Lipid Particles Research Articles

Lipid changes across menopause status point to increased cardiovascular risk

Abstract Background While women develop cardiovascular disease (CVD) approximately ten years later than men, risk of CVD in women rises precipitously following menopause. The mechanisms underlying this acceleration in CVD risk are not well elucidated, but adverse changes in lipid measures are known to occur during the perimenopause period. Previous investigations have been largely restricted to traditional lipid measures and have not examined changes in lipoprotein particles including lipid subfractions and particle number. Purpose We sought to examine longitudinal changes in lipoprotein particles that occur during the menopause transition. Methods A total of 1305 participants in the Dallas Heart Study with known menopause status underwent measurement of LDL-P, HDL-P, sd-LDL, and ld-HDL by NMR LipoProfile LP4 algorithm (LabCorp, Raleigh Durham, NC, U.S.A.) at 2 examinations (between 7-8 years between DHS studies). We compared longitudinal changes in lipoprotein measures between pre-, peri-, post-menopausal women and men using multivariable adjusted linear regression models. For our analysis peri- is the group that was pre-menopause at DHS I and post-menopause at DHS 2, not to mean the period before menopause. Results There 1346 men (referent group) included in the study with a mean age of 43 ± 9.4 years. There was a total of 1246 women with a mean age of 42 ± 5.6 for peri-group, 54 ± 6.2 for post-group, and 34 ± 3.08 for the pre-group. Of the women 440 (35.3%) were pre-menopausal, 298 (23.9%) were peri-menopausal, and 508 (40.8%) were post-menopausal. Over a median follow-up time of 7 years. All three groups had an increase in LDL-P but the greatest percent change is between peri and post, 18.30 (SE 3.05, P<0.001). When compared to men the post-group has the greatest percent change of HDL-P with a negative change of 4.77 (SE 0.948 P<0.0001). Small-dense LDL had the highest percent change in the peri- group when compared to men with a change of 578.62 (SE 288.45, P<0.045). Large-dense HDL had greatest percent change in the post- group when compared to men with negative change of 37.84 (SE 12.83, P<0.0032). Conclusions We found that menopause is associated with adverse changes in lipoprotein profiles, with the most pronounced changes in LDL-particles and subfractions observed for peri-menopausal women. By contrast, post-menopausal women demonstrated the greatest reductions in HDL-particles and subfractions. Taken together, these changes suggest that menopause is associated with a transition to a more atherogenic lipoprotein profile. Further research is needed to investigate whether these adverse changes in lipoproteins translate to greater CV risk.

Association between lipoprotein particle concentration and size and progression of coronary plaque: the MACS Longitudinal Coronary CT angiography study

Abstract Background People living with HIV have greater risk of cardiovascular diseases (CVD) than people without HIV and tend to have different risk profiles, including higher serum triglycerides and lower LDL cholesterol levels. Nuclear magnetic resonance (NMR) provides a detailed phenotype of lipoproteins. Purpose To examine the associations between lipoprotein particle concentrations and size and progression of coronary artery plaque among people living with and without HIV, and whether these associations differ by HIV serostatus. Methods Men with no clinical CVD in the Multicenter AIDS Cohort Study (MACS) who underwent a coronary CT angiography at baseline (2010-13) and follow-up (2015-17) were included. NMR spectroscopy was completed on fasting serum samples at baseline. Logistic regression models for the change in total coronary plaque volume (in tertiles) were estimated with NMR-derived lipoproteins as predictors. Levels were log-transformed and standardized to make results comparable. Models were adjusted for demographics, statin use and HIV serostatus (model 1) with addition of CVD risk factors (model 2). Interactions by HIV serostatus were also tested. Results A total of 549 men (314 with HIV; 235 without HIV) were included. Mean age was 53 ±7 years; 58% were White, 30% Black, and 12% Hispanic. Coronary plaque was present in 70% and plaque volume progressed in 79% of the cohort. Among men with HIV, 81% had undetectable HIV RNA and 12% had a diagnosis of AIDS at baseline. Men with HIV had significantly higher levels of small LDL-P, and total, medium and large VLDL-P levels compared to men without HIV, and lower levels of total, small and large HDL-P (Table 1). Men with HIV had significantly greater progression of plaque volume (37 mm3) compared to men without HIV (31 mm3, p<0.05). Levels of total and small LDL-P concentrations were directly associated with plaque progression, whereas large HDL-P was inversely associated with plaque progression in the combined sample (Model 2). Associations between total and small LDL-P with plaque progression were stronger in men with HIV than in men without HIV in models 1 and 2 (interaction p<0.01). While associations in fully adjusted models for total VLDL-P and small VLDL-P were significant in men without HIV, there were no significant associations between these particle concentrations with coronary plaque progression among men without HIV (interaction p< 0.01) (Model 2, Table 2). Conclusion Associations between lipid particle concentrations and coronary plaque progression differed between men with and without HIV, with stronger associations seen in men without HIV for total and small LDL-P. Despite having higher VLDL and lower HDL particle concentrations at baseline, these particle concentrations were only associated with plaque progression in men without HIV. Further research is needed to elucidate HIV specific factors for plaque progression to tailor risk reduction strategies.

On the Properties of Styrene–Maleic Acid Copolymer–Lipid Nanoparticles: A Solution NMR Perspective

The production of functionally active membrane proteins (MPs) in an adequate membrane environment is a key step in structural biology. Polymer–lipid particles based on styrene and maleic acid (SMA) represent a promising type of membrane mimic, as they can extract properly folded MPs directly from their native lipid environment. However, the original SMA polymer is sensitive to acidic pH levels, which has led to the development of several modifications: SMA-EA, SMA-QA, and others. Here, we introduce a novel SMA derivative with a negatively charged taurine moiety, SMA-tau, and investigate the formation and characteristics of lipid–SMA-EA and lipid–SMA-tau membrane-mimicking particles. Our findings demonstrate that both polymers can form nanodiscs with a patch of lipid bilayer that can undergo phase transitions at temperatures close to those of the lipid bilayer membranes. Finally, we discuss the potential applications of these SMAs for NMR spectroscopy.

Optimization, Formulation, and Ex vivo Evaluation of Solid Lipid Nanoparticles for Transdermal Delivery of Diltiazem Hydrochloride.

Cardiac arrhythmia, is a medical condition that reduces the heart's efficiency in pumping blood, and can be fatal, requires long-term management with conventional drugs, despite their limited efficacy. Diltiazem hydrochloride, chosen as a model drug, has a short biological half-life and extensive metabolism. Administering drug through skin is challenging, particularly due to the penetration via stratum corneum. However, solid lipid nanoparticles as a particulate carrier system can enhance its permeation and bioavailability. The study aimed to develop a matrix type transdermal patch with diltiazem hydrochloride encapsulated in solid lipid nanoparticles Methods: The study used the solvent diffusion technique to prepare SLNs by mixing the drug and solid lipid in an organic phase at 80°C, then slowly adding it to an aqueous phase with continuous stirring for 45 minutes. The resulting nanodispersion was freeze-dried and analyzed for morphological studies, encapsulation efficiency & drug content. A patch was formulated using solvent evaporation technique, incorporating HPMC E50 (2% w/v), propylene glycol, and ethanolic oleic acid (1.5% v/v). SLNs loaded with diltiazem hydrochloride taken equivalent to diltiazem hydrochloride dose in the transdermal patch. The patch was then evaluated for In vitro and skin permeation studies. The result showed a positive correlation between lipid concentration and particle size. Probe sonication and homogenization increased particle size, while stirring speed reduced it. SEM and TEM images confirmed spherical particles with a size of 488.1±4.01nm and an entrapment efficiency of 55.03±1.99%. Drug release studies demonstrated 70.7% drug release from lipid matrix over 24 hrs. The formulated patch with uniform SLN distribution, had a drug content 89.37 ± 0.04% with a surface pH of 6.1 ± 0.53, close to skin pH. The uniformity of content in 3x3 patch estimated to be 14.587 ± 1.404 mg, close to the theoretical content 16.318 ± 1.08 mg, confirmed homogenous distribution of diltiazem hydrochloride SLNs throughout the patch diameter. Cumulative amount released from patch formulation at pH 5.6 and pH 7.4 was 518.1414μg/cm2 and 404.4466 μg/cm2. Synergistic flux enhancement was observed with oleic acid propylene glycol blend. Ex vivo study of the patch showed steady-state flux of 6.9 μg/cm2/hr, permeability coefficient 0.00362 cm/hr, diffusion coefficient 0.000103 cm/hr, cumulative drug permeation (Dmax) 814.885 μg after 24 hrs, and followed a Higuchi-matrix release model. The developed patch possessed improved bioavailability with reduced dosing and enhanced patient compliance.

Physicochemical and biological characterization of the lipid particles with bovine serum albumin corona

Diacylglycerol–based nanoparticles are promising bioactive delivery systems. However, limited understanding of their interaction with biological entities restricts their clinical use. This study investigated the protein corona formed on medium and long chain diacylglycerol (MLCD)-based solid lipid nanoparticles (NPs) modified by Polyoxethylene stearate (PEG) and compared to glyceryl tristearate (TG) and cetyl palmitate (CP) nanoparticles. Bovine serum albumin (BSA) formed corona with MLCD NPs through hydrophobic interactions and hydrogen bonding, contributing to a decrease in α–helix, an increase in β–sheet and a change in the microenvironment of Tyr residues. Owing to higher lipid hydrophilicity, MLCD NPs showed a much lower affinity for BSA than TG and CP NPs, and the binding constant with BSA was increased for larger NPs. PEG modification and the protein corona reduced the uptake of NPs by macrophages but exerted little influence on B16 cell. Among the NPs with different lipid core, the MLCD NPs showed a lower macrophages cell uptake but higher B16 cell uptake, suggesting a longer circulation time in blood but higher cancer cell internalization. This work shed light on the interactions between MLCD NPs and proteins, which is significant for application as nanocarriers with improved biological efficacy.

A-119 Lipemia Interference

Abstract Background Lipemic specimens is a common problem in clinical laboratories. Analytical results may be perturbed by lipemia, leading to misdiagnosis and unnecessary treatments for patients. Serum index testing is an important preanalytical test for assessing the potential effect of endogenous HIL interferents (hemoglobin (H), bilirubin (I) or lipids (L)) on test results. Automated HIL systems are not standardized and differ in their response. HIL induced interference should be verified by all clinical laboratories. Intralipid, a commercial lipid emulsion with particle size ranges from 200 to 600 nm is often used to verify the L index. However, intralipid lacks particles that mimic large VLDL, as well as the lower and upper ranges for chylomicrons size. In contrast, patient samples contain a complex mixture of macromolecular lipid and protein structures. Therefore, lipemia induced by Intralipid is not identical to lipemia in patient serum samples. The purpose of this study is to increase awareness of lipid interference and demonstrate the relationship of a lipid L Index to intralipid and triglyceride interference. Methods A set of 16 panels were prepared from a commercially available Triglyceride rich Lipoprotein material. These panels spanned a lipid concentration from 0 to 3000 mg/dL. Panels were tested on the Alinity c and ARCHITECT c8000 TRIG2 assays (04U0615 and 04T1016 respectively) on 2 reagent lots in a single run to determine the Triglyceride concentration. Then these samples were assessed for an HIL L score using the Abbott HIL saline protocol. Results The relationship between the Triglyceride rich Lipoprotein and the L Index was linear with a high correlation (r= 0.999) for Alinity and ARCHITECT respectively. The L Index underestimated the Triglyceride Rich Lipoprotein concentration. The reason for the lower estimate of Triglyceride rich lipoprotein specimens on an L Index is likely due to the differences in size of the lipid particles between the two artificial lipid materials, Intralipid and Triglyceride rich lipoprotein. In addition, while the triglyceride assay provides a quantitative measurement of the lipemic concentration, the L Index is designed to provide an estimated result. Conclusions Intralipid is an acceptable material used to verify spectrophotometric HIL systems. The L Index provides an estimate of sample turbidity, not the concentration of Triglyceride. Vendor purchased human derived Triglyceride rich lipoprotein, which contains a heterological mixture of lipid particles, may be regarded as a more appropriate material for assessing lipid interference. Thus, while recovery of the L Index correlates well to the Intralipid concentration, it can have a poorer correlation with vendor purchased samples containing Triglyceride due to the different vesicle sizes in these materials. This study demonstrates the Triglyceride rich material used to assess lipid interference in Sigma Strong assays provides a difference in response between the Triglyceride concentration of this material determined on a Triglyceride assay vs the L Index. The choice of lipemic material to use, (eg. artificial, native), can influence the results. Thus, care should be taken in comparing results for these materials.

Vinyl Ether Maleic Acid Polymers: Tunable Polymers for Self-Assembled Lipid Nanodiscs and Environments for Membrane Proteins.

Native lipid bilayer mimetics, including those that use amphiphilic polymers, are important for the effective study of membrane-bound peptides and proteins. Copolymers of vinyl ether monomers and maleic anhydride were developed with controlled molecular weights and hydrophobicity through reversible addition-fragmentation chain-transfer polymerization. After polymerization, the maleic anhydride units can be hydrolyzed, giving dicarboxylates. The vinyl ether and maleic anhydride copolymerized in a close to alternating manner, giving essentially alternating hydrophilic maleic acid units and hydrophobic vinyl ether units along the backbone after hydrolysis. The vinyl ether monomers and maleic acid polymers self-assembled with lipids, giving vinyl ether maleic acid lipid particles (VEMALPs) with tunable sizes controlled by either the vinyl ether hydrophobicity or the polymer molecular weight. These VEMALPs were able to support membrane-bound proteins and peptides, creating a new class of lipid bilayer mimetics.

From foes to friends; bacterial proteins for optimal wart cryotherapy

Warts are a common skin complaint caused by viral infections. Cryotherapy is a well-established approach for wart removal, which apply low temperatures to freeze and destroy infectious cells. However, this process may face-up several unwanted side effect on healthy nearby tissues. Besides, proper penetration of such temperature is also required to cause irreversible damages in deep-root infectious layers. In this respect, ice-producing proteins that are naturally found in some bacterial species, knowing as ice nucleation active (INA) bacteria, may be practical. In the current work, we hypothesized purification and encapsulation of these proteins into vesicular lipid particles (such as liposomes, niosomes, and exosomes) for an intralesional injection. Thereby, effective wart removal would be achieved even at low temperatures without undesirable effects.

Review of Intranasal Active Pharmaceutical Ingredient Delivery Systems.

In recent decades, there has been an increased interest in the development of intranasal delivery systems for active pharmaceutical ingredients (APIs) not only for treating local nasal diseases but also for treating systemic diseases, central nervous system (CNS) disorders, and vaccine delivery. The nasal cavity possesses a unique set of anatomical characteristics for delivering active pharmaceutical ingredients, but there are several limitations that recent research in the field of the intranasal administration of APIs aims to overcome. For the effective delivery of nasal preparations, active pharmaceutical ingredients are incorporated into various micro- and nanosystems. Some of the most commonly encountered API delivery systems in the scientific literature include liposomal systems, polymer particles with mucoadhesive properties, in situ gels, nano- and microemulsions, and solid lipid particles. This article provides a review of research on the development of nasal preparations for treating local nasal cavity diseases (in particular, for antibiotic delivery), systemic diseases (analgesics, drugs for cardiovascular diseases, antiviral and antiemetic drugs), CNS disorders (Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia, depression), and vaccine delivery. The literature data show that active research is underway to reformulate drugs of various pharmacotherapeutic groups into a nasal form.

Pickering Foam Stabilized by Diacylglycerol-Based Solid Lipid Nanoparticles: Effect of Protein Modification.

Pickering foams have great potential for applications in aerated foods, but their foaming ability and physical stability are still far from satisfactory. Herein, solid lipid particles (SLNs) were fabricated by using diacylglycerol of varying acyl chain lengths with modification by a protein. The SLNs showed different crystal polymorphisms and air-water interfacial activity. C14-DAG SLN with a contact angle ∼ 79° formed aqueous foam with supreme stability and high plasticity. Whey protein isolate and sodium caseinate (0.1 wt %) considerably enhanced the foamability and interfacial activity of SLNs and promoted the packing of particles at the bubble surface. However, high protein concentration caused foam destruction due to the competitive adsorption effect. β-sheet increased in protein after adsorption and changed the polymorphism and thermodynamic properties of SLN. The foam collapsing behaviors varied in the presence of protein. The results gave insights into fabricating ultrastable aqueous foams by using high-melting DAG particles. The obtained foams demonstrated good temperature sensitivity and plasticity, which showed promising application prospects in the food and cosmetic fields.

Study of the Effects of Plasma Pretreatment on the Microstructure of Peanuts

In this study, cold plasma treatments are employed to modify peanuts. This study systematically investigates the effects of various plasma treatment conditions, including power, duration, and gas type, on the microstructure of peanut seed coats and embryos. Observations under a scanning electron microscope (SEM) reveal that as plasma treatment power increases from 100 W to 500 W, the etching level of peanut seed coats significantly intensifies, surface roughness deepens, and concavities become more pronounced. Additionally, micro-pores on the seed coat gradually enlarge and form cracks. Specifically, when the plasma treatment is set at 200 W for 60 s, the oxygen (O2) treatment group shows interconnected cracks on the peanut seed coat surface, with lipid particles exuding and protein particles and polymers decomposing. In contrast, the helium (He) treatment group displays clear cell structures and deep grooves, with no noticeable lipid particles exuding around surface cracks. The argon (Ar) treatment group exhibits a distinct rectangular cell structure with clear boundaries, and although surface cracks form, only a few protein particles escape from the cracks. The embryo surface structure becomes looser after plasma treatment, leading to the disintegration of lipid particles, protein particles, and polymers, affecting the fusion and migration of large and small lipid bodies within the peanut’s internal structure. Increasing treatment duration intensifies the etching phenomenon, resulting in more lipid particles exuding, which indicates a positive correlation between lipid particles exuding and treatment duration. This study sheds light on the mechanisms underlying changes in peanut microstructure due to cold plasma treatment, providing scientific evidence for improving peanut quality, enhancing oil extraction efficiency, and optimizing food processing techniques.

Latest Delivery Advancements of Lipid Nanoparticles for Cancer Treatment.

As one of the primary causes of illness and death globally, cancer demands novel and potent treatment approaches, which is why lipid nanoparticles (LNPs) have gained attention as a promising delivery system for anticancer drugs with precision and efficacy. The article discusses the salient characteristics of LNPs, such as the lipid components, particle size, polydispersity index, and encapsulation efficiency, followed by strategies that enhance their remarkable drug delivery capabilities. The articles explore LNPs ability to improve the solubility, stability, and bioavailability of various chemotherapeutics, nucleic acids, and immunotherapeutic modalities. It also highlights the recent advancement in surface modification of LNPs, which is essential to improve their effectiveness. Tailored coatings of LNPs improve targeting precision, stability, and biocompatibility; enhancing their transport to boost therapeutic efficacy for cancer targeting. The review summarizes the recent advancements made in using LNPs to treat different forms of cancer and focuses on the most recent clinical studies. Overall, the review highlights that the LNPs can target and treat cancer in a tailored manner through gene therapy, RNA interference, and immunotherapy.

A Review on Solid Lipid Nanoparticles as Nano Drug Delivery Transporters

Abstract: Solid lipid nanoparticles (SLN) have several potential uses in research for medicine such as drug discovery and drug delivery, an area at the forefront of evolving area of nanobiotechnology. In general, SLNs were created to address the drawbacks of conventional colloidal carriers, including emulsions, liposomes, and polymeric nanoparticles since they provide various advantages such as favourable release profiles and tailored drug delivery with outstanding physical-chemical stability. Solid lipid nanoparticles are spherical solid lipid particles that are distributed in water or an aqueous surfactant solution and are in the nanometer size range. Therefore, SLN is used to deliver hydrophilic and lipophilic drugs. The review article focuses on various aspects of SLN including the structure, the influence of excipients, the drug incorporation model, the principle of release, the method of preparation, characterization, the route of administration and biodistribution, and the application of SLN.

Lipid vesicle formation by encapsulation of SMALPs in surfactant-stabilised droplets

Understanding the intricate functions of membrane proteins is pivotal in cell biology and drug discovery. The composition of the cell membrane is highly complex, with different types of membrane proteins and lipid species. Hence, studying cellular membranes in a complexity-reduced context is important to enhance our understanding of the roles of these different elements. However, reconstitution of membrane proteins in an environment that closely mimics the cell, like giant unilamellar vesicles (GUVs), remains challenging, often requiring detergents that compromise protein function. To address this challenge, we present a novel strategy to manufacture GUVs from styrene maleic acid lipid particles (SMALPs) that utilises surfactant-stabilised droplets as a template. As a first step towards the incorporation of membrane proteins, this work focusses on the conversion of pure lipid SMALPs in GUVs. To evaluate the method, we produced a new form of SMA linked to fluorescein, referred to as FSMA. We demonstrate the assembly of SMALPs at the surfactant-stabilised droplet interface, resulting in the formation of GUVs when released upon addition of a demulsifying agent. The released vesicles appear similar to electroformed vesicles imaged with confocal light microscopy, but a fluorescein leakage assay and cryo-TEM imaging reveal their porous nature, potentially as a result of residual interactions of SMA with the lipid bilayer. Our study represents a significant step towards opening new avenues for comprehensive protein research in a complexity-reduced, yet biologically relevant, setting.

Bioactive peptides inhibit feeding activity in the grey garden slug, Deroceras reticulatum.

The grey garden slug (Deroceras reticulatum) is considered the most damaging slug pest in global agriculture. Control methods primarily rely on chemical pesticides, which pose environmental risks and potential hazards to human health. There is a need for sustainable management alternatives such as biologically-based slug control options. However, the efficacy of nonchemical measures for controlling pest slug populations remains limited, particularly in the context of variable outdoor conditions. Neuropeptides and their corresponding receptors have been proposed as promising biological targets for the development of new pest management strategies. A total of 23 bioactive peptides belonging to the PRX family, previously identified from the grey garden slug, D. reticulatum, were injected into or fed to this species. The detrimental effects of these peptides, including a reduction in body weight and an inhibition of feeding activity, were evaluated in feeding choice tests with D. reticulatum. Furthermore, the bioactive peptide formulated with a lipid particle demonstrated a feeding deterrent effect. One of the myomodulin (MM) peptides, APPLPRY, demonstrated a significant reduction in feeding activity, resulting in a reduction in slug weight or mortality in just 30 min. The results represent the first evidence of a bioactive peptide having detrimental effects on D. reticulatum including causing feeding deterrent for this slug pest. The in vivo results provide insights into the potential development of active ingredients for managing slugs in the field. © 2024 Society of Chemical Industry.

Unveiling the protein-lipid interaction mechanism: How the sturgeon lipids diminish the surimi gel properties

Sturgeon, with 4 times higher lipid content than silver carp (ubiquitously applied for surimi production in China), affects surimi gelling properties. However, how the flesh lipids affect gelling properties remains unclear. This study investigated how flesh lipids impact surimi gelling properties and elucidated the interaction mechanism between lipids and proteins. Results revealed yellow meat contains 7 times higher lipids than white meat. Stronger ionic protein-protein interactions were replaced by weaker hydrophobic forces and hydrogen bonds in protein-lipid interaction. Protein-lipid interaction zones encapsulated lipid particles, changing protein structure from α-helix to β-sheet structure thereby gel structure becomes flexible and disordered, significantly diminishing surimi gel strength. Docking analysis validated fatty acid mainly binding at Ala577, Ile461, Arg231, Phe165, His665, and His663 of myosin. This study first reported the weakened surimi gelling properties from the perspective of free fatty acids and myosin interactions, offering a theoretical basis for sturgeon surimi production.

Effect of the composition of combined solid lipid particles with gefitinib and a photosensitizer on their size, stability and cytotoxic activity

The creation of combined nanomedicines and their controlled release under the influence of photoinduction is an actively developing branch of scientific research. This work is devoted to the development of models of solid lipid nanoparticles for a well-known antitumor drug – gefitinib in combination with a photoindicating agent – a photosensitizer from the phthalocyanine group. Nanoparticles were obtained by several methods: hot homogenization with stearic acid, sesame oil and Tween 80 and by one-step dispersion with copolymers of lactic and glycolic acids and polyvinyl alcohol. In vitro experiments when irradiating particles with a laser in the near-infrared range (about 730 nm) proved the advantage of using combined nanoparticles with gefitinib and a photosensitizer compared to monotherapy, while the activity in terms of IC50 was 5.1-8.7 times higher for gefitinib and 1.5-1.8 times for the photosensitizer.

Yeast Particle Encapsulation of Azole Fungicides for Enhanced Treatment of Azole-Resistant Candida albicans.

Addressing the growing problem of antifungal resistance in medicine and agriculture requires the development of new drugs and strategies to preserve the efficacy of existing fungicides. One approach is to utilize delivery technologies. Yeast particles (YPs) are 3-5 µm porous, hollow microspheres, a byproduct of food-grade Saccharomyces cerevisiae yeast extract manufacturing processes and an efficient and flexible drug delivery platform. Here, we report the use of YPs for encapsulation of tetraconazole (TET) and prothioconazole (PRO) with high payload capacity and stability. The YP PRO samples were active against both sensitive and azole-resistant strains of Candida albicans. The higher efficacy of YP PRO versus free PRO is due to interactions between PRO and saponifiable lipids in the YPs. Encapsulation of PRO in glucan lipid particles (GLPs), a highly purified form of YPs that do not contain saponifiable lipids, did not result in enhanced PRO activity. We evaluated the co-encapsulation of PRO with a mixture of the terpenes: geraniol, eugenol, and thymol. Samples co-encapsulating PRO and terpenes in YPs or GLPs were active on both sensitive and azole-resistant C. albicans. These approaches could lead to the development of more effective drug combinations co-encapsulated in YPs for agricultural or GLPs for pharmaceutical applications.

Enhancing pulmonary delivery and immunomodulation of respiratory diseases through virus-mimicking nanoparticles

This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air-liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non-exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40-fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro-inflammatory IL-6 expression, and elevated anti-inflammatory IL-10 expression. These findings suggest a potential mechanism to regulate the excessive IL-6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases.

Evolution of the Umbilical Cord Blood Proteome Across Gestational Development.

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 24 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. Proteins that function in structural development and growth (e.g., extracellular matrix organization, lipid particle remodeling, and blood vessel development) are more abundant earlier in gestation. In later gestations, proteins with increased abundance are in immune response and inflammatory pathways, including complements and calcium-binding proteins. Furthermore, these data contribute to the knowledge of the physiologic state of neonates across gestational age, which is crucial to understand as we strive to best support postnatal development in preterm infants, determine mechanisms of pathology causing adverse health outcomes, and develop cord blood biomarkers to help tailor our diagnosis and therapeutics for critical neonatal conditions.