Lipid Formulations Research Articles

Inhibition of sphingosine kinase 1 attenuates LPS-induced acute lung injury by suppressing endothelial cell pyroptosis

Acute lung injury (ALI) is a frequent complication of sepsis, with pyroptosis playing a pivotal role. Analysis of Gene Expression Omnibus (GEO) mouse sepsis datasets revealed the upregulation of sphingosine kinase 1 (SphK1) in septic mouse lung tissues, which was validated in lipopolysaccharide (LPS)-treated mice. Therefore, this study aimed to explore the potential role and underlying mechanisms of SphK1, the primary kinase responsible for catalyzing the formation of the bioactive lipid sphingosine-1-phosphat, in sepsis development. Mice received an intraperitoneal injection of SphK1 inhibitor prior to LPS administration. Mouse lung vascular endothelial cells (MLVECs) were exposed to LPS and SphK1 inhibitor. The SphK1 inhibitor mitigated ALI, as evidenced by hematoxylin and eosin (H&E) staining and the wet-to-dry (W/D) weight ratio and reduced Evans blue dye leakage. Furthermore, the SphK1 inhibitor inhibited the activation of the NOD-like receptor protein 3 inflammasome and the subsequent induction of pyroptosis both in vivo and in vitro. Intriguingly, using co-immunoprecipitation (Co-IP) combined with mass spectrometry, our findings revealed that SphK1 associates with pyruvate kinase M2 (PKM2), facilitating PKM2 phosphorylation and its nuclear translocation. TEPP-46, which has the ability to stabilize PKM2 and inhibit the phosphorylation and nuclear translocation of PKM2, markedly reduced the expression of pyroptosis-associated markers and alleviated lung injury. Concludingly, our results suggest that targeting SphK1 is a promising therapeutic strategy for ALI.

Incompatibility of antimalarial drugs: challenges in formulating combination products for malaria

Lipophilic drugs require more advance formulation, especially if the intention is to make solutions or semisolid formulations. This also accounts for most antimalarial drugs. Although some of these antimalarial drugs are soluble in lipid vehicles, few of them, such as lumefantrine (LF), are also poorly soluble in oily vehicles. Trying to dissolve and formulate LF as a liquid formulation together with other antimalarial drugs is, therefore, a major task. When mixed in solution together with artemether (AR), precipitation occurs, sometimes with LF precipitating out on its own, and sometimes with AR precipitating out alongside LF. In this study, it was hypothesized that the use of fatty acids could lead to enhanced solubility in lipid formulation. Addition of the fatty acid solved the dissolution challenges, making LF soluble for over a year at room temperature (21–23 °C); but further research is needed to test the mechanism of action of the fatty acid. In addition, design of experiments (MODDE® 13) revealed that the amount of fatty acid in the formulation was the only significant factor for LF precipitation.

The Regulatory Mechanism of Smilax China L. Saponins against Nonalcoholic Fatty Liver Is Revealed by Metabolomics and Transcriptomics.

This study was to investigate the effects of Smilax China L. saponins (SCS) on non-alcoholic fatty liver disease (NAFLD). Rats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, followed by SCS treatment for 8 weeks. The effect of SCS on liver injury was observed by H&E staining and the regulative mechanism of SCS on lipid formation was exposed by detecting Oil red O, insulin resistance (IR), and fatty acids synthesis (FAS). Furthermore, transcriptomics and metabolomics were performed to analyze the potential targets. The experimental results indicated that SCS exerted a positive curative effect in alleviating HFD-induced overweight, hepatic injury, steatosis, and lipid formation and accumulation in rats, and the preliminary mechanism studies showed that SCS could alleviate IR, inhibit FAS expression, and reduce Acetyl-CoA levels. Besides, the integrative analysis of transcriptomics and metabolomics exposed the targets of SCS to regulate lipid production likely being the sphingolipid metabolism and glycerophospholipid metabolism pathways. This study demonstrates that SCS significantly ameliorates lipid metabolic disturbance in rats with NAFLD by relieving insulin resistance, inhibiting the FAS enzymes, and regulating the sphingolipid and glycerophospholipid metabolism pathways.

3D-printed microfluidic device for high-throughput production of lipid nanoparticles incorporating SARS-CoV-2 spike protein mRNA.

Lipid nanoparticles (LNPs) are drug carriers for protecting nucleic acids for cellular delivery. The first mRNA vaccines authorized by the United States Food and Drug Administration are the mRNA-1273 (Moderna) and BNT162b (BioNTech/Pfizer) vaccines against coronavirus disease 2019 (COVID-19). We designed a 3D printed Omnidirectional Sheath-flow Enabled Microfluidics (OSEM) device for producing mRNA-loaded LNPs that closely resemble the Moderna vaccine: we used the same lipid formulations to encapsulate mRNA encoding SARS-CoV-2 spike protein. The OSEM device is made of durable methacrylate-based materials that can support flow rates in the mL min-1 range and was fabricated by stereolithography (SLA), incorporating readily adaptable interfaces using commercial fluidic connectors. Two key features of the OSEM device are: 1) a 4-way hydrodynamic flow focusing region and 2) a staggered herringbone mixer (SHM). Superior to conventional planar fluid junctions, the 4-way sheath flow channel generates an evenly focused, circular center flow that facilitates the formation of LNPs with low polydispersity. Downstream, fluid mixing in the SHM is intensified by incorporating a zig-zag fluidic pathway to deliver high mRNA encapsulation efficiency. We characterized the mRNA-loaded LNPs produced in the OSEM device and showed that the enhanced 3D microfluidic structures enable a 5-fold higher throughput production rate (60 mL min-1) of LNPs compared to commercial multi-thousand-dollar micromixers. The device produced LNPs of diameter less than 90 nm, with low polydispersity (2-8%) and high mRNA encapsulation efficiency (>90%). The 3D-printed device provides a cost-effective and easily prepared solution for high-throughput LNP production.

Soybean Oil-Derived Lipids for Efficient mRNA Delivery.

The rapid progress in the development of COVID-19 mRNA vaccines during the initial year of the pandemic has highlighted the significance of lipid nanoparticles in therapeutic delivery. Various lipid types have been investigated for the effective delivery of mRNA, each with unique functions and versatile applications. These range from their use in cancer immunotherapy and gene editing to their role in developing vaccines against infectious diseases. Nonetheless, continued exploration of novel lipids and synthetic approaches is necessary to further advance the understanding and expand the techniques for optimizing mRNA delivery. In this work, new lipids derived from FDA-approved soybean oil are facilely synthesized and these are employed for efficient mRNA delivery. EGFP and Fluc mRNA are used to evaluate the delivery efficacy of the lipid formulations both in vitro and in vivo. Furthermore, organ-specific targeting capabilities are observed in certain formulations, and their outstanding performance is demonstrated in delivering Cre mRNA for gene editing. These results showcase the potential of soybean oil-derived lipids in mRNA delivery, offering utility across a broad spectrum of bioapplications.

Mucormycosis in COVID-19 Pandemic

Background Coronavirus disease-2019 (COVID-19) has been associated with a wide range of opportunistic fungal infections. Many countries have seen an unprecedented rise in cases of COVID-19-associated mucormycosis (CAM). The purpose of this study is to identify the correlation between the COVID-19 epidemic and mucormycosis. Our study also provides details on factors causing CAM. Methods A retrospective study from November 2020 to February 2022 includes four cases of COVID-19-associated rhino-orbital mucormycosis treated at Habib Thameur Hospital’s ENT Department. Results The mean age of patients was 67.5-years, 75% were males, and the most frequent underlying conditions were diabetes mellitus (100%). The median time interval between the diagnosis of COVID-19 and the first evidence of mucormycosis infection was 15-days; two patients required hospitalization in a COVID unit, and two patients received oxygen therapy at home. All patients received corticosteroid therapy at a dose of 1 mg/kg/d for an average of 10-days. Treatment using antifungals and surgery was described in all the patients. Amphotericin B deoxycholate was used in 75% and lipid formulation in 25%. Two patients presented renal insufficiency due to amphotericin B; the doses were adapted with good evolution. In that report, the case fatality rate was 75%. Conclusion Mucormycosis is a fatal fungal infection that usually affects patients with altered immunity. Several cases of mucormycosis in people with COVID-19 have been increasingly reported worldwide. Diabetes mellitus (DM), steroid overdose, immunosuppression, and high iron levels, combined with other factors such as prolonged hospitalization, unhygienic conditions, and the use of ventilators, combine to create an ideal environment for contracting mucormycosis. Lastly, there is a need to create awareness about fungal diseases among clinicians in order to help identify early symptoms and restrict the spread of lethal fungal diseases. A collaborative team of otolaryngologists, ophthalmologists, anesthesiologists, and resuscitators will be required in hospitals to accelerate optimal management.

Designing and Synthesis of an Anti-Candida parapsilosis Thymoquinone Lipid Formulation

Background: Candida parapsilosis complex, as an opportunistic pathogen, can cause various infections, especially in immunocompromised patients. Objectives: This study investigated a novel thymoquinone-liposomal nanoparticle to increase the stability of thymoquinone with antifungal effects against C. parapsilosis isolates. Methods: The thymoquinone was encapsulated in liposomal nanoparticles using a thin-film hydration technique and then analyzed by transmission electron microscopy (TEM), particle size, zeta potential, and UV-visible spectrophotometer. Also, the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used on peripheral blood mononuclear cells (PBMCs) for cell metabolic activity. The antifungal activity of thymoquinone-liposomal nanoparticle against 15 clinical isolates of C. parapsilosis and the reference strain was examined based on the M27-A3 guideline. Results: The synthesized thymoquinone-liposomal nanoparticle was approved by the TEM, particle size, zeta potential, and UV-Vis. The thymoquinone-liposomal nanoparticle showed no toxic effect on PBMCs following the MTT assay. The minimum inhibitory concentration (MIC) range of free thymoquinone and liposomal formulations with inhibitory effects on Candida isolates was 50 to 6.25 and 150 to 18.75 µg/mL, respectively. The MIC50 and MIC90 values of free thymoquinone and thymoquinone-liposomal nanoparticle were 25 and 50, and 75 and 150 µg/mL. Conclusions: The synthesized thymoquinone-liposomal nanoparticle shows significant antifungal activity against C. parapsilosis isolates compared to free thymoquinone. However, because of its hydrophilicity and hydrophobicity, biocompatibility, particle size, non-toxic effect, and higher cell viability, the thymoquinone-liposomal nanoparticle is a more effective approach for treating fungal infections.

Cryptococcosis in kidney transplant recipients: Current understanding and practices.

Cryptococcosis is the third most commonly occurring invasive fungal disease in solid organ transplant recipients (SOT). It is caused by encapsulated yeast, Cryptococcus species, predominantly Cryptococcus neoformans and Cryptococcus gattii. Though kidney transplant recipients are at the lowest risk of cryptococcosis when compared to other solid organ transplant recipients such as lung, liver or heart, still this opportunistic infection causes significant morbidity and mortality in this subset of patients. Mortality rates with cryptococcosis range from 10%-25%, while it can be as high as 50% in SOT recipients with central nervous system involvement. The main aim of diagnosis is to find out if there is any involvement of the central nervous system in disseminated disease or whether there is only localized pulmonary involvement as it has implications for both prognostication and treatment. Detection of cryptococcal antigen (CrAg) in cerebrospinal fluid or plasma is a highly recommended test as it is more sensitive and specific than India ink and fungal cultures. The CrAg lateral flow assay is the single point of care test that can rapidly detect cryptococcal polysaccharide capsule. Treatment of cryptococcosis is challenging in kidney transplant recipients. Apart from the reduction or optimization of immunosuppression, lipid formulations of amphotericin B are preferred as induction antifungal agents. Consolidation and maintenance are done with fluconazole; carefully monitoring its interactions with calcineurin inhibitors. This review further discusses in depth the evolving developments in the epidemiology, pathogenesis, diagnostic assays, and management approach of cryptococcosis in kidney transplant recipients.

Physicochemical properties and composition of the liposome lipids from lecithin depending on conditions that lead to the formation of liposome lipids

The effects of the composition and physicochemical properties of lecithin lipids, ultrasound exposure and centrifugation time on the composition and physicochemical properties of liposomes formed from lecithin were studied. It was found that the intensity of lipid peroxidation of liposomes is interrelated by the reversal correlation with the phospholipids share in the total lipid composition of lecithin and the direct correlation with the relative content of cardiolipin in the lecithin phospholipid composition. It was shown that ultrasound exposure and centrifugation produce stage changes in the composition and properties of the liposome lipids. Decreases in the levels of medium pH and the intensity of lipid peroxidation of liposomes were observed under centrifugal conditions. It was found that the stage changes in the ability of liposome lipids for oxidation depending on the time of ultrasound exposure and centrifugation are due to the relative changes in the sum share of the acid minor fractions in the composition of their phospholipids.

Harnessing Nanovaccines for Effective Immunization─A Special Concern on COVID-19: Facts, Fidelity, and Future Prospective.

Nanotechnology has emerged as a transformative pathway in vaccine research and delivery. Nanovaccines, encompassing lipid and nonlipid formulations, exhibit considerable advantages over traditional vaccine techniques, including enhanced antigen stability, heightened immunogenicity, targeted distribution, and the potential for codelivery with adjuvants or immune modulators. This review provides a comprehensive overview of the latest advancements and applications of lipid and non-lipid-based nanovaccines in current vaccination strategies for immunization. The review commences by outlining the fundamental concepts underlying lipid and nonlipid nanovaccine design before delving into the diverse components and production processes employed in their development. Subsequently, a comparative analysis of various nanocarriers is presented, elucidating their distinct physicochemical characteristics and impact on the immune response, along with preclinical and clinical studies. The discussion also highlights how nanotechnology enables the possibility of personalized and combined vaccination techniques, facilitating the creation of tailored nanovaccines to meet the individual patient needs. The ethical aspects concerning the use of nanovaccines, as well as potential safety concerns and public perception, are also addressed. The study underscores the gaps and challenges that must be overcome before adopting nanovaccines in clinical practice. This comprehensive analysis offers vital new insights into lipid and nonlipid nanovaccine status. It emphasizes the significance of continuous research, collaboration among interdisciplinary experts, and regulatory measures to fully unlock the potential of nanotechnology in enhancing immunization and ensuring a healthier, more resilient society.

Quantitative biodistribution of nanoparticles in plants with lanthanide complexes

The inefficient distribution of fertilizers, nutrients, and pesticides on crops is a major challenge in modern agriculture that leads to reduced productivity and environmental pollution. Nanoformulation of agrochemicals is an attractive approach to enable the selective delivery of agents into specific plant organs, their release in those tissues, and improve their efficiency. Already commercialized nanofertilizers utilize the physiochemical properties of metal nanoparticles such as size, charge, and the metal core to overcome biological barriers in plants to reach their target sites. Despite their wide application in human diseases, lipid nanoparticles are rarely used in agricultural applications and a systematic screening approach to identifying efficacious formulations has not been reported. Here, we developed a quantitative metal-encoded platform to determine the biodistribution of different lipid nanoparticles in plant tissues. In this platform lanthanide metal complexes were encapsulated into four types of lipid nanoparticles. Our approach was able to successfully quantify payload accumulation for all the lipid formulations across the roots, stem, and leaf of the plant. Lanthanide levels were 20- to 57-fold higher in the leaf and 100- to 10,000-fold higher in the stem for the nanoparticle encapsulated lanthanide complexes compared to the unencapsulated, free lanthanide complex. This system will facilitate the discovery of nanoparticles as delivery carriers for agrochemicals and plant tissue-targeting products.

Lipids with negative spontaneous curvature decrease the solubility of the cancer drug paclitaxel in liposomes.

Paclitaxel (PTX) is a hydrophobic small-molecule cancer drug that loads into the membrane (tail) region of lipid carriers such as liposomes and micelles. The development of improved lipid-based carriers of PTX is an important objective to generate chemotherapeutics with fewer side effects. The lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and glyceryl monooleate (GMO) show propensity for fusion with other lipid membranes, which has led to their use in lipid vectors of nucleic acids. We hypothesized that DOPE and GMO could enhance PTX delivery to cells through a similar membrane fusion mechanism. As an important measure of drug carrier performance, we evaluated PTX solubility in cationic liposomes containing GMO or DOPE. Solubility was determined by time-dependent kinetic phase diagrams generated from direct observations of PTX crystal formation using differential-interference-contrast optical microscopy. Remarkably, PTX was much less soluble in these liposomes than in control cationic liposomes containing univalent cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), which are not fusogenic. In particular, PTX was not substantially soluble in GMO-based cationic liposomes. The fusogenicity of DOPE and GMO is related to the negative spontaneous curvature of membranes containing these lipids, which drives formation of nonlamellar self-assembled phases (inverted hexagonal or gyroid cubic). To determine whether PTX solubility is governed by lipid membrane structure or by local intermolecular interactions, we used synchrotron small-angle X-ray scattering. To increase the signal/noise ratio, we used DNA to condense the lipid formulations into lipoplex pellets. The results suggest that local intermolecular interactions are of greater importance and that the negative spontaneous curvature-inducing lipids DOPE and GMO are not suitable components of liposomal carriers for PTX delivery.

Comparison of the effect of various sources of saturated fatty acids on infant follow-on formulas oxidative stability and nutritional profile.

Fortification of infant follow-on formulas (IFF) with docosahexaenoic acid (DHA), which is prone to lipid oxidation, is required by European regulation. This study aimed to identify lipid formulation parameters that improve the nutritional profile and oxidative stability of IFF. Model IFF were formulated using different lipid and emulsifier sources, including refined (POM) or unrefined red palm oil (RPOM), coconut oil (COM), dairy fat (DFOM), soy lecithin, and dairy phospholipids (DPL). After an accelerated storage, RPOM and DFOM with DPL had improved oxidative stability compared to other IFF. Specifically, they had a peroxide value twice lower than POM and 20% less loss of tocopherols for DFOM-DPL. This higher stability was mainly explained by the presence of compounds such as carotenoids in RPOM and sphingomyelin in DFOM-DPL very likely acting synergistically with tocopherols. Incorporation of dairy lipids and carotenoids into DHA-enriched IFF compositions seems promising to enhance their stability and nutritional quality.

Biophysical Interaction Landscape of Mycobacterial Mycolic Acids and Phenolic Glycolipids with Host Macrophage Membranes.

Lipidic adjuvant formulations consisting of immunomodulatory mycobacterial cell wall lipids interact with host cells following administration. The impact of this cross-talk on the host membrane's structure and function is rarely given enough consideration but is imperative to rule out nonspecific perturbation underlying the adjuvant. In this work, we investigated changes in the plasma membranes of live mammalian cells after exposure to mycobacterial mycolic acid (MA) and phenolic glycolipids, two strong candidates for lipidic adjuvant therapy. We found that phenolic glycolipid 1 softened the plasma membrane, lowering membrane tension and stiffness, but MA did not significantly change the membrane characteristics. Further, phenolic glycolipid 1 had a fluidizing impact on the host plasma membrane, increasing the fluidity and the abundance of fluid-ordered-disordered coexisting lipid domains. Notably, lipid diffusion was not impacted. Overall, MA and, to a lesser extent, phenolic glycolipid 1, due to minor disruption of host cell membranes, may serve as appropriate lipids in adjuvant formulations.

Mitoguardin 1 and 2 promote granulosa cell proliferation by activating AKT and regulating the Hippo-YAP1 signaling pathway

Mitochondria have been identified to be involved in oxidative phosphorylation, lipid metabolism, cell death, and cell proliferation. Previous studies have demonstrated that mitoguardin (Miga), a mitochondrial protein that governs mitochondrial fusion, mitochondria-endoplasmic reticulum (ER) contacts, lipid formation, and autophagy, is crucial for ovarian endocrine and follicular development. Nevertheless, whether mammalian MIGA1 or MIGA2 (MIGA1,-2) regulates ovarian granulosa cell proliferation remains unclear. This study revealed that mammalian MIGA1,-2 promotes cell proliferation and regulates the phosphorylation and localization of Yes-associated protein 1 (YAP1) in ovarian granulosa cells. MIGA2 upregulation resulted in reduced YAP1 activity, while MIGA2 removal led to increased YAP1 activity. Further analysis indicated that MIGA1,-2 regulated YAP1 via the Hippo signaling pathway and regulated protein kinase B (AKT) activity in collaboration with YAP1. In addition, lysophosphatidic acid (LPA) regulated MIGA2 expression and AKT activity by activating YAP1. Briefly, we demonstrated that the mitochondrial MIGA1 and MIGA2, especially MIGA2, promoted cellular proliferation by activating AKT and regulating the Hippo/YAP1 signaling pathway in ovarian granulosa cells, which may contribute to the molecular pathogenesis of reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS).

Enhanced intracellular accumulation and cytotoxicity of bortezomib against liver cancer cells using N-stearyl lactobionamide surface modified solid lipid nanoparticles

Asialoglycoprotein receptors (ASGPRs) are highly expressed on hepatocytes and have been used for liver-targeted delivery and hepatocellular carcinoma (HCC) therapy. However, targeted delivery of bortezomib (BTZ) to HCC has not been reported. In this study, N-stearyl lactobionamide (N-SALB) with galactose (Gal) moiety was synthesized as a targeting agent and its structure was confirmed by FT-IR and NMR analyses. N-SALB surface-modified solid lipid nanoparticles (SLNs) loaded with BTZ (Gal-SLNs/BTZ) were developed to target BTZ delivery into HCC cancer cells. The Gal-SLNs/BTZ had an average particle size of 116.3 nm, polydispersity index (PDI) of 0.210, and zeta potential of −13.8 mV. TEM analysis showed their nanometer-sized spherical morphology. The encapsulation efficiency (EE) and drug loading (DL) capacity were 84.5 % and 1.16 %, respectively. Release studies showed that BTZ loaded inside the SLNs was slowly released over a period of 72 h at pH 7.4. Flow cytometry analysis showed significantly higher intracellular uptake of N-SALB-targeted nanoparticles than non-targeted nanoparticles in HepG2 cells. All lipid formulations showed good biocompatibility in the cytotoxicity study using MTT assay. Concentration-dependent cytotoxicity was observed for all formulations, with N-SALB-targeted nanoparticles demonstrating more cytotoxicity against HepG2 cells. The highest percentage of apoptosis was obtained for N-SALB-targeted nanoparticles compared to non-targeted nanoparticles (42.2 % and 8.70 %, respectively). Finally, biodistribution studies in HepG2 bearing nude mice showed that the accumulation of targeted nanoparticles in the tumor was significantly higher than non-targeted nanoparticles.

The use of polymorphic state modifiers in solid lipid microparticles: The role of structural modifications on drug release performance

This study investigates the correlation between the structural and release properties of solid lipid microparticles (MPs) of tristearin containing 5 % w/w of four different liquid additives used as crystal modifiers: isopropyl myristate (IM), ethyl oleate (EO), oleic acid (OA) and medium chain triglycerides (MCT). All additives accelerated the conversion of the unstable α-form of tristearin, formed after the MPs manufacturing, to the stable β-polymorph and the transformation was completed within 24 h (for IM and EO) or 48 h (for OA and MCT). The kinetic of polymorphic transition at 25 °C was investigated by simultaneous synchrotron SAXS/WAXS and DSC analysis after melting and subsequent cooling of the lipid mixture. After crystallization in the α-phase, additives accelerate the solid-solid phase transformation to β-tristearin. SAXS data showed that two types of structural modifications occurred on MPs during storage: compaction of the crystal packing (slight decrease in lamellar thickness) and crystal growth (increased number of stacked lipid lamellae). The release behavior of a model hydrophilic drug (caffeine) at two different amounts (15 % and 30 %) from MPs was studied in water and biorelevant media simulated the gastric and intestinal environment. It was particularly significant that the introduction of IM, EO and MCT were able to prolong the drug release in water, passing from a diffusion-based Higuchi kinetics to a perfect zero-order kinetic. Moreover, the overall release profiles were higher in biorelevant media, where erosion/digestion of MPs was observed. After 6 months, a moderate but statistically significant change in release profile was observed for the MPs with IM and EO, which can be correlated with the time-dependent structural alterations (i.e. larger average crystallite size) of these formulations; while MPs with OA or MCT displayed stable release profiles. These findings help to understand the correlation between release behavior, polymorphism and supramolecular‐level structural modification of lipid formulations containing crystal modifiers.

Interplay between Vitamin D and Adipose Tissue: Implications for Adipogenesis and Adipose Tissue Function.

Adipose tissue encompasses various types, including White Adipose Tissue (WAT), Brown Adipose Tissue (BAT), and beige adipose tissue, each having distinct roles in energy storage and thermogenesis. Vitamin D (VD), a fat-soluble vitamin, maintains a complex interplay with adipose tissue, exerting significant effects through its receptor (VDR) on the normal development and functioning of adipocytes. The VDR and associated metabolic enzymes are widely expressed in the adipocytes of both rodents and humans, and they partake in the regulation of fat metabolism and functionality through various pathways. These encompass adipocyte differentiation, adipogenesis, inflammatory responses, and adipokine synthesis and secretion. This review primarily appraises the role and mechanisms of VD in different adipocyte differentiation, lipid formation, and inflammatory responses, concentrating on the pivotal role of the VD/VDR pathway in adipogenesis. This insight furnishes new perspectives for the development of micronutrient-related intervention strategies in the prevention and treatment of obesity.

Self-emulsifying drug delivery systems (SEDDS) disrupt the gut microbiota and trigger an intestinal inflammatory response in rats

Self-emulsifying drug delivery systems (i.e. SEDDS, SMEDDS and SNEDDS) are widely employed as solubility and bioavailability enhancing formulation strategies for poorly water-soluble drugs. Despite the capacity for SEDDS to effectively facilitate oral drug absorption, tolerability concerns exist due to the capacity for high concentrations of surfactants (typically present within SEDDS) to induce gastrointestinal toxicity and mucosal irritation. With new knowledge surrounding the role of the gut microbiota in modulating intestinal inflammation and mucosal injury, there is a clear need to determine the impact of SEDDS on the gut microbiota. The current study is the first of its kind to demonstrate the detrimental impact of SEDDS on the gut microbiota of Sprague-Dawley rats, following daily oral administration (100 mg/kg) for 21 days. SEDDS comprising a lipid phase (i.e. Type I, II and III formulations according to the Lipid Formulation Classification Scheme) induced significant changes to the composition and diversity of the gut microbiota, evidenced through a reduction in operational taxonomic units (OTUs) and alpha diversity (Shannon’s index), along with statistically significant shifts in beta diversity (according to PERMANOVA of multi-dimensional Bray-Curtis plots). Key signatures of gut microbiota dysbiosis correlated with the increased expression of pro-inflammatory cytokines within the jejunum, while mucosal injury was characterised by significant reductions in plasma citrulline levels, a validated biomarker of enterocyte mass and mucosal barrier integrity. These findings have potential clinical ramifications for chronically administered drugs that are formulated with SEDDS and stresses the need for further studies that investigate dose-dependent effects of SEDDS on the gastrointestinal microenvironment in a clinical setting.

Antibacterial activity of biosynthesized zinc oxide nanoparticles using Kombucha extract

Antibacterial resistance is a growing global vital medical problem when the innovation and development of new antibiotics are dwindling. Different nanomaterials were synthesized and developed as safe and effective alternative antimicrobial agents. The current study highlights the effect of the antibacterial activity of newly biosynthesized zinc oxide nanoparticles (ZnO NPs) obtained from Kombucha extract. Production of ZnO NPs was optimized and the synthesized nanoparticles were characterized using UV–visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Zeta potential and transmission electron microscope (TEM) analysis. The optimum conditions for ZnO NPs production were at temperature 30 °C, pH 9 and 25 mM of Zn(NO3)2.6H2O. The ZnO NPs biosynthesis was detected in the extract within 24 h. at 35 °C in dark conditions. The XRD pattern displayed 100, 101, 110, and 103 crystal planes. FTIR spectrum showed bands of 1° and 2° amines at 2922.6 cm−1 and a stretching vibration band of vinyl at 1657.5 cm−1. In addition, the results confirmed the positive charge (19 ± 3 mV) and crystalline nature of spherical-shaped ZnO NPs with an average size of 23 ± 1.5 nm. The antibacterial activity of ZnO NPs was tested against different American-type culture collection strains. ZnO NPs exhibited minimum inhibition concentration (MIC) values of 25 µg/ml against Escherichia coli ATCC25922, 30 µg/ml against Staphylococcus aureus ATCC25923 and Pseudomonas aeruginosa ATCC27853, 35 µg/ml against Serratia liquefaciens OQ071699.1 and S. saprophyticus OQ071703.1 and 40 µg/ml against Lysinibacillus fusiformis OQ071701.1 and Klebsiella pneumoniae ATCC33495. Ultrastructure TEM study of the treated bacteria by MIC of ZnO NPs confirmed their highly toxic action on the bacterial cell wall, resulting in bacterial cell membrane rupture. Treated bacteria appeared as extensively damaged cells with the formation of vacuoles and lipids. The provided approach of ZnO NPs in combination with Kombucha SCOBY has a promising future in overcoming bacterial resistance problems in place of using antibiotics.