Egg Lecithin Research Articles

Enhanced bioavailability through quality by design optimization of ceritinib nanostructured lipid carriers: Formulation, characterization, and stability evaluation

Ceritinib is a lung cancer treatment that inhibits the Anaplastic Lymphoma Kinase (ALK). ALK is a protein involved in cell signaling and growth regulation. Initially discovered in anaplastic large cell lymphoma, ALK has since been found to play critical roles in various cancers and neurodevelopmental processes. Targeted therapies that inhibit ALK have revolutionized treatment for ALK-positive cancers, improving outcomes significantly. Research continues to explore ALK’s intricate mechanisms and its potential as a therapeutic target beyond oncology, highlighting its broad biological importance. In this study, Ceritinib-drug loaded nanostructured lipid carriers were produced using a modified homogenization process by increasing number of homogenisation cycles followed by probe sonication. A central composite design was utilised to investigate the effect of liquid lipid (A), emulsifier (B), and co-surfactant (C) concentrations on particle size (Response 1) and entrapment efficiency (Response 2). The specific impacts of these parameters on particle size and entrapment efficiency were shown in response surfaces, using Derringer’s desirability technique. Formulation 8 with 0.1% Capmul, 0.15% egg lecithin, and 0.37% poloxamer 188 was subjected to further evaluation as it had minimal particle size and maximum entrapment efficiency. The SEM analysis was performed to confirm the size of the particle which was within the nano range. The in vitro studies indicated the maximum drug release (84.6%±2.3% in 12 hours) from that of the marketed formulation (54.2%±2.5% in 12 hours). After 90 days of stability testing, there was no significant variation (p < 0.05) in parameters like particle size and entrapment efficiency.

Enhanced Delivery of 5-Aminolevulinic Acid by Lecithin Invasomes in 3D Melanoma Cancer Model.

Photodynamic therapy (PDT) is a noninvasive therapeutic approach for the treatment of skin cancer and diseases. 5-Aminolevulinic acid is a prodrug clinically approved for PDT. Once internalized by cancer cells, it is rapidly metabolized to the photosensitizer protoporphyrin IX, which under the proper light irradiation, stimulates the deleterious reactive oxygen species (ROS) production and leads to cell death. The high hydrophilicity of 5-aminolevulinic acid limits its capability to cross the epidermis. Lipophilic derivatives of 5-aminolevulinic acid only partly improved skin penetration, thus making its incorporation into nanocarriers necessary. Here we have developed and characterized 5-aminolevulinic acid loaded invasomes made of egg lecithin, either 1,2-dilauroyl-sn-glycero-3-phosphocholine or 1,2-dioleoyl-sn-glycero-3-phosphocholine, and the terpene limonene. The obtained invasomes are highly thermostable and display a spherical morphology with an average size of 150 nm and an encapsulation efficiency of 80%; moreover, the ex vivo epidermis diffusion tests established that nanovesicles containing the terpene led to a much higher skin penetration (up to 80% in 3 h) compared to those without limonene and to the free fluorescent tracer (less than 50%). Finally, in vitro studies with 2D and 3D human cell models of melanoma proved the biocompatibility of invasomes, the enhanced intracellular transport of 5-aminolevulinic acid, its ability to generate ROS upon irradiation, and consequently, its antiproliferative effect. A simplified scaffold-based 3D skin model containing melanoma spheroids was also prepared. Considering the results obtained, we conclude that the lecithin invasomes loaded with 5-aminolevulinic acid have a good therapeutic potential and may represent an efficient tool that can be considered a valid alternative in the topical treatment of melanoma and other skin diseases.

A liposomal platform for the delivery of ion channel proteins for treatment of channelopathies — Application in therapy of cystic fibrosis

Channelopathies arise from ion channel dysfunction. Successful treatment entails delivery of functional ion channels to replace dysfunctional ones. Glycine receptor (GlyR)-rich cell membrane fragments (CMF) were previously delivered to target cell membranes using fusogenic liposomes. Here, cystic fibrosis transmembrane conductance regulator (CFTR)-bearing CMF were similarly delivered to target cells. We studied the effect of lipid composition on liposomes' ability to incorporate CMF and fuse with target cell membranes to deliver functional CFTR. Four formulations were prepared using thin-film hydration out of different lecithin sources, egg and soy lecithin (EL and SL), in the presence and absence of cholesterol (CHOL): EL + CHOL, EL-CHOL, SL + CHOL, and SL-CHOL. EL liposomes incorporated more CMF than SL liposomes, with CHOL only increasing CMF incorporation in SL liposomes. SL + CHOL fused better with target cell membranes than EL + CHOL. SL + CHOL and EL + CHOL equally delivered CFTR to target cell membranes, owing to the former's superior fusogenic capacity and the latter's superior CMF-incorporation capacity. SL-CHOL and EL-CHOL delivered CFTR to a lesser extent, indicating the importance of CHOL for fusion. Patch-clamp electrophysiology and confocal laser scanning microscopy (CLSM) confirmed CFTR delivery to target cell membranes by SL + CHOL. Therefore, CMF-bearing fusogenic liposomes offer a promising universal platform for the treatment of channelopathies.

The anacardic acid-loaded nanoliposomes improved the anticancer activity in vitro

Anacardic acid accounts for approximately 77% of the cashew nut shell liquid from Anacardium occidentale, which was reported to have anticancer potential. Due to its water insolubility, the compound is hard to absorb leading to less bioavailability. Currently, using nanolipsomes as drug carriers in general and for anacardic acid in particular could be an effective solution. In this research, anacardic acid was incorporated into nanoliposomes by employing the thin-film method. The results showed that the fabricated nanoliposomes with egg lecithin, cholesterol, and DSPE-PEG as components will have higher encapsulatted efficiency when compared with the fomula using soybean lecithin. The obtained anacardic acid nanoliposomes (AAL) present a size of 135.2 nm, a PDI of 0.095, and a negative zeta voltage of -27.9 mV. The AAL nanoparticles were also evaluated for their growth inhibitory capacity on several cancer cell lines by MTT assay. The GI50 (growth inhibition concentration at 50%) values were determined to range from 80.13 µM to 95.29 µM, of which AAL showed the strongest activity on NTERA-2 human cancer stem cells (80.13 µM). The NTERA-2 cell cycle was also significantly arrested at the S phase (19.43%) under treatment with anacardic acid nanoliposomes. This is the first time for AAL reported activity against cancer stem cells. The activity suggests the potential anti-cancer stem cells of anacardic acid nanolposomes.

SOLID LIPID NANOPARTICLES OF GABAPENTIN FOR PARTIAL SEIZURES

The goal of this research was to create a stable formulation of gabapentin solid lipid nanoparticles which would allow it to pass across the blood-brain barrier more easily. They were prepared by solvent evaporation method. In the present investigation, beeswax and carnauba wax were used as solid lipids, egg lecithin was used as a surfactant and Tween 80 was used as a co-surfactant. Nine formulations were formulated using different concentrations of solid lipid and surfactant. The prepared formulations were evaluated for various tests. The results shown that F6 formulation, containing higher concentration of egg lecithin, was a better formulation as percentage drug content was 97.57±0.62%, entrapment efficiency was 95.95±0.07% and in vitro release of gabapentin was 97.18±1.02% at the end of 12 h. After in vivo testing, it was observed that animals treated with gabapentin loaded solid lipid nanoparticles had seizures that appeared later than animals treated with traditional gabapentin formulations. Hence it was concluded that solid lipid nanoparticles is a promising drug delivery system to achieve increased permeability through blood brain barrier.

Formulation and Statistical Evaluation of Tablets Containing Pitavastatin- Self Nano Emulsifying Drug Delivery Systems.

To formulate and characterize tablets containing Pitavastatin that have been loaded with a self-nano emulsifying drug delivery system (SNEDDS). Pitavastatin SNEDDS were prepared with a variety of oils, surfactants, co-surfactants, and solvents to improve the dissolution rate and bioavailability of the HMG-CoA reductase inhibitor. The SNEDDS components were preliminarily investigated for drug solubility in various vehicles, excipient miscibility, emulsification rate, and ternary phase diagrams. The tablets were made using a porous carrier made of Aerosil 200 and then loaded with SNEDDS using a simple absorption method. Physical parameters such as tablet hardness, weight variation, disintegration, drug content, and in-vitro drug release were then measured on the tablets. Labrafac Lipophilewl1349 (Oil), Tween 80 (Surfactant) and Egg lecithin (Co-surfactant) were selected for the preparation of SNEDDS. Tablets with high porosity suitable for loading with SNEDDS and containing the super-disintegrants, achieved complete dissolution of Pitavastatin from the tablets. In vitro release of Pitavastatin from SNEDDS and the tablets was similar (p < 0.05). SNEDDS of Pitavastatin is a promising approach to achieving a solid dosage form of the liquid-loaded drug delivery systems for enhancing the solubility and dissolution rate of the drug, and hence also its bioavailability.

Preparation and evaluation of radiolabeled gliclazide parenteral nanoemulsion as a new tracer for pancreatic β-cells mass

Purpose The present investigation aims to develop and evaluate a radiopharmaceutical for targeting and assessing β-cells mass based on gliclazide, an antidiabetic drug that specifically binds the sulfonylurea receptor unique to the β-cells of the pancreas. Methods Conditions were optimized to radiolabel gliclazide with radioiodine via electrophilic substitution reaction. Then, it was formulated as a nanoemulsion system using olive oil and egg lecithin by hot homogenization followed by ultrasonication. The system was assessed for its suitability for parenteral administration and drug release. Then, the tracer was evaluated in silico and in vivo in normal and diabetic rats. Results and conclusions The labeled compound was obtained with a high radiochemical yield (99.3 ± 1.1%) and good stability (>48 h). The radiolabeled nanoemulsion showed an average droplet size of 24.7 nm, a polydispersity index of 0.21, a zeta potential of −45.3 mV, pH 7.4, an osmolality of 285.3 mOsm/kg, and viscosity of 1.24 mPa.s, indicating suitability for parenteral administration. In silico assessment suggested that the labeling did not affect the biological activity of gliclazide. The suggestion was further supported by the in vivo blocking study. Following intravenous administration of nanoemulsion, the pancreas uptake was highest in normal rats (19.57 ± 1.16 and 12 ± 0.13% ID) compared to diabetic rats (8.51 ± 0.16 and 5 ± 0.13% ID) at 1 and 4 h post-injection, respectively. All results supported the feasibility of radioiodinated gliclazide nanoemulsion as a tracer for pancreatic β-cells.

Do cross-food allergies to propofol exist?

Propofol is a short and rapidly acting intravenous anesthetic extensively used for the induction and maintenance of general anesthesia. It is a lipid emulsion that contains soybean oil, purified egg phosphatide, and egg lecithin. Therefore, the package leaflet indicates that its administration is contraindicated in patients allergic to soy, eggs, or peanuts. Our study aimed to determine whether patients with proven food allergies are allergic to propofol. Patients of all ages allergic to soy, eggs, or peanuts who agreed to undergo skin testing for propofol allergies were included. The subjects first underwent a skin test to confirm food allergies. If candidates were negative, they were excluded. If the result was positive, a propofol skin test was performed. Sixty-four patients with confirmed food allergies underwent a propofol skin test. Only one was positive in the propofol skin test (1.6%). The patient was allergic to peanuts and soybeans. These results reinforce the idea that there is no justification for avoiding propofol use in these subjects. Propofol can be safely administered to patients allergic to soy, eggs, or peanuts. We recommend caution in patients with a history of anaphylaxis after ingestion of the above-mentioned foods.

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.

Production of a High-Phosphatidylserine Lecithin That Synergistically Inhibits Lipid Oxidation with α-Tocopherol in Oil-in-Water Emulsions.

Phosphatidylserine (PS) was shown to work synergistically with tocopherols to extend the shelf life of oil-in-water emulsions. However, the high cost of PS prevents it from being used as a food additive. This work investigated the potential use of a high-PS enzyme-modified lecithin to be used along with α-tocopherol to extend the lag phase of oil-in-water emulsions stabilized using Tween 20. Phospholipase D from Streptomyces sp. and L-serine were used to modify lecithin to increase the PS concentration. Enzyme activity was optimized as a function of pH and temperature using high-phosphatidylcholine (PC) soybean, sunflower, or egg lecithins. Under optimal conditions, the final PS concentrations were 92.0 ± 0.01%, 88.0 ± 0.01%, and 63.0 ± 0.02% for high-PC soybean, sunflower, and egg lecithins, respectively. α-Tocopherol (3.0 µmol/kg emulsion) alone increased the lag phase of hydroperoxide and hexanal lag phases by 3 and 4 days compared to the control. Phospholipase-D-modified high-PS soy lecithin increased hydroperoxide and hexanal lag phases by 3 and 4 days, respectively. The addition of phospholipase-D-modified high-PS sunflower and egg lecithin did not have any considerable effects on lag phases compared to the control. The combination of phospholipase-D-modified high-PS lecithins (15.0 µmol/kg emulsion) and α-tocopherol (3.0 µmol/kg emulsion) increased the antioxidant activity of α-tocopherol, increasing the hydroperoxide and hexanal lag phase by 6 and 9 days for soy, 5 and 7 days for sunflower, and 4 and 6 days for egg lecithin, respectively. All phospholipase-D-modified high-PS lecithin–tocopherol combinations resulted in synergistic antioxidant activity (interaction index > 1.0), except for α-tocopherol and high-PS egg lecithin, which showed an additive effect. This research showed that the combination of enzyme-modified high-PS lecithin and α-tocopherol could be an effective and commercially viable clean label antioxidant strategy to control lipid oxidation in emulsions.

Inhalation of nebulized omega-3 fatty acids mitigate LPS-induced acute lung inflammation in rats: Implications for treatment of COPD and COVID-19

Many current treatment options for lung inflammation and thrombosis come with unwanted side effects. The natural omega-3 fatty acids (O3FA) are generally anti-inflammatory and antithrombotic. O3FA are always administered orally and occasionally by intravenous (IV) infusion. The main goal of this study is to determine if O3FA administered by inhalation of a nebulized formulation mitigates LPS-induced acute lung inflammation in male Wistar rats. Inflammation was triggered by intraperitoneal injection of LPS once a day for 14 days. One hour post-injection, rats received nebulized treatments consisting of egg lecithin emulsified O3, Budesonide and Montelukast, and blends of O3 and Melatonin or Montelukast or Cannabidiol; O3 was in the form of free fatty acids for all groups except one group with ethyl esters. Lung histology and cytokines were determined in n = 3 rats per group at day 8 and day 15. All groups had alveolar histiocytosis severity scores half or less than that of the disease control (Cd) treated with LPS and saline only inhalation. IL-6, TNF-α, TGF-β, and IL-10 were attenuated in all O3FA groups. IL-1β was attenuated in most but not all O3 groups. O3 administered as ethyl ester was overall most effective in mitigating LPS effects. No evidence of lipid pneumonia or other chronic distress was observed. These preclinical data suggest that O3FA formulations should be further investigated as treatments in lung inflammation and thrombosis related lung disorders, including asthma, chronic obstructive pulmonary disease, lung cancer and acute respiratory distress such as COVID-19.

Biocompatible, photo-responsive layer-by-layer polymer nanocapsules with an oil core: in vitro and in vivo study.

In cancer therapy, stimulus-responsive drug delivery systems are of particular interest for reducing side effects in healthy tissues and improving drug selectivity in the tumoral ones. Here, a strategy for the preparation of a photo-responsive cross-linked trilayer deposited onto an oil-in-water nanoemulsion via a layer-by-layer technique is reported. The system is made of completely biocompatible materials such as soybean oil, egg lecithin and glycol chitosan, with heparin as the polymeric shell. The oil core is pre-loaded with curcumin as a model lipophilic active molecule with anti-tumoral properties. The trilayer cross-linkage is performed via a photoinitiator-free thiol-ene 'click' reaction. In particular, the system is implemented with an o-nitrobenzyl group functionalized with a thiol moiety which can perform both the thiol-ene 'click' reaction and the cleavage meant for controlled drug release at two different wavelengths, respectively. So the preparation and characterization of a photo-responsive natural nanocarrier (PNC) that is stable under physiological conditions owing to the thiol-ene cross-linkage are reported. PNC performance has been assessed in vitro on melanoma cells as well as in vivo on xenograft tumour-induced mice.

Assessment of Amentoflavone Loaded Sub-Micron Particle Preparation using Supercritical Antisolvent for its Antitumor Activity.

The amentoflavone (AMF) loaded polymeric sub-micron particles were prepared using supercritical antisolvent (SAS) technology with the aim of improving the anticancer activity of AMF. Zein and phospholipid mixtures composed of Hydrogenated Phosphatidylcholine (HPC) and egg lecithin (EPC) were used as carrier materials and, the effects of carrier composition on the product morphology and drug release behavior were investigated. When the mass ratio of Zein/HPC/ EPC was 7/2/1, the AMF loaded particles were spherical shape and sub-micron sized around 400 nm, with a drug load of 4.3±0.3 w% and entrapment efficacy of 87.8±1.8%. The in vitro drug release assay showed that adding EPC in the wall materials could improve the dispersion stability of the released AMF in an aqueous medium, and the introduction of HPC could accelerate the drug release speed. MTT assay demonstrated that AMF-loaded micron particles have an improved inhibitory effect on A375 cells, whose IC50 was 37.39μg/ml, compared with that of free AMF(130.2μg/ml). It proved that the AMF loaded sub-micron particles prepared by SAS were a prospective strategy to improve the antitumor activity of AMF, and possibly promote the clinical use of AMF preparations.

Fabrication and characterization of nanostructured lipid carrier system for effective delivery of poorly water-soluble drug quetiapine fumarate

The aim of present study is to investigate the potential of nanostructured lipid carriers (NLCs) in improving the oral bioavailability of quetiapine fumarate, a second-generation antipsychotic drug. Quetiapine Fumarate (QF) loaded NLC were prepared by hot homogenization followed by an ultrasonication method. Response surface methodology - central composite design (CCD) was used to systemically examine the influence of concentration of capmul MCM EP, concentration of poloxamer 188 and concentration of egg lecithin on particle size (PS) and % entrapment efficiency (% EE) and to optimize the NLC formulation. The CCD consists of three factored design with five levels, plus and minus alpha (axial points), plus and minus 1 (factorial points) and the centre point. A mathematical relationship between variables was created by using Design Expert software Version 12. The statistical evaluations revealed that three independent variables were the important factors that affected the PS and % EE of QF loaded NLC. The best fitted mathematical model was linear and quadratic for PS and % EE respectively. The optimized formulations found with 218.1±0.14nm of PS and 93±0.16% of % EE. Results illustrated the superiority of developed QF loaded NLC formulation as a stable drug delivery system, providing better bioavailability with the possibility of better treatment for psychological disorders.

Freeze-thaw stability and oil crystallization behavior of phospholipids/whey protein-costabilized acidic emulsions with four oil types

The physical properties and freeze-thaw behavior of mayonnaise-like emulsions prepared from 60% (v/v) olive oil (OLO), peanut oil (PNO), palm oil (PO), and coconut oil (CNO) at pH 3.0 using whey protein isolate (WPI) as the stabilizer and soybean lecithin (SL) or egg lecithin (EL) as supplementary surfactants were investigated. For all oil types, the addition of SL or EL decreased emulsion stability due to partial displacement of WPI at the interface. Nevertheless, both surfactants generally improved the emulsion freeze-thaw stability except for OLO emulsion. The thermometry of fat crystal formation in PNO (Tfat = 0.4 °C), PO (Tfat = 6.6 °C) and CNO (Tfat = −1.4 °C) emulsions was higher than that of ice crystal (Tice = −10 °C) formation. On the other hand, ice crystallization occurred prior to fat crystal formation (Tfat = −14 °C) in OLO emulsions. Upon freezing, serum phase ice crystals protruded into OLO emulsion droplets with a mixed SL-protein thin membrane leading to a reduced stability than WPI-alone emulsion. Compared with SL, EL was more capable of facilitating fine fat crystal formation, and partial fat crystallization generally increased emulsion viscosity. Overall, both small surfactants promoted crystallization behavior and freeze-thaw stability of WPI-based PNO, PO, and CNO emulsions; although slightly less effective than EL, SL showed a strong efficacy in the emulsion system.

A Comparative Study on Isolation and Characterization of Lecithin from Gallus gallus and Gallus gallus Domesticus Using Analytical Methods

The present study mainly focuses on the extraction and purification of lecithin from both Gallus gallus and Gallus gallus domesticus. The comparative study shows a great significance in the amount and quality of lecithin extracted from both the sources. The egg lecithin was standardized by Thin Layer Chromatography (TLC) analysis and Fourier transform infrared spectroscopy (FTIR) spectroscopy. TLC analysis was done and calculated for both standard and the samples. It was found to be the same for the test sample and standard soya lecithin. FTIR analysis shows the presence of Methyl group, alkane, carbonyl group, alkenes, hydroxyl alkyl ketone. FTIR helps to compare the in- tensity of functional groups in both lecithin isolated from Gallus gallus and Gallus domesticus.

Preparation and Evaluation of Lipid Emulsion Containing 13 Vitamins for Injection Without Anaphylactoid Reactions.

ObjectiveMultivitamins containing Tween 80 can cause anaphylactoid reactions. The objective of this study was to develop a new lipid emulsion containing 13 fat- and water-soluble vitamins for injection (13V-LE) that were simultaneously dissolved in one bottle and to evaluate the stability of and anaphylactoid reactions to 13V-LE.MethodsParticle size, ζ-potential, and polydispersity of 13V-LE were assayed with a Zetasizer Nano ZS. Entrapment efficiency of 13V-LE was determined with HPLC. Behavior, histamine, and blood pressure of beagle dogs were investigated by observation, fluorospectrophotometry, and sphygmomanometry.ResultsThe 13V-LE with the smallest particles and highest entrapment efficiency with stable ζ-potential was composed of soybean oil, glycerin (2.25%, w:v), egg lecithin (1.2%, w:v), and purified water. There was no obvious change in characteristics of the 13V-LE samples in terms of appearance, size distribution, ζ-potential, pH value, or concentration over 6 months. In anaphylactoid reactions tests, when being administered with the multivitamin Infuvite Adult containing Tween 80, six beagles showed grade IV symptoms (P<0.01 vs control), low blood pressure, and high plasma-histamine concentrations (P<0.05 or P<0.01). However, there were no significant differences in behavior, blood pressure, or histamine concentration in the dogs before and after administration in the 13V-LE group.ConclusionThe 13V-LE formulation is a suitable intravenous lipid emulsion without anaphylactoid reactions.

Pharmacokinetic and pharmacodynamic studies of iloperidone-loaded lipid nanoemulsions via oral route of administration

Iloperidone (IL) is practically insoluble in water and has significant first-pass metabolism, resulting in low oral bioavailability in humans (36%). IL lipid nanoemulsions (IL-LNEs) were prepared to improve oral bioavailability. IL-LNEs were formulated by hot homogenization and ultrasonication method. Soybean oil and egg lecithin in various concentrations as emulsifier were used in the preparation of LNEs. Dynamic light scattering technique was used for globule size analysis. All LNE formulations showed narrow size distribution and the average globule size and Poly Dispersity Index (PDI) were found to be in between 182.2 ± 2.8 to 222.3 ± 1.9 nm and 0.200 ± 0.004 to 0.274 ± 0.005 respectively. Zeta potential values varied from −20.0 ± 0.15 to −28.9 ± 0.30 mV which indicated stability of prepared LNEs. All formulations showed good entrapment efficiency ranging from 99.07 ± 0.01 to 99.28 ± 0.01% when separated using centrisart tubes and the drug content varied from 96.99 ± 0.94 to 99.06 ± 0.36%. Physical stability testing indicated the stability of all LNEs and optimized LNE-IL4 was found stable for 3 months at both refrigerated (4 °C) and room temperature (25 °C). During in vivo studies in wistar rats, the optimized LNE showed 2.47-fold improvement in the oral bioavailability and superior (1.22-fold) pharmacodynamic activity when compared to marketed tablet suspension (Ilosure-4®) in suppressing the hyperlocomotor activity, being induced by MK-801 (Dizocilpine).

Increased levels of hexacosanoic acid in the brain of Wistar rats: a behavioral study

Introduction: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal metabolic disorder associated with mutations in the ATP-binding cassette sub-family D member1 ( ABCD1 ) gene. Practically all male patients with X-ALD develop adrenocortical insufficiency during childhood and progressive myelopathy and peripheral neuropathy in adulthood. However, some male patients develop a fatal cerebral demyelinating disease named cerebral adrenoleukodystrophy. Although the exact mechanisms underlying brain damage in X-ALD are still poorly elucidated, it is known that hexacosanoic acid (C26:0) accumulation represents a hallmark in the pathogenesis of this disease. In this study, we examined whether an overload of C26:0 injected in Wistar rats was capable of causing behavioral changes in these animals. Methods: Egg lecithin in ethanol was dried under a nitrogen stream and mixed with C26:0 methyl ester. Male Wistar rats at 2–3 weeks of age were obtained from Universidade Federal do Rio Grande do Sul (UFRGS), divided into 8 groups, and submitted to an open field test. We then analyzed line crossings (locomotion and exploration), rearing (orienting and investigatory responses), grooming (anxiety manifestation), and latency to move for each animal. Results: Animals subjected to C26:0 administration presented fewer crossings and rearing episodes and a higher latency to move 45 minutes after C26:0 injection. The present work yields experimental evidence that C26:0, the main accumulated metabolite in X-ALD, can cause behavioral alterations in rats such as the impairment of locomotion and exploratory capabilities, as well as a reduction in orienting and investigatory responses. Conclusion: Although our results are preliminary, they are extremely important for future studies that investigate C26:0 accumulation and locomotor impairment in patients with X-ALD.

Brain targeting of agomelatine egg lecithin based chitosan coated nanoemulsion

Intranasal drug delivery system has been proposed as an alternative delivery system to target agomelatine (AGO) to the brain and improving its bioavailability. Mucoadhesive egg lecithin nanoemulsions were optimized using D-optimal design and by investigating the effect of four independent variables: oil concentration (A), chitosan concentration (B), type of oil (C) and egg lecithin: oil (D). The responses of globule size, polydispersity index, zeta potential and drug content were evaluated. The optimized agomelatine mucoadhesive nanoemulsion (AGO MNE) with a desirability value of 0.856 was subjected to further investigations for mucoadhesion, in vitro diffusion, transmission electron microscopy and in vivo biodistribution. It showed significantly successful distribution to the brain, the optimized AGO MNE intranasal gave a brain targeting efficiency (BTE) of 278.71% indicating increased drug brain targeting by the nasal route compared with the intravenous route. Additionally, the optimized AGO MNE by intranasal had a direct transport percentage (DTP) of 64.109%, which indicates a significant contribution of the direct nose-to-brain pathway in the brain drug delivery. The study proposed egg lecithin mucoadhesive nanoemulsion as a successful and promising strategy to directly and efficiently deliver drug to the brain.