Ratio Of Phosphatidylcholine Research Articles

Three Diterpene Lactones from Andrographis paniculata (Burm. f) Nees In vitro, In silico Assessment of the Anticancer and Novel Liposomal Encapsulation Efficiency

: Three compounds from Andrographis paniculata (Burm. f) Nees leaf were isolated and identified using 1H, 13C, 2D-NMR, and HR-MS techniques for the first time. Compound 3,19-Di-O-acetylandrographolide (3,19-DAA) or (4) is produced by acetylating compound (2). Compounds (2) and (4) have been investigated for their cytotoxic effects on three human cancer cell lines (SK-LU-1, Hela, and HepG2) using the MTT method. Compound (4) demonstrated significant cytotoxicity against all three cancer cell lines, with IC50 values ranging from 8.38 to 10.15 μM. This represents an increase in cytotoxicity of 2.67 to 3.12-fold compared to compound (2). One way to deal with the problem of low water solubility is by encapsulating (4) into liposomes using a thin-film hydration technique. The optimal conditions for maximizing encapsulation efficiency involve molar ratios of phosphatidylcholine, 3,19-DAA, and cholesterol at 4:1:1. Encapsulating compound (4) within nanoscale liposomes increases its water solubility compared to the free form of compound (4). Pose 324 of compound (4) demonstrated the best conformation among 500 docking conformations when docked to enzyme 1T8I in a in silico docking study. The free Gibbs energy and inhibition constant were determined to be -7.09 Kcal/mol and 6.32 μM, respectively. These values help elucidate the strong interaction between compound (4) and the enzyme in the ligand interaction model. The molecular dynamics simulation using Desmond software in the Linux environment was conducted for a duration of 0 to 100 nanoseconds on the complex formed by pose 324 and 1T8I. The results showed effective interactions within the complex, with stability observed from 0 to 60 nanoseconds. Throughout the simulation, specific amino acids such as Ala 499 (involved in 90% of the simulation time with hydrogen bonding via a water bridge) and Thr 501 (involved in 50% of the simulation time with one hydrogen bond via a water bridge) were found to play significant roles. The majority of torsion bondings are C-O bondings in the acetyl group of compound (4), with torsion energy values of 13.47 Kcal/mol. Carbon atom C-29 at position 324 exhibits the highest fluctuation.

Leishmania donovani Modulates Macrophage Lipidome During Infection

ABSTRACTObligate intracellular protozoan parasite, Leishmania donovani, causative agent of visceral leishmaniasis, led to impaired macrophage functions. It is well documented that many of these changes were induced by parasite‐mediated reduction in macrophage cholesterol content. Leishmania‐mediated alteration in the other lipids has not been explored in detail yet. Here, we found that the expression of key cholesterol biosynthetic genes and total cellular cholesterol were reduced during L. donovani infection. Further, we have also identified that this reduction in the cholesterol led to increased membrane fluidity and inhibition of antigen‐presenting potential of macrophages. In addition to this, we studied the relative changes in different lipids in THP‐1‐derived macrophages during L. donovani infection through liquid chromatography‐mass spectrometry. We found that Sphingomyelin (16:0) and ceramide (20:1, 26:0 and 26:1) were significantly reduced in infected macrophages. We further observed that the majority of different sub‐classes of phospholipids were downregulated significantly. Overall ratio of phosphatidylcholine versus phosphotidylethanolamine was decreased which indicated the compensatory mechanism of cell in response to cholesterol reduction. The observed Leishmania‐mediated alteration in macrophage‐lipidome provided the novel insights into mechanism of host‐pathogen interactions.

The Novel Ceramide- and Phosphatidylcholine-Based Risk Score for the Prediction of New-Onset of Hypertension.

Ceramides and other sphingolipids are implicated in vascular dysfunction and inflammation. They have been suggested as potential biomarkers for hypertension. However, their specific association with hypertension prevalence and onset requires further investigation. This study aimed to identify specific ceramide and phosphatidylcholine species associated with hypertension prevalence and onset. The 2002 FINRISK (Finnish non-communicable risk factor survey) study investigated the association between coronary event risk scores (CERT1 and CERT2) and hypertension using prevalent and new-onset hypertension groups, both consisting of 7722 participants, over a span of 10 years. Ceramide and phosphatidylcholine levels were measured using tandem liquid chromatography-mass spectrometry. Ceramide and phosphatidylcholine ratios, including ceramide (d18:1/18:0), ceramide (d18:1/24:1), phosphatidylcholine (16:0/16:0), and the ratio of ceramide (d18:1/18:0)/(d18:1/16:0), are consistently associated with both prevalence and new-onset hypertension. Ceramide (d18:1/24:0) was also linked to both hypertension measures. Adjusting for covariates, CERT1 and CERT2 showed no-longer-significant associations with hypertension prevalence, but only CERT2 predicted new-onset hypertension. Plasma ceramides and phosphatidylcholines are crucial biomarkers for hypertension, with imbalances potentially contributing to its development. Further research is needed to understand the underlying mechanisms by which ceramides will contribute to the development of hypertension.

The Metabolic Footprint of Systemic Effects in the Blood Caused by Radiotherapy and Inflammatory Conditions: A Systematic Review.

Response to radiotherapy (RT) includes tissue toxicity, which may involve inflammatory reactions. We aimed to compare changes in metabolic patterns induced at the systemic level by radiation and inflammation itself. Patients treated with RT due to head and neck cancer and patients with inflammation-related diseases located in the corresponding anatomical regions were selected. PubMed and Web of Science databases were searched from 1 January 2000 to 10 August 2023. Twenty-five relevant studies where serum/plasma metabolic profiles were analyzed using different metabolomics approaches were identified. The studies showed different metabolic patterns of acute and chronic inflammatory diseases, yet changes in metabolites linked to the urea cycle and metabolism of arginine and proline were common features of both conditions. Although the reviewed reports showed only a few specific metabolites common for early RT response and inflammatory diseases, partly due to differences in metabolomics approaches, several common metabolic pathways linked to metabolites affected by radiation and inflammation were revealed. They included pathways involved in energy metabolism (e.g., metabolism of ketone bodies, mitochondrial electron transport chain, Warburg effect, citric acid cycle, urea cycle) and metabolism of certain amino acids (Arg, Pro, Gly, Ser, Met, Ala, Glu) and lipids (glycerolipids, branched-chain fatty acids). However, metabolites common for RT and inflammation-related diseases could show opposite patterns of changes. This could be exemplified by the lysophosphatidylcholine to phosphatidylcholine ratio (LPC/PC) that increased during chronic inflammation and decreased during the early phase of response to RT. One should be aware of dynamic metabolic changes during different phases of response to radiation, which involve increased levels of LPC in later phases. Hence, metabolomics studies that would address molecular features of both types of biological responses using comparable analytical and clinical approaches are needed to unravel the complexities of these phenomena, ultimately contributing to a deeper understanding of their impact on biological systems.

Membrane lytic activity of antibacterial ionenes, critical role of phosphatidylcholine (PC) and cardiolipin (CL).

Understanding the mechanism by which an antibacterial agent interacts with a model membrane provides vital information for better design of future antibiotics. In this study, we investigated two antibacterial polymers, hydrophilic C0-T-p and hydrophobic C8-T-p ionenes, known for their potent antimicrobial activity and ability to disrupt the integrity of lipid bilayers. Our hypothesize is that the composition of a lipid bilayer alters the mechanism of ionenes action, potentially providing an explanation for the observed differences in their bioactivity and selectivity. Calcein release experiments utilizing a range of liposomes to examine the impact of (i) cardiolipin (CL) to phosphatidylglycerol (PG) ratio, (ii) overall vesicle charge, and (iii) phosphatidylethanolamine (PE) to phosphatidylcholine (PC) ratio on the activity of ionenes were performed. Additionally, polymer-bilayer interactions were also investigated through vesicle fusion assay and the black lipid membrane (BLM) technique The activity of C0-T-p is strongly influenced by the amount of cardiolipin, while the activity of C8-T-p primarily depends on the overall vesicle charge. Consequently, C0-T-p acts through interactions with CL, whereas C8-T-p modifies the bulk properties of the membrane in a less-specific manner. Moreover, the presence of a small amount of PC in the membrane makes the vesicle resistant to permeabilization by tested molecules. Intriguingly, more hydrophilic C0-T-p retains higher membrane activity compared to the hydrophobic C8-T-p. However, both ionenes induce vesicle fusion and increase lipid bilayer ion permeability.

A comparative analyses of lipid ratios representing desaturase enzyme activity between preterm and term infants within the first ten weeks of life

BackgroundDesaturase enzymes play a key role in several pathways including biosynthesis of poly- and mono- unsaturated fatty acids (PUFAs, MUFA). In preterm infants, desaturase enzyme activity (DA) may be a rate-limiting step in maintaining PUFAs levels during this critical developmental window and impact on long term metabolic health. The study tested the hypothesis that DA is altered in preterm infants compared to term infants in early life and may be a marker of risk or contribute to later alterations in metabolic health.MethodsLipidomic analyses were conducted using blood samples from two established UK-based cohorts, involving very preterm (n = 105) and term (n = 259) infants. Blood samples were taken from term infants at birth, two and six weeks and from preterm infants when established on enteral feeds and at term corrected age. DA of the 2 groups of infants were estimated indirectly from product/precursor lipids ratios of phosphatidylcholine (PC) and triglycerides (TG) species and reported according to their postmenstrual and postnatal ages.ResultsThere were changes in lipid ratios representing desaturase enzyme activity in preterm infants in the first weeks of life with higher delta 6 desaturases (D6D) triglyceride (TG) indices but significantly lower delta 9 desaturase (D9D) and D6D(PC) indices. In comparison to term infants, preterm have lower delta 5 desaturase (D5D) but higher D6D indices at all postnatal ages. Although point levels of desaturase indices were different, trajectories of changes in these indices over time were similar in preterm and term infants.ConclusionsThis study findings suggest the patterns of desaturase indices in preterm infants differ from that of term infants but their trajectories of change in the first 10 weeks of life were similar. These differences of DA if they persist in later life could contribute to the mechanism of diseases in preterm adulthood and warrant further investigations.

Preparation of the Levo-Tetrahydropalmatine Liposome Gel and Its Transdermal Study.

The aim of this study was to develop a liposome gel containing levo-tetrahydropalmatine (l-THP) and evaluate its transdermal properties. A L16 (43) orthogonal experiment was conducted to optimize the preparation of l-THP liposomes and assess their characterization and stability in a gel. The transdermal features were analyzed through in vivo and in vitro experiments on rats and Strat-M® membrane, respectively. The metabolism of l-THP in liver and skin S9 fractions was also studied. The optimization of the orthogonal experiment revealed that the ideal mass ratio of phosphatidylcholine, cholesterol, and l-THP during preparation was 10:1:3. The resulting liposome exhibited a particle size of 68 nm, a PDI of 0.27, a drug loading of 4.33%, an encapsulation of 18.79%, and a zeta potential of -41.27 mV. Both the l-THP and its liposome-gel formulation were found to be stable for a duration of 45 days at 4 °C and 30 °C. During the in vivo transdermal study, the maximum concentration (Cmax) of l-THP from the liposome gel was 0.16 μg/mL, and the time to reach this maximum concentration (tmax) was 1.2 hours. The relative bioavailability of l-THP in the liposome gel was 233.8% compared to the emulsion. The concentration of l-THP (prepared in PBS) decreased at a rate of 0.0067 μg/mL/min in the liver S9 fraction and 0.0027 μg/mL/min in the skin S9 fraction, however, this difference was not observed when l-THP was encapsulated in liposomes. l-THP passed through the Strat-M® membrane at a rate of 0.0032 mg/cm2/h and 0.002 mg/cm2/h for the emulsion and liposome gel, respectively. The optimal process for the preparation of l-THP liposomes was obtained. Compared to the emulsion, the liposomes provided greater bioavailability when used transdermally. The liposomes also provided greater stability for l-THP during storage.

Preparation and Physicochemical Evaluation of Injectable Sustained-Release Risperidone by Lipid Liquid Crystal Vehicle

Introduction: Risperidone is a highly effective medicine in patients with mental disorders. Since maintaining blood concentrations of risperidone within the therapeutic index is pivotal during treatment, these patients should receive medication daily and continuously. Method: In this study, an optimal lipid liquid crystal was designed according to the maximum release for 60 days based on different ratios of phosphatidylcholine (PC) to sorbitan monooleate (PC:SMO), tween 80 (w/w%), and tocopherol acetate (w/w%) using Design Expert software with the Central Composite Design (CCD) method. Release evaluations were conducted in vitro to compare the effects of lipid liquid crystal and Risperdal CONSTA®. The structure evaluation was also tested using polarized electron microscopy and in vitro assessment via cell culture. Results: The optimal formulation was selected based on the maximum release (100%) of the drug obtained within 2 months with a PC: SMO ratio of 58.6%, tween 0.82% (w/w), and tocopherol acetate 3.6% (w/w). A hexagonal mesophase with a dihedral structure was observed in the liquid crystal structure. No toxicity was observed in the cell culture test. Conclusion: The comparison of the results of in vitro studies of the liquid crystal formulation containing risperidone and the commercial formulation, Risperdal CONSTA®, showed that the liquid crystal system provides better and more uniform drug release for 60 days. Therefore, it can increase patient compliance and ease the problems of oral administration

Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by 99mTc radiolabeling technique

Zolmitriptan (ZT) is a potent second generation triptan, commonly administered to alleviate migraine attacks. ZT suffers various limitations; massive hepatic first pass metabolism, P-gp efflux transporters susceptibility, and limited (≈40%) oral bioavailability. Transdermal route of administration could be explored to enhance its bioavailability. A 23.31 full factorial design was constructed to developed twenty-four ZT loaded terpesomes via thin film hydration technique. The influence of drug: phosphatidylcholine ratio, terpene type, terpene concentration and sodium deoxycholate concentration on the characterization of the developed ZT-loaded terpesomes was assessed. Particle size (PS), zeta potential (ZP), ZT entrapment efficiency (EE%), drug loading (DL%) and drug released percentages after 6 h (Q6h) were the selected dependent variables. Further morphological, crystallinity, and in-vivo histopathological studies were conducted for the optimum terpesomes (T6). 99mTc-ZT and 99mTc-ZT-T6 gel were radio-formulated for in-vivo biodistribution studies in mice following transdermal application of 99mTc-ZT-T6 gel, relative to 99mTc-ZT oral solution. T6 terpesomes [comprising ZT and phosphatidylcholine (1:15), cineole (1% w/v) and sodium deoxycholate (0.1% w/v)] were optimum with respect to spherical PS (290.2 nm), ZP (-48.9 mV), EE% (83%), DL% (3.9%) and Q6h (92.2%) with desirability value of 0.85. The safety of the developed T6 terpesomes was verified by the in-vivo histopathological studies. 99mTc-ZT-T6 gel showed maximum brain concentration (5 ± 0.1%ID/ g) with highest brain to blood ratio of 1.92 ± 0.1 at 4 h post transdermal application. Significant improvement of ZT brain relative bioavailability (529%) and high brain targeting efficiency (315%) were revealed with 99mTc-ZT-T6 gel, which confirmed successful ZT delivery to the brain. Terpesomes could be safe, successful systems capable of improving ZT bioavailability with high brain targeting efficiency.Graphical

Prolonged local delivery of doxorubicin to cancer cells using lipid liquid crystalline system

Exploring efficient strategies to eradicate the tumor tissue and enhance patient outcomes still remained a serious challenge. Systemic toxicity of the current chemotherapeutics and their low concentration in the tumor site limited reaching a practical approach in their administration and combinational therapy. Besides, complicated delivery platforms could not receive the marketing approval due to difficulties in scale up procedures. To this aim, we developed a simple injectable local delivery platform which provided a sufficient dose of the chemotherapeutic in the cancerous tissue with sustained release properties. Herein, various injectable in situ forming LLC formulations loaded with doxorubicin (DOX) were developed. Although there were many previous studies on lipid liquid crystal (LLC) based formulations, their performance as an injectable intratumoral depot system for local chemotherapy has not been extensively investigated yet. In the current study we developed 18 formulations of DOX loaded LLCs using Box-Behnken method via different ratios of phosphatidyl choline: sorbitan monooleate (PC: SMO), N-Methyl-2-pyrrolidone (NMP), and tween 80. The physicochemical properties of the formulations were investigated and their in vivo tumor inhibition efficiencies in C26 tumor bearing mouse model was further studied. The results indicated that DOX loaded PC: SMO/NMP/Tween 80 (50:50/50/2 w/w%) and DOX loaded PC: SMO/NMP (50:50/50 w/w%) formulations were syringeable with pseudoplastic behavior. Also, they could release the cargo in a sustained manner for 60 days. Compared to intravascular administration of DOX, intratumoral injection of the developed formulations led to a significant decrease in tumor volume and enhancement of the survival rate in murine tumor model. Additionally, animal imaging studies proved their prolonged accumulation in the tumor site. Histopathological studies showed that treatment with the DOX-loaded LLC formulations did not cause any systemic toxicity to vital organs. Taken together, we believe that the developed simple and efficient local delivery platform can be further used in combinational therapies and treatment of various solid tumors.

SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination

Lipid droplets (LDs) are involved in various biological events in cells along with their primary role as a storage center for neutral lipids. Excessive accumulation of LDs is highly correlated with various diseases, including metabolic diseases. Therefore, a basic understanding of the molecular mechanism of LD degradation would be beneficial in both academic and industrial research. Lipophagy, a selective autophagy mechanism/LD degradation process, has gained increased attention in the research community. Herein, we sought to elucidate a novel lipophagy mechanism by utilizing the LD-degrading small molecule, SB2301, which activates ubiquitin-mediated lipophagy. Using a label-free target identification method, we revealed that ethanolamine-phosphate cytidylyltransferase 2 (PCYT2) is a potential target protein of SB2301. We also demonstrated that although SB2301 does not modulate PCYT2 function, it induces the cellular translocation of PCYT2 to the LD surface and spatially increases the phosphatidylethanolamine (PE)/phosphatidylcholine (PC) ratio of the LD membrane, causing LD coalescence, leading to the activation of lipophagy process to maintain energy homeostasis.

Lipidomic Analysis of Liver Lipid Droplets after Chronic Alcohol Consumption with and without Betaine Supplementation.

The earliest manifestation of alcohol-associated liver disease is hepatic steatosis, which is characterized by fat accumulation in specialized organelles called lipid droplets (LDs). Our previous studies reported that alcohol consumption elevates the numbers and sizes of LDs in hepatocytes, which is attenuated by simultaneous treatment with the methyl group donor, betaine. Here, we examined changes in the hepatic lipidome with respect to LD size and dynamics in male Wistar rats fed for 6 weeks with control or ethanol-containing liquid diets that were supplemented with or without 10 mg betaine/mL. At the time of sacrifice, three hepatic LD fractions, LD1 (large droplets), LD2 (medium-sized droplets), and LD3 (small droplets) were isolated from each rat. Untargeted lipidomic analyses revealed that each LD fraction of ethanol-fed rats had higher phospholipids, cholesteryl esters, diacylglycerols, ceramides, and hexosylceramides compared with the corresponding fractions of pair-fed controls. Interestingly, the ratio of phosphatidylcholine to phosphatidylethanolamine (the two most abundant phospholipids on the LD surface) was lower in LD1 fraction compared with LD3 fraction, irrespective of treatment; however, this ratio was significantly lower in ethanol LD fractions compared with their respective control fractions. Betaine supplementation significantly attenuated the ethanol-induced lipidomic changes. These were mainly associated with the regulation of LD surface phospholipids, ceramides, and glycerolipid metabolism in different-sized LD fractions. In conclusion, our results show that ethanol-induced changes in the hepatic LD lipidome likely stabilizes larger-sized LDs during steatosis development. Furthermore, betaine supplementation could effectively reduce the size and dynamics of LDs to attenuate alcohol-associated hepatic steatosis.

Oral Delivery of Psoralidin by Mucoadhesive Surface-Modified Bilosomes Showed Boosted Apoptotic and Necrotic Effects against Breast and Lung Cancer Cells

This study aims to design and optimize chitosan-coated bilosomal formulations loaded with psoralidin (Ps-CS/BLs) with improved physicochemical properties, oral bioavailability, and boosted apoptotic and necrotic effects. In this regard, uncoated bilosomes loaded with Ps (Ps/BLs) were nanoformulated using the thin-film hydration technique using different molar ratios of phosphatidylcholine (PC), cholesterol (Ch), Span 60 (S60), and sodium deoxycholate (SDC) (1:0.4:0.2:0.125, 1:0.4:0.2:0.25, and 1:0.4:0.2:0.5, respectively). The best-optimized formulation with respect to size, PDI, zeta potential, and EE% was selected and then coated with chitosan at two different concentrations (0.125 and 0.25 w/v%), forming Ps-CS/BLs. The optimized Ps/BLs and Ps-CS/BLs showed a spherical shape and relatively homogenous size with negligible apparent agglomerations. Additionally, it was demonstrated that coating Ps/BLs with chitosan has significantly increased the particle size from 123.16 ± 6.90 in the case of Ps/BLs to 183.90 ± 15.93 nm in the case of Ps-CS/BLs. In addition, Ps-CS/BLs exhibited higher zeta potential (+30.78 ± 1.44 mV) as compared to Ps/BLs (-18.59 ± 2.13 mV). Furthermore, Ps-CS/BL showed enhanced entrapment efficiency (EE%) of 92.15 ± 7.20% as compared to Ps/BLs (68.90 ± 5.95%). Moreover, Ps-CS/BLs exhibited a more sustained release behavior of Ps compared to Ps/BLs over 48 h, and both formulations were best obeying the Higuchi diffusion model. More importantly, Ps-CS/BLs displayed the highest mucoadhesive efficiency% (74.89 ± 3.5%) as compared to Ps/BLs (26.78 ± 2.9%), indicating the ability of the designed nanoformulation to improve oral bioavailability and extend the residence time inside the gastrointestinal tract upon oral administration. Moreover, upon evaluating the apoptotic and necrotic effects of free Ps and Ps-CS/BLs on human breast cancer cell lines (MCF-7) and human lung adenocarcinoma cell lines (A549), there was a dramatic increase in the percentages of the apoptotic and necrotic cell compared to the control and free Ps. Our findings suggest the possible oral use of Ps-CS/BLs in hampering breast and lung cancers.

Optimization of Soya Phosphatidylcholine and Tween 80 As A Preparation of Diclofenac Sodium Transfersome Vesicles Using Design-Expert

Background: Diclofenac sodium is a non-steroidal anti-inflammatory drug (NSAID) widely prescribed for inflammation and pain. However, when used orally, diclofenac sodium has poor bioavailability because it undergoes first-pass metabolism in the liver, so only about 50% of the drug reaches systemic circulation. Therefore, the transdermal delivery system, in this case, transfersome nanovesicles, was chosen as an alternative to overcome these problems. Transfersome is a lipid vesicle with the best deformability in penetrating the skin layer among other nanovesicles. Transfersomes consist of active substances, phospholipids, surfactants, and other ingredients. The composition of phosphatidylcholine as a phospholipid and tween 80 as a surfactant is a variable that can affect the optimization of the transfersome formula. Therefore, the ratio of phospholipids and surfactants should be varied to obtain the most stable transfersome formula with high drug entrapment efficiency. Optimization as an approach to get the best combination of a formula can be done in a more efficient way using software called Design-Expert. This software is used to help carry out experimental designs, such as determining the optimum formula for a preparation. Objectives: This study aims to determine the ratio of soya phosphatidylcholine as a phospholipid and tween 80 as a surfactant in the optimum formula of diclofenac sodium transfersome vesicles using Design-Expert and to determine the characteristics of the resulting transfersome vesicles. Material and Methods: Optimizing the transfersome Diclofenac Sodium formula using the factorial design 22 with soya phosphatidylcholine and tween 80 factors, particle size response, and entrapment efficiency. The thin layer hydration method carried out the process of making diclofenac sodium transfersome. Results: The results obtained from this study, namely the optimum formula based on Design-Expert, obtained a ratio of soya phosphatidylcholine and tween 80 of 4.5%: 0.5%. The results of the characterization of the optimum formula obtained a particle size of 224.3 nm, a zeta potential of -57.1 mV, and entrapment efficiency of 99.85%. Conclusions: The results of the characterization of the diclofenac sodium transfersome have met the specifications required for each test.

Development of a Liposomal Gel for Prolonged Ophthalmic Soluble Drug Delivery

AbstractLiposome, as a drug delivery vehicle, entraps drugs, releases them sustainably, and modifies release patterns. This entrapment has diminished exposure of the drug to the eye medium, which could minimize adverse effects. In this investigation, 18 formulations in 3 key categories (liposome, gel and lipogel) of cromolyn sodium (CS) were prepared and evaluated as a water‐soluble drug. Then, liposome formulations (L1‐L6) were developed using the thin‐film hydration method. The macroscopic and microscopic assessments comprised drug entrapment efficiency, release rate, release mechanism, liposome stability, and vesicle size were evaluated to evaluate liposomes and lipogel. The results revealed that applying cholesterol in formulations ranging from 33 % to 44 % w/w increased the liposome drug entrapment efficiency, stability, and release time. The optimum phosphatidylcholine (PC) ratio to cholesterol in the L4 formulation was 2 : 1, which prolonged drug release time by up to 5 hours. The carbomer® 934 containing lipogel (0.5 % w/v) showed the longest release time (9 hours) with a zero‐order release. CS release from HPMC (2 % w/v) lipogel was assumed to follow first‐order release kinetics. The prolongation of drug release time in a carboxymethylcellulose lipogels was shorter than carbomer® 934 (5 hours). Finally, a sustained release formulation of CS liposome was produced; it was developed as lipogels to enhance its release duration; finally, release kinetic were modified.

Formulation and in-vitro Evaluation of Ethosomes using Anastrozole as a Modeling Drug

Anastrozole (ANZ) is a potent non-steroidal aromatase II inhibitor (AI) used to decrease or delay the progression of breast tumor growth in some women. Since ANZ could be delivered transdermally due to its physicochemical characteristics as (log p of 3.5, aqueous solubility of 0.5 mg /mL, low dosage and half-life of 46.8 hr.) so, it could be used as a modelling drug evaluation of ethosomes, the current study aimed to formulate ANZ loaded ethosomes and evaluate the formulated ethosomes for particle size and PDI, entrapment efficiency and in vitro release profile. Film hydration method was used to prepare ANZ-loaded ethosoms. using different ratios of phospholipid (Soy phosphatidyl choline) and ethanol at variables probe sonication energy and time ratios.
 polydispersity index and particle size were used to evaluate the prepared ANZ-loaded ethosoms. The optimized formula of ethosomes which contain (1% Soy phosphatidyl choline,20% ethanol subjected to 300watt sonication energy with 1/3 sonication on /off ratio) was studied for in vitro drug release. It had 127.75±0.36 nm particle diameter and 74.7136 ± 3.457 % entrapment efficiency, the release kinetics obey Korsmeyer-Peppas and non-Fickian release as R2=0.9779 and n=0.737.
 The ratios of Soy phosphatidyl choline, ethanol, sonication energy and duration had a significant impact on the particle size of ethosomes at (p0.05). The preformulating analysis of Powder X-ray diffraction (P-XRD) indicate amorphous ethosomes. Fourier transform infrared (FTIR) showed the inertness among components.

Phosphatidylserine in Diabetes Research.

Phospholipids are lipids that constitute the basic structure of cell membranes. In-depth research has shown that in addition to supporting cell structures, phospholipids participate in multiple cellular processes, including promoting cell signal transduction, guiding protein translocation, activating enzymatic activity, and eliminating dysfunctional/redundant organelles/cells. Diabetes is a chronic metabolic disease with a complicated etiology and pathology. Studies have shown that the level of certain phospholipids, for example, the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver tissue, is negatively associated with insulin sensitivity. In addition, PS is a phospholipid exhibiting extensive cellular functions in diabetes. For this review, we analyzed many PS studies focusing on diabetes and insulin sensitivity in recent years and found that PS participates in controlling insulin secretion, regulating insulin signaling transduction, and participating in the progression of diabetic complications by mediating coagulation disorders in the microvasculature or targeting mitochondria. Moreover, PS supplements in food and PS-containing liposomes have been shown to protect against type 1 and type 2 diabetes (T1D and T2D, respectively) in animal studies. Therefore, by summarizing the regulatory roles played by PS in diabetes and the potential of successfully using PS or PS-containing liposomes for diabetic therapy, we hope to provide new ideas for further research into the mechanisms of diabetes and for drug development for treating diabetes and its complications.

Effects of acute intravenous lipopolysaccharide administration on the plasma lipidome and metabolome in lactating Holstein cows experiencing hyperlipidemia.

The effects of lipopolysaccharides (i.e., endotoxin; LPS) on metabolism are poorly defined in lactating dairy cattle experiencing hyperlipidemia. Our objective was to explore the effects of acute intravenous LPS administration on metabolism in late-lactation Holstein cows experiencing hyperlipidemia induced by intravenous triglyceride infusion and feed restriction. Ten non-pregnant lactating Holstein cows (273 ± 35 d in milk) were administered a single bolus of saline (3 mL of saline; n [Formula: see text] 5) or LPS (0.375 [Formula: see text]g of LPS/kg of body weight; n [Formula: see text] 5). Simultaneously, cows were intravenously infused a triglyceride emulsion and feed restricted for 16 h to induce hyperlipidemia in an attempt to model the periparturient period. Blood was sampled at routine intervals. Changes in circulating total fatty acid concentrations and inflammatory parameters were measured. Plasma samples were analyzed using untargeted lipidomics and metabolomics. Endotoxin increased circulating serum amyloid A, LPS-binding protein, and cortisol concentrations. Endotoxin administration decreased plasma lysophosphatidylcholine (LPC) concentrations and increased select plasma ceramide concentrations. These outcomes suggest modulation of the immune response and insulin action. Lipopolysaccharide decreased the ratio of phosphatidylcholine to phosphatidylethanomanine, which potentially indicate a decrease in the hepatic activation of phosphatidylethanolamine N-methyltransferase and triglyceride export. Endotoxin administration also increased plasma concentrations of pyruvic and lactic acids, and decreased plasma citric acid concentrations, which implicate the upregulation of glycolysis and downregulation of the citric acid cycle (i.e., the Warburg effect), potentially in leukocytes. Acute intravenous LPS administration decreased circulating LPC concentrations, modified ceramide and glycerophospholipid concentrations, and influenced intermediary metabolism in dairy cows experiencing hyperlipidemia.

Comparison of different types of liposomal nano structures for microRNA transfection to human mesenchymal stem cell line S1939

Background: Liposomes are utilized as a drug delivery carrier in various fields of biomedicine. They are synthesized in the nanometer-size range and are becoming a viable drug delivery carrier for the treatment of different diseases. MicroRNAs as regulatory elements could be transferred to cells for changing their morphology or physiology. The study’s major aim is to find the optimized formula of liposomes for transfection of microRNA to human mesenchymal stem cell line S1939 (HMSCs). Materials and Methods: Various ratios of soybean phosphatidylcholine (SPC), cholesterol, 1, 2 dioleoyloxy-3- (trimethylammonium) propane (DOTAP), and polyethylene glycol (PEG) were combined. The mean diameter of all formulations and their surface properties were determined by a zeta sizer device and scanning electron microscope, respectively. The cytotoxicity of formulations was assessed using MTT (3,4,5-dimethyl thiazol-2-yl) (2,5-diphenyltetrazolium bromide) assay. The transfection effectiveness of liposomal miRNA vs empty liposomes was determined using agarose gel electrophoresis. Results: The optimized liposome vesicles were prepared using 45:30:27.5:5 molar ratios of SPC:DOTAP:cholesterol: DSPE-PEG. The liposome formulations F10 and F18 were the best in terms of biocompatibility because of the higher viabilities of treated cells. The best formulation (F18, containing 0.7 µg of miRNA and 10 µg of liposome) was nearly 100% efficient in sequestering and fixing miRNA. Phase-contrast and fluorescent microscopic examinations showed intra-nuclear as well as intracytoplasmic localization of the particles. Conclusion: Some easily prepared liposomal formulation vehicles are quite efficient in the transfection of miRNA into the HMSCs and could be used for in vitro applications in regenerative medicine.

Dynamic Changes in Membrane Lipid Metabolism and Antioxidant Defense During Soybean (Glycine max L. Merr.) Seed Aging.

Seed viability depends upon the maintenance of functional lipids; however, how membrane lipid components dynamically change during the seed aging process remains obscure. Seed storage is accompanied by the oxidation of membrane lipids and loss of seed viability. Understanding membrane lipid changes and their effect on the cell membrane during seed aging can contribute to revealing the mechanism of seed longevity. In this study, the potential relationship between oxidative stress and membrane lipid metabolism was evaluated by using a non-targeted lipidomics approach during artificial aging of Glycine max L. Merr. Zhongdou No. 27 seeds. We determined changes in reactive oxygen species, malondialdehyde content, and membrane permeability and assessed antioxidant system activity. We found that decreased non-enzymatic antioxidant contents and catalase activity might lead to reactive oxygen species accumulation, resulting in higher electrolyte leakage and lipid peroxidation. The significantly decreased phospholipids and increased glycerolipids and lysophospholipids suggested that hydrolysis of phospholipids to form glycerolipids and lysophospholipids could be the primary pathway of membrane metabolism during seed aging. Moreover, the ratio of phosphatidylcholine to phosphatidylethanolamine, double bond index, and acyl chain length of phospholipids were found to jointly regulate membrane function. In addition, the observed changes in lipid metabolism suggest novel potential hallmarks of soybean seed aging, such as diacylglycerol 36:4; phosphatidylcholine 34:2, 36:2, and 36:4; and phosphatidylethanolamine 34:2. This knowledge can be of great significance for elucidating the molecular mechanism underlying seed aging and germplasm conservation.