Lecithin Vesicles Research Articles

Electrochemical Characterization of the Encapsulation and Release of 5-Fluorouracil in Nanocarriers Formed from Soy Lecithin Vesicles.

5-Fluorouracil (5-FU) is an antineoplastic agent known for its low bioavailability and limited cellular penetration, often resulting in adverse effects on healthy cells. Thus, finding vehicles that enhance bioavailability, enable controlled release, and mitigate adverse effects is crucial. The study focuses on encapsulating 5-FU within soy lecithin vesicles (SLVs) and assessing its impact on the carrier's properties and functionality. Results show that incorporating 5-FU does not affect SLVs' size or polydispersity, even postlyophilization. Liberation of 5-FU from SLVs requires system disruption rather than spontaneous release, with an encapsulation efficiency of approximately 43% determined using Square Wave Voltammetry. Cytotoxicity assays on colorectal cancer cells reveal SLV-based delivery's significant efficacy, surpassing free drug solution effects with 45% cell viability after 72 h vs 73% viability. The research addresses 5-FU's limited bioavailability by creating a biocompatible nanocarrier for efficient drug delivery, highlighting SLVs as promising for targeted cancer therapy due to sustained antiproliferative effects and improved cellular uptake. The study underscores the importance of tailored drug delivery systems in enhancing therapeutic outcomes and suggests SLV/5-FU formulations as a potential advancement in cancer treatment strategies.

Giant multilamellar and large unilamellar lecithin vesicles for the encapsulation and oral delivery of cannabinoids

The spontaneous formation of phospholipid vesicles was explored for the production of liposomal encapsulations of bioactive compounds. Low-energy processing methods were used to produce stable large unilamellar vesicles (LUVs) and giant multilamellar vesicles (GMVs) from unrefined, deoiled soybean and sunflower lecithin dispersions. The presence of these structures was confirmed by particle size analysis, bright-field and cryogenic transmission electron microscopy. Moreover, the liposomes were determined to be in a liquid crystalline state. Through molecular modelling, these liposomes were predicted to be capable of encapsulating cannabinoids within their membrane based on their structural and chemical similarity to cholesterol. The encapsulation capacities of cannabis oil in soybean and sunflower LUVs and spontaneous GMVs were then assessed based on these models. These liposomes demonstrated high thermal and oxidative stability, making them suitable for various food applications.

Lipid Membrane Flexibility in Protic Ionic Liquids.

Here, we determine by neutron spin echo spectrometry (NSE) how the flexibility of egg lecithin vesicles depends on solvent composition in two protic ionic liquids (PILs) and their aqueous mixtures. In combination with small-angle neutron scattering (SANS), dynamic light scattering (DLS), and fluorescent probe microscopy, we show that the bending modulus is up to an order of magnitude lower than in water but with no change in bilayer thickness or nonpolar chain composition. This effect is attributed to the dynamic association and exchange of the IL cation between the membrane and bulk liquid, which has the same origin as the underlying amphiphilic nanostructure of the IL solvent itself. This provides a new mechanism by which to tune and control lipid membrane behavior.

Triggering Tautomerization of Curcumin by Confinement into Liposomes

AbstractAlthough solvent polarity, pH and temperature have been reported to affect the keto‐enol equilibrium of curcumin, the synergistic effect of concentration and confinement is demonstrated for the first time herein. To this end, curcumin was encapsulated into vesicles of soy lecithin of about 100 nm in diameter. The keto form is favoured in the dilute regime (up to 2 μM). Above this concentration, tautomerization is shifted towards the enol form, as shown by fluorescence and compression isotherm studies. Moreover, molecular modeling and free‐energy profiles, together with simulation of the optical properties of the curcumin isomers, allowed us to dissect the interaction of the keto and enol forms with a model membrane and confirm the concentration‐triggered tautomerization of curcumin under confinement.

Multilamellar-to-Unilamellar Transition Induced by Diphenylalanine in Lipid Vesicles

In the present work, we investigate the effect of two short phenylalanine-based peptides on lipid membranes. A simplified model membrane composed of lecithin vesicles was used to incorporate different amounts of the two amino acid sequences, the dimmer l,l-diphenylallanine (FF) and the trimmer cysteine-diphenylallanine (CFF). Spectroscopic and scattering techniques were applied to probe in detail the structural behavior of lipid membranes in the presence of the peptides. The experimental results demonstrate that both peptides are located mainly at the interface of the membrane interacting with phosphate groups modifying membrane thickness and flexibility. The multilamellar structure of the vesicles is preserved with inclusion of small amounts of FF, accompanied by changes in membrane thickness and elasticity. Finally, a multi- to unilamellar transition is observed as a result of peptide self-association into a crystalline structure onto the membrane interface.

Anhydrous reverse micelle lecithin nanoparticles/PLGA composite microspheres for long-term protein delivery with reduced initial burst

To address the issue of initial burst release from poly (lactic-co-glycolic) acid (PLGA) microspheres prepared by water-in-oil-in-water (W/O/W) double emulsion technique, PLGA composite microspheres containing anhydrous reverse micelle (ARM) lecithin nanoparticles were developed by a modified solid-in-oil-in-water (S/O/W) technique. Bovine serum albumin (BSA) loaded ARM lecithin nanoparticles, which were obtained by initial self-assembly and subsequent lipid inversion of the lecithin vesicles, were then encapsulated into PLGA matrix by the S/O/W technique to form composite microspheres. In vitro release study indicated that BSA was slowly released from the PLGA composite microspheres over 60 days with a reduced initial burst (11.42 ± 2.17% within 24 h). The potential mechanism of reduced initial burst and protein protection using this drug delivery system was analyzed through observing the degradation process of carriers and fitting drug release data with various kinetic models. The secondary structure of encapsulated BSA was well maintained through the steric barrier effect of ARM lecithin nanoparticles, which avoided exposure of proteins to the organic solvent during the preparation procedure. In addition, the PLGA composite microspheres exhibited superior biocompatibility without notable cytotoxicity. These results suggested that ARM lecithin nanoparticles/PLGA composite microspheres could be a promising platform for long-term protein delivery with a reduced initial burst.

Effects of ursolic acid on the structural and morphological behaviours of dipalmitoyl lecithin vesicles

Effects of ursolic acid on the structural and morphological characteristics of dipalmitoyl lecithin(DPPC)-water system was studied by using differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SWAXS), freeze-fracture method combined with transmission electron-microscopy (FF-TEM) and infrared spectroscopy (FT-IR). The surface of the uncorrelated lipid system is rippled or grained and a huge number of small, presumably unilamellar vesicles are present if the UA/DPPC molar ratio is 0.1mol/mol or higher. Besides the destroyed layer packing of regular multilamellar vesicles, non-bilayer (e.g. cubic or hexagonal) local structures are evidenced by SAXS and FF-TEM methods. The ability of UA to induce non-bilayer structures in hydrated DPPC system originates from the actual geometry form of associated lipid and UA molecules as concluded from the FT-IR measurements and theoretical calculations. Beside numerous beneficial e.g. chemopreventive and chemotherapeutic effect of ursolic acid against cancer, their impact to modify the lipid bilayers can be utilized in liposomal formulations.

Application of a Novel Near Infrared-Fluorescence Giant Vesicle-and Polymerasome-based Tissue Marker for Endoscopic and Laparoscopic Navigation

In this study, we describe the development of a novel tissue marker that can be injected from within the digestive tract by using an endoscopic instrument, and visualized using near-infrared (NIR) fluorescence imaging. The marker was prepared in three steps, (i) mixing NIR-fluorescent indocyanine green (ICG) with giant vesicles (GVs) of lecithin, (ii) suspending the ICG-containing giant vesicles (ICG-GV) in an oil phase dissolving polyglycerol-polyricinoleate (PGPR), and (iii) centrifugation of the suspension layered on a buffered solution to obtain a giant polymer vesicle (polymerasome) containing ICG-GV. We injected the tissue marker into the inner gastric surface of an anesthetized pig using an endoscopic syringe, and observed the injection site using a fluorescence laparoscopic camera. The diameter of the spot blur was approximately 2 cm over a 5-h period, demonstrating the utility of this procedure as a tissue marker for tumor marking, and suggesting its potential for assisting navigation during surgical procedures.

Effects of pulsed electric fields on the permeabilization of calcein-filled soybean lecithin vesicles

Effects of PEF on permeabilization of calcein-filled large unilamellar vesicles (LUV) with average diameter of 1705.64±55.91nm and small unilamellar vesicles (SUV) with average diameter of 213.06±5.50nm, suspended in an isosmotic sucrose solution (150mM) were investigated. The suspensions of vesicles were exposed to PEF at various electric field strengths in the interval of 0–50kV/cm and different treatment times ranging from 0 to 4.8ms. The intensity of permeabilization induced by PEF was analyzed in terms of the changes of fluorescence intensity of the suspension solution and the average diameter of vesicles, due to the leakage of self-quench calcein encapsulated in vesicles. Results indicated that the permeability of LUV was increased with increasing intensity of electric field (>10kV/cm) and treatment time, and the release percentage of calcein (R value) was increased by 57.98% (from 0.46% to 58.44%) with the increase of the electric field strength (from 10 to 50kV/cm) at 4.8ms. However, the R value was only increased by 14.62% (from 43.82% to 58.44%) with the increase of the treatment time (from 1.2 to 4.8ms) at 50kV/cm. Average diameter of LUV was sharply decreased from 1705.64±55.91 to 465.60±37.12nm with the maximum value at 50kV/cm and 4.8ms. Results also showed that shrinkage or rupture of LUV happened, as confirmed by the change of size distribution of LUV after treatment by PEF. However, as for SUV, the changes of the permeability of vesicles and average diameter were not observed. In addition, it was demonstrated that the magnitude of the induced transmembrane potential was proportional to the radius of the vesicle, and larger vesicles could be polarized or ruptured at relatively lower field strength than smaller vesicles.

PH-responsive polymer core-shell nanospheres for drug delivery

Stimuli-responsive polymer nanoparticles are playing an increasingly more important role in drug delivery applications. However, limited knowledge has been accumulated about processes which use stimuli-responsive polymer nanospheres (matrix nanoparticles whose entire mass is solid) to carry and deliver hydrophobic therapeutics in aqueous solution. In this research, pyrene was selected as a model hydrophobic drug and a pyrene-loaded core-shell structured nanosphere named poly(DEAEMA)-poly(PEGMA) was designed as a drug carrier where DEAEMA and PEGMA represent 2-(diethylamino)ethyl methacrylate and poly(ethylene glycol) methacrylate, respectively. The pyrene-loaded core-shell nanospheres were prepared via an in situ two-step semibatch emulsion polymerization method. The particle size of the core-shell nanosphere can be well controlled through adjusting the level of surfactant used in the polymerization where an average particle diameter of below 100 nm was readily achieved. The surfactant was removed via a dialysis operation after polymerization. Egg lecithin vesicles (liposome) were prepared to mimic the membrane of a cell and to receive the released pyrene from the nanosphere carriers. The in vitro release profiles of pyrene toward different pH liposome vesicles were recorded as a function of time at 37 °C. It was found that release of pyrene from the core-shell polymer matrix can be triggered by a change in the environmental pH. In particular the pyrene-loaded nanospheres are capable of responding to a narrow window of pH change from pH = 5, 6, to 7 and can achieve a significant pyrene release of above 80% within 90 h. The rate of release increased with a decrease in pH. A first-order kinetic model was proposed to describe the rate of release with respect to the concentration of pyrene in the polymer matrix. The first-order rate constant of release k was thus determined as 0.049 h−1 for pH = 5; 0.043 h−1 for pH = 6; and 0.035 h−1 for pH = 7 at 37 °C. The release of pyrene was considered to follow a diffusion-controlled mechanism. The synthesis and encapsulation process developed herein provides a new approach to prepare smart nanoparticles for efficient delivery of hydrophobic drugs. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4440–4450

Les onychodystrophies en consultation externe de dermatologie au CHU/YO

The structure of the major protein constituent of photosynthetic membranes in higher plants, the chlorophyll a/b-light harvesting complex (LHC), was studied by x-ray diffraction and electron microscopy. The LHC was purified from Triton X-100 solubilized thylakoid membranes of the pea, and contained 6 mol of chlorophylls a and b per mole of a polypeptide of 27,000 molecular weight. X-ray diffraction showed that in the presence of 10 mM MgCl2, purified LHC forms planar aggregates that stack with a period of 51 A. Within each layer, LHC molecules pack with a center-to-center distance of 85 A but without long-range order. However, when LHC is incorporated into single-walled vesicles of plant lecithin, the addition of NaCl above 10 mM, or MgCl2 above 2 mM, led to the formation of plaques of hexagonal lattices, with a lattice constant of 125 A. The large domain size and high degree of order in the plane of the membrane are evident from the sharp lattice lines observed to 7 A resolution on the equator of the x-ray pattern. Freeze-fracture electron micrographs demonstrated an aligned stacking of the lattices in adjacent membranes, resulting in crystallinity in the third dimension over short distances. Micrographs of negatively stained membranes revealed a hexagonal lattice of the same lattice constant, formed by surface-exposed parts of the LHC molecules which are probably responsible for the ordered stacking of lattices. In both the LHC aggregates and in the reconstituted membrane lattices the diffracted x-ray intensities at 10-A spacing on the equator indicate that the LHC molecule contains paralled alpha-helices or beta-sheets that are oriented perpendicular to the planar arrays.

Hamartome folliculo-sébacé kystique : à propos de quatre cas

The structure of the major protein constituent of photosynthetic membranes in higher plants, the chlorophyll a/b-light harvesting complex (LHC), was studied by x-ray diffraction and electron microscopy. The LHC was purified from Triton X-100 solubilized thylakoid membranes of the pea, and contained 6 mol of chlorophylls a and b per mole of a polypeptide of 27,000 molecular weight. X-ray diffraction showed that in the presence of 10 mM MgCl2, purified LHC forms planar aggregates that stack with a period of 51 A. Within each layer, LHC molecules pack with a center-to-center distance of 85 A but without long-range order. However, when LHC is incorporated into single-walled vesicles of plant lecithin, the addition of NaCl above 10 mM, or MgCl2 above 2 mM, led to the formation of plaques of hexagonal lattices, with a lattice constant of 125 A. The large domain size and high degree of order in the plane of the membrane are evident from the sharp lattice lines observed to 7 A resolution on the equator of the x-ray pattern. Freeze-fracture electron micrographs demonstrated an aligned stacking of the lattices in adjacent membranes, resulting in crystallinity in the third dimension over short distances. Micrographs of negatively stained membranes revealed a hexagonal lattice of the same lattice constant, formed by surface-exposed parts of the LHC molecules which are probably responsible for the ordered stacking of lattices. In both the LHC aggregates and in the reconstituted membrane lattices the diffracted x-ray intensities at 10-A spacing on the equator indicate that the LHC molecule contains paralled alpha-helices or beta-sheets that are oriented perpendicular to the planar arrays.

Single step, pH induced gold nanoparticle chain formation in lecithin/water system

Gold nanoparticle (AuNP) chains have been formed by a single step method in a lecithin/water system where lecithin itself plays the role of a reductant and a template for AuNP chain formation. Two preparative strategies were explored: (1) evaporating lecithin solution with aqueous gold chloride (HAuCl4) at different pHs and (2) dispersing lecithin vesicles in aqueous HAuCl4 solutions of various pHs in the range of 2.5-11.3. In method 1, at initial pH 2.5, 20-50nm AuNPs are found attached to lecithin vesicles. When pH is raised to 5.5 there are no vesicles present and 20nm monodisperse particles are found aggregating. Chain formation of fine nanoparticles (3-5nm) is observed from neutral to basic pH, between 6.5–10.3 The chains formed are hundreds of nanometers to micrometer long and are usually 2-3 nanoparticles wide. On further increasing pH to 11.3, particles form disk-like or raft-like structures. When method (ii) was used a little chain formation was observed. Most of the nanoparticles formed were found either sitting together as raft like structures or scattered on lecithin structures.

Liposomes for Topical Use: A Physico-Chemical Comparison of Vesicles Prepared from Egg or Soy Lecithin

Developments in nanotechnology and in the formulation of liposomal systems provide the opportunity for cosmetic dermatology to design novel delivery systems. Determination of their physico-chemical parameters has importance when developing a nano-delivery system. The present study highlights some technological aspects/characteristics of liposomes formulated from egg or soy lecithins for topical use. Alterations in the pH, viscosity, surface tension, and microscopic/macroscopic appearance of these vesicular systems were investigated. The chemical composition of the two types of lecithin was checked by mass spectrometry. Caffeine, as a model molecule, was encapsulated into multilamellar vesicles prepared from the two types of lecithin: then zeta potential, membrane fluidity, and encapsulation efficiency were compared. According to our observations, samples prepared from the two lecithins altered the pH in opposite directions: egg lecithin increased it while soy lecithin decreased it with increased lipid concentration. Our EPR spectroscopic results showed that the binding of caffeine did not change the membrane fluidity in the temperature range of possible topical use (measured between 2 and 50 °C). Combining our results on encapsulation efficiency for caffeine (about 30% for both lecithins) with those on membrane fluidity data, we concluded that the interaction of caffeine with the liposomal membrane does not change the rotational motion of the lipid molecules close to the head group region. In conclusion, topical use of egg lecithin for liposomal formulations can be preferred if there are no differences in the physico-chemical properties due to the encapsulated drugs, because the physiological effects of egg lecithin vesicles on skin are significantly better than that of soy lecithin liposomes.

Flow cytometric assessment of the protectants for enhanced in vitro survival of probiotic lactic acid bacteria through simulated human gastro-intestinal stresses

The aim of this study was to apply flow cytometric (FCM) analysis to assess the use of sucrose and lecithin vesicles for the protection of probiotic lactic acid bacteria in response to the challenge of gastric acidity and bile salts. FCM analysis in combination with fluorescent probes carboxyfluorescein (cF) and propidium iodide was used to reveal the physiological heterogeneity in the stressed bacteria population. Three subpopulations (intact, stressed, and damaged) were differentiated by FCM in all six examined strains. Significant changes were observed in the presence of the selected protectants. The addition of 20mM sucrose in the simulated gastric fluid substantially increased the number of intact cells over 20 folds and reduced the damaged subpopulation by half. The presence of 2% (w/v) lecithin vesicles was shown to protect 50% more intact cells from the challenge of bile salts. The improved survival as evaluated by FCM analysis was further assessed for the proliferation capacity by sorting a number of cells from each subpopulation on nutrient agar plate. The result confirmed conformity between the proliferation-based cultivability and the probe-indicated viability in the samples of the intact and the damaged subpopulations. However, it also revealed the complexities of the stressed (injured) subpopulation. In conclusion, FCM analysis confirmed that the selected protectants could improve the survival of the probiotic strains in the simulated GI environments. The FCM analysis also proved to be a useful analytical tool for the probiotics research.

Wide-Bore Capillary Hydrodynamic Chromatography with ICP-MS Detection for Evaluation of Lanthanide Uptake by Molecular Aggregates

Wide-bore capillary hydrodynamic chromatography (W-HDC) resolves analytes on the basis of a difference in the extent of radial diffusion simply by their passage through an empty capillary. The combination of this method with ICP-MS proves efficient for the evaluation of the interaction of metal ions with molecular aggregates. Lecithin vesicles are suitable molecular aggregates for the uptake of the lanthanide ions in the presence of the first row transition metal ions, suggesting that the present method is applicable to the screening of the molecular aggregate system suitable for selective extraction of a particular targeted small molecule. The visual inspection of the elution profiles gives us qualitative but useful information on the interaction between the vesicle and metal ions. In addition, studying the slope of the front edge of an elution curve provides more quantitative implications.

Kinetics of lecithin oxidation in liposomal aqueous solutions

The peculiarities of egg phosphatidylcholine (lecithin) oxidation with molecular oxygen in aqueous media are investigated. Under the action of ultrasound, lecithin forms multilamellar liposomes or vesicles in aqueous solutions. Lecithin is oxidized through a chain free-radical mechanism. The nonlinear dependence of the rate of oxygen absorption on the substrate concentration and the imitation of the linear termination of the oxidation chain are observed. The study of the inhibited oxidation of phosphatidylcholine suggests that catecholamines, such as dopamine, noradrenalin, and adrenalin, are markedly more efficient antioxidants than quercetin and α-tocopherol. Phosphate buffer solution is shown to strongly influence the ways of adrenalin transformation in reactions with peroxyl radicals.

Development of a novel probiotic delivery system based on microencapsulation with protectants

The establishment of the health-promoting benefits of probiotics is challenged by the antimicrobial bio-barriers throughout the host's gastrointestinal (GI) tract after oral administration. Although microencapsulation has been frequently utilised to enhance the delivery of probiotics, microcapsules of sub-100 μm were found to be ineffective and therefore questioned as an effective delivery vehicle for viable probiotics despite the sensory advantage. In this study, four probiotics strains were encapsulated in chitosan-coated alginate microcapsules of sub-100 μm. Only a minor protective effect was observed from this original type of microcapsule. In order to enhance the survival of these probiotics, sucrose, a metabolisable sugar, and lecithin vesicles were added to the wall material. Both of the ingredients could be readily encapsulated with the probiotics, and protected them from stresses in the simulated GI fluids. The metabolisable sugar effectively increased the survival of the probiotics in gastric acid, mainly through energizing the membrane-bound F1F0-ATPases. The lecithin vesicles proved to alleviate the bile salt stress, and hence notably reduced the viability loss at the elevated bile salt concentrations. Overall, three out of the total four probiotics in the reinforced sub-100 μm microencapsules could significantly survive through an 8-h sequential treatment of the simulated GI fluids, giving less than 1-log drop in viable count. The most vulnerable strain of bifidobacteria also yielded a viability increase of 3-logs from this protection. In conclusion, the sub-100 μm microcapsules can be a useful vehicle for the delivery of probiotics, as long as suitable protectants are incorporated in the wall matrix.

A biologically friendly approach for silver nanoparticle formation and their in situ attachment to lecithin vesicles

There has been a keen interest for developing a biologically friendly approach for the preparation of silver nanoparticles for their application reasons. A biocompatible, single step method is established for the preparation of silver nanoparticles in lecithin (Egg phosphatidylcholine)/water systems where lecithin itself acts as a reductant for silver nitrate to form the silver nanoparticles. In another attempt, silver nanoparticles were successfully synthesized inside the lecithin vesicles and were found attached to the bilayers of lecithin vesicles. To the best of our knowledge, this is the first report where a biological surfactant has acted as a mild reducing agent for silver nitrate by itself to form silver nanoparticles.

A biologically friendly single step method for gold nanoparticle formation

There has been a keen interest for developing a biologically friendly approach for the preparation of gold nanoparticles for their application reasons. A biocompatible, quick and single step method is established for the preparation of gold nanoparticles in lecithin (Egg phosphatidylcholine)/water systems where lecithin itself acts as a reductant for hydrogen tetrachloro aurate (HAuCl(4)) to form the gold nanoparticles. Small gold nanoparticles (5-7 nm in diameter) were prepared in lamellar phases formed by lecithin within 6-7h of HAuCl(4) addition. Sonication of aqueous mixture of lecithin/HAuCl(4) reduces the time of reduction process to seconds when a sonicator with probe (100 W) is used. Most of the particles are found attached to lecithin structures and are comparatively large in size. Some 10nm particles are found attached to small lecithin vesicles (∼100 nm) formed during sonication. The nanoparticles formed were stabilized by an anionic surfactant sodium dodecylsulfate (SDS) which proved to be a good stabilizer, the nanoparticles being stable up to six months. To the best of our knowledge, this is the first report where a biological surfactant lecithin itself has acted as a reductant and no other chemical reductants were required for the gold nanoparticle formation. Particles were characterized by Uv-vis spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS). Lamellar phases were characterized by a polarizing microscope.