ABSTRACT
The advancement of the Penaeus vannamei industry in a sustainable manner necessitates the creation of eco-friendly and exceptionally effective feed additives. To achieve this, 720 similarly-sized juvenile shrimp (0.88 ± 0.02 g) were randomly divided into four groups in this study, with each group consisting of three replicates, each tank (400 L) containing 60 shrimp. Four experimental diets were formulated by adding 0, 500, 1000, and 1500 mg kg-1 glycerol monolaurate (GML) to the basal diet, and the feeding trial lasted for 42 days. Subsequently, a 72-h White Spot Syndrome Virus (WSSV) challenge test was conducted. Polynomial orthogonal contrasts analysis revealed that with the increase in the concentration of GML, those indicators related to growth, metabolism and immunity, exhibit linear or quadratic correlations (P < 0.05). The results indicate that the GML groups exhibited a significant improvement in the shrimp weight gain rate, specific growth rate, and a reduction in the feed conversion ratio (P < 0.05). Furthermore, the GML groups promoted the lipase activity and reduced lipid content of the shrimp, augmented the expression of triglyceride and fatty acid decomposition-related genes and lowered the levels of plasma triglycerides (P < 0.05). GML can also enhanced the humoral immunity of the shrimp by activating the Toll-like receptor and Immune deficiency immune pathways, improved the phagocytic capacity and antibacterial ability of shrimp hemocytes. The challenge test revealed that GML significantly reduced the mortality of the shrimp compared to control group. The 16S rRNA sequencing indicates that the GML group can increases the abundance of beneficial bacteria. However, 1500 mg kg-1 GML adversely affected the stability of the intestinal microbiota, significantly upregulating intestinal antimicrobial peptide-related genes and tumor necrosis factor-alpha levels (P < 0.05). In summary, 1000 mg kg-1 GML was proven to enhance the growth performance, lipid absorption and metabolism, humoral immune response, and gut microbiota condition of P. vannamei, with no negative physiological effects.
Subject(s)
Animal Feed , Diet , Dietary Supplements , Gastrointestinal Microbiome , Laurates , Lipid Metabolism , Monoglycerides , Penaeidae , Animals , Penaeidae/immunology , Penaeidae/growth & development , Penaeidae/drug effects , Penaeidae/microbiology , Gastrointestinal Microbiome/drug effects , Lipid Metabolism/drug effects , Diet/veterinary , Animal Feed/analysis , Laurates/pharmacology , Laurates/administration & dosage , Monoglycerides/administration & dosage , Monoglycerides/pharmacology , Dietary Supplements/analysis , Random Allocation , Immunity, Innate/drug effects , White spot syndrome virus 1/physiology , Dose-Response Relationship, Drug , Digestion/drug effectsABSTRACT
The objective of this study was to evaluate the effects of different levels of glycerol monolaurate (GML) on laying performance, egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens. A total of 480 Hy-Line Variety Brown hens (age 54 wk) were randomly assigned to 5 treatments: the control group (basal diet) and 4 GML groups (basal diet supplemented with 100, 200, 300, and 400 mg/kg GML). Each treatment consisted of 8 replicates with 12 hens each and the trial lasted for 8 wk. The results showed that dietary inclusion of GML increased the ADFI in the entire experimental period and the average egg weight in wk 5 to 8 and wk 1 to 8 of the experiment (linear, P < 0.05). Dietary GML addition linearly increased albumen height, Haugh unit and yolk color, and quadratically increased eggshell thickness (P < 0.05). The serum SOD activity, T-AOC and IgG concentrations in the 200 mg/kg GML group, and GSH-Px activity in 200 and 300 mg/kg GML groups were increased, while the MDA concentration in 200 and 300 mg/kg GML groups was decreased than those in the control group (P < 0.05). The jejunal villus height and villus height: crypt depth in 300 mg/kg GML group were higher than that in the control group (P < 0.05). The mRNA expression of TLR4, IL-1ß and TNF-α in spleen and jejunum decreased with the increase of dietary GML concentration (linear, P < 0.05). In conclusion, dietary GML supplementation could improve egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens, and dietary 300 mg/kg GML inclusion is suggested.
Subject(s)
Animal Feed , Antioxidants , Chickens , Diet , Dietary Supplements , Intestines , Laurates , Monoglycerides , Ovum , Animals , Chickens/physiology , Chickens/immunology , Chickens/growth & development , Dietary Supplements/analysis , Diet/veterinary , Female , Antioxidants/metabolism , Animal Feed/analysis , Laurates/administration & dosage , Laurates/pharmacology , Monoglycerides/administration & dosage , Monoglycerides/pharmacology , Intestines/drug effects , Intestines/anatomy & histology , Intestines/physiology , Ovum/drug effects , Ovum/physiology , Random Allocation , Dose-Response Relationship, Drug , Reproduction/drug effectsABSTRACT
Inflammatory bowel disease (IBD) is a type of immune-mediated chronic and relapsing inflammatory gastrointestinal symptoms. IBD cannot be completely cured because of the complex pathogenesis. Glycerol monolaurate (GML), naturally found in breast milk and coconut oil, has excellent antimicrobial, anti-inflammatory, and immunoregulatory functions. Here, the protective effect of GML on dextran sodium sulfate (DSS)-induced mouse colitis and the underlying gut microbiota-dependent mechanism were assessed in C57BL/6 mice pretreated or cotreated with GML and in antibiotic-treated mice transplanted with GML-modulated microbiota. Results showed that GML pretreatment has an advantage over GML cotreatment in alleviating weight loss and reducing disease activity index (DAI), colonic histological scores, and proinflammatory responses. Moreover, the amounts of Lactobacillus and Bifidobacterium and fecal propionic acid and butyric acid were elevated only in mice pretreated with GML upon DSS induction. Of note, fecal microbiota transplantation (FMT) from GML-pretreated mice achieved faster and more significant remission of DSS-induced colitis, manifested as reduced DAI, longer colon, decreased histological scores, and enhanced colonic Foxp3+ regulatory T cells (Tregs) and ratio of serum anti-inflammatory/proinflammatory cytokines, as well as the reconstruction of microbial communities, including elevated Helicobacter ganmani and decreased pathogenic microbes. In conclusion, GML-mediated enhancement of Bifidobacterium and fecal short-chain fatty acids (SCFAs) could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Importantly, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved. IMPORTANCE The gut microbiota, which can be highly and dynamically affected by dietary components, is closely related to IBD pathogenesis. Here, we demonstrated that food-grade glycerol monolaurate (GML)-mediated enhancement of Bifidobacterium and fecal SCFAs could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Collectively, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved, which further provided a perspective to identify specific microbial members and those responsible for the anticolitis effect, such as Bifidobacterium and Helicobacter.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Colitis/drug therapy , Colitis/microbiology , Gastrointestinal Microbiome , Laurates/administration & dosage , Monoglycerides/administration & dosage , Sulfates/adverse effects , Animals , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Colitis/chemically induced , Colitis/immunology , Cytokines/genetics , Cytokines/immunology , Gastrointestinal Microbiome/drug effects , Humans , Male , Mice , Mice, Inbred C57BL , T-Lymphocytes, Regulatory/immunologyABSTRACT
There is enormous interest in utilizing biologically active fatty acids and monoglycerides to treat phospholipid membrane-related medical diseases, especially with the global health importance of membrane-enveloped viruses and bacteria. However, it is difficult to practically deliver lipophilic fatty acids and monoglycerides for therapeutic applications, which has led to the emergence of lipid nanoparticle platforms that support molecular encapsulation and functional presentation. Herein, we introduce various classes of lipid nanoparticle technology and critically examine the latest progress in utilizing lipid nanoparticles to deliver fatty acids and monoglycerides in order to treat medical diseases related to infectious pathogens, cancer, and inflammation. Particular emphasis is placed on understanding how nanoparticle structure is related to biological function in terms of mechanism, potency, selectivity, and targeting. We also discuss translational opportunities and regulatory needs for utilizing lipid nanoparticles to deliver fatty acids and monoglycerides, including unmet clinical opportunities.
Subject(s)
Drug Carriers , Drug Delivery Systems , Fatty Acids/administration & dosage , Lipids/chemistry , Monoglycerides/administration & dosage , Nanoparticles/chemistry , Nanotechnology , Chemical Phenomena , Humans , Liposomes , Micelles , Nanocapsules/chemistry , Nanotechnology/methodsABSTRACT
Porcine epidemic diarrhea virus (PEDV) has reemerged as the main pathogen of piglets due to its high mutation feature. Monolaurin (ML) is a natural compound with a wide range of antibacterial and antiviral activities. However, the role of ML in PEDV infection is still unknown. This study aimed to evaluate the effect of ML on the growth performance, intestinal function, virus replication and cytokine response in piglets infected with PEDV, and to reveal the mechanism through proteomics analysis. Piglets were orally administrated with ML at a dose of 100 mg/kg·BW for 7 days before PEDV infection. Results showed that although there was no significant effect on the growth performance of piglets, ML administration alleviated the diarrhea caused by PEDV infection. ML administration promoted the recovery of intestinal villi, thereby improving intestinal function. Meanwhile, PEDV replication was significantly inhibited, and PEDV-induced expression of IL-6 and IL-8 were decreased with ML administration. Proteomics analyses showed that 38 proteins were differentially expressed between PEDV and ML+PEDV groups and were significantly enriched in the interferon-related pathways. This suggests ML could promote the restoration of homeostasis by regulating the interferon pathway. Overall, the present study demonstrated ML could confer a protective effect against PEDV infection in piglets and may be developed as a drug or feed additive to prevent and control PEDV disease.
Subject(s)
Coronavirus Infections/prevention & control , Interferons/metabolism , Laurates/pharmacology , Monoglycerides/pharmacology , Porcine epidemic diarrhea virus/drug effects , Signal Transduction/drug effects , Swine Diseases/prevention & control , Animals , Animals, Newborn , Chromatography, Liquid/methods , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Cytokines/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/virology , Laurates/administration & dosage , Monoglycerides/administration & dosage , Porcine epidemic diarrhea virus/genetics , Porcine epidemic diarrhea virus/physiology , Protective Agents/pharmacology , Proteome/metabolism , Proteomics/methods , Swine , Swine Diseases/metabolism , Swine Diseases/virology , Tandem Mass Spectrometry/methods , Viral Load/drug effects , Viral Load/geneticsABSTRACT
Silica-lipid hybrid (SLH) microparticles are a solidified lipid-based drug delivery system under investigation for their aptitude to enhance the oral bioavailability of poorly water-soluble drugs. The cholesterol-lowering agent, simvastatin (SIM), is poorly water-soluble and undergoes extensive first pass metabolism, resulting in a low oral bioavailability of approximately 5%. Hence, the current pre-clinical studies investigated the application of SLH technology to SIM with a supersaturation approach, aiming to enhance bioavailability and drug loading capacity. Additionally, the effect of silica was explored by evaluating the performance of SLH fabricated with silica of different particle geometries. SLH microparticles with supersaturated SIM loading levels ranging from 100% to 400% above the equilibrium solubility were successfully fabricated using either Aerosil® 300 or Syloid® 244 silica. All SLH formulations existed as white free-flowing powders, consisting of spherical porous microparticles for Aerosil® 300, and aggregated irregular microparticles for Syloid® 244. During in vitro dissolution in pH 7.0 media, the SLH formulations performed up to 4.4-fold greater than pure SIM powder. Furthermore, in vivo oral pharmacokinetics in male Sprague-Dawley rats revealed that the SLH formulations enhanced the oral bioavailability of SIM up to 6.1-fold and 2.9-fold, in comparison to pure SIM powder and a commercially available formulation (Simvastatin Sandoz®), respectively. The greatest in vivo performance enhancement was observed for the SLH formulation manufactured with Syloid® 244 silica with a supersaturation level of 200%. SLH technology demonstrated to be a successful formulation strategy to significantly improve the oral bioavailability of SIM in rodents and therefore, has a strong potential to also improve the oral bioavailability of SIM in humans.
Subject(s)
Caprylates/administration & dosage , Diglycerides/administration & dosage , Drug Carriers/administration & dosage , Glycerides/administration & dosage , Hypolipidemic Agents/administration & dosage , Monoglycerides/administration & dosage , Silicon Dioxide/administration & dosage , Simvastatin/administration & dosage , Administration, Oral , Animals , Biological Availability , Caprylates/chemistry , Caprylates/pharmacokinetics , Diglycerides/chemistry , Diglycerides/pharmacokinetics , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Liberation , Glycerides/chemistry , Glycerides/pharmacokinetics , Hypolipidemic Agents/blood , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacokinetics , Male , Monoglycerides/chemistry , Monoglycerides/pharmacokinetics , Rats, Sprague-Dawley , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacokinetics , Simvastatin/blood , Simvastatin/chemistry , Simvastatin/pharmacokineticsABSTRACT
Liquid crystalline nanostructures (LCNs), for instance cubosomes, have been widely used as a promising carrier for drug delivery through the last few years. To date, the ophthalmic application of these platforms was not well explored, and the effect of integrating penetration enhancers (PEs) into LCNs has not been investigated yet. Hence, the present work aimed coupling novel PEs into glyceryl monooleate-based cubosomes for ocular administration. Various enhancers viz, free fatty acids (oleic and linoleic acids), natural terpenes (D-limonene and cineole), medium-chain triglycerides (Captex® 1000 and Captex® 8000), mono-/di-glycerides (Capmul® MCM, Capmul® PG-8, and Capmul® PG-12) were tested at different amounts. The morphology of the formed LCNs was investigated using transmission electron microscopy (TEM). The crystallinity and thermal behavior studies were also conducted. The ocular safety of optimized formulae was tested via hen's egg test-chorioallantoic membrane (HET-CAM), rabbit eye Draize test, and histopathological examinations of ocular tissues. Confocal laser scanning microscopy (CLSM) was utilized to assess the enhanced permeation of fluorescently-labeled LCNs across corneal layers. The acceptable formulations exhibited relatively homogenous particle nano-sizes ranging from 139.26 ± 3.68 to 590.56 ± 24.86 nm carrying negative surface charges. TEM images, X-ray patterns and DSC thermograms demonstrated the influential effect of PEs in developing altered crystalline structures. The ocular compatibility of optimized LCNs was confirmed. The corneal distribution using CLSM proved the disseminated fluorescence intensity of LCNs enriched with oleic acid, Captex® 8000 and Capmul® MCM. Selected LCNs showed good physical stability upon storage and lyophilization. The results demonstrated the efficiency of tailored PE-modified LCNs in enhancing the ocular transport with no evidence of any irritation potential, and hence suggested their prospective applicability in ophthalmic drug delivery.
Subject(s)
Cornea/drug effects , Drug Carriers , Glycerides/chemistry , Nanoparticles , Ocular Absorption/drug effects , Pharmaceutical Preparations/administration & dosage , Surface-Active Agents/administration & dosage , Administration, Ophthalmic , Animals , Chick Embryo , Cornea/metabolism , Diglycerides/administration & dosage , Diglycerides/chemistry , Drug Compounding , Glycerides/toxicity , Liquid Crystals , Male , Monoglycerides/administration & dosage , Monoglycerides/chemistry , Oleic Acid/administration & dosage , Oleic Acid/chemistry , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/metabolism , Rabbits , Surface-Active Agents/chemistry , Surface-Active Agents/toxicityABSTRACT
Numerous benefits are attributed to omega-3 fatty acids (OM3) especially in cardiovascular health. However, bioavailability and clinical efficacy depend on numerous factors, including OM3 form, food matrix effects (especially the lipid content of the diet), and metabolic capacity. Here, we show in humans that a "pre-digested" OM3-sn-1(3)-monoacylglycerol lipid structure (OM3-MAG) has a significantly greater absorption at high therapeutic doses (2.9 g/day) than the most commonly OM3-ethyl ester (3.1 g/day) form (used for the treatment of hypertriglyceridemia), and a comparable profile to other pre-digested OM3 free fatty acids (OM3-FFA) structure (3.2 g/day). Nutritional supplement doses of MAG resulted in similar increases in OM3 blood level, compared to OM3 triacylglycerols (OM3-TAG) supplements in obese subjects (1.2 g/day) under low fat diet, and in children with cystic fibrosis (1.0 g/day). These results suggest that both forms of pre-digested OM3-MAG and OM3-FFA are effectively absorbed and re-incorporated effectively into triacylglycerols inside the enterocytes, before being exported into the chylomicrons lipid transport system. The pre-digested OM3-MAG might provide a more effective therapy in severe cardiovascular conditions where high doses of OM3 are required and a low-fat diet is indicated, which limited digestive lipase activity.
Subject(s)
Cystic Fibrosis/drug therapy , Dietary Supplements , Fatty Acids, Omega-3 , Hypertriglyceridemia/drug therapy , Monoglycerides , Obesity/drug therapy , Adult , Biological Availability , Chylomicrons/metabolism , Cystic Fibrosis/blood , Cystic Fibrosis/pathology , Enterocytes/metabolism , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/pharmacokinetics , Female , Humans , Hypertriglyceridemia/blood , Hypertriglyceridemia/pathology , Male , Middle Aged , Monoglycerides/administration & dosage , Monoglycerides/pharmacokinetics , Obesity/blood , Obesity/pathology , Triglycerides/bloodABSTRACT
Obesity and associated metabolic disorders are worldwide public health issues. The gut microbiota plays a key role in the pathophysiology of diet-induced obesity. Glycerol monolaurate (GML) is a widely consumed food emulsifier with antibacterial properties. Here, we explore the anti-obesity effect of GML (1,600 mg/kg of body weight) in high-fat diet (HFD)-fed mice. HFD-fed mice were treated with 1,600 mg/kg GML. Integrated microbiome, metabolome, and transcriptome analyses were used to systematically investigate the metabolic effects of GML, and antibiotic treatment was used to assess the effects of GML on the gut microbiota. Our data indicated that GML significantly reduced body weight and visceral fat deposition, improved hyperlipidemia and hepatic lipid metabolism, and ameliorated glucose homeostasis and inflammation in HFD-fed mice. Importantly, GML modulated HFD-induced gut microbiota dysbiosis and selectively increased the abundance of Bifidobacterium pseudolongum Antibiotic treatment abolished all the GML-mediated metabolic improvements. A multiomics (microbiome, metabolome, and transcriptome) association study showed that GML significantly modulated glycerophospholipid metabolism, and the abundance of Bifidobacterium pseudolongum strongly correlated with the metabolites and genes that participated in glycerophospholipid metabolism. Our results indicated that GML may be provided for obesity prevention by targeting the gut microbiota and regulating glycerophospholipid metabolism.
Subject(s)
Diet, High-Fat , Gastrointestinal Microbiome/drug effects , Laurates/administration & dosage , Monoglycerides/administration & dosage , Obesity/prevention & control , Animals , Bifidobacterium/metabolism , Body Weight , Dysbiosis , Hyperlipidemias/prevention & control , Inflammation/prevention & control , Lipid Metabolism/drug effects , Liver/drug effects , Male , Metabolome , Mice , Mice, Inbred C57BL , Obesity/microbiology , TranscriptomeABSTRACT
Glycerol monolaurate (GML) has been widely used as an effective antibacterial emulsifier in the food industry. A total of 360 44-week-old Hy-Line brown laying hens were randomly distributed into four groups each with six replicates of 15 birds, and fed with corn-soybean-meal-based diets supplemented with 0, 0.15, 0.30, and 0.45 g/kg GML, respectively. Our results showed that 0.15, 0.30, and 0.45 g/kg GML treatments significantly decreased feed conversion ratios (FCRs) by 2.65%, 7.08%, and 3.54%, respectively, and significantly increased the laying rates and average egg weights. For egg quality, GML drastically increased albumen height and Haugh units, and enhanced yolk color. Notably, GML increased the concentrations of polyunsaturated and monounsaturated fatty acids and reduced the concentration of total saturated fatty acids in the yolk. The albumen composition was also significantly modified, with an increase of 1.02% in total protein content, and increased contents of His (4.55%) and Glu (2.02%) under the 0.30 g/kg GML treatment. Additionally, GML treatments had positive effects on the lipid metabolism of laying hens, including lowering the serum triglyceride and total cholesterol levels and reducing fat deposition in abdominal adipose tissue. Intestinal morphology was also improved by GML treatment, with increased villus length and villus height to crypt depth ratio. Our data demonstrated that GML supplementation of laying hens could have beneficial effects on both their productivity and physiological properties, which indicates the potential application of GML as a functional feed additive and gives us a new insight into this traditional food additive.
Subject(s)
Intestines/cytology , Laurates/administration & dosage , Monoglycerides/administration & dosage , Oviposition/drug effects , Ovum , Albumins/analysis , Animals , Chickens , Diet , Dietary Supplements , Egg Yolk/chemistry , Female , Gonadal Steroid Hormones/blood , Lipid Metabolism , Oxidative StressSubject(s)
Anti-Infective Agents/blood , Coconut Oil/metabolism , Infant, Extremely Premature , Laurates/blood , Monoglycerides/blood , Premature Birth , Administration, Cutaneous , Anti-Infective Agents/administration & dosage , Candida albicans/drug effects , Candida albicans/growth & development , Coconut Oil/administration & dosage , Female , Gestational Age , Humans , Infant, Newborn , Laurates/administration & dosage , Male , Monoglycerides/administration & dosage , Neonatal Sepsis/microbiology , Neonatal Sepsis/prevention & control , Randomized Controlled Trials as Topic , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/growth & developmentABSTRACT
SCOPE: The gut microbiota plays an important role in the development of diet-induced obesity and metabolic syndrome. Glycerol monolaurate (GML), a widely consumed food emulsifier, is reported to promote metabolic disorder and gut microbiota dysbiosis in low-dose supplementation upon low-fat-diet feeding. However, little is known about whether GML produce the same effects in mice fed a high-fat diet (HFD). METHODS AND RESULTS: C57BL/6 mice are fed a HFD with or without GML supplementation (150, 300, and 450 mg kg-1 ) for 10 weeks. The results demonstrated that higher GML treatment (450 mg kg-1 ) ameliorates HFD-induced metabolic disorders, supported by prevented visceral fat deposition, improved hyperlipidemia, modulated hepatic lipid metabolism, and reduced serum proinflammatory cytokine, TNF-α. Additionally, all doses of GML attenuated circulating lipopolysaccharide load and insulin resistance. Notably, GML ameliorates HFD-induced gut microbiota dysbiosis, with increases in Bacteroides uniformis, Akkermansia, Bifidobacterium, and Lactobacillus and decreases in Escherichia coli, Lactococcus, and Flexispira. Spearman's correlation analysis indicates that these enriched specific genera are significantly associated with the metabolic improvements of GML. CONCLUSION: The findings identify the links between gut microbiota and GML-induced metabolic improvements, suggesting that the attenuation of HFD-induced metabolic disorders by higher GML supplementation may occur through targeting gut microbiota.
Subject(s)
Diet, High-Fat/adverse effects , Gastrointestinal Microbiome/drug effects , Laurates/pharmacology , Metabolic Syndrome/diet therapy , Monoglycerides/pharmacology , Animals , Dietary Supplements , Dose-Response Relationship, Drug , Dysbiosis/diet therapy , Gastrointestinal Microbiome/genetics , Laurates/administration & dosage , Lipid Metabolism/drug effects , Liver/drug effects , Liver/metabolism , Male , Metabolic Syndrome/etiology , Metabolic Syndrome/microbiology , Mice, Inbred C57BL , Monoglycerides/administration & dosage , RNA, Ribosomal, 16SABSTRACT
Due to their ultrafine network structures, electrospun nanofibres have been potentially used for wound application. In order to develop a desired wound dressing material, shellac (SHL) was blended with polyvinyl pyrrolidone (PVP). Monolaurin (ML), which is a natural antimicrobial lipid, was incorporated into the SHL-PVP blended fibres to prevent delayed wound healing resulting from microbial infection. A full factorial design with three replicated centre points was employed in order to determine the main and interaction effects of various factors including SHL ratio in SHL-PVP blended solution, ML content and applied voltage on the multiple responses such as morphology, surface wettability, absorbency and mechanical properties. According to the results, an increase in the PVP content could lead to a significant increase in tensile strength and elongation. In addition, the presence of PVP contributed to an improvement in the drug loading capacity and dissolution rate. The fabricated fibres loaded with ML exhibited an excellent activity against Staphylococcus aureus and Candida albicans, and also provided an enhanced ability in the cell adhesion. Therefore, SHL-PVP blended fibres loaded with ML might be effectively used for application in wound healing.
Subject(s)
Anti-Infective Agents/administration & dosage , Laurates/administration & dosage , Monoglycerides/administration & dosage , Nanofibers/administration & dosage , Povidone/administration & dosage , Resins, Plant/administration & dosage , Candida albicans/drug effects , Cell Adhesion , Drug Compounding/methods , Drug Design , Fibroblasts , Humans , Staphylococcus aureus/drug effects , Wettability , Wound HealingABSTRACT
Glycerol monolaurate (GML), known as lauric acid, is a chemical compound formed from lauric acid and glycerol that presents strong antimicrobial activity. Therefore, our hypothesis is that MGL can replace conventional antimicrobials, being a new alternative to poultry farming. The aim of this study was to evaluate whether the addition of GML as a replacement for antibiotics could have positive effects on health and performance of broiler chickens. For this, 240, one-day-old, Cobb 500 broiler chicks were weighed and randomly distributed into four groups with four repetitions each (nâ¯=â¯15). The control group, T0, received a basal diet containing antibiotic (60â¯ppm of bacitracin), while the T100, T200, and T300 groups received a basal diet supplemented with 100, 200, and 300â¯mg/kg of GML, respectively. The birds were weighed at intervals of seven days, as well as at the end of the experiment (day 42). Blood samples were collected for evaluating animal health, stool for counting bacteria and coccidian, as well as muscle (chest) to measure meat quality, respectively. At the end of the experiment (day 42), body weight, weight gain, and daily weight gain of broiler chickens in the T300 group were higher than the T0 group (Pâ¯<â¯0.05). Indeed, feed conversion was lower compared to T0. Animals that received diets containing GML showed lower amounts of Eimeria spp. oocysts on day 42 in comparison to the control group. Low total bacterial counts on day 21 of the experiment were also observed in the treated groups. Conversely, plasma levels of total protein, globulins, uric acid, and glucose were higher in animals that received GML when compared to the control group. It was also observed higher carcass yields in the breast muscle of the T100 group when compared to other groups. Lower water holding capacity was observed in breast meat of animals of the groups T100, T200, and T300 when compared to T0. Histopathological findings were compatible with coccidiosis, and the degree of these lesions did not differ among groups. Based on these results, GML in the diets of broiler chickens, showing potent antimicrobial effect, growth promoter capacity, and lack of toxicity. Therefore, GML is a promising alternative to replace conventional antimicrobials used in the diets of broiler chickens.
Subject(s)
Anti-Infective Agents/administration & dosage , Chickens/growth & development , Diet/methods , Laurates/administration & dosage , Monoglycerides/administration & dosage , Animals , Anti-Infective Agents/adverse effects , Blood Chemical Analysis , Body Weight , Diet/adverse effects , Feces/microbiology , Feces/parasitology , Food Quality , Laurates/adverse effects , Meat , Monoglycerides/adverse effects , Treatment OutcomeABSTRACT
Bacterial infections are mostly due to bacteria in their biofilm-mode of growth, while penetrability of antimicrobials into infectious biofilms and increasing antibiotic resistance hamper infection treatment. In-vitro, monolaurin lipid nanocapsules (ML-LNCs) carrying adsorbed antimicrobial peptides (AMPs) displayed synergistic efficacy against planktonic Staphylococcus aureus, but it has not been demonstrated, neither in-vitro nor in-vivo, that such ML-LNCs penetrate into infectious S. aureus biofilms and maintain synergy with AMPs. This study investigates the release mechanism of AMPs from ML-LNCs and possible antimicrobial synergy of ML-LNCs with the AMPs DPK-060 and LL-37 against S. aureus biofilms in-vitro and in a therapeutic, murine, infected wound-healing model. Zeta potentials demonstrated that AMP release from ML-LNCs was controlled by the AMP concentration in suspension. Both AMPs demonstrated no antimicrobial efficacy against four staphylococcal strains in a planktonic mode, while a checkerboard assay showed synergistic antimicrobial efficacy when ML-LNCs and DPK-060 were combined, but not for combinations of ML-LNCs and LL-37. Similar effects were seen for growth reduction of staphylococcal biofilms, with antimicrobial synergy persisting only for ML-LNCs at the highest level of DPK-060 or LL-37 adsorption. Healing of wounds infected with bioluminescent S. aureus Xen36, treated with ML-LNCs alone, was faster when treated with PBS, while AMPs alone did not yield faster wound-healing than PBS. Faster, synergistic wound-healing due to ML-LNCs with adsorbed DPK-060, was absent in-vivo. Summarizing, antimicrobial synergy of ML-LNCs with adsorbed antimicrobial peptides as seen in-vitro, is absent in in-vivo healing of infected wounds, likely because host AMPs adapted the synergistic role of the AMPs added. Thus, conclusions regarding synergistic antimicrobial efficacy, should not be drawn from planktonic data, while even in-vitro biofilm data bear little relevance for the in-vivo situation.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Antimicrobial Cationic Peptides/administration & dosage , Laurates/administration & dosage , Monoglycerides/administration & dosage , Nanocapsules/administration & dosage , Staphylococcus aureus/drug effects , Adsorption , Anti-Bacterial Agents/chemistry , Antimicrobial Cationic Peptides/chemistry , Biofilms/drug effects , Drug Therapy, Combination , Laurates/chemistry , Lipids/administration & dosage , Lipids/chemistry , Monoglycerides/chemistry , Nanocapsules/chemistry , Staphylococcus aureus/physiologyABSTRACT
Glycerol monolaurate (GML) has been widely used as an effective antibacterial emulsifier in the food industry. A total of 360 44-week-old Hy-Line brown laying hens were randomly distributed into four groups each with six replicates of 15 birds, and fed with corn-soybean-meal-based diets supplemented with 0, 0.15, 0.30, and 0.45 g/kg GML, respectively. Our results showed that 0.15, 0.30, and 0.45 g/kg GML treatments significantly decreased feed conversion ratios (FCRs) by 2.65%, 7.08%, and 3.54%, respectively, and significantly increased the laying rates and average egg weights. For egg quality, GML drastically increased albumen height and Haugh units, and enhanced yolk color. Notably, GML increased the concentrations of polyunsaturated and monounsaturated fatty acids and reduced the concentration of total saturated fatty acids in the yolk. The albumen composition was also significantly modified, with an increase of 1.02% in total protein content, and increased contents of His (4.55%) and Glu (2.02%) under the 0.30 g/kg GML treatment. Additionally, GML treatments had positive effects on the lipid metabolism of laying hens, including lowering the serum triglyceride and total cholesterol levels and reducing fat deposition in abdominal adipose tissue. Intestinal morphology was also improved by GML treatment, with increased villus length and villus height to crypt depth ratio. Our data demonstrated that GML supplementation of laying hens could have beneficial effects on both their productivity and physiological properties, which indicates the potential application of GML as a functional feed additive and gives us a new insight into this traditional food additive.
Subject(s)
Animals , Female , Albumins/analysis , Chickens , Diet , Dietary Supplements , Egg Yolk/chemistry , Gonadal Steroid Hormones/blood , Intestines/cytology , Laurates/administration & dosage , Lipid Metabolism , Monoglycerides/administration & dosage , Oviposition/drug effects , Ovum , Oxidative StressABSTRACT
Nanocarriers based on inverse hexagonal liquid crystalline phases (hexosomes) show promising potential as vaccine delivery systems. Their unique internal structure, composed of both lipophilic domains and water-containing channels, renders them capable of accommodating immunopotentiating compounds and antigens. However, their adjuvant properties are poorly understood. We hypothesized that the supramolecular structure of the lyotropic liquid crystalline phase influences the immunostimulatory activity of lipid-based nanocarriers. To test this, hexosomes were designed containing the lipid phytantriol (Phy) and the immunopotentiator monomycoloyl glycerol-1 (MMG-1). Self-assembly of Phy and MMG-1 into nanocarriers featuring an internal hexagonal phase was confirmed by small-angle X-ray scattering and cryogenic transmission electron microscopy. The effect of the nanostructure on the adjuvant activity was studied by comparing the immunogenicity of Phy/MMG-1 hexosomes with MMG-1-containing lamellar liquid crystalline nanoparticles (liposomes, CAF04). The quality and magnitude of the elicited immune responses were determined after vaccination of CB6/F1 mice using the Chlamydia trachomatis major outer membrane protein (MOMP) as antigen. MMG-1-based hexosomes potentiated significantly stronger MOMP-specific humoral responses than CAF04 liposomes. The liposome-based vaccine formulation induced a much stronger MOMP-specific cell-mediated immune response compared to hexosome-adjuvanted MOMP, which elicited minimal MOMP-specific T-cell stimulation after vaccination. Hence, our data demonstrates that hexosomal and liposomal adjuvants activate the immune system via different mechanisms. Our work provides valuable insights into the adjuvant potential of hexosomes and emphasizes that engineering of the supramolecular structure can be used to design adjuvants with customized immunological properties.
Subject(s)
Adjuvants, Immunologic/pharmacology , Bacterial Vaccines/pharmacology , Chlamydia Infections/prevention & control , Chlamydia trachomatis/immunology , Fatty Alcohols/pharmacology , Monoglycerides/pharmacology , Porins/pharmacology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/chemistry , Animals , Antibody Formation/drug effects , Bacterial Vaccines/administration & dosage , Chlamydia Infections/immunology , Drug Carriers/chemistry , Fatty Alcohols/administration & dosage , Fatty Alcohols/chemistry , Female , Liquid Crystals/chemistry , Mice , Monoglycerides/administration & dosage , Monoglycerides/chemistry , Nanoparticles/chemistry , Porins/administration & dosage , VaccinationABSTRACT
Phospholipids (PL) or partial acylglycerols such as sn-1(3)-monoacylglycerol (MAG) are potent dietary carriers of long-chain polyunsaturated fatty acids (LC-PUFA) and have been reported to provide superior bioavailability when compared to conventional triacylglycerol (TAG). The main objective of the present study was to compare the incorporation of docosahexaenoic acid (DHA) in plasma, erythrocytes, retina and brain tissues in adult rats when provided as PL (PL-DHA) and MAG (MAG-DHA). Conventional dietary DHA oil containing TAG (TAG-DHA) as well as control chow diet were used to evaluate the potency of the two alternative DHA carriers over a 60-day feeding period. Fatty acid profiles were determined in erythrocytes and plasma lipids at time 0, 7, 14, 28, 35 and 49 days of the experimental period and in retina, cortex, hypothalamus, and hippocampus at 60 days. The assessment of the longitudinal evolution of DHA in erythrocyte and plasma lipids suggest that PL-DHA and MAG-DHA are efficient carriers of dietary DHA when compared to conventional DHA oil (TAG-DHA). Under these experimental conditions, both PL-DHA and MAG-DHA led to higher incorporations of DHA erythrocytes lipids compared to TAG-DHA group. After 60 days of supplementation, statistically significant increase in DHA level incorporated in neural tissues analyzed were observed in the DHA groups compared with the control. The mechanism explaining hypothetically the difference observed in circulatory lipids is discussed.
Subject(s)
Fatty Acids/pharmacokinetics , Monoglycerides/blood , Phospholipids/blood , Triglycerides/blood , Animals , Biological Availability , Body Composition , Diet , Dietary Fats/administration & dosage , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Erythrocytes/metabolism , Fatty Acids/administration & dosage , Fatty Acids/blood , Male , Monoglycerides/administration & dosage , Phospholipids/administration & dosage , Rats , Rats, Wistar , Sample Size , Soybean Oil/administration & dosage , Sunflower Oil/administration & dosage , Triglycerides/administration & dosage , Weight GainABSTRACT
The objective of the study was to develop a self-microemulsifying drug delivery system (SMEDDS), also known as microemulsion preconcentrate, for oral delivery of five poorly water-soluble nutraceuticals or bioactive agents, namely, vitamin A, vitamin K2, coenzyme Q10, quercetin and trans-resveratrol. The SMEDDS contained a 1:1 mixture (w/w) of Capmul MCM NF (a medium chain monoglyceride) and Captex 355 EP/NF (a medium chain triglyceride) as the hydrophobic lipid and Tween 80 (polysorbate 80) as the hydrophilic surfactant. The lipid and surfactant were mixed at 50:50 w/w ratio. All three of the SMEDDS components have GRAS or safe food additive status. The solubility of nutraceuticals was determined in Capmul MCM, Captex 355, Tween 80, and the SMEDDS (microemulsion preconcentrate mixture). The solubility values of vitamin A palmitate, vitamin K2, coenzyme Q10, quercetin, and trans-resveratrol per g of SMEDDS were, respectively, 500, 12, 8, 56, and 87 mg. Appropriate formulations of nutraceuticals were prepared and filled into hard gelatin capsules. They were then subjected to in vitro dispersion testing using 250 mL of 0.01 N HCl in USP dissolution apparatus II. The dispersion test showed that all SMEDDS containing nutraceuticals dispersed spontaneously to form microemulsions after disintegration of capsule shells with globule size in the range of 25 to 200 nm. From all formulations, except that of vitamin K2, >80-90% nutraceuticals dispersed in 5-10 min and there was no precipitation of compounds during the test period of 120 min. Some variation in dispersion of vitamin K2 was observed due to the nature of the material used (vitamin K2 pre-adsorbed onto calcium phosphate). The present report provides a simple and organic cosolvent-free lipid-based SMEDDS for the oral delivery of poorly water-soluble nutraceuticals. Although a 50:50 w/w mixture of lipid to surfactant was used, the lipid content may be increased to 70:30 without compromising the formation of microemulsion.
Subject(s)
Dietary Supplements/standards , Diglycerides/administration & dosage , Glycerides/chemistry , Lipids/chemistry , Monoglycerides/administration & dosage , Polysorbates/chemistry , Surface-Active Agents/chemistry , Triglycerides/chemistry , Diglycerides/chemistry , Drug Compounding , Drug Delivery Systems , Monoglycerides/chemistry , Polysorbates/administration & dosage , Solubility , WaterABSTRACT
The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of â¼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques.