lead to misunderstandings and misinterpretations of their properties and applications was also undertaken. Finally, the regulatory aspects of intravenous nanoemulsions, the state of the art in the field of intravenous emulsifiers, and the future perspectives were presented.

Improving the Safety of Clinical Management of COVID-19 Patients Receiving Aminoglycosides and Parenteral Nutrition: Y-site Compatibility Studies.

PURPOSE: Aminoglycosides (AMGs) are broad-spectrum bactericidal antibiotics that can resolve bacterial infections co-existing with COVID-19 or exploit their potential antiviral activities. Patients presenting the most severe forms of COVID-19 due to escalating catabolism and significant lean body mass loss often require the concomitant administration of parenteral nutrition (PN) and antibiotics. The Y-site administration is one of the approaches allowing the co-administration of two intravenous medications in patients with limited vascular access. Our study aimed to investigate the compatibility of AMGs and selected commercial PN admixtures enriched in omega-3 fatty acids. METHODS: Gentamycin (GM), amikacin (AM), and tobramycin (TM) solutions for infusion were combined with Nutriflex Omega Special (NOS) and Smofkabiven (SFK). Three different volume ratios were investigated: 1:2, 1:1, and 2:1, simulating Y-site administration. Samples underwent visual examination and determination of the lipid emulsion particle size, zeta potential, and pH immediately after preparation and after four hours of storage at room temperature (22 ± 2 °C) with sunlight exposure. RESULTS: GM and AM combined with NOS in all studied ratios met the set-up acceptance criteria. The addition of TM to NOS in a 2:1 volume ratio and all tested AMGs to SFK in all studied combinations significantly influenced the stability of the oil-water system leading to the appearance of globules larger than 5 µm exceeding the pharmacopeial limit of 0.05% immediately after preparation or after four hours of storage. CONCLUSION: In conclusion, our study showed that NOS was less prone to destabilization of oil-in-water systems by AMGs than SFK. In justified clinical cases, due to the lack of appearance of precipitate or enlarged lipid droplets, the combined administration of GM and AM with the NOS could be considered, provided tested volume ratios of the drug and MCB in the infusion line are maintained. However, it should be noted that such an infusion may be associated with the risk of changes in the pharmacokinetics of the drug.

Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles.

BACKGROUND: Glioblastoma (GBM) is the most frequently occurring primary malignant central nervous system tumor, with a poor prognosis and median survival below two years. Administration of a combination of non-steroidal anti-inflammatory drugs and natural compounds that exhibit a curative or prophylactic effect in cancer is a new approach to GBM treatment. This study aimed to investigate the synergistic antitumor activity of etoricoxib (ETO) and cannabidiol (CBD) in a GBM cell line model, and to develop poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for these two substances. METHODS: The activity of ETO+CBD was determined using the MTT test, cell-cycle distribution assay, and apoptosis analysis using two GBM cell lines, namely, T98G and U-138 MG. The PLGA-based NPs were developed using the emulsification and solvent evaporation method. Their physicochemical properties, such as shape, size, entrapment efficiency (EE%), in vitro drug release, and quality attributes, were determined using scanning electron microscopy, diffraction light scattering, high-performance liquid chromatography, infrared spectroscopy, and differential scanning calorimetry. RESULTS: The combination of ETO and CBD reduced the viability of cells in a dose-dependent manner and induced apoptosis in both tested GBM cell lines. The developed method allowed for the preparation of ETO+CBD-NPs with a spherical shape, mean particle size (MPS) below 400 nm, zeta potential (ZP) values from -11 to -17.4 mV, polydispersity index (PDI) values in the range from 0.029 to 0.256, and sufficient EE% of both drugs (78.43% for CBD, 10.94% for ETO). CONCLUSIONS: The combination of ETO and CBD is a promising adjuvant therapeutic in the treatment of GBM, and the prepared ETO+CBD-NPs exhibit a high potential for further pharmaceutical formulation development.

Cellular senescence in skin-related research: Targeted signaling pathways and naturally occurring therapeutic agents.

Despite the growing interest by researchers into cellular senescence, a hallmark of cellular aging, its role in human skin remains equivocal. The skin is the largest and most accessible human organ, reacting to the external and internal environment. Hence, it is an organ of choice to investigate cellular senescence and to target root-cause aging processes using senolytic and senomorphic agents, including naturally occurring plant-based derivatives. This review presents different aspects of skin cellular senescence, from physiology to pathology and signaling pathways. Cellular senescence can have both beneficial and detrimental effects on the skin, indicating that both prosenescent and antisenescent therapies may be desirable, based on the context. Knowledge of molecular mechanisms involved in skin cellular senescence may provide meaningful insights for developing effective therapeutics for senescence-related skin disorders, such as wound healing and cosmetic skin aging changes.

Honokiol-Loaded Nanoemulsion for Glioblastoma Treatment: Statistical Optimization, Physicochemical Characterization, and an In Vitro Toxicity Assay.

BACKGROUND: Glioblastoma (GBM) is an extremely invasive and heterogenous malignant brain tumor. Despite advances in current anticancer therapy, treatment options for glioblastoma remain limited, and tumor recurrence is inevitable. Therefore, alternative therapies or new active compounds that can be used as adjuvant therapy are needed. This study aimed to develop, optimize, and characterize honokiol-loaded nanoemulsions intended for intravenous administration in glioblastoma therapy. METHODS: Honokiol-loaded nanoemulsion was developed by incorporating honokiol into Lipofundin MCT/LCT 20% using a horizontal shaker. The Box-Behnken design, coupled with response surface methodology, was used to optimize the incorporation process. The effect of the developed formulation on glioblastoma cell viability was determined using the MTT test. Long-term and short-term stress tests were performed to evaluate the effect of honokiol on the stability of the oil-in-water system and the effect of different stress factors on the stability of honokiol, respectively. Its physicochemical properties, such as MDD, PDI, ZP, OSM, pH, and loading efficiency (LE%), were determined. RESULTS: The optimized honokiol-loaded nanoemulsion was characterized by an MDD of 201.4 (0.7) nm with a PDI of 0.07 (0.02) and a ZP of -28.5 (0.9) mV. The LE% of honokiol was above 95%, and pH and OSM were sufficient for intravenous administration. The developed formulation was characterized by good stability and a satisfactory toxicity effect of the glioblastoma cell lines. CONCLUSIONS: The honokiol-loaded nanoemulsion is a promising pharmaceutical formulation for further development in the adjuvant therapy of glioblastoma.

Y-Site Compatibility Studies of Ketoprofen with Parenteral Nutrition Admixtures for Central and Peripheral Administration.

Ketoprofen (KTF) is often used in hospital wards, especially in its intravenous form. According to the literature review, the compatibility of ketoprofen with parenteral nutrition (PN) admixtures has not yet been investigated. For this reason, we aimed to provide data contributing to physical compatibility to ensure the safe co-administration of these medications. In this study, we examined the compatibility of KTF with eight selected commercial PN admixtures intended for central (Lipoflex Special, Omegaflex Special, Kabiven, SmofKabiven) and peripheral (Lipoflex peri, Omegaflex peri, Kabiven Peripheral, Olimel Peri N4E) administration. The KTF solution for infusion was combined in three different volume ratios with studied PN admixtures reflecting the conditions in clinical practice. The evaluation of undesirable physical destabilization of oil-in-water system or precipitate formation involved the visual inspection and the determination of mean droplet diameter, zeta potential, pH, and turbidity changes. The results of compatibility of KTF with eight commercial PN admixtures showed that three of them: Kabiven, SmofKabiven, and Kabiven Peripheral, are incompatible with KTF and should not be concomitantly administered.

Role of curcumin in selected head and neck lesions. Limitations on the use of the Hep-2 cell line: A critical review.

Neoplastic diseases of the upper respiratory airways, as well as head and neck cancers, are a frequent cause of death and significantly affect the quality of life of both patients and survivors. As the frequency increases, new and improved treatment techniques are sought. Promising properties in this respect are expressed by a natural compound - curcumin. Along with its derivatives, it was found useful in the treatment of a series of cancers. Curcumin was found to be effective in clinical trials and in vitro, in vivo anticancer experiments. Nanoformulations (e.g., poly(lactide-co-glycolic acid)-based nanoparticles, nanoemulsions), and modifications of curcumin, as well as its combinations with other substances (e.g., catechins, cisplatin) or treatments (e.g., radiotherapy or local use in inhalation), were found to enhance the antitumor effect. This review aims to summarize the recent findings for the treatment of head and neck diseases, especially squamous cell carcinomas (HNSCCs), including drawing attention to the constant use of the misidentified Hep-2 cell line and proposing databases purposed at eliminating this problem. Moreover, this manuscript focuses on pointing out the molecular mechanisms of therapy that have been reached and emphasizing the shortcomings that still need to be addressed.

Sodium Valproate Incompatibility with Parenteral Nutrition Admixtures-A Risk to Patient Safety: An In Vitro Evaluation Study.

Epilepsy is defined as a group of concerning problems related to the nervous system; its defining feature is a predisposition to epileptic seizures. The frequency of seizures in intensive care units (ICU) ranges from 3.3% to 34%, and ICU antiepileptic treatment is routine practice. The administration of drugs through the same infusion line is not recommended but is common clinical practice, especially in ICU. Incompatibilities between parenteral drugs and between drugs and parenteral nutrition admixtures (PNAs) are common medical errors and pose risks to patient safety. The co-administration of drugs must always be confirmed and clearly defined. The simultaneous infusion of sodium valproate (VPA, drug used to treat seizures and epilepsy) with parenteral PNAs has not yet been studied. During the experiment reported in this study, a visual control, pH, osmolality, zeta potential, particle size, polydispersity index, and turbidity were measured. The conducted research shows that the lipid emulsion composition has a significant influence on drug-PN (drug-parenteral nutrition) compatibility. The acceptance criteria were met only for PNs containing omega-3-acid-triglycerides (Omegaflex special and peri). The second fraction of particles above 1000 nm was observed for most of the tested PNAs (Lipoflex special, Lipoflex peri, Kabiven, SmofKabiven, Kabiven Peripheral, and Olimel Peri N4E), which disqualifies their simultaneous administration with VPA.

APTES-Modified SBA-15 as a Non-Toxic Carrier for Phenylbutazone.

Improvement of the bioavailability of poorly soluble medicinal substances is currently one of the major challenges for pharmaceutical industry. Enhancing the dissolution rate of those drugs using novel methods allows to increase their bioavailability. In recent years, silica-based mesoporous materials have been proposed as drug delivery systems that augment the dissolution rate. The aim of this study was to analyse the influence of phenylbutazone adsorption on SBA-15 on its dissolution rate. Moreover, we examined the cytotoxicity of the analyzed silica. The material was characterized by SEM, TEM, DSC, 1H-NMR, XRD, and FT-IR. The phenylbutazone did not adsorb on unmodified SBA-15, while the adsorption on APTES-modified SBA-15 resulted in 50.43 mg/g of loaded phenylbutazone. Phenylbutazone adsorbed on the APTES-modified SBA-15 was then released in the hydrochloric acidic medium (pH 1.2) and phosphate buffer (pH 7.4) and compared to the dissolution rate of the crystalline phenylbutazone. The release profiles of the amorphous form of adsorbed phenylbutazone are constant in different pH, while the dissolution rate of the crystalline phenylbutazone depends on the pH. The cytotoxicity assays were performed using the Caco-2 cell line. Our results indicate that the analyzed material ensured phenylbutazone adsorption in an amorphous state inside the mesopores and increased its dissolution rate in various pH levels. Furthermore, the cytotoxicity assay proved safety of studied material. Our study demonstrated that APTES-modified SBA-15 can serve as a non-toxic drug carrier that improves the bioavailability of phenylbutazone.

All-in-One Pediatric Parenteral Nutrition Admixtures with an Extended Shelf Life-Insight in Correlations between Composition and Physicochemical Parameters.

The administration of three-in-one parenteral nutrition (PN) admixtures to pediatric patients requires special consideration, specifically concerning quality and physicochemical stability. The introduction of a new parenteral amino acid solution into the market prompted us to evaluate Aminoplasmal Paed-based PN admixtures' stability. The study aimed to determine the physicochemical parameters of the chosen variations of PN admixtures and search for a correlation between its composition and those parameters. One hundred and sixty-eight variations of PN admixtures intended for patients weighing from 10 to 25 kg and aged from 1 to 12 years and differing in the quantitative composition of electrolytes were selected for the study. The samples were prepared using each of the four intravenous lipid emulsions dedicated to pediatric patients: Intralipid 20%, Clinoleic 20%, Lipidem 20%, and Smoflipid 20%. The stability of the PN admixtures was assessed by visual inspection and determination of pH, osmolality, zeta potential, and hydrodynamic mean droplet diameter (MDD) immediately upon preparation and after seven days of storage at the temperature of 5 ± 1 °C with light protection. Pearson's correlation was used to quantify the relationships between selected ingredients of the PN admixtures and the physicochemical parameters. The PN admixtures were characterized by pH ranging from 5.91 to 7.04, osmolality ranging from 1238 to 1678 mOsm/kg, and zeta potential ranging from -41.3 to -2.16 mV. The changes in pH and osmolality after seven days of storage did not exceed 0.2 and 4.4%, respectively. The homogeneity of the PN admixtures was confirmed by determining the polydispersity index, which ranged from 0.06 to 0.2. The MDD of the studied formulas ranged from 235 to 395 nm and from 233 to 365 nm immediately upon preparation and after the storage period, respectively. Correlations between selected components of the PN admixtures and some physicochemical parameters were found. All Aminoplasmal Paed 10%-based PN admixtures were characterized by appropriate physicochemical quality to be administered via the central veins, both immediately upon preparation and after seven days of storage at the temperature of 5 ± 1 °C with light protection. The applied electrolyte concentrations ranges and types of lipid emulsions in the selected macronutrient quantitative compositions allowed the PN admixtures to remain stable for seven days within the specified limits.

Stability and Compatibility Aspects of Drugs: The Case of Selected Cephalosporins.

Intravenous drug incompatibilities are a common cause of medical errors, contributing to ineffective therapy and even life-threatening events. The co-administration of drugs must always be supported by studies confirming compatibility and thus guarantee the therapy's safety. Particular attention should be paid to the possible incompatibilities or degradation of intravenous cephalosporins in different infusion regimens since the administration of drugs with inadequate quality may cause treatment failure. Therefore, an appropriate stability test should be performed. The study aimed to present various aspects of the stability and compatibility of five cephalosporins: cefepime (CFE), cefuroxime (CFU), ceftriaxone (CFX), ceftazidime (CFZ), and cefazoline (CFL). The degradation studies in parenteral infusion fluids and PN admixtures were conducted for CFE and CFU. The interactions between CFX or CFZ and PN admixtures, as well as the compatibility of CFL with five commercial parenteral nutrition (PN) admixtures, were investigated. The content of CFX and CFZ in PN admixture after 24 h was >90%. CFL administered simultaneously with PN admixture by the same infusion set using Y-site was compatible only with Nutriflex Lipid Special. CFE and CFU were stable in all tested infusion fluids for a minimum of 48 h and decomposed in PN admixtures during storage.

Toward Safe Pharmacotherapy: The Interplay between Meropenem and Parenteral Nutrition Admixtures.

Simultaneous administration of parenteral nutrition (PN) admixtures with intravenous antibiotics is a common clinical problem. Coadministration of drugs incompatible with PN admixture may affect its stability, especially in the context of lipid droplet size, which is a crucial parameter for patient safety. In the present study, we investigate the in vitro compatibility of meropenem (Meropenem 1000, MPM) with five commercial PN admixtures used worldwide: Kabiven, Olimel N9E, Nutriflex Lipid Special, Nutriflex Omega Special, and SmofKabiven. The appropriate volumetric ratios, reflecting their clinical practice ratios, were used to prepare the MPM-PN admixture samples. Physicochemical properties of MPM-PN admixtures samples were determined upon preparation and after four hours of storage. The pH changes for all MPM-PN admixtures samples did not exceed the assumed level of acceptability and ranged from 6.41 to 7.42. After four hours of storage, the osmolarity changes were ±3%, except MPM-Olimel N9E samples, for which differences from 7% to 11% were observed. The adopted level of acceptability of changes in zeta potential after four hours of storage (±3 mV) was met for MPM-Kabiven, MPM-Nutriflex Lipid Special, and MPM-Nutriflex Omega Special. The mean droplet diameter for all samples was below 500 nm. However, only in the case of Nutriflex Lipid Special and Nutriflex Omega Special, the addition of MPM did not cause the formation of the second fraction of lipid droplets. The coadministration of MPM via Y-site with Kabiven, Olimel N9E, and Smofkabiven should be avoided due to osmolarity fluctuations (MPM-Olimel), significant differences in zeta potential (MPM-Olimel, MPM-Smofkabiven), and the presence of the second fraction of lipid droplets >1000 nm (MPM-Kabiven, MPM-Olimel, and MPM-Smofkabiven). The assumed acceptance criteria for MPM compatibility of MPM with PN admixtures were met only for Nutriflex Lipid Special and Nutriflex Omega Special in 1:1, 2:1, and 4:1 volume ratios.