Nanoformulations are regarded as a promising tool to enable the efficient delivery of active pharmaceutical ingredients to the target site. One of the best-known and most studied nanoformulations are liposomes—spherical phospholipid bilayered nanocarriers resembling cell membranes. In order to assess the possible effect of a mixture of polyphenols on both the stability of the formulation and its biological activity, two compounds were embedded in the liposomes—(i) curcumin (CUR), (ii) a peracetylated derivative of (−)-epigallocatechin 3-O-gallate (pEGCG), and (iii) a combination of the aforementioned. The stability of the formulations was assessed in two different temperature ranges (4–8 and 20 °C) by monitoring both the particle size and their concentration. It was found that after 28 days of the experiment, the liposomes remained largely unchanged in terms of the particle size distribution, with the greatest change from 130 to 146 nm. The potential decomposition of the carried substances was evaluated using HPLC. The combined CUR and pEGCG was sensitive to temperature conditions; however its stability was greatly increased when compared to the solutions of the individual compounds alone—up to 9.67% of the initial concentration of pEGCG in liposomes after 28 days storage compared to complete decomposition within hours for the non-encapsulated sample. The potential of the prepared formulations was assessed in vitro on prostate (LNCaP) and bladder cancer (5637) cell lines, as well as on a non-cancerous human lung fibroblast cell line (MRC-5), with the highest activity of IC50 equal 15.33 ± 2.03 µM for the mixture of compounds towards the 5637 cell line.
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.
Glioblastoma (GBM) is the most common malignant neoplasm in adults among all CNS gliomas, with the 5-year survival rate being as low as 5%. Among nanocarriers, liposomal nanoformulations are considered as a promising tool for precise drug delivery. The herein presented study demonstrates the possibility of encapsulating four selected natural compounds (curcumin, bisdemethoxycurcumin, acteoside, and orientin) and their mixtures in cationic liposomal nanoformulation composed of two lipid types (DOTAP:POPC). In order to determine the physicochemical properties of the new drug carriers, specific measurements, including particle size, Zeta Potential, and PDI index, were applied. In addition, NMR and EPR studies were carried out for a more in-depth characterization of nanoparticles. Within biological research, the prepared formulations were evaluated on T98G and U-138 MG glioblastoma cell lines in vitro, as well as on a non-cancerous human lung fibroblast cell line (MRC-5) using the MTT test to determine their potential as anticancer agents. The highest activity was exhibited by liposome-entrapped acteoside towards the T98G cell line with IC50 equal 2.9 ± 0.9 µM after 24 hours of incubation. Noteworthy, curcumin and orientin mixture in liposomal formulation exhibited a synergistic effect against GBM. Moreover, the impact on the expression of apoptosis-associated proteins (p53 and Caspase-3) of acteoside as well as curcumin and orientin mixture, as the most potent agents, was assessed, showing nearly 40% increase as compared to control U-138 MG and T98G cells. It should be emphasized that a new and alternative method of extrusion of the studied liposomes was developed.
Objective: To develop a comprehensive operative report schema based on the accuracy of primary operative reports (OpR) assessed on a department’s experience with parotid gland tumor re-operations. Design: Retrospective cross-sectional study. Setting: A tertiary referral center, the Department of Otolaryngology and Laryngological Surgery, Poznan University of Medical Sciences, Poland from 2008 to 2017. Subjects: Out of 1154 surgeries, 71 patients underwent reoperation. Their OpR were categorized into accurate and non-accurate, and re-operation field and re-operation course were categorized as anticipated or unanticipated, according to defined criteria. Intervention: None Main outcome measures: The impact of accuracy of the first OpR on re-operation course. Results: In this series, OpR were 39% (14/36) accurate, 61% (22/36) non-accurate. Re-operation fields were 16% (11/71) anticipated, 37% (26/71) unanticipated. Re-operation courses were 37% (26/71) anticipated, 63% (45/71) unanticipated. An anticipated re-operation course followed 20% (5/26) of accurate and 20% (5/26) of non-accurate primary OpR. An unanticipated re-operation course followed 20% (9/45) of accurate and 40% (18/45) of non-accurate OpR. There is no significant relationship between the re-operation course and accuracy of the first OpR (Chi2(1)=0.69; p=0.40466). The most common variable that affected non-accuracy of the OpR was facial nerve function after surgery (6/12). Conclusions: The operative report should be based on clear criteria, robust classification and comprehensive protocol. This will improve follow-up and facilitate the planning of re-operation.
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.
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