Chemistry and Physics of Lipids最新文献

{"title":"In silico and in vitro investigation of bile salts as coformers for edaravone coamorphous dispersion- Part I","authors":"Dhrumi Patel,&nbsp;Sarika Wairkar","doi":"10.1016/j.chemphyslip.2023.105302","DOIUrl":"10.1016/j.chemphyslip.2023.105302","url":null,"abstract":"<div><p><span><span>In the present study, we aimed to design the spray-dried coamorphous dispersion (COAM) of a neuroprotective agent-edaravone (EDR) with bile salts<span> to improve oral bioavailability. After the initial screening of different bile salts, EDR-sodium taurocholate (NaTC) COAM showed 4-fold solubility than a pure drug in 1–7 pH range. </span></span>In silico studies<span> to select coformer for COAM revealed a narrow energy gap, easy charge transfer and high chemical reactivity between EDR and NaTC. The optimized EDR-NaTC COAM in a 1:1 molar ratio was characterized for solid state characterizations and </span></span>in vitro release<span><span><span><span> study. Hydrogen bond formation between the </span>pyrazolone<span> ring of EDR and the -OH group of the phenanthrene<span> ring of NaTC was observed in the ATR-FTIR spectra of COAM. The DSC and </span></span></span>XRPD<span> data indicated the formation of an amorphous halo, whereas SEM photographs demonstrated porous, spherical particles of COAM. The pH-independent in vitro drug release of COAM was observed in 0.1 N HCl, pH 4.5 and 6.8 buffers which was 3-fold higher than EDR. The COAM was stable for 6 months at accelerated condition without showing a change in drug content or devitrification (Initial: 98.002 ± 0.942 %; Accelerated condition: 97.016 ± 1.110 %). Although coamorphous form and </span></span>hydrogen bonding<span><span> between EDR-NaTC dispersion were primarily responsible for improved dissolution, NaTC, an exceptional surfactant, has also contributed to it. Moreover, its exclusive structural characteristics could prevent the recrystallization of the drug in supersaturated conditions of the GIT and also minimize the effect of food on </span>oral absorption of EDR which will be studied in animals in the second part of this work.</span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"253 ","pages":"Article 105302"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymeric nanoparticles containing babassu oil: A proposed drug delivery system for controlled release of hydrophilic compounds","authors":"João Vitor Raupp de Oliveira ,&nbsp;Pedro Leardin Silveira ,&nbsp;Gabriela Spingolon ,&nbsp;Gabriel Antonio Lopes Alves ,&nbsp;Flávia Pires Peña ,&nbsp;Tanira Alessandra Silveira Aguirre","doi":"10.1016/j.chemphyslip.2023.105304","DOIUrl":"10.1016/j.chemphyslip.2023.105304","url":null,"abstract":"<div><p><span><span><span>Different drug delivery systems are prepared on the nanoscale to improve performance in drug formulations, such as nanoparticles<span> or nanoemulsions<span>. Polymeric nanoparticles have been used to encapsulate drugs for several applications because of some characteristics of these carriers to control drug delivery, transport molecules to a specific tissue, protect the drugs, and increase drug bioavailability. When using nanocapsules, an essential parameter for encapsulating different hydrophilic or lipophilic molecules is the characteristics of the core. Babassu oil (BBS) is a </span></span></span>natural product<span><span> from Brazil, composed majoritary of short-chain saturated fatty acids. BBS has an elevated hydrophilic-lipophilic balance (HLB), which may promote interaction of the oil with hydrophilic drugs. In this study, we developed and characterized particles containing babassu oil, solely or combined with sorbitan monostearate (Span® 60) or medium chain </span>triglycerides<span> (MCT) in the core to test different HLB and evaluated the encapsulation of a model hydrophilic molecule. Different techniques were used to characterize all formulations in terms of size and distribution, and in vitro drug release by dialysis technique was performed. The BBS was also characterized and presented 46,05 ± 1,11% and 15,38 ± 0,06% of lauric and myristic acid, respectively; saponification<span> index of 248.87 ± 0.64 mg of KOH per gram of BBS, and no oxidation of the oil was indicated by means of peroxide index. Evaporation of solvent carried in the room or reduced pressure influenced the particles' size; nevertheless, all had a z-average smaller than 220 nm. Nanoparticles with a ratio among aqueous phase and organic phase of 2.8 were considered adequate to encapsulate diclofenac </span></span></span></span>sodium. The particles size/zeta potential were 189.83 ± 7.86 nm / − 10.39 ± 2.52 mV, 156.80 ± 4.77 nm / − 9.27 ± 4.61 mV, and 168.87 ± 5.22 nm / − 12.98 ± 4.66 mV to nanoparticles prepared with BBS + MCT, BBS, and BBS + Span® 60, respectively. All formulations exhibited an amount of drug content close to the theoretical amount (1.0 mg mL</span>⁻¹<span>), and no difference was observed in the release profile among the three nanoparticles. Formulation containing only babassu oil in the core displayed 66.78 ± 15.62% of encapsulation efficiency to diclofenac sodium, the highest value among all formulations tested. Results demonstrate that the innovative nanoparticles containing BBS promote the encapsulation of a model hydrophilic molecule, and other components can be evaluated to change the core’s hydrophilicity and encapsulation of molecules.</span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"253 ","pages":"Article 105304"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A lipid activatable fluorescence probe for atherosclerosis imaging","authors":"Bing Han ,&nbsp;Ming Bai ,&nbsp;Jin Zhang ,&nbsp;Xiaoxue Meng ,&nbsp;Zheng Zhang","doi":"10.1016/j.chemphyslip.2022.105272","DOIUrl":"10.1016/j.chemphyslip.2022.105272","url":null,"abstract":"<div><p>Lipid has been considered as a promising target for atherosclerosis diagnosis. However, there is still no available lipid imaging technology in clinic. Herein, we have prepared a fluorescence probe TPN for lipid-specific imaging in atherosclerosis. TPN exhibited extremely weak emission in water, while its emission was significantly enhanced in lipid environment at 666 nm. Meanwhile, TPN has showed low cytotoxicity and great intracellular lipid-specific fluorescence imaging ability with high signal-to-noise ratio. Importantly, TPN could specifically stain the lipid in atherosclerotic plaque, which would be a potential candidate for the diagnosis of atherosclerosis.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"253 ","pages":"Article 105272"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9947270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ionizable lipids penetrate phospholipid bilayers with high phase transition temperatures: perspectives from free energy calculations","authors":"Inna Ermilova,&nbsp;Jan Swenson","doi":"10.1016/j.chemphyslip.2023.105294","DOIUrl":"10.1016/j.chemphyslip.2023.105294","url":null,"abstract":"<div><p>The efficacies of modern gene-therapies strongly depend on their contents. At the same time the most potent formulations might not contain the best compounds. In this work we investigated the effect of phospholipids and their saturation on the binding ability of (6<em>Z</em>,9<em>Z</em>,28<em>Z</em>,31<em>Z</em>)-heptatriacont-6,9,28,31-tetraene-19-yl 4-(dimethylamino) butanoate (DLin-MC3-DMA) to model membranes at the neutral pH. We discovered that DLin-MC3-DMA has affinity to the most saturated monocomponent lipid bilayer 1,2-dimyristoyl-<em>sn</em>-glycero-3-phosphocholine (DMPC) and an aversion to the unsaturated one 1,2-dioleoyl-<em>sn</em>-glycero-3-phosphocholine (DOPC). The preference to a certain membrane was also well-correlated to the phase transition temperatures of phospholipid bilayers, and to their structural and dynamical properties. Additionally, in the case of the presence of DLin-MC3-DMA in the membrane with DOPC the ionizable lipid penetrated it, which indicates possible synergistic effects. Comparisons with other ionizable lipids were performed using a model lipid bilayer of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC). Particularly, the lipids heptadecan-9-yl 8-[2-hydroxyethyl-(6-oxo-6-undecoxyhexyl)amino]octanoate (SM-102) and [(4-hydroxybutyl) azanediyl] di(hexane-6,1-diyl) bis(2-hexyldecanoate) (ALC-0315) from modern mRNA-vaccines against COVID-19 were investigated and force fields parameters were derived for those new lipids. It was discovered that ALC-0315 binds strongest to the membrane, while DLin-MC3-DMA is not able to reside in the bilayer center. The ability to penetrate the membrane POPC by SM-102 and ALC-0315 can be related to their saturation, comparing to DLin-MC3-DMA.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"253 ","pages":"Article 105294"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308423000166/pdfft?md5=15a1d1a3c809e93e8b2b6f59454ae110&pid=1-s2.0-S0009308423000166-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9579644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atomic force microscopy study of the complexation of sterols and the glycoalkaloid α-tomatine in Langmuir-Blodgett monolayers","authors":"Bishal Nepal,&nbsp;Keith J. Stine","doi":"10.1016/j.chemphyslip.2023.105293","DOIUrl":"10.1016/j.chemphyslip.2023.105293","url":null,"abstract":"<div><p><span>Glycoalkaloids<span> are secondary metabolites produced by plants that aid in their protection from pathogens and pests. They are known to form 1:1 complexes with 3β-hydroxysterols such as cholesterol causing membrane disruption. So far, the visual evidence showcasing the complexes formed between glycoalkaloids and sterols in monolayers has been mainly restricted to some earlier studies using Brewster angle </span></span>microscopy<span> which were of low resolution showing the formation of floating aggregates of these complexes. This study is aimed at using atomic force microscopy<span><span><span><span> (AFM) for topographic and morphological analysis of the aggregates of these sterol-glycoalkaloid complexes. Langmuir-Blodgett (LB) transfer of mixed monolayers of the glycoalkaloid α-tomatine, sterols, and </span>lipids in varying molar ratios onto mica followed by AFM examination was performed. The AFM method allowed visualization of the aggregation of sterol-glycoalkaloid complexes at nanometer resolution. While aggregation was observed in mixed monolayers of α-tomatine with cholesterol and in mixed monolayers with </span>coprostanol<span><span>, no sign of complexation was observed for the mixed monolayers of epicholesterol and α-tomatine, confirming their lack of interaction found in prior monolayer studies. Aggregates were observed in transferred monolayers of ternary mixtures of α-tomatine with cholesterol and the </span>phospholipids 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or egg </span></span>sphingomyelin (egg SM). The formation of aggregates was found to be less prevalent for mixed monolayers of DMPC and cholesterol containing α-tomatine than it was for mixed monolayers containing egg SM and cholesterol with α-tomatine. The observed aggregates were generally elongated structures, of a width ranging from about 40–70 nm.</span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"252 ","pages":"Article 105293"},"PeriodicalIF":3.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9504063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol stabilization of phospholipid vesicles against bile-induced solubilization","authors":"Patrick Tai ,&nbsp;Andrew J. Clulow ,&nbsp;Ben J. Boyd ,&nbsp;Matt Golding ,&nbsp;Harjinder Singh ,&nbsp;David W. Everett","doi":"10.1016/j.chemphyslip.2023.105289","DOIUrl":"10.1016/j.chemphyslip.2023.105289","url":null,"abstract":"<div><p><span>Sphingomyelin (SM) and cholesterol complex to form functional liquid-ordered (L</span>_o<span><span><span>) domains. It has been suggested that the detergent resistance of these domains plays a key role during gastrointestinal digestion of the milk fat globule membrane (MFGM), which is rich in both SM and cholesterol. Small-angle X-ray scattering was employed to determine the structural alterations that occur when milk sphingomyelin (MSM)/cholesterol, egg sphingomyelin (ESM)/cholesterol, </span>soy<span> phosphatidylcholine<span> (SPC)/cholesterol, and milk fat globule membrane (MFGM) phospholipid/cholesterol model bilayer systems were incubated with bovine bile under physiological conditions. The persistence of diffraction peaks was indicative of multilamellar vesicles of MSM with cholesterol concentrations &gt; 20 % mol, and also for ESM with or without cholesterol. The complexation of ESM with cholesterol is therefore capable of inhibiting the resulting vesicles from disruption by bile at lower cholesterol concentrations than MSM/cholesterol. After subtraction of background scattering by large aggregates in the bile, a </span></span></span>Guinier<span> fitting was used to determine changes in the radii of gyration (R</span></span>_g<span>s) over time for the biliary mixed micelles<span> after mixing the vesicle dispersions with bile. Swelling of the micelles by phospholipid<span> solubilization from vesicles was a function of cholesterol concentration, with less swelling of the micelles occurring as the cholesterol concentration was increased. With 40% mol cholesterol, the R</span></span></span>_gs of the bile micelles mixed with MSM/cholesterol, ESM/cholesterol, and MFGM phospholipid/cholesterol were equal to the control (PIPES buffer + bovine bile), indicating negligible swelling of the biliary mixed micelles.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"252 ","pages":"Article 105289"},"PeriodicalIF":3.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9802127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of redox-sensitive liposomes modified by glycyrrhetinic acid and evaluation of anti-hepatocellular carcinoma activity","authors":"Jie Hu ,&nbsp;Yongsheng Zheng ,&nbsp;Zhijie Wen ,&nbsp;Hudie Fu ,&nbsp;Xuedan Yang ,&nbsp;Xuexin Ye ,&nbsp;Shengpeng Zhu ,&nbsp;Li Kang ,&nbsp;Xiaojun Li ,&nbsp;Xinzhou Yang ,&nbsp;Yan Hu","doi":"10.1016/j.chemphyslip.2023.105292","DOIUrl":"10.1016/j.chemphyslip.2023.105292","url":null,"abstract":"<div><p><span><span>The aim of this study was to construct a bifunctional liposome with hepatic-targeting capacity by modifying with a targeting ligand and an intracellular tumor reduction response functional group to deliver drugs precisely to focal liver tissues and release them in large quantities in hepatocellular carcinoma cells. This could improve drug efficacy and reduce toxic side effects at the same time. First, the bifunctional ligand for liposome was successfully obtained by chemically synthesizing it from the hepatic-targeting </span>glycyrrhetinic acid<span> (GA) molecule, cystamine<span><span><span>, and the membrane component cholesterol. Then the ligand was used to modify the liposomes. The particle size, PDI and </span>zeta potential of the liposomes were determined with a </span>nanoparticle sizer, and the morphology was observed by </span></span></span>transmission electron microscopy<span>. The encapsulation efficiency and drug release behavior were also determined. Further, the stability in vitro of the liposomes and the changes in the simulated reducing environment were determined. Finally, the antitumor activity in vitro and cellular uptake efficiency of the drug-loaded liposomes were investigated by performing cellular assays. The results showed that the prepared liposomes had a uniform particle size of 143.6 ± 2.86 nm with good stability and an encapsulation rate of 84.3 ± 2.1 %. Moreover, the particle size of the liposomes significantly increased and the structure was destroyed in a DTT reducing environment. Cellular experiments showed that the modified liposoes had better cytotoxic effects on hepatocarcinoma cells than both normal liposomes and free drugs. This study has great potential for tumor therapy and provides novel ideas for the clinical use of oncology drugs in dosage forms.</span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"252 ","pages":"Article 105292"},"PeriodicalIF":3.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9504062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the deformability of additivated phosphatidylcholine liposomes: Molecular dynamic regimes and membrane elasticity","authors":"M.B. Marzola Coronel,&nbsp;C.C. Fraenza ,&nbsp;E. Anoardo","doi":"10.1016/j.chemphyslip.2023.105290","DOIUrl":"10.1016/j.chemphyslip.2023.105290","url":null,"abstract":"<div><p><span>Liposomes with enhanced elasticity have been proven to increase the efficiency of drug transport across the skin. The understanding of the background physicochemical processes driving the liposome viscoelastic properties is an essential feature for the design of effective formulations involving different lipids and additive molecules. In this work we use field-cycled nuclear magnetic resonance relaxometry to analyze both the mechanical properties of </span>liposome membranes<span>, and their relationship with the involved molecular dynamics<span>. Different liposomal formulations were considered. We show a correlation between the molecular dynamical regime and mesoscopic physical parameters that define the expected deformability of the vesicles. Results strongly suggest that the purity of the used lipids may influence the elastic properties of the membranes in an appreciable way. Common features in the behaviour of the involved dynamic variables were identified by comparing formulations with surfactants of similar molecular weight.</span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"252 ","pages":"Article 105290"},"PeriodicalIF":3.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9441943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In situ monitoring of galactolipid digestion by infrared spectroscopy in both model micelles and spinach chloroplasts","authors":"Moulay Sahaka ,&nbsp;Eduardo Mateos-Diaz ,&nbsp;Sawsan Amara ,&nbsp;Jutarat Wattanakul ,&nbsp;David Gray ,&nbsp;Dominique Lafont ,&nbsp;Brigitte Gontero ,&nbsp;Hélène Launay ,&nbsp;Frédéric Carrière","doi":"10.1016/j.chemphyslip.2023.105291","DOIUrl":"10.1016/j.chemphyslip.2023.105291","url":null,"abstract":"<div><p><span>Galactolipids<span> are the main lipids from plant photosynthetic membranes and they can be digested by </span></span>pancreatic lipase<span><span><span><span><span> related protein 2 (PLRP2), an enzyme found in the </span>pancreatic secretion in many animal species. Here, we used transmission Fourier-transform infrared spectroscopy (FTIR) to monitor continuously the </span>hydrolysis of galactolipids by PLRP2, in situ and in real time. The method was first developed with a model substrate, a synthetic monogalactosyl </span>diacylglycerol<span> with 8-carbon acyl chains (C8-MGDG), in the form of mixed micelles with a </span></span>bile salt<span><span>, sodium<span><span><span> taurodeoxycholate (NaTDC). The concentrations of the residual substrate and reaction products (monogalactosylmonoglyceride, MGMG; monogalactosylglycerol, MGG; octanoic acid) were estimated from the carbonyl and carboxylate vibration bands after calibration with reference standards. The results were confirmed by </span>thin layer chromatography analysis (TLC) and specific staining of galactosylated compounds with </span>thymol and </span></span>sulfuric acid<span><span>. The method was then applied to the lipolysis of more complex substrates, a natural extract of MGDG with long acyl chains, micellized with NaTDC, and intact chloroplasts isolated from spinach leaves. After a calibration performed with α-linolenic acid, the main fatty acid (FA) found in plant galactolipids, FTIR allowed </span>quantitative measurement of chloroplast lipolysis by PLRP2. A full release of FA from membrane galactolipids was observed, that was not dependent on the presence of bile salts. Nevertheless, the evolution of amide vibration band in FTIR spectra suggested the interaction of membrane proteins with NaTDC and lipolysis products.</span></span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"252 ","pages":"Article 105291"},"PeriodicalIF":3.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9449247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of psychedelic tryptamine derivatives with a lipid bilayer","authors":"Fateme Zohairi ,&nbsp;Himanshu Khandelia ,&nbsp;Ali Asghar Hakami Zanjani","doi":"10.1016/j.chemphyslip.2023.105279","DOIUrl":"10.1016/j.chemphyslip.2023.105279","url":null,"abstract":"<div><p>Naturally occurring psychedelics have been used for a long time as remedies or in religious ceremonies and recreational activities. Recent studies have proven the therapeutic potential of some psychedelic compounds to safely treat a wide range of diseases such as anxiety, depression, migraine, and addiction. It is hypothesized that psychedelic compounds like tryptamines can exert their effects by two possible mechanisms: binding to the transmembrane serotonin receptor and/or modifying the properties of the neuronal membrane that can alter the conformational equilibrium and desensitize receptors. The impact of three different tryptamine class compounds with a tertiary amine (dimethyltryptamine, bufotenine, and 5-MeO-DMT) in both neutral and charged forms on a model bilayer lipid membrane are studied using all-atom MD simulations. All compounds partition into the bilayer, and change membrane properties, but to different extents. We determine the tendency of compounds to partition into the membrane by free energy calculations. Neutral tryptamines partition into the bilayer almost completely. Dimethyltryptamine and 5-MeO-DMT cross the membrane spontaneously during the simulation time, but bufotenine does not, although it has the maximum effect on the structural properties of the membrane. However, protonated compounds partition partially into the bilayer and cannot pass through the middle of the membrane during the simulation time. In this way, subtle alteration of chemical structure can play a significant role in the improvement or deterioration of partitioning of these compounds into the bilayer and their passage across the membrane.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"251 ","pages":"Article 105279"},"PeriodicalIF":3.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308423000014/pdfft?md5=0879cdcbf1baff8ad1c6730e6a9a6017&pid=1-s2.0-S0009308423000014-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9130542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}