Phospholipid Complex Research Articles

The effect of naringenin-phospholipid complex on thermal oxidative stability of soybean oil under heating condition

Naringenin (NGE), a typical flavanone abundant in citrus fruits, exhibits remarkable antioxidant activities. However, its low solubility in oil restricts its widespread use in inhibiting lipid oxidation. In this study, we present a novel and effective approach to address this limitation by developing a naringenin-phospholipid complex (NGE-PC COM). Comprehensive analytical techniques including Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were employed to confirm the formation of the NGE-PC COM and elucidate the interaction mechanism between NGE and phospholipids molecules. Notably, the oil-solubility of NGE was significantly enhanced by approximately 2700-fold when formulated as a phospholipid complex in soybean oil. The improved oil-solubility of NGE-PC COM enabled effective inhibition of oil thermal oxidation under high temperature conditions. Generally, this investigation proposed a novel and promising strategy for employing flavanones with strong antioxidant activities to enhance the thermal oxidative stability of edible oil during heating processes.

Formulation and Characterization of Phytosomes as Drug Delivery System of Formononetin: An Effective Anti-Osteoporotic Agent.

Formononetin (FNT), a methoxy isoflavone, is a potential phytoconstituent utilized for refurbishing fractures in bone tissue. Conceding to its involvement in first-pass metabolism followed by glucuronidation, its absorption efficacy is limited. Hence, it belongs to the BCS class II classification. We designed the present work to enhance FNT oral bioavailability by using Phospholipids (PL) as a promising carrier. Formononetin Phospholipid Complex (FNT-PC) was prepared by the solvent evaporation method and characterized. FNT-PC was prepared by solvent evaporation method and characterization (FNT-PC) was performed using aqueous/n-octanol solubility and partition coefficient, FTIR, NMR, SEM, and in vivo</i> pharmacokinetic study in female SD rats at 50 mg/kg. Physicochemical properties like aqueous/n-octanol solubility and partition coefficient were enhanced in FNT-PC. The FTIR spectrum confirmed there was no involvement of functional groups in the preparation of FNT-PC. Whereas, the NMR study resulted in the attachment of carbon (C-8) position of FNT by replacing the quaternary amine of PL to form FNT-PC. When scrutinized for its surface morphology, the FNT-PC exhibited the amorphous geometry that remarkably enhanced the dissolution of FNT (p</i><0.05) from its pure form. This dissolution effect was also affirmed by the per-oral administration of FNT-PC in female Sprague Dawley (SD) rats at 50 mg/kg dose. The pharmacokinetic profile showed the free FNT levels were markedly increased, correspondingly decreasing the conjugated FNT levels in rat plasma. To summarize, FNT-PC could substantially reduce the first-pass metabolism with enhanced free concentration, improving oral bioavailability for therapeutic use.

Formulation and Evaluation of Phytosomes of Pterocarpus santalinus Extract

Abstract: Novel drug delivery system (NDDS) phytosomes were prepared by complexing phospholipids: Cholesterol and Leaves extract of Pterocarpus santalinus can act as molecular adhesive to bind components together. Their ability to penetrate lipid-rich biomembranes and shield the essential components of the herbal extract from being destroyed by digestive secretions and gut bacteria increases bioavailability. The bioavailability of the herbal formulation is increased by phytosomes' ability to distribute the standardised plant extracts and phytoconstituents through different routes of drug administration methods. The present study directed toward the development and evaluation of phytosomes of Pterocarpus santalinus. Through an in-vitro dissolution study, the produced complex's physicochemical characteristics were examined. The outcome demonstrated that there was no formation of a novel chemical between the hydroalcoholic extract and the phospholipids in the Methanolic extract-phospholipid complex. Prepared Pterocarpus santalinus extract phytosomes showed better bioavailability.

Hydrolysis and Transport Characteristics of Phospholipid Complex of Alkyl Gallates: Potential Sustained Release of Alkyl Gallate and Gallic Acid.

Phospholipid complexes of alkyl gallates (A-GAs) including ethyl gallate (EG), propyl gallate (PG), and butyl gallate (BG) were successfully prepared by the thin film dispersion method. HPLC-UV analysis in an everted rat gut sac model indicated that A-GAs can be liberated from phospholipid complexes, which were further hydrolyzed by intestinal lipase to generate free gallic acid (GA). Both A-GAs and GA are able to cross the membrane, and the hydrolysis rate of A-GAs and the transport rate of GA are positively correlated with the alkyl chain length. Especially, compared with the corresponding physical mixtures, the phospholipid complexes exhibit slower sustained-release of A-GAs and GA. Therefore, the formation of phospholipid complexes is an effective approach to prolong the residence time in vivo and additionally enhance the bioactivities of A-GAs and GA. More importantly, through regulating the carbon skeleton lengths, controlled-release of alkyl gallates and gallic acid from phospholipid complexes will be achieved.

Solubility enhancement of meloxicam by phospholipid complexation

The best solubility enhancement approach is phospholipids complexation. It has been effectively employed by a number of writers to enhance the permeability, oral bioavailability, and solubility of several medicinal substances. The meloxicam is a member of BCS Class II, and because of its poor solubility and high permeability, its clinical application may have been constrained. Therefore, it is necessary to use a method that modifies the biopharmaceutical features. In this work, meloxicam, an NSAID with demonstrated anticancer action, was combined with phospholipid to increase its solubility. Utilizing solvent evaporation, the meloxicam phospholipid complex was produced. Particle size, zeta potential, SEM analysis, in vitro drug release, and solubility were assessed for the produced complex. The results obtained in this study showed the smaller particle size in nanometer range and physical stability with desired zeta potential. Meloxicam's prolonged release from the phospholipid complex is demonstrated by the in vitro drug release investigation. The apparent solubility analysis of meloxicam phospholipid complex. Pure meloxicam showed that the drug's solubility was several times higher than that of the pure form. Hence in conclusion we can say that the phospholipid complexation could be the ideal method for solubility enhancement of drug like meloxicam.&#x0D; Keyword: Meloxicam, phospholipid complex, solubility, drug release

The novel lactoferrin and DHA-codelivered liposomes with different membrane structures: Fabrication, in vitro infant digestion, and suckling pig intestinal organoid absorption

Inspired by membrane structure of breast milk and infant formula fat globules, four liposomes with different particle size (large and small) and compositions (Single phospholipids contained phosphatidylcholine, complex phospholipids contained phosphatidylcholine, phosphatidylethanolamine and sphingomyelin) were fabricated to deliver lactoferrin and DHA. In vitro infant semi-dynamic digestive behavior and absorption in intestinal organoids of liposomes were investigated. Liposomal structures were negligible changed during semi-dynamic gastric digestion while damaged in intestine. Liposomal degradation rate was primarily influenced by particle size, and complex phospholipids accelerated DHA hydrolysis. The release rate of DHA (91.7 ± 1.3 %) in small-sized liposomes (0.181 ± 0.001 μm) was higher than free DHA (unencapsulated, 64.6 ± 3.4 %). Complex phospholipids liposomal digesta exhibited higher transport efficiency (3.4-fold for fatty acids and 2.0-fold for amino acids) and better organoid growth than digesta of bare nutrients. This study provided new insights into membrane structure-functionality relationship of liposomes and may aid in the development of novel infant nutrient carriers.

Drug- Phospholipid complex: A novel strategy for Lymphatic Filariasis treatment

One of the most terrifying and ugly forms of filariasis to humans is lymphatic filariasis, where adult worms 7-10 cm long are found in the lymphatic system. Mf continues to multiply in the bloodstream of the host and translocates eventually to the LS. Filariasis-causing parasites block the human blood vessels and lymph nodes.The impasse allows fluid to drain into the terminus of the body and accumulate in tissues, causing severe swelling christened “lymphoedema”. LF is caused due Filariodiaceae family roundworms, often these are of three types (Wuchereria bancrofti, Brugia malayi and Brugia timori). All of these are handed down through Anopheles mosquitoes, Aedes mosquitoes and Culex pipiens. In worldwide over 90% of infectious diseases are caused by W. bancrofti. Several synthetic drugs are currently used to treat this disease. However these drugs are not as effective as killing adult worms and at the same time, some side effects are also seen. Conversely, plant actives ingredients complex with phospholipids to form nano-sized vesicles. As parasites live in the small intestine, nanometer-sized phyto vesicles can protect plant actives from deterioration in the stomach and easily reach their target and kill parasites without side effects.

Liver-Targeting Composite Nanocarrier Delivery System Based on Chitosan Nanoparticles and Phospholipid Complexes.

Liver fibrosis is mainly caused by excessive accumulation of extracellular matrix and structural changes in the liver, ultimately leading to cirrhosis if left untreated. Reducing hyaluronan synthesis by inhibiting hyaluronic acid deposition or regulating the expression of hyaluronic synthase can ameliorate liver fibrosis symptoms. In this study, we aimed to improve the bioavailability and liver-targeting capacity of hydroxymethyl coumarin (4-MU) using a newly developed phospholipid complex chitosan nanoparticle (4-MU PC/CNP) optimized using the Box-Behnken design. The composite nanocarrier delivery system was formulated using solvent evaporation technology, and formulation and process parameters were evaluated. Furthermore, 4-MU PC/CNPs and their pharmacokinetics were characterized. The established 4-MU PC/CNPs had an average particle size of 153.07 ± 0.29 nm, a polydispersity index value of 0.383, and a positive zeta potential of ∼35.4 mV. Compared with 4-MUs, 4-MU PC/CNPs exhibited significantly improved water solubility, faster plasma clearance and tissue distribution, and better liver targeting. Pharmacokinetic analysis showed that the oral bioavailability of 4-MU in 4-MU PC/CNPs was significantly higher than that of simple 4-MU. In conclusion, 4-MU PC improved drug lipid (oil-water distribution coefficient of 1.31 ± 0.03) and water solubilities (2.05 times the drug substance). 4-MU PC/CNPs significantly improved 4-MU oral bioavailability, representing a promising approach for enhancing drug solubility. This study demonstrates that the targeting parameters of 4-MU PC/CNPs in the liver were all greater than 1, indicating that they specifically targeted the liver, thereby potentially alleviating liver fibrosis.

FormulationAI: a novel web-based platform for drug formulation design driven by artificial intelligence.

Today, pharmaceutical industry faces great pressure to employ more efficient and systematic ways in drug discovery and development process. However, conventional formulation studies still strongly rely on personal experiences by trial-and-error experiments, resulting in a labor-consuming, tedious and costly pipeline. Thus, it is highly required to develop intelligent and efficient methods for formulation development to keep pace with the progress of the pharmaceutical industry. Here, we developed a comprehensive web-based platform (FormulationAI) for in silico formulation design. First, the most comprehensive datasets of six widely used drug formulation systems in the pharmaceutical industry were collected over 10years, including cyclodextrin formulation, solid dispersion, phospholipid complex, nanocrystals, self-emulsifying and liposome systems. Then, intelligent prediction and evaluation of 16 important properties from the six systems were investigated and implemented by systematic study and comparison of different AI algorithms and molecular representations. Finally, an efficient prediction platform was established and validated, which enables the formulation design just by inputting basic information of drugs and excipients. FormulationAI is the first freely available comprehensive web-based platform, which provides a powerful solution to assist the formulation design in pharmaceutical industry. It is available at https://formulationai.computpharm.org/.

Ring Opening of Glycerol Cyclic Phosphates Leads to a Diverse Array of Potentially Prebiotic Phospholipids.

Phospholipids are the primary constituents of cell membranes across all domains of life, but how and when phospholipids appeared on early Earth remains unknown. Pressingly, most prebiotic syntheses of complex phospholipids rely upon substrates not yet shown to have been available on early Earth. Here, we describe potentially prebiotic syntheses of a diverse array of complex phospholipids and their building blocks. First, we show that choline could have been produced on early Earth by stepwise N-methylation of ethanolamine. Second, taking a systems chemistry approach, we demonstrate that the intrinsically activated glycerol-2,3-cyclic phosphate undergoes ring opening with combinations of prebiotic amino alcohols to yield complex phospholipid headgroups. Importantly, this pathway selects for the formation of 2-amino alcohol-bearing phospholipid headgroups and enables the accumulation of their natural regioisomers. Finally, we show that the dry-state ring opening of cyclic lysophosphatidic acids leads to a range of self-assembling lysophospholipids. Our results provide new prebiotic routes to key intermediates on the way toward modern phospholipids and illuminate the potential origin and evolution of cell membranes.

Charge Inversion of Mono- and Dianions to Cations via Triply Charged Metal Complexes: Application to Lipid Mixtures.

Electrospray ionization (ESI) of mixtures can give rise to ions with different masses and charges with overlapping mass-to-charge (m/z) ratios. Such a scenario can be particularly problematic for the detection of low-abundance species in the presence of more highly abundant mixture components. For example, negative mode ESI of polar lipid extracts can result in highly abundant singly charged glyerophospholipids (GPLs), such as phosphatidylethanolamines (PE) and phosphatidylglycerols (PG), that can obscure much less abundant cardiolipins (CLs), which are complex phospholipids with masses roughly double those of GPLs that mostly form doubly charged anions. Despite their low relative abundance, CLs are lipidome components that perform vital biological functions. To facilitate the study of CLs in lipid mixtures without resorting to offline or online separations, we have developed a gas-phase approach employing ion/ion reactions to charge invert anionic lipid species using a trivalent metal-complex. Specifically, ytterbium(III) is shown to readily complex with three neutral ligands, N,N,N',N'-tetra-2-ethylhexyl diglycolamide (TEHDGA), to form [Yb(TEHDGA3)]3+ using ESI. Herein, we describe pilot studies to evaluate [Yb(TEHDGA)3]3+ as an ion/ion reagent to allow for chemical separation of doubly and singly charged anions, using lipid mixtures as examples, without neutralizing ions of either charge state.

Cytotoxicity and bioavailability assessment from thiamin-phospholipid complexation loaded Ajwain oil based self nanoemulsifying system

Poor bioavailability (<5%) of thiamin hydrochloride (TH) primarily relates to its impaired permeability across gut mucosa. To modulate its permeability, a dual system based approach consisting of phospholipid complexation embedded into a self nanoemulsifying system was investigated. Thiamin-Phospholipid Complex (TPC) was developed and its Ajwain oil (AJO)-based self nanoemulsifying formulations (SNFs) were evaluated. Formation of TPC complexation was resulted from molecular interactions held between free bases of thiamin and phospholipid (PL). FTIR characterization reveals that the amino group (-NH2) in the free base of thiamin was physically interacted to phosphate linkage in PL. Single endothermic event in TPC & TH, reveals complexation between PL & free bases as interpreted from DSC data. Their corresponding melting point was 127 °C and 258 °C, respectively. Heat of fusion (ΔHf) in TPC was higher than TH or PL. TPC exhibits a poor conductive environment over TH when diluted with ethanol/Tween20 (T2) medium. Lipophilic character of TPC was confirmed from partition coefficient (log P). Exact combination where ternary components produced fully dilutable nanoemulsion system, was identified using ternary diagram drawn between AJO (incorporated with TPC) as oil phase, and Tween20/Polyethylene glycol 600 (PEG600) as Surfactant/co-surfactant (Smix) at ratios 1:1; 1:2 & 2:1. Seven TPC-loaded self nanoemulsifying formulations (SNFs) were designed which, upon subjected to aqueous phase dilution yielded nanoemulsion with droplet size range 95–190 nm with zeta potential −1.78 ± 0.10 mV. Conductivity and Refractive index (RI) data of SNFs were in the range of 98 ± 7.0 to 231 ± 27 μS/cm and 1.458 to 1.463 units, respectively. In vitro TH release from SNF was determined in hydrochloric (HCl) buffer at pH 1.2, and in phosphate buffer solution (PB) at pH 6.8, data interpretation reveals that TPC delayed the release pattern compared to TH and could be attributed to lipophilic behavior of TPC. Intestinal permeability of drug was assessed from optimized SNF (F1) vs. TH across intestinal gut sac model (Apical to basolateral A→B) resulted in a significant difference in permeability coefficient (1.09 × 10−5cm/h). Antioxidant potential of SNF was demonstrated in the DPPH method. MTT assay of TPC formulation conducted on MCF-7 and MDA-MB-231 (Breast cancer) cell lines showed the developed system from AJO possessed cytotoxicity effect. Pharmacokinetic assessment showed that optimized SNFs produced more than four-fold enhancement in bioavailability over control (TH solution) in the Wistar rat model. Meanwhile Area under curve (AUC) data obtained from TPC (in coarse emulsion) vs.TH produced a significant difference (p < 0.001). It can be concluded that developed SNFs via phospholipid complexation produced lipophilic transformation of TH and its SNFs modulated permeability as well as bioavailability enhancement of thiamin.

Metabolomics Analysis of DRG and Serum in the CCI Model of Mice.

Neuropathic pain (NP) is a chronic and intractable disease that is widely present in the general population. It causes painful behavior and even mood changes such as anxiety and depression by altering the metabolism of substances. However, there have been limited metabolomics studies conducted in relation to neuropathic pain. Therefore, in this study, the effects of NP on metabolites in serum and the dorsal root ganglion (DRG) were investigated using a non-targeted metabolomics approach detected by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) to uncover differential metabolites and affected metabolic pathways associated with NP. Sixty mice were divided into the following two groups: a chronic constriction injury (CCI) of the sciatic nerve group and a sham group (n = 30, each). After 7 days of CCI modeling, the metabolite profiles of serum and the DRG were analyzed using GC/LC-MS for both the CCI and sham groups of mice. Multivariate analysis revealed differential metabolites and altered metabolic pathways between the CCI and sham groups. In the CCI group, our findings provided insights into the complex phospholipid, amino acid and acylcarnitine metabolic perturbations of DRG metabolism. In addition, phospholipid metabolic disorders and impaired glucose metabolism were observed in the serum. Moreover, the metabolic differences in the DRG and serum were correlated with each other. The results from this untargeted metabolomics study provide a perspective on the metabolic impact of NP on serum and the DRG.

Selective expression of light-harvesting complexes alters phospholipid composition in the intracytoplasmic membrane and core complex of purple phototrophic bacteria

Phospholipid–protein interactions play important roles in regulating the function and morphology of photosynthetic membranes in purple phototrophic bacteria. Here, we characterize the phospholipid composition of intracytoplasmic membrane (ICM) from Rhodobacter (Rba.) sphaeroides that has been genetically altered to selectively express light-harvesting (LH) complexes. In the mutant strain (DP2) that lacks a peripheral light-harvesting (LH2) complex, the phospholipid composition was significantly different from that of the wild-type strain; strain DP2 showed a marked decrease in phosphatidylglycerol (PG) and large increases in cardiolipin (CL) and phosphatidylcholine (PC) indicating preferential interactions between the complexes and specific phospholipids. Substitution of the core light-harvesting (LH1) complex of Rba. sphaeroides strain DP2 with that from the purple sulfur bacterium Thermochromatium tepidum further altered the phospholipid composition, with substantial increases in PG and PE and decreases in CL and PC, indicating that the phospholipids incorporated into the ICM depend on the nature of the LH1 complex expressed. Purified LH1–reaction center core complexes (LH1–RC) from the selectively expressing strains also contained different phospholipid compositions than did core complexes from their corresponding wild-type strains, suggesting different patterns of phospholipid association between the selectively expressed LH1–RC complexes and those purified from native strains. Effects of carotenoids on the phospholipid composition were also investigated using carotenoid-suppressed cells and carotenoid-deficient species. The findings are discussed in relation to ICM morphology and specific LH complex–phospholipid interactions.

Formulation and Evaluation of Gastro-retentive Drug Delivery System of Novel Famotidine Phospholipid Complex

Famotidine is an H2 receptor antagonist belonging to the BCS Class II, characterized by low solubility and limited oral bioavailability. The current study encompasses the formulation of novel famotidine phospholipid complex (FHC) with the aid of design of experiments (Central Composite Design) using solvent evaporation technique to overcome the disadvantages of Famotidine. To further enhance the physicochemical properties of FHC, it was incorporated into gastro-retentive floating tablets (GRDDS) using direct compression technique with sodium bicarbonate as a gas generating agent and its properties were compared to famotidine floating tablets. The pre-compression parameters, namely bulk density, tapped density, Hausner’s ratio, Carr’s compressibility index and angle of repose were evaluated. The flow properties of FHC granules were found to be better than the plain famotidine granules. The postcompression parameters, namely thickness, hardness, friability, weight variation, drug content and swelling index showed better results for FHC as compared to famotidine floating tablets. In-vitro buoyancy study indicated that the floating lag time for FHC tablets (110 ± 0.021 seconds) was higher than famotidine tablets (36 ± 0.033 seconds) owing to the higher molecular weight of phosphatidylcholine. But the total floating time for FHC tablets was found to be more than 18 hours and for famotidine tablets it was ~12 hours, indicating the improved residence time and buoyancy. The in-vitro dissolution study depicted that the cumulative release for FHC tablets (99.84 ± 0.058%) was enhanced 1.07 fold than Famotidine tablets (92.73 ± 0.028%) and 1.6 fold than marketed tablet, Famocid (62.24 ± 0.023%). When kinetic modeling was performed, famotidine tablet followed zero order kinetics, whereas FHC tablet followed Higuchi model indicating a modified and sustained release pattern. The statistical analysis for %cumulative release performed using ANOVA and Dunnett’s test showed the p-value to be below 0.05 (0.0043) indicating that the analysis model was significant. An accelerated stability study was performed for a period of 6 months at 25 ± 2°C; 60 ± 5% RH. FHC tablets showed a better stability profile than famotidine tablets. In conclusion, FHC gastro-retentive floating tablets showed improved flow properties, post compression properties, better drug content, improved in-vitro buoyancy and enhanced cumulative release and stability profile.

Formulation and Evaluation of Phytosomes of Hydroalcoholic Extract of Adiantum capillus-veneris for Antimicrobial Activity

Pharmacognosy Research,2023,15,3,468-477.DOI:10.5530/pres.15.3.048Published:June 2023Type:Original Article Authors:Supriya Ganesh Jagtap, Vedant Vinay Kajale, Mukta Mahesh Abhyankar, Aditi Shrinivas Kulkarni, and Minal Rushikesh Ghante Author(s) affiliations:Supriya Ganesh Jagtap1,*, Vedant Vinay Kajale2, Mukta Mahesh Abhyankar1, Aditi Shrinivas Kulkarni1, Minal Rushikesh Ghante2 1Department of Pharmacognosy, STES’s, Smt. Kashibai Navale College of Pharmacy, Kondhwa (Bk), Pune, Maharashtra, INDIA. 2Department of Pharmaceutical Quality Assurance, STES’s, Smt. Kashibai Navale College of Pharmacy, Kondhwa (Bk), Pune, Maharashtra, INDIA. Abstract:Background: Natural plant extracts and phytoconstituents have high in vitro bioactivity but low in vivo bioactivity because of poor lipid solubility, multiple ring large molecules, or digestion in the gut. Polyphenolic phytoconstituents were complexed with phospholipids, mainly phosphatidylcholine, which molecularly attaches components to one another to produce novel drug delivery systems like phytosomes. The important constituents of the herbal extract are designed to protect from being disrupted by gastric juices and gut bacteria, as phytosomes have the ability to cross the bio-membranes that which are lipid enriched and boost bioavailability. Objectives: The current work is aimed to formulate and evaluate phytosomes from Adiantum capillus-veneris (ACV) hydroalcoholic extract for antimicrobial activity. Materials and Methods: Antisolvent precipitation method was chosen on the basis of the solubility of hydroalcoholic extract in dichloromethane. The prepared trial batches of the phytosomes complex were characterized by using particle size, zeta potential, drug entrapment efficiency, drug content, and in vitro drug release study. The optimized batch of phytosomes was characterized for compatibility studies by using Infrared Spectrometry (IR), Transmission Electron Microscopy (TSM), Differential Scanning Calorimetry (DSC), and further for stability studies. Results: The results revealed that ACV hydroalcoholic extract and phosphatidylcholine were found to be connected by a non-covalent bond and did not generate a new molecule in the ACV hydroalcoholic extract-phosphatidylcholine complex and showed enhanced in vitro antimicrobial activity as compared to the hydroalcoholic extract. Conclusion: The complex's dissolution profile was found to be improved. As a result, the phospholipid complex of ACV extract can therefore be concluded to have the potential to enhance bioavailability. Keywords:Adiantum capillus-veneris (ACV), Antimicrobial activity., H-ACV extract phytosomes, Hydroalcoholic extract, PhytosomesView:PDF (549.56 KB)

The state of intermediate metabolism and antioxidant protection of the organism of quail during denitrifation

Purpose : the study of the exposure of the prototype of sagging and the phospholipid complex of lecithin for the intermediate exchange and enzymatic activity of the anti -radical protection of the body of quails in the presence of a subtoxic dose of nitrates in the compound feeds. Materials and methods . To carry out a scientific and production experiment, meat caves "Pharaoh" were used. From per diem, 4 groups of experimental birds of 50 goals in each were formed on the principle of groups of groups analogues. Compound feeds used for feeding are quittered, grown for meat, were prosperous in the presence of nitrates. With this in mind, for the purity of the experiment, they additionally introduced sodium nitrate in a dose of 40 g/t feed in their composition for all groups in the role of the source of these xenobiotics. At the same time, the presence of nitrates in the diet in a subtoxic dose was ensured. A sagitol’s sagitot at a dose of 1250 g/t, for the 3rd group-1000 g/t lacitin, for the 4th-1250 g/t of the sagitol test + 1000 g/t Lecin, was added to the feed. The 1st group was controlled - for birds of these groups in compensation, sagitol and lecithin were not added to determine the effectiveness of denitrification studied the basic morphological and biochemical parameters of blood and the activity of enzymes of anti -radical protection of the body of quails (5 heads in the group) aged 42 days. Results . In the course of the studies, it was first established that joint supplements in the diets of produces of produces of sagol at a dose of 1.25 kg/t of feed and lecithin at a dose of 1.0 kg/t food contributed to effective denitrification in the body of the plyona breed. This was manifested in a reliable (p &lt;0.05) increase in the bird of the 3rd experimental group regarding control in the liquid internal environment of the number of red blood cells and hemoglobin, as well as in a decrease in the concentration of metghemoglobin by 45.17% (p &lt;0.05) . With joint additives in the diets of probiotic and lecithin, an improvement in the state of natural resistance and antioxidant protection of the poultry body was observed, which was manifested in an increase in the quails of the 3rd experimental group regarding control of lysozymic activity by 2.99% (p &lt;0.05), bacticipid by 11.09% (p &lt;0.05) and the activity of glutathioneperoxidase - by 43.22% (p &lt;0.05) with a decrease in catalase activity - by 17.46% (p &lt;0.05). Under the influence of these drugs, the quails of 3 of the experimental group observed the best level of denitrification, which in the blood serum increased the amount of uric acid by 42.56% (p &lt;0.05) due to a decrease in nitrates by 50.54% (p &lt;0 , 05) and nitrites - by 60.55% (p &lt;0.05).

Nanoemulsions of Hydroxysafflor Yellow A for Enhancing Physicochemical and In Vivo Performance.

Stroke was always a disease that threatened human life and health worldwide. We reported the synthesis of a new type of hyaluronic acid-modified multi-walled carbon nanotube. Then, we produced hydroxysafflor yellow A-hydroxypropyl-β-cyclodextrin phospholipid complex water-in-oil nanoemulsion with hyaluronic acid-modified multi-walled carbon nanotubes and chitosan (HC@HMC) for oral treatment of an ischemic stroke. We measured the intestinal absorption and pharmacokinetics of HC@HMC in rats. We found that the intestinal absorption and the pharmacokinetic behavior of HC@HMC was superior to that of HYA. We measured intracerebral concentrations after oral administration of HC@HMC and found that more HYA crossed the blood-brain barrier (BBB) in mice. Finally, we evaluated the efficacy of HC@HMC in middle cerebral artery occlusion/reperfusion (MCAO/R)-injured mice. In MCAO/R mice, oral administration of HC@HMC demonstrated significant protection against cerebral ischemia-reperfusion injury (CIRI). Furthermore, we found HC@HMC may exert a protective effect on cerebral ischemia-reperfusion injury through the COX2/PGD2/DPs pathway. These results suggest that oral administration of HC@HMC may be a potential therapeutic strategy for the treatment of stroke.

FORMULATION AND DEVELOPMENT OF GALLEN GUM LOADED SELF-ASSEMBLED MIXED MICELLES SYSTEM BASED ON FLAVONOID PHOSPHOLIPID COMPLEX

Objective: Research on the development of pharmaceutical self-assembled mixed micells systems is in that they have the advantage of keeping the drug's encapsulating qualities while also enhancing its physicochemical characteristics. The goal of this study was to make the class II biopharmaceutical quercetin more soluble in water and more bioavailable when taken orally (QCT). The enhancement of encapsulation and flavonoids loading within mixed micelles using solvent evapouration technique. Methods: In the present study, pharmaceutical mixed micells of a BCS class II drug, QCT were prepared using solvent evapouration technique method. Prepared mixed micells were characterized using Critical micelle concentration (CMC), Fourier Transform Infrared (FT-IR), Particle size and zeta potential, Powder X-Ray Diffract meter (PXRD), In vitro dissolution, Transmission electron microscopy (TEM). In addition In vitro drug release studies were also performed. Results: The results of the characterization studies indicated the designing of gallen gum loaded self-assembled mixed micelles system based on flavonoid phospholipid complex. The CMC of LS-75 and LS-100 binary mixture had shows good results to be 0.0013%. The FTIR spectra of complex showed characteristic peak of QCT shows abundant effect on O-H (aromatic), C-O (aromatic), C-C, and aromatic C-O is observed at 3282.2, 1620.1, 1058.7, and 1162.2 respectively. The average particle size of design-optimized quercetin mixed micells (QCT-MMs) was demonstrated to be ~116.1 nm, as evaluated by Malvern. From the obtained particle size, it indicated that the particle size of QCT in QCT-MMs was widely distributed. The polydispersity index (PDI) for QCT-MMs was found in the range of ~ 1.000, zeta potential value for QCT-MMs as evaluated by Malvern was observed to be ~-99.2 mV. The P-XRD, SEM, showed good powder diffraction results with having good flow property. Also formulation were evaluated for the In vitro drug dissolution study for rate of extent of drug release and dissolution rate release of QCT from QCT-MMs was sustained up to 72 h. TEM images of QCT-MMs, where the micelles exhibited relatively regular dark stained shapes appearing more or less spherical or spheroid. Conclusion: It can be concluded that the QCT-MMs enhance the aqueous solubility of the QCT and increased the bioavailability and retention time.

Protective effect and mechanism insight of purified Antarctic krill phospholipids against mice ulcerative colitis combined with bioinformatics

Antarctic krill oil is functional oil and has a complex phospholipids composition that poses difficulties in elucidating its effect mechanism on ulcerative colitis (UC). The mechanism of UC action was studied by bioinformatics, and the therapeutic effect of Antarctic krill phospholipids (APL) on dextran sulfate sodium (DSS)-induced colitis mice was verified. GO functional enrichment analysis uncovered an enrichment of these genes in the regulation of cell–cell adhesion, membrane region, signaling receptor activator activity, and cytokine activity. Meanwhile, the KEGG results revealed the genes were enriched in the TNF signaling pathway, pathogenic Escherichia coli infection, inflammatory bowel disease and tight junction. Animal experiments showed that APL treatment alleviated the UC symptoms and reduced inflammatory damage. Meanwhile, the expressions of the tight junction (TJ) proteins, ZO-1 and occludin, were restored, and the levels of IL-6 and TNF-α were reduced. Moreover, Firmicutes/Bacteroidetes ratio in the intestinal microbiota was regulated, and the contents of short-chain fatty acids metabolites were raised. These findings would provide an insight for the beneficial effects of APL and dietary therapy strategies for UC.