Lipid Phase Research Articles

Tailoring the plasmonic properties of gold-liposome nanohybrids as a potential powerful tool for light-mediated therapies

A fast and environmentally-friendly methodology has been developed by in situ synthesis of gold nanoparticles (AuNPs) on thermosensitive liposomes in different phase-states, obtaining nanohybrids with controllable and tunable plasmon modes within the visible/near-infrared region. Lipid phase, charge and synthesis temperature influence the final arrangement of AuNPs, so when the synthesis is performed on zwitterionic liposomes in fluid phase, discrete AuNPs with plasmon peaks in the visible region are obtained, while in gel phase AuNPs tend to aggregate forming nanoclusters, leading to plasmon bands gradually shifted to the infrared as the synthesis temperature decreases. The formed nanohybrids retain the physical properties of the liposomes (fluidity, degree of hydration, cooperativity) by maintaining the transition temperature in the mild-hyperthermia range, while preserving their light-to-heat conversion properties. Therefore, these nanohybrids can be considered excellent candidates as versatile photothermal agents with controlled drug delivery capacity, being powerful tools for light-mediated therapies.

Lutein-Fortified Plant-Based Egg Analogs Designed to Improve Eye Health: Formation, Characterization, In Vitro Digestion, and Bioaccessibility.

Lutein is a carotenoid found in real eggs that has been reported to have beneficial effects on eye health by reducing the risk of age-related macular degeneration. However, lutein is not often included in plant based (PB) egg analogs. It would, therefore, be advantageous to fortify PB eggs with this health-promoting carotenoid. Moreover, lutein is a natural pigment with a bright red to yellowish color depending on its concentration and environment. It can, therefore, also be used as a plant-based pigment to mimic the desirable appearance of egg yolk. Some of the main challenges to using lutein as a nutraceutical and pigment in PB foods are its poor water-solubility, chemical stability, and bioavailability. In this study, we encapsulated lutein in oil-in-water emulsions, which were then utilized to formulate whole egg analogs. Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) protein isolated from a sustainable plant-based source (duckweed) was used to mimic the thermally irreversible heat-set gelling properties of globular egg proteins, with the aim of obtaining a similar cookability and texture as real eggs. The lutein content (80 mg/100 g) of the egg analogs was designed to be at a level where there should be health benefits. The protein (12.5 wt.%) and oil (10 wt.%) contents of the egg analogs were selected to match those of real egg. The effects of oil droplet size and oil type on the bioaccessibility of the encapsulated lutein were examined using the INFOGEST in vitro digestion model. For the emulsions formulated with long chain triglycerides (LCTs, corn oil), lutein bioaccessibility significantly increased when the initial droplet diameter decreased from around 10 to 0.3 μm, which was attributed to more rapid and complete digestion of the lipid phase for smaller droplets. For medium chain triglycerides (MCTs), however, no impact of droplet size on lutein bioaccessibility was observed. A high lutein bioaccessibility (around 80%) could be obtained for both LCTs and MCTs emulsions containing small oil droplets. Thus, both types of oil can be good carriers for lutein. In summary, we have shown that lutein-fortified PB eggs with good digestibility and bioaccessibility can be created, which may play an important role in ensuring the health of those adopting a more plant-based diet.

Interactions of Bacterial Quorum Sensing Signals with Model Lipid Membranes: Influence of Membrane Composition on Membrane Remodeling.

We report the influence of membrane composition on the multiscale remodeling of multicomponent lipid bilayers initiated by contact with the amphiphilic bacterial quorum sensing signal N-(3-oxo)-dodecanoyl-l-homoserine lactone (3-oxo-C12-AHL) and its anionic headgroup hydrolysis product, 3-oxo-C12-HS. We used fluorescence microscopy and quartz crystal microbalance with dissipation (QCM-D) to characterize membrane reformation that occurs when these amphiphiles are placed in contact with supported lipid bilayers (SLBs) composed of (i) 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) containing varying amounts of cholesterol or (ii) mixtures of DOPC and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE, a conical zwitterionic lipid) or 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS, a model anionic lipid). In general, we observe these mixed-lipid membranes to undergo remodeling events, including the formation and subsequent collapse of long tubules and the formation of hemispherical caps, upon introduction to biologically relevant concentrations of 3-oxo-C12-AHL and 3-oxo-C12-HS in ways that differ substantially from those observed in single-component DOPC membranes. These differences in bilayer reformation and their associated dynamics can be understood in terms of the influence of membrane composition on the time scales of molecular flip-flop, lipid packing defects, and lipid phase segregation in these materials. The lipid components investigated here are representative of classes of lipids that comprise both naturally occurring cell membranes and many useful synthetic soft materials. These studies thus represent a first step toward understanding the ways in which membrane composition can impact interactions with this important class of bacterial signaling molecules.

Development of Plant-Based Adipose Tissue Analogs: Freeze-Thaw and Cooking Stability of High Internal Phase Emulsions and Gelled Emulsions.

There is great interest in the development of plant-based alternatives to meat products to meet the rising demand from vegans, vegetarians, and flexitarians. Ideally, these products should look, feel, taste, and behave like the meat products they are designed to replace. In this study, we investigated the impact of simulated freeze-thaw and cooking treatments on the properties of plant-based adipose tissues formulated using high internal phase emulsions (HIPEs) or gelled emulsions (GEs). The HIPEs consisted of 75% oil, 2% soybean protein, 23% water, while the GEs consisted of 60% oil, 2% soybean protein, 2% agar and 36% of water. Low melting point (soybean oil) and high melting point (coconut oil) oils were used to create emulsions with either liquid or partially crystalline lipid phases at ambient temperature, respectively. In general, GEs were harder than HIPEs, and emulsions containing coconut oil were harder than those containing soybean oil at ambient temperatures. The thermal behavior of the plant-based adipose tissue was compared to that of beef adipose tissue. Beef adipose tissue was an opaque whitish semi-solid at ambient temperature. These properties could be mimicked with all types of HIPEs and GEs. The structure of the beef adipose tissue was resistant to freezing/thawing (-20/+20 °C) but not cooking (90 °C, 30 min). Soybean HIPEs and GEs were relatively stable to simulated cooking but not freeze-thawing. Conversely, coconut HIPEs and GEs exhibited the opposite behavior. These results have important implications for the formulation of alternatives to animal adipose tissue in plant-based foods.

Storage stability, heat stability, controlled release and antifungal activity of liposomes as alternative fungal preservation agents

The aim of this study was to investigate the characteristics of liposomes encapsulated ethanolic Cinnamomum verum, Curcuma longa, Zingiber officinale, Syzygium aromaticum and Laurus nobilis extract prepared using lipid phase containing phosphatidylcholine/extract mixture of 10:1. The antifungal activity, size, zeta (ζ) potential, morphology, physical stability, heat stability, release in in-vitro digestion, color and differential scanning calorimetry (DSC) were conducted to determine the characteristics of liposomes. All extract-loaded liposomes showed prominently antifungal activity against Aspergillus sp. and Penicillium sp. The encapsulation efficiency of all samples was 86.60%–92.87%. Curcuma longa loaded liposome had high encapsulation efficiency after freeze dry-rehydration (FD-RH), long-term and freeze-thaw (FT) storage treatment. The thermal stability of Syzygium aromaticum loaded liposomes was higher than the others. The highest release values in the in-vitro gastric and intestinal condition were detected in Laurus nobilis loaded liposome. DSC data of liposomes demonstrated to be the endothermic phase at three different temperature ranges: lipid bilayers transition from gel state to liquid crystal form (1.69–5.31 °C), the pre-phase transition temperature (102.16–133.10 °C) and the main phase transition temperature (116.47–165.22 °C).

Synthesis of Lipid Nanoparticles Incorporated with Ferula assa-foetida L. Extract

Solid Lipid Nanoparticles (SLN) have been prepared by high-pressure homogenization and optimized in order to protect ferulic acid from Ferula assa-foetida L. extract. The influence of lipid and surfactant concentration on the mean particle size (Z-Ave), polydispersity index (PDI), and zeta potential (ZP) of SLN was analyzed. In addition, other parameters for the preparation of ferulic acid-loaded nanoparticles, such as extract concentration and variable parameters for the synthesis method used (e.g., pressure), were adjusted to obtain the smallest particle size and polydispersity index, as well as the highest value for zeta potential, which are characteristic of the stable SLN. The established formulation obtained from the optimized synthesis was composed of 6.0 wt.% of the lipid phase and 1.5 wt.% of surfactant, giving stable SLN with Z-Ave, PDI, and ZP values of 163.00 ± 1.06 nm, 0.16 ± 0.01, and −41.97 ± 0.47 mV, respectively. The loading of ferulic acid from Ferula assa-foetida L. extract within the SLN resulted in particles with a mean size of 155.3 ± 1.1 nm, polydispersity index of 0.16 ± 0.01, zeta potential of −38.00 ± 1.12 mV, and encapsulation efficiency of 27%, the latter being quantified on the basis of RP-HPLC analysis. Our findings highlight the added value of SLN as a delivery system for phenolic phytochemical compounds extracted from Ferula assa-foetida L.

Nanodisc Lipids Exhibit Singular Behaviors Implying Critical Phenomena.

Nanodiscs are broadly used for characterization of membrane proteins as they are generally assumed to provide a near-native environment. In fact, it is an open question whether the physical properties of lipids in nanodiscs and membrane vesicles of the same lipid composition are identical. Here, we investigate the properties of lipids (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dilauroyl-sn-glycero-3-phosphocholine, and their mixtures) in two different sample types, nanodiscs and multilamellar vesicles, by means of spin-label electron spin resonance techniques. Our results provide a quantitative description of lipid dynamics and ordering, elucidating the molecular details of how lipids in the two sample types behave differently in response to temperature and lipid composition. We show that the properties of lipids are altered in nanodiscs such that the dissimilarity of the fluid and gel lipid phases is reduced, and the first-order phase transitions are largely abolished in nanodiscs. We unveil that the ensemble of lipids in the middle of a nanodisc bilayer, as probed by the end-chain spin-label 16-PC, is promoted to a state close to a miscibility critical point, thereby rendering the phase transitions continuous. Critical phenomena have recently been proposed to explain features of the heterogeneity in native cell membranes. Our results lay the groundwork for how to establish a near-native environment in nanodiscs with simple organization of lipid components.

Pioglitazone-loaded nanostructured lipid carriers: In-vitro and in-vivo evaluation for improved bioavailability

Pioglitazone (PZ), a highly lipophilic Class II drug with poor aqueous solubility possesses low oral bioavailability. The oral bioavailability of pioglitazone can be improved by incorporating into nanostructured lipid carriers (NLCs). Pioglitazone-loaded nanostructured lipid carriers (PZ-loaded NLCs) were developed by using the solvent emulsification evaporation method. The lipid phase of the formulation consists of a solid and liquid lipid mixture (fatty acids and oils) and surfactants (Tween 20, Span 40) were used for the stability of the formulation. PZ-loaded NLCs were characterized for physicochemical characteristics including particle size, zeta potential, polydispersity index (PDI), fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) and stability studies. Moreover, drug entrapment efficiency, drug loading capacity, drug release, toxicity studies, permeation studies, and in-vivo studies were performed to evaluate enhanced bioavailability. PZ-loaded NLCs have shown an average particle size of 152 nm, PDI of 0.19, and a negative value of zeta potential. Drug entrapment efficiency and loading capacity were about 83% and 5.8%, respectively. SEM results delineated the smooth homogenous surface in nano-sized range, whereas FTIR spectra demonstrated no interaction between components of PZ-loaded NLCs formulation. For drug release studies, the dialysis bag method confirmed a biphasic release behavior in beginning followed by slow, controlled release up to 24 h. Furthermore, permeation studies showed enhanced permeability and in-vivo studies confirmed the enhanced bioavailability of pioglitazone. Based on the above finding, it can be concluded that NLCs are a versatile tools for enhancing the bioavailability of poorly soluble Class II drugs.

Thermodynamic and kinetic analysis of human epidermal penetration of phenolic compounds: I. Stratum corneum solubility and partitioning

Warming of the skin is now an accepted means of promoting skin permeation. Accordingly, the usually quite onerous thermodynamic studies on solute transport through the skin have practical applications. Phenolic compounds permeate through the skin by partitioning into and diffusing through the stratum corneum (SC) intercellular lipids, with their size being the main determinant of their maximal solute flux through skin. This paper sought to characterise the enthalpic and entropic changes associated with the solubility and equilibrium partitioning into the human SC of a series of phenols similar in size but with differing log P from aqueous vehicles.The solubilities of 9 phenolic compounds, covering a range of polarities, were determined in water and SC following 72 h at 4, 24, 32 and 37 °C which allowed the estimation of the SC-water partition coefficients. Van’t Hoff plots were then used to estimate the enthalpies and entropies for the SC solubility, water solubility and SC partitioning of phenols. In addition, partition coefficients of 3 of the 9 phenols from mineral oil into hydrated and dehydrated SC were measured at the same temperatures. Van’t Hoff plots were then used to estimate the enthalpies and entropies for the SC solubility, water solubility and SC partitioning of phenols from the oil.The SC solubility for the polar phenols increased more with temperature than the non-polar phenols, with the SC-water partition coefficients increasing with temperature for the polar phenols but decreasing with temperature for the non-polar phenols. Thermodynamic analyses suggest that, while enthalpy and entropy effects are involved in the SC partitioning of the non-polar solutes, the SC partitioning of the polar phenols were almost entirely entropy driven. The resultant thermodynamic parameters are consistent with the polar phenols being mainly associated with the SC polar head groups whereas the nonpolar phenols were more likely to be located in the interior interface SC lipid region adjacent to the polar head groups. Further, hydrating the SC led to an increase in the enthalpy of partitioning for both the polar and non-polar phenols studied. The estimated entropy of the partitioning for solutes from dehydrated SC suggests this is not only a hydrophobic effect in water but that the partitioning arises from the nature of phenolic compound - SC intercellular lipid interactions and SC intercellular lipid entropy. This partitioning process is dominated more by the extent of interaction between the SC and solute than the hydrophobic effect in water and is likely to be even greater above the SC lipid phase transition at around 36 °C for hydrated epidermal membranes.

Optimisation of Curcumin Microemulsions Using Palm Oil

Curcumin is a natural hydrophobic polyphenol derived from the curcuminoids of Curcuma longa. Curcumin is commonly known as turmeric and it gains the interest of scientific and clinical researchers as it exhibits great pharmacological benefits such as anti-cancer, antiinflammatory and anti-oxidant properties. Nevertheless, curcumin is still not an approved drug in clinical settings due to its poor aqueous solubility and low oral bioavailability. Therefore, a self-microemulsifying drug delivery system (SMEDDS) was used as an approach to enhance the solubility and bioavailability of curcumin. The microemulsion was devised in a pre-formulation phase using a surfactant (Tween 80), a co-surfactant (polyethylene glycol, PEG 400), a lipid phase (palm oil) and an aqueous phase (water). A ternary phase diagram was used to identify the self-microemulsifying region in a formulation. Five of these formulations (F1, F2, F4, F7 and F10) were found to be stable with no phase separation observed upon overnight storage. All of the five formulations (except F4) possessed a high percentage of transmittance (86%–100%), which signified the formation of a stable microemulsion when they were diluted in a 1:100 ratio by water. Curcumin microemulsions were formulated by loading curcumin into F1, F2, F7 and F10. Only F1 and F2 curcumin microemulsions exhibit a clear appearance, however, F7 and F10 form a turbid solution, which indicates the formation of the emulsion. The results indicated that F1 and F2 which contain a high surfactant/co-surfactant-to-oil ratio of 9:1 is optimum to formulate the curcumin microemulsions.

MaMYB13 is involved in response to chilling stress via activating expression of VLCFAs and phenylpropanoids biosynthesis-related genes in postharvest banana fruit

Fruit chilling injury is the result of physiological dysfunction due to membrane lipid phase change, oxidative damage of biomacromolecules and respiratory metabolism abnormality. However, the involvement of transcription factors in response to fruits chilling tolerance remains largely unclear. Here, MaMYB13 was identified to participate in banana fruit response to chilling stress. MaMYB13 has transcriptional activation activity. When exposed to low temperature, expression of MaMYB13 was enormously induced. Moreover, MaMYB13 promoter was activated by chilling stress. MaMYB13 bound to the promoters of several important very-long-chain fatty acids (VLCFAs) and phenylpropanoids biosynthesis-related genes, including MaKCS11, Ma4CL6 and MaAAE1, and activated their transcription. Furthermore, MaKIN10 X1/3 interacted with MaMYB13 and enhanced MaMYB13-mediated transcriptional activation possibly via phosphorylation. Altogether, our results unravel the mechanism of MaMYB13-MaKIN10 X1/3 interaction regulating banana fruit chilling tolerance through activating the expression of MaKCS11, Ma4CL6 and MaAAE1, providing new insights into the regulatory network of MYB transcription factor.

Improved accuracy and reproducibility of spontaneous liposome leakage measurements by the use of supported lipid bilayer-modified quartz cuvettes

Recent studies have revealed avid interactions between liposomes and several solid materials, such as quartz, polystyrene (PS) and poly(methyl methacrylate) (PMMA), commonly found in cuvettes used for spectroscopic measurements. These interactions risk leading to detrimental changes in liposome structure and integrity that, if overlooked, may compromise the measurements. In case of leakage experiments based on probing the spontaneous release of encapsulated hydrophilic markers, the liposome-cuvette interactions may result in the recording of erroneously high degrees of leakage. In the present study we investigate the possibilities of preventing unwanted liposome-cuvette interactions through the use of quartz cuvettes passivated with supported lipid bilayers (SLBs). The results show that this strategy leads to higher reproducibility and significantly improved accuracy of the leakage measurements. The usefulness of the method is validated in comparative experiments focused on how changes in temperature and lipid phase state, as well as inclusion of poly(ethylene glycol)-conjugated lipids (PEG-lipids), affect the release of liposome encapsulated carboxyfluorescein (CF).

Биоэлектрические эффекты отмывания клеток Сhara fragilis от растворов фитокомпозиции одуванчик-зверобой-календулы

By using of microelectrode techniques, patterns of change in the potential (φm) and resistance (Rm) of the plasma membrane (PM) of Chara fragilis cells under the influence of Dandelion–Hypericum-Calendula (DHC) phytocomposition solutions were studied. The values of φm and Rm are widely scattered: -90 ÷ -300 mV and 1 ÷ 32.6 Ohm·m2, respectively under the standard conditions. The average value of φm was -183 ± 4.9 mV, Rm = 9.2 ± 1.2 Ohm·m2. Using the dependences of φm, Rm on the concentration of K+ in the external environment, the ranges of activation of the K+ - channels to the inward (KCİR) and outward rectification (KCOR) were determined. Under the action of the DHC phytocomposition, while the cell was in the medium with the concentration of the composite 10-1 or 1 mg/ml, we did not detect changes in φm and Rm for 25 min. Stimulation or suppression of transport processes under the influence of composites occurred only with the exclusion of DHC from the composition of the nutrient medium and with a stepwise increase in the concentration of the composition in the medium. The electrophysiological effects of the action of the DHC composition are discussed from the point of view of its action on the lipid phase of the plasma membrane of the experimental cells.

Potential use of carnauba wax oleogel to replace saturated fat in ice cream

AbstractThe objective of this study was to develop a wax‐oleogel (soybean oil—SBO, peanut oil—PNO, and carnauba wax—CBW) to be used as a fat replacer for ice cream formulations. The oleogels were structured with 6%, 8%, and 10% of CBW and were characterized by oil binding capacity (OBC), visual evaluation, thermal properties (DSC), and microstructure by polarized light microscopy (PLM). All oleogels resulted in a firm and stable gel for 60 days, regardless of the concentrations (6%, 8%, and 10%) and temperatures (5 and 25°C). The OBC of oleogels at 8% and 10% addition were significantly higher (p < 0.05) than the oleogels with 6% of CBW. However, the oleogel formed with 6% of CBW showed more than 84% of oil retention after 60 days, indicating that the 6% of CBW was sufficient to develop a network that could hold the liquid oil into a gel‐like structure. Larger crystals (μm) were observed with 10% CBW addition (2.15 ± 0.16 μm SBO and 2.08 ± 0.22 mm PNO). After preliminary sensory studies, the SBO oleogel with 6% of CBW was chosen to be applied in the ice‐cream formulation. The ice cream preparations were analyzed by overrun, melting rate, fat composition, and sensory acceptance. The oleogel fat replacement (50% and 100%) reduced the melting rate of ice creams; however, it negatively affected the ice cream overrun. These results show that 50% replacement of the traditional lipid phase by CBW oleogel can be performed without causing sensory impairment.

NanoSPECT imaging reveals the uptake of 123I-labelled oxidized low-density lipoprotein in the brown adipose tissue of mice via CD36.

The liver is the major organ shown to remove oxidized low-density lipoprotein (oxLDL) from the circulation. Given increased evidence that thermogenic adipose tissue has anti-effects, we used 123I-labelled oxLDL as a tracer to reveal oxLDL accumulation in the brown adipose tissue (BAT) of mice. We also explored the mechanisms of oxLDL accumulation in BAT. We used high-resolution nanoSPECT/CT to investigate the tissue distribution of 123I-oxLDL and 123I-LDL (control) following intravenous injection into conscious mice. 123I-oxLDL distribution was discovered in BAT at an intensity equivalent to that in the liver, whereas 123I-LDL was detected mostly in the liver. Consistent with the function of BAT related to sympathetic nerve activity, administering anaesthesia in mice almost completely eliminated the accumulation of 123I-oxLDL in BAT, and this effect was reversed by administering β3-agonist. Furthermore, exposing mice to cold stress at 4°C enhanced 123I-oxLDL accumulation in BAT. Because in 123I-oxLDL, the protein of oxLDL was labelled, we performed additional experiments with DiI-oxLDL in which the lipid phase of oxLDL was fluorescently labelled and observed similar results, suggesting that the whole oxLDL particle was taken up by BAT. To identify the receptor responsible for oxLDL uptake in BAT, we analysed the expression of known oxLDL receptors (e.g. SR-A, CD36, and LOX-1) in cultured brown adipocyte cell line and primary brown adipocytes and found that CD36 was the major receptor expressed. Treatment of cells with CD36 siRNA or CD36 neutralizing antibody significantly inhibited DiI-oxLDL uptake. Finally, CD36 deletion in mice abolished the accumulation of 123I-oxLDL and DiI-oxLDL in BAT, indicating that CD36 is the major receptor for oxLDL in BAT. We show novel evidence for the CD36-mediated accumulation of oxLDL in BAT, suggesting that BAT may exert its anti-atherogenic effects by removing atherogenic LDL from the circulation.

Modulation of gastric lipase adsorption onto mixed galactolipid-phospholipid films by addition of phytosterols

The rapid and preferential adsorption of a gastric lipase recombinant dog gastric lipase (rDGL) in heterogeneous films of phospholipids and triacylglycerols has previously been unveiled using Langmuir films analyzed by tensiometry, ellipsometry and Langmuir-Blodgett transfer coupled to atomic force microscopy. Here we invest the adsorption behavior of rDGL in heterogeneous galactolipid and mixed galactolipid-phospholipid or galactolipid-phospholipid-phytosterol films representative of plant membrane. Again rDGL, preferentially got adsorbed at the expanded lipid phases of the films underlining the genericity of such adsorption behavior. The addition of phytosterols to these mixtures resulted in the creation of defects, favoring the adsorption of rDGL at the fluid phases, but also improving the adsorption capacities of the lipase at the phase boundaries and towards the defects in the condensed phase. rDGL, like all gastric lipases, does not show any activity on galactolipids and phospholipids but its adsorption impacts their lateral organization and may change the adsorption and activity of other lipolytic enzymes in the course of digestion.

Preparation of Darunavir Cubosomal Gel to Treat HIV Infections

HIV (human immunodeficiency virus) is a virus that attacks the body's system. AIDS could be a chronic potentially life threatening condition caused by HIV. This article provides a summary of studies assessing the pharmacokinetics of antiretroviral drug Darunavir. Darunavir is a BCS class II drug which inhibits the HIV protease enzyme by forming an inhibitor-enzyme complex there by preventing cleavage of the polyproteins. This research work aims to increase the penetration of Darunavir into deeper layers of skin by formulating cubosomes of Darunavir into a genital Gel that helps in enhancing the Bioavailablity by providing first pass metabolism. Cubosomes were prepared by the Top- down approach (Emulsification method) employing GMO as a lipid phase vehicle, poloxamer 407 as a stabilizer and distill water as an aqueous phase. Darunavir is an antiretro viral drug with good bioavailablity. The prepared cubosomes were characterized by Visual examination, Entrapment efficiency, Particle size, Zeta potential, In-vitro drug release studies. Optimised formulation (F4) showed good response among all the opposite cubosomal preparation. This (F4) cubosomal prepration was made as Gel using Carbopol 974 BP,and are studied for pH, Drug content,and Diffusion studies. Among all the prepration DARf6 was found for example the utmost drug release. This novel cubosomal genital gel would be promising system for effective drug delivery.

Vitamin E Does Not Disturb Polyunsaturated Fatty Acid Lipid Domains.

The function of vitamin E in biomembranes remains a prominent topic of discussion. As its limitations as an antioxidant persist and novel functions are discovered, our understanding of the role of vitamin E becomes increasingly enigmatic. As a group of lipophilic molecules (tocopherols and tocotrienols), vitamin E has been shown to influence the properties of its host membrane, and a wealth of research has connected vitamin E to polyunsaturated fatty acid (PUFA) lipids. Here, we use contrast-matched small-angle neutron scattering and differential scanning calorimetry to integrate these fields by examining the influence of vitamin E on lipid domain stability in PUFA-based lipid mixtures. The influence of α-tocopherol, γ-tocopherol, and α-tocopherylquinone on the lateral organization of a 1:1 lipid mixture of saturated distearoylphosphatidylcholine (DSPC) and polyunsaturated palmitoyl-linoleoylphosphatidylcholine (PLiPC) with cholesterol provides a complement to our growing understanding of the influence of tocopherol on lipid phases. Characterization of domain melting suggests a slight depression in the transition temperature and a decrease in transition cooperativity. Tocopherol concentrations that are an order of magnitude higher than anticipated physiological concentrations (2 mol percent) do not significantly perturb lipid domains; however, addition of 10 mol percent is able to destabilize domains and promote lipid mixing. In contrast to this behavior, increasing concentrations of the oxidized product of α-tocopherol (α-tocopherylquinone) induces a proportional increase in domain stabilization. We speculate how the contrasting effect of the oxidized product may supplement the antioxidant response of vitamin E.

Interaction of GC376, a SARS-COV-2 MPRO inhibitor, with model lipid membranes

Partitioning and effect of antiviral GC376, a potential SARS-CoV-2 inhibitor, on model lipid membranes was studied using dynamic light scattering (DLS), UV–VIS spectrometry, Excimer fluorescence, Differential scanning calorimetry (DSC) and Small- and Wide-angle X-ray scattering (SAXS/WAXS). Partition coefficient of GC376 between lipid and water phase was found to be low, reaching KP = 46.8 ± 18.2. Results suggest that GC376 partitions into lipid bilayers at the level of lipid head-groups, close to the polar/hydrophobic interface. Changes in structural and thermodynamic properties strongly depend on the GC376/lipid mole ratio. Already at lowest mole ratios GC376 induces increase of lateral pressures, mainly in the interfacial region of the bilayer. Hereby, the pre- and main-transition temperature of the lipid system increases, what is attributed to tighter packing of acyl chains induced by GC376. At GC376/DPPC ≥ 0.03 mol/mol we detected formation of domains with different GC376 content resulting in the lateral phase separation and changes in both, main transition temperature and enthalpy. The observed changes are attributed to the response of the system on the increased lateral stresses induced by partitioning of GC376. Obtained results are discussed in context of liposome-based drug delivery systems for GC376 and in context of indirect mechanism of virus replication inhibition.

Leveraging the Exploratory and Predictive Capabilities of Design of Experiments in Development of Intraarticular Injection of Imatinib Mesylate Containing Lipospheres.

An intraarticular, liposphere-based, formulation of Imatinib mesylate for weekly administration was developed. Lipospheres were prepared using double emulsion technique using dierucoyl phosphatidylcholine, 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt), cholesterol, and tricaprylin as lipid phase in dichloromethane in a four-step process. Primary emulsion, formed using a high-pressure homogenizer, was diluted using a secondary aqueous phase in an Inline mixer to form the liposomal dispersion. Nitrogen flushing was done to remove dichloromethane, and the dispersion was finally centrifuged and adjusted for potency. The amount of cholesterol and triglyceride was taken as formulation variables, and speed of homogenization was used as a process variable in the Box-Behnken design while particle size, % drug entrapment, and drug release at the end of 4h and 5days were taken as response variables. Multivariate data analysis grouped the variables in two latent variable sets, one based on the speed and the other on the composition of lipospheres. Multiple linear regression analysis was used to generate mathematical model for each response. Constraints were put on the values of responses, as per the requirements of the final product, and the "freedom to operate" design space was located using an overlay plot. The center point batch sufficed all the set criteria, and Monte Carlo simulations on the factor variables indicated a defect rate of 5%. The center point batch was characterized for viscosity, osmolality, pH, drug release, and lipocrit value. The dispersion was charged in a prefilled syringe and studied for stability. The product was found to be stable at 2-8°C over a period of 6months.