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1.
J Nutr Sci Vitaminol (Tokyo) ; 70(3): 273-279, 2024.
Article in English | MEDLINE | ID: mdl-38945893

ABSTRACT

The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical performance-muscle strength, agility and muscle power-in healthy young adults. The study was designed as a randomized, double-blind, and placebo-controlled trial. Twenty healthy young adults received either an MFGM powder containing 1.6 g of fat and 160 mg of sphingomyelin or an isocaloric placebo powder daily throughout 4 wk of power or agility training. Physical performance tests and body composition measurements were conducted before and after the 4-wk intervention. Ingestion of MFGM did not affect isometric or isokinetic muscle strength, but it was associated with a greater increase in vertical jump peak power compared with placebo. There were no significant changes in body weight or lean body mass during the intervention period in either group, and no significant differences between groups. We conclude that daily MFGM supplementation combined with exercise training has the potential to improve physical performance in young adults; however, further studies with larger sample sizes should be conducted to obtain more evidence supporting achievement of improved physical performance through MFGM supplementation.


Subject(s)
Body Composition , Dietary Supplements , Exercise , Glycolipids , Glycoproteins , Lipid Droplets , Muscle Strength , Humans , Double-Blind Method , Glycolipids/administration & dosage , Glycolipids/pharmacology , Glycoproteins/administration & dosage , Male , Young Adult , Female , Muscle Strength/drug effects , Exercise/physiology , Pilot Projects , Adult , Physical Functional Performance , Body Weight , Sphingomyelins/administration & dosage , Muscle, Skeletal/physiology , Muscle, Skeletal/drug effects
2.
J Mater Chem B ; 9(1): 147-158, 2021 01 07.
Article in English | MEDLINE | ID: mdl-33226396

ABSTRACT

Pore-forming toxins (PFTs), the most common virulence proteins, are promising therapeutic keys in bacterial infections. CAL02, consisting of sphingomyelin (Sm) and containing a maximum ratio of cholesterol (Ch), has been applied to sequester PFTs. However, Sm, a saturated phospholipid, leads to structural rigidity of the liposome, which does not benefit PFT combination. Therefore, in order to decrease the membrane rigidity and improve the fluidity of liposomes, we have introduced an unsaturated phospholipid, phosphatidylcholine (Pc), to the saturated Sm. In this report, a soft nanoliposome (called CSPL), composed of Ch, Sm and Pc, was artificially prepared. In order to further improve its antibacterial effect, vancomycin (Van) was loaded into the hydrophilic core of CSPL, where Van can be released radically at the infectious site through transmembrane pores formed by the PFTs in CSPL. This soft Van@CSPL nanoliposome with detoxification/drug release was able to inhibit the possibility of antibiotic resistance and could play a better role in treating severe invasive infections in mice.


Subject(s)
Anti-Bacterial Agents/metabolism , Cholesterol/metabolism , Explosive Agents/metabolism , Nanoparticles/metabolism , Sphingomyelins/metabolism , Staphylococcal Skin Infections/metabolism , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/metabolism , Cholesterol/administration & dosage , Explosive Agents/administration & dosage , Female , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Liposomes , Mice , Nanoparticles/administration & dosage , Sphingomyelins/administration & dosage , Staphylococcal Skin Infections/drug therapy , Staphylococcus aureus/drug effects , Staphylococcus aureus/metabolism , Virulence/drug effects , Virulence/physiology
3.
Curr Drug Deliv ; 17(9): 806-814, 2020.
Article in English | MEDLINE | ID: mdl-32735519

ABSTRACT

AIM: This study aimed to investigate the existence of phospholipase-A (PLA) activity in Soluble L. major Antigens (SLA) because of no reports for it so far. Liposomes were used as sensors to evaluate PLA activity. OBJECTIVES: Liposomal SLA consisting of Egg Phosphatidylcholine (EPC) or Sphingomyelin (SM) were prepared by two different methods in different pH or temperatures and characterized by Dynamic Light Scattering (DLS) and Thin Layer Chromatography (TLC). METHODS: Lipid hydrolysis led to the disruption of EPC liposomal SLA in both methods but the Film Method (FM) produced more stable liposomes than the Detergent Removal Method (DRM). RESULT: The preparation of EPC liposomal SLA at pH 6 via FM protected liposomes from hydrolysis to some extent for a short time. EPC liposomes but not SM liposomes were disrupted in the presence of SLA. CONCLUSION: Therefore, a phospholipid without ester bond such as SM should be utilized in liposome formulations containing PLA as an encapsulating protein.


Subject(s)
Leishmania major/enzymology , Leishmaniasis Vaccines/chemistry , Leishmaniasis, Cutaneous/prevention & control , Phospholipases A/metabolism , Protozoan Proteins/chemistry , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/metabolism , Antigens, Protozoan/administration & dosage , Antigens, Protozoan/chemistry , Antigens, Protozoan/metabolism , Drug Compounding/methods , Drug Stability , Enzyme Assays , Humans , Hydrogen-Ion Concentration , Hydrolysis , Leishmania major/immunology , Leishmaniasis Vaccines/administration & dosage , Leishmaniasis Vaccines/metabolism , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Liposomes/chemistry , Liposomes/metabolism , Phosphatidylcholines/administration & dosage , Phosphatidylcholines/metabolism , Phospholipases A/isolation & purification , Protozoan Proteins/administration & dosage , Protozoan Proteins/metabolism , Sphingomyelins/administration & dosage , Sphingomyelins/metabolism
4.
J Nutr Biochem ; 79: 108351, 2020 05.
Article in English | MEDLINE | ID: mdl-32007663

ABSTRACT

Milk sphingomyelin (SM), a polar lipid (PL) component of milk fat globule membranes, is protective against dyslipidemia. However, it is unclear whether ingestion of milk PLs protect against atherosclerosis. To determine this, male LDLr-/- mice (age 6 weeks) were fed ad libitum either a high-fat, added-cholesterol diet (CTL; 45% kcal from fat, 0.2% cholesterol by weight; n=15) or the same diet supplemented with 1% milk PL (1% MPL; n=15) or 2% milk PL (2% MPL; n=15) added by weight from butter serum. After 14 weeks on diets, mice fed 2% MPL had significantly lower serum cholesterol (-51%) compared to CTL (P<.01), with dose-dependent effects in lowering VLDL- and LDL-cholesterol. Mice fed 2% MPL displayed lower inflammatory markers in the serum, liver, adipose and aorta. Notably, milk PLs reduced atherosclerosis development in both the thoracic aorta and the aortic root, with 2% MPL-fed mice having significantly lower neutral lipid plaque size by 59% (P<.01) and 71% (P<.02) compared to CTL, respectively. Additionally, the 2% MPL-fed mice had greater relative abundance of Bacteroidetes, Actinobacteria and Bifidobacterium, and lower Firmicutes in cecal feces compared to CTL. Milk PL feeding resulted in significantly different microbial communities as demonstrated by altered beta diversity indices. In summary, 2% MPL strongly reduced atherogenic lipoprotein cholesterol, modulated gut microbiota, lowered inflammation and attenuated atherosclerosis development. Thus, milk PL content may be important to consider when choosing dairy products as foods for cardiovascular disease prevention.


Subject(s)
Atherosclerosis/prevention & control , Cholesterol/metabolism , Gastrointestinal Microbiome/drug effects , Lipoproteins/metabolism , Milk/chemistry , Sphingomyelins/pharmacology , Animals , Atherosclerosis/metabolism , Cholesterol/blood , Cholesterol, Dietary/pharmacology , Diet, High-Fat , Diet, Western , Feces/microbiology , Inflammation/metabolism , Lipoproteins/blood , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Milk/metabolism , Plaque, Atherosclerotic/metabolism , Receptors, LDL/metabolism , Sphingomyelins/administration & dosage
5.
Nutr Neurosci ; 23(12): 931-945, 2020 Dec.
Article in English | MEDLINE | ID: mdl-30806182

ABSTRACT

During the development of the central nervous system, oligodendrocytes (OLs) are responsible for myelination, the formation of the myelin sheath around axons. This process enhances neuronal connectivity and supports the maturation of emerging cognitive functions. In humans, recent evidence suggests that early life nutrition may affect myelination. In the present study, we investigated the impact of a blend containing docosahexaenoic acid, arachidonic acid, vitamin B12, vitamin B9, iron and sphingomyelin, or each of these nutrients individually, on oligodendrocyte precursor cells (OPCs) proliferation and maturation into OLs as well as their myelinating properties. By using an in vitro model, developed to study each step of myelination, we found that the nutrient blend increased the number of OPCs and promoted their differentiation and maturation into OLs, as measured by quantifying A2B5 positive cells, myelin-associated glycoprotein (MAG) positive cells and area, myelin binding protein (MBP) positive cells and area, respectively. Moreover, measuring myelination by quantifying the overlapping signal between neurofilament and either MAG or MBP revealed a positive effect of the blend on OLs myelinating properties. In contrast, treatment with each individual nutrient resulted in differential effects on the various readouts. This work suggests that dietary intake of these nutrients during early life, might be beneficial for myelination.


Subject(s)
Arachidonic Acid/administration & dosage , Docosahexaenoic Acids/administration & dosage , Folic Acid/administration & dosage , Iron/administration & dosage , Myelin Sheath/drug effects , Neurons/drug effects , Sphingomyelins/administration & dosage , Vitamin B 12/administration & dosage , Animals , Cells, Cultured , Myelin Sheath/physiology , Neurons/physiology , Oligodendrocyte Precursor Cells/drug effects , Oligodendrocyte Precursor Cells/physiology , Rats, Wistar
6.
J Nutr Biochem ; 73: 108224, 2019 11.
Article in English | MEDLINE | ID: mdl-31654895

ABSTRACT

The identification of natural bioactive compounds aimed at promoting optimal gut health and improving lipid metabolism is paramount in the prevention of chronic disease. In this review, we summarize basic science and clinical research examining the protective properties of milk sphingomyelin (SM) against dysfunctional lipid metabolism, gut dysbiosis, and inflammation. Dietary SM dose-dependently reduces the intestinal absorption of cholesterol, triglycerides, and fatty acids in cell culture and rodent studies. Overall, rodent feeding studies show dietary milk SM, milk polar lipid mixtures, and milk fat globule membrane reduce serum and hepatic lipid concentrations. Furthermore, these hypolipidemic effects are observed in some supplementation studies in humans, although the extent of reductions in serum cholesterol is typically smaller and only one trial was conducted with purified SM. Dietary milk SM has been reported to affect the gut microbiota in rodent studies and its hydrolytic product, sphingosine, displays bactericidal activity in vitro. Milk SM may also improve gut barrier function to prevent the translocation of inflammatory gut bacteria-derived molecules. Current evidence from pre-clinical studies indicates that dietary milk SM has protective properties against dysfunctional lipid metabolism, gut dysbiosis, and inflammation. The hypolipidemic effects of milk SM observed in animal studies have been reported in some human studies, although the magnitude of such effects is typically smaller. More research is warranted to clearly define how dietary milk SM influences lipid metabolism, gut microbiota, and inflammation in humans.


Subject(s)
Dysbiosis/prevention & control , Inflammation/prevention & control , Lipid Metabolism/drug effects , Milk/chemistry , Sphingomyelins/administration & dosage , Animals , Cholesterol, Dietary/pharmacokinetics , Diet , Diet, Western , Dietary Fats/pharmacokinetics , Digestion/drug effects , Gastrointestinal Microbiome/drug effects , Humans , Intestinal Absorption/drug effects , Lipids/analysis , Lipids/blood , Liver/chemistry , Liver/drug effects , Sphingomyelins/pharmacokinetics
7.
Int J Nanomedicine ; 14: 3069-3086, 2019.
Article in English | MEDLINE | ID: mdl-31118623

ABSTRACT

Background: Synthetic HDLs (sHDLs), small nanodiscs of apolipoprotein mimetic peptides surrounding lipid bilayers, were developed clinically for atheroma regression in cardiovascular patients. Formation of HDL involves interaction of apolipoprotein A-I (ApoA-I) with phospholipid bilayers and assembly into lipid-protein nanodiscs. Purpose: The objective of this study is to improve understanding of physico-chemical aspects of HDL biogenesis such as the thermodynamics of ApoA-I-peptide membrane insertion, lipid binding, and HDL self-assembly to improve our ability to form homogeneous sHDL nanodiscs that are suitable for clinical administration. Methods: The ApoA-I-mimetic peptide, 22A, was combined with either egg sphingomyelin (eSM) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid vesicles to form sHDL. The sHDL assembly process was investigated through lipid vehicle solubilization assays and characterization of purity, size, and morphology of resulting nanoparticles via gel permeation chromatography (GPC), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Peptide-lipid interactions involved were further probed by sum frequency generation (SFG) vibrational spectroscopy and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). The pharmacokinetics of eSM-sHDL and POPC-sHDL nanodiscs were investigated in Sprague Dawley rats. Results: sHDL formation was temperature-dependent, with spontaneous formation of sHDL nanoparticles occurring only at temperatures exceeding lipid transition temperatures as evidenced by DLS, GPC, and TEM characterization. SFG and ATR-FTIR spectroscopy findings support a change in peptide-lipid bilayer interactions at temperatures above the lipid transition temperature. Lipid-22A interactions were stronger with eSM than with POPC, which resulted in the formation of more homogeneous sHDL nanoparticles with longer in vivo circulation time as evidenced the PK study. Conclusion: Physico-chemical characteristics of sHDL are in part determined by phospholipid composition. Optimization of phospholipid composition may be utilized to improve the stability and homogeneity of sHDL.


Subject(s)
Apolipoprotein A-I/metabolism , Lipoproteins, HDL/metabolism , Nanoparticles/chemistry , Peptides/metabolism , Phospholipids/metabolism , Amino Acid Sequence , Animals , Apolipoprotein A-I/chemistry , Dynamic Light Scattering , Kinetics , Lipid Bilayers/chemistry , Lipoproteins, HDL/chemistry , Male , Nanoparticles/ultrastructure , Peptides/chemistry , Peptides/pharmacokinetics , Phosphatidylcholines/administration & dosage , Rats, Sprague-Dawley , Solubility , Spectroscopy, Fourier Transform Infrared , Sphingomyelins/administration & dosage , Thermodynamics , Vibration
8.
J Nutr Biochem ; 65: 128-138, 2019 03.
Article in English | MEDLINE | ID: mdl-30685581

ABSTRACT

Milk polar lipids (MPL) are specifically rich in milk sphingomyelin (MSM) which represents 24% of MPL. Beneficial effects of MPL or MSM have been reported on lipid metabolism, but information on gut physiology is scarce. Here we assessed whether MPL and MSM can impact tight junction expression. Human epithelial intestinal Caco-2/TC7 cells were incubated with mixed lipid micelles devoid of MSM (Control) or with 0.2 or 0.4 mM of MSM via pure MSM or via total MPL. C57Bl/6 mice received 5 or 10 mg of MSM via MSM or via MPL (oral gavage); small intestinal segments were collected after 4 h. Impacts on tight junction and cytokine expressions were assessed by qPCR; IL-8 and IL-8 murine homologs (Cxcl1, Cxcl2) were analyzed. In vitro, MSM increased tight junction expression (Occludin, ZO-1) vs Control, unlike MPL. However, no differences were observed in permeability assays (FITC-dextran, Lucifer yellow). MSM increased the secretion and gene expression of IL-8 but not of other inflammatory cytokines. Moreover, cell incubation with IL-8 induced an overexpression of tight junction proteins. In mice, mRNA level of Cxcl1 and Cxcl2 in the ileum were increased after gavage with MSM vs NaCl but not with MPL. Altogether, these results suggest a specific action of MSM on intestinal tight junction expression, possibly mediated by IL-8. Our study provides clues to shed light on the beneficial effects of MPL on intestinal functions and supports the need for further mechanistic exploration of the direct vs indirect effects of MSM and IL-8 on the gut barrier.


Subject(s)
Interleukin-8/metabolism , Lipids/pharmacology , Milk/chemistry , Tight Junctions/metabolism , Animals , Caco-2 Cells , Chemokine CXCL1/genetics , Chemokine CXCL2/genetics , Dose-Response Relationship, Drug , Gene Expression Regulation/drug effects , Humans , Intestines/cytology , Lipids/chemistry , Male , Mice, Inbred C57BL , Sphingomyelins/administration & dosage , Sphingomyelins/pharmacology , Tight Junction Proteins/genetics
9.
Exp Dermatol ; 28 Suppl 1: 28-31, 2019 02.
Article in English | MEDLINE | ID: mdl-30698876

ABSTRACT

Excessive exposure to ultraviolet (UV) radiation can chemically alter biological molecules and is one of the major environmental health risks with potential to damage the structure and function of the skin. Numerous dietary supplements are known to optimize the skin's defenses against radiation exposure. Several studies in which the beneficial roles of functional food components, that can protect against UV-induced skin damage, have been demonstrated. Supplemental dietary sphingomyelin maintains covalently bound ω-hydroxy ceramides to avert skin barrier defects after UVB irradiation. The oral administration of collagen hydrolysates has been shown to limit decreases in skin elasticity via increases in the dermal hyaluronic acid content. Milk fermented with lactic acid bacteria has been shown to augment DNA repair mechanisms and improve skin immunity in the aftermath of UVB damage. Furthermore, long-term ingestion of fermented milk containing lactic acid bacteria, collagen hydrolysates and sphingomyelin increases the minimal erythema dose (MED) in human subjects with moderate sunburn or redness and tanned skin after exposure to UV solar radiation. Thus, products containing these functional food components are one means by which the adverse effects of UV radiation on the skin can be mitigated.


Subject(s)
Functional Food , Skin/radiation effects , Sunburn/diet therapy , Sunburn/prevention & control , Ultraviolet Rays/adverse effects , Administration, Oral , Adult , Animals , Collagen/administration & dosage , DNA Repair , Dietary Supplements , Female , Fermented Foods , Humans , Japan , Lactobacillales , Middle Aged , Milk , Randomized Controlled Trials as Topic , Sphingomyelins/administration & dosage , Sunlight
10.
EBioMedicine ; 33: 211-217, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29936135

ABSTRACT

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), typified by the pulse-field type USA300, is an emerging endemic pathogen that is spreading rapidly among healthy people. CA-MRSA causes skin and soft tissue infections, life-threatening necrotizing pneumonia and sepsis, and is remarkably resistant to many antibiotics. Here we show that engineered liposomes composed of naturally occurring sphingomyelin were able to sequester cytolytic toxins secreted by USA300 and prevent necrosis of human erythrocytes, peripheral blood mononuclear cells and bronchial epithelial cells. Mass spectrometric analysis revealed the capture by liposomes of phenol-soluble modulins, α-hemolysin and other toxins. Sphingomyelin liposomes prevented hemolysis induced by pure phenol-soluble modulin-α3, one of the main cytolytic components in the USA300 secretome. In contrast, sphingomyelin liposomes harboring a high cholesterol content (66 mol/%) were unable to protect human cells from phenol-soluble modulin-α3-induced lysis, however these liposomes efficiently sequestered the potent staphylococcal toxin α-hemolysin. In a murine cutaneous abscess model, a single dose of either type of liposomes was sufficient to significantly decrease tissue dermonecrosis. Our results provide further insights into the promising potential of tailored liposomal therapy in the battle against infectious diseases.


Subject(s)
Bacterial Proteins/antagonists & inhibitors , Methicillin-Resistant Staphylococcus aureus/metabolism , Sphingomyelins/administration & dosage , Staphylococcal Skin Infections/therapy , Animals , Cell Line , Community-Acquired Infections , Disease Models, Animal , Hemolysin Proteins/antagonists & inhibitors , Humans , Liposomes , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Necrosis , Sphingomyelins/pharmacology , Treatment Outcome
11.
PLoS One ; 12(12): e0189523, 2017.
Article in English | MEDLINE | ID: mdl-29240800

ABSTRACT

Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans. As SM has a choline head group, we ask in this study if dietary SM accelerates atherosclerotic lesion development by increasing circulating SM and TMAO levels. Three studies were performed: (Study 1) C57BL/6 mice were maintained on a high fat diet with or without SM supplementation for 4 weeks prior to quantification of serum TMAO and SM levels; (Study 2) atherosclerosis was studied in apoE-/- mice after 16 weeks of a high fat diet without or with SM supplementation and (Study 3) apoE-/- mice were maintained on a chow diet for 19 weeks without or with SM supplementation and antibiotic treatment prior to quantification of atherosclerotic lesions and serum TMAO and SM levels. SM consumption did not increase circulating SM levels or atherosclerosis in high fat-fed apoE-/- mice. Serum TMAO levels in C57BL/6 mice were low and had no effect atherosclerosis lesion development. Dietary SM supplementation significantly reduced atherosclerotic lesion area in the aortic arch of chow-fed apoE-/- mice. This study establishes that dietary SM does not affect circulating SM levels or increase atherosclerosis in high fat-fed apoE-/- mice, but it is anti-atherogenic in chow-fed apoE-/- mice.


Subject(s)
Atherosclerosis/pathology , Dietary Supplements , Sphingomyelins/administration & dosage , Animals , Apolipoproteins E/genetics , Atherosclerosis/blood , Diet, High-Fat , Methylamines/blood , Mice , Mice, Inbred C57BL , Mice, Knockout , Sphingomyelins/blood
13.
Lipids ; 52(5): 423-431, 2017 05.
Article in English | MEDLINE | ID: mdl-28357619

ABSTRACT

Supplementation with sphingomyelin has been reported to prevent disease and maintain good health. However, intact sphingomyelin and ceramides are poorly absorbed compared with glycerolipids. Therefore, if the bioavailability of dietary sphingomyelin can be increased, supplementation would be more effective at lower doses. The aim of this study in rats was to evaluate the effect of fermented milk on the bioavailability of dietary sphingomyelin in rats. After the rats had fasted for 15 h, test solutions were administrated orally. Blood samples were collected from the tail vein before and 90, 180, 270, and 360 min after administration. Compared with sphingomyelin/milk phospholipids concentrate (MPL) alone, co-ingestion of sphingomyelin/MPL with fermented milk caused an approximate twofold significant increase in serum ceramides containing d16:1 sphingosine with 16:0, 22:0, 23:0 and 24:0 fatty acids, which was derived from the ingested sphingomyelin. While nonfat milk also increased the serum levels of these ceramides, fermented milk was more effective. Co-ingestion of the upper layer of fermented milk or exopolysaccharide concentrate prepared from fermented milk significantly increased serum ceramide levels. X-ray diffraction analysis also showed addition of fermented milk or EPS concentrate to sphingomyelin eliminated the characteristic peak of sphingomyelin. This study demonstrated for the first time that co-ingestion of dietary sphingomyelin and fermented milk, compared with ingestion of dietary sphingomyelin alone, caused a significant increase in the absorption of sphingomyelin. Our results indicate exopolysaccharides in fermented milk may contribute to inhibition of sphingomyelin crystallization, resulting in enhanced absorption of dietary sphingomyelin in rats.


Subject(s)
Fermentation , Lactobacillales/physiology , Milk/chemistry , Sphingomyelins/pharmacokinetics , Administration, Oral , Animals , Biological Availability , Ceramides/blood , Fatty Acids/blood , Male , Phospholipids/blood , Rats , Rats, Sprague-Dawley , Sphingomyelins/administration & dosage
14.
Int J Urol ; 24(4): 262-271, 2017 04.
Article in English | MEDLINE | ID: mdl-28258657

ABSTRACT

Over the past two decades, there has been lot of interest in the use of liposomes as lipid-based biocompatible carriers for drugs administered by the intravesical route. The lipidic bilayer structure of liposomes facilitates their adherence to the apical membrane surface of luminal cells in the bladder, and their vesicular shape allows them to co-opt the endocytosis machinery for bladder uptake after instillation. Liposomes have been shown to enhance the penetration of both water-soluble and insoluble drugs, toxins, and oligonucleotides across the bladder epithelium. Empty liposomes composed entirely of the endogenous phospholipid, sphingomyelin, could counter mucosal inflammation and promote wound healing in patients suffering from interstitial cystitis. Recent clinical studies have tested multilamellar liposomes composed entirely of sphingomyelin as a novel intravesical therapy for interstitial cystitis. In addition, liposomes have been used as a delivery platform for the instillation of botulinum toxin in overactive bladder patients. The present review discusses the properties of liposomes that are important for their intrinsic therapeutic effect, summarizes the recently completed clinical studies with intravesical liposomes and covers the latest developments in this field.


Subject(s)
Botulinum Toxins/administration & dosage , Cystitis, Interstitial/drug therapy , Drug Carriers/administration & dosage , Sphingomyelins/administration & dosage , Urinary Bladder, Overactive/drug therapy , Administration, Intravesical , Clinical Trials as Topic , Cystitis, Interstitial/epidemiology , Cystitis, Interstitial/etiology , Drug Carriers/chemistry , Endocytosis/drug effects , Humans , Liposomes , Prevalence , Urinary Bladder/metabolism , Wound Healing/drug effects
15.
Theranostics ; 6(13): 2329-2336, 2016.
Article in English | MEDLINE | ID: mdl-27877238

ABSTRACT

Porphyrin-phospholipid (PoP) liposomes can entrap anti-cancer agents and release them in response to near infrared (NIR) light. Doxorubicin, when remotely loaded via an ammonium sulfate gradient at a high drug-to-lipid ratio, formed elongated crystals that altered liposome morphology and could not be loaded into liposomes with higher PoP content. On the other hand, irinotecan could also be remotely loaded but did not form large crystals and did not induce liposome elongation. The loading, stability, and NIR light-triggered release of irinotecan in PoP liposomes was altered by the types of lipids used and the presence of PEGylation. Sphingomyelin, which has been explored previously for liposomal irinotecan, was found to produce liposomes with relatively improved serum stability and rapid NIR light-triggered drug release. PoP liposomes composed from sphingomyelin, cholesterol and 2 molar percent PoP rapidly released irinotecan in vivo in response to NIR irradiation as monitored by intravital microscopy and also induced effective tumor eradication in mice bearing MIA Paca-2 subcutaneous tumor xenografts.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Camptothecin/analogs & derivatives , Drug Carriers/administration & dosage , Liposomes/administration & dosage , Phospholipids/administration & dosage , Porphyrins/administration & dosage , Sphingomyelins/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/pharmacokinetics , Camptothecin/administration & dosage , Camptothecin/pharmacokinetics , Disease Models, Animal , Drug Carriers/chemistry , Heterografts , Infrared Rays , Irinotecan , Mice , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Treatment Outcome , Pancreatic Neoplasms
16.
Food Funct ; 7(9): 3854-67, 2016 Sep 14.
Article in English | MEDLINE | ID: mdl-27501823

ABSTRACT

Purified milk sphingomyelin (SM) was obtained from lipid concentrated butter serum (LC-BS) by successive separations involving solvent fractionation, selective saponification, and silicic acid column chromatography. The SM obtained was given to obese/diabetic KK-A(y) mice and wild-type C57BL/6J mice. SM supplementation significantly increased fecal lipids paralleled with a decrease in non-HDL cholesterol levels in the serum and neutral lipids and in cholesterol levels in the livers of KK-A(y) mice. The reduction of liver lipid levels also resulted in a decrease in the total fatty acid content of the KK-A(y) mice livers, while n-3 fatty acids derived from the conversion of α-linolenic acid (18:3n-3) increased due to SM supplementation. In contrast to the KK-A(y) mice, little change in the serum and liver lipids was observed in wild-type C57BL/6J mice. The present study suggests that SM may be effective only in subjects with metabolic disorders.


Subject(s)
Diabetes Mellitus/metabolism , Diet , Lipid Metabolism/drug effects , Milk/chemistry , Obesity/metabolism , Sphingomyelins/administration & dosage , Animals , Cholesterol/blood , Fatty Acids, Omega-3/metabolism , Feces/chemistry , Lipids/analysis , Lipids/blood , Liver/chemistry , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Obese , alpha-Linolenic Acid/metabolism
17.
Biol Pharm Bull ; 39(5): 786-93, 2016.
Article in English | MEDLINE | ID: mdl-27150148

ABSTRACT

The effects of orally administered sphingomyelin-based liposomes (SM-lipo) on muscle function were investigated in senescence-accelerated mice prone 1 (SAMP1) for the purpose of protection against or treatment of sarcopenia. SM-lipo were prepared by thin lipid-film hydration followed by extrusion. Their spherical shape was observed by transmission electron microscopy. The obtained liposomes were stable in gastric liquid and intestinal fluid models as well as in water. In in vitro tests liposomalization of sphingomyelin significantly increased its transport into human intestinal epithelial Caco-2 cells. In addition, SM-lipo upregulated the proliferation of murine C2C12 myoblasts compared with free sphingomyelin or phosphatidylcholine-based liposomes (PC-lipo). Finally, SM-lipo orally administered to SAMP1 for 10 weeks significantly increased quadriceps femoris weight and extended swimming time until fatigue compared with PC-lipo. In conclusion, these findings indicate that SM-lipo are well absorbed into the body and improve muscle weakness caused by senescence.


Subject(s)
Sarcopenia/drug therapy , Sphingomyelins/administration & dosage , Aging , Animals , Caco-2 Cells , Cell Line , Cell Proliferation/drug effects , Humans , Liposomes , Male , Mice , Muscle Weakness/drug therapy , Myoblasts/cytology , Myoblasts/drug effects , Sphingomyelins/pharmacokinetics , Sphingomyelins/therapeutic use
18.
PLoS One ; 10(8): e0136377, 2015.
Article in English | MEDLINE | ID: mdl-26302442

ABSTRACT

Exposure to ultraviolet-B (UV-B) irradiation causes skin barrier defects. Based on earlier findings that milk phospholipids containing high amounts of sphingomyelin (SM) improved the water content of the stratum corneum (SC) in normal mice, here we investigated the effects of dietary milk SM on skin barrier defects induced by a single dose of UV-B irradiation in hairless mice. Nine week old hairless mice were orally administrated SM (146 mg/kg BW/day) for a total of ten days. After seven days of SM administration, the dorsal skin was exposed to a single dose of UV-B (20 mJ/cm2). Administration of SM significantly suppressed an increase in transepidermal water loss and a decrease in SC water content induced by UV-B irradiation. SM supplementation significantly maintained covalently-bound ω-hydroxy ceramide levels and down-regulated mRNA levels of acute inflammation-associated genes, including thymic stromal lymphopoietin, interleukin-1 beta, and interleukin-6. Furthermore, significantly higher levels of loricrin and transglutaminase-3 mRNA were observed in the SM group. Our study shows for the first time that dietary SM modulates epidermal structures, and can help prevent disruption of skin barrier function after UV-B irradiation.


Subject(s)
Milk Proteins/administration & dosage , Skin Abnormalities/diet therapy , Skin/drug effects , Sphingomyelins/administration & dosage , Animals , Humans , Mice , Mice, Hairless , Skin/radiation effects , Skin Abnormalities/pathology , Ultraviolet Rays/adverse effects , Water/metabolism
19.
J Dairy Sci ; 98(10): 6706-12, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26277314

ABSTRACT

Sphingomyelin (SM), an essential phospholipid for the skin, is contained largely in the milk fat globule membrane surrounding milk fat, concentrated fractions of which are also generated concurrently during the manufacture of dairy products. Such an SM-containing milk phospholipid concentrate (SM-MPC) is useful for investigating the benefits of dietary SM. Here, we examined the effect of consuming SM-MPC on the condition of skin in a double-blind, placebo-controlled, randomized trial. Ninety-six healthy subjects aged 20 to 39 yr with low skin hydration were randomly assigned to 3 groups: a high-SM group supplemented with SM-MPC at a dose equivalent to 10 mg/d of SM, a low-SM group supplemented with SM-MPC equivalent to 5 mg/d of SM, and a placebo group fed a vehicle composed of olive oil and beeswax. During daily supplementation for 12 wk, parameters related to the condition of skin were evaluated at baseline and every 3 wk. Skin hydration at the heel was significantly increased at wk 9 and 12 in the low-SM group compared with the placebo group. Skin elasticity in the region below the eye was significantly increased at wk 9 in the high-SM group versus placebo. Questionnaire-based subjective perceptions of skin conditions were significantly improved for facial skin moisture at wk 3 and 12, and in the wrinkle around the eyes at wk 9 and 12 in the high-SM group versus placebo. Our results indicate that constant and long-term supplementation with SM-MPC is capable of improving the general condition of skin.


Subject(s)
Phospholipids/pharmacology , Sebum/metabolism , Skin Physiological Phenomena/drug effects , Sphingomyelins/pharmacology , Water Loss, Insensible/drug effects , Adult , Animals , Dietary Supplements/analysis , Double-Blind Method , Female , Humans , Male , Milk/chemistry , Phospholipids/administration & dosage , Sebum/drug effects , Sphingomyelins/administration & dosage , Young Adult
20.
Lipids ; 50(10): 987-96, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26233817

ABSTRACT

Supplementation with sphingomyelin has been reported to have beneficial effects on disease prevention and health maintenance. However, compared with glycerolipids, intact sphingomyelin and ceramides are poorly absorbed. Therefore, if the bioavailability of dietary sphingomyelin is increased, then the dose administered can be reduced. This study was designed to identify molecular species of ceramide in rat lymph after the ingestion of milk sphingomyelin, and to compare the effect of purified sphingomyelin with milk phospholipids concentrate (MPL, 185 mg sphingomyelin/g) on lymphatic absorption of milk sphingomyelin. Lymph was collected hourly for 6 h from lymph-cannulated rats (n = 8/group) after the administration of a control emulsion (triolein, bovine serum albumin, and sodium taurocholate), a sphingomyelin emulsion (control + purified sphingomyelin), or a MPL emulsion (control + MPL). Molecular species of ceramide in lymph were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Molecular species of ceramide, containing not only d18:1, but also d17:1 and d16:1 sphingosine with 16:0, 22:0, 23:0, and 24:0 fatty acids (specific to milk sphingomyelin), were increased in rat lymph after the administration of milk sphingomyelin. Their molecular species were similar to those of dietary milk sphingomyelin. Recovery of ceramide moieties from dietary sphingomyelin was 1.28- to 1.80-fold significantly higher in the MPL group than in the sphingomyelin group. Our results demonstrated that dietary sphingomyelin from milk was transported to lymph as molecular species of ceramide hydrolyzed from milk sphingomyelin and co-ingestion of sphingomyelin with glycerophospholipids enhanced the bioavailability of dietary sphingomyelin.


Subject(s)
Dietary Fats/pharmacokinetics , Lymph/chemistry , Milk/chemistry , Phospholipids/administration & dosage , Sphingomyelins/pharmacokinetics , Animals , Biological Availability , Ceramides/pharmacokinetics , Dietary Fats/administration & dosage , Intestinal Absorption/drug effects , Male , Milk/metabolism , Rats , Rats, Sprague-Dawley , Sphingomyelins/administration & dosage
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