Trevor A. Paratore, Greta E. Schmidt, Alonzo H. Ross, Arne Gericke
{"title":"Thermal stability of bivalent cation/phosphoinositide domains in model membranes","authors":"Trevor A. Paratore, Greta E. Schmidt, Alonzo H. Ross, Arne Gericke","doi":"10.1016/j.chemphyslip.2024.105424","DOIUrl":"10.1016/j.chemphyslip.2024.105424","url":null,"abstract":"<div><p>As key mediators in a wide array of signaling events, phosphoinositides (PIPs) orchestrate the recruitment of proteins to specific cellular locations at precise moments. This intricate spatiotemporal regulation of protein activity often necessitates the localized enrichment of the corresponding PIP. We investigate the extent and thermal stabilities of phosphatidylinositol-4-phosphate (PI(4)P), phosphatidylinositol-4,5-bisphosphate (PI(4,5)P<sub>2</sub> and phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P<sub>3</sub>) clusters with calcium and magnesium ions. We observe negligible or minimal clustering of all examined PIPs in the presence of Mg<sup>2+</sup> ions. While PI(4)P shows in the presence of Ca<sup>2+</sup> no clustering, PI(4,5)P<sub>2</sub> forms with Ca<sup>2+</sup> strong clusters that exhibit stablity up to at least 80°C. The extent of cluster formation for the interaction of PI(3,4,5)P<sub>3</sub> with Ca<sup>2+</sup> is less than what was observed for PI(4,5)P<sub>2</sub>, yet we still observe some clustering up to 80°C. Given that cholesterol has been demonstrated to enhance PIP clustering, we examined whether bivalent cations and cholesterol synergistically promote PIP clustering. We found that the interaction of Mg<sup>2+</sup> or Ca<sup>2+</sup> with PI(4)P remains extraordinarily weak, even in the presence of cholesterol. In contrast, we observe synergistic interaction of cholesterol and Ca<sup>2+</sup> with PI(4,5)P<sub>2</sub>. Also, in the presence of cholesterol, the interaction of Mg<sup>2+</sup> with PI(4,5)P<sub>2</sub> remains weak. PI(3,4,5)P<sub>3</sub> does not show strong clustering with cholesterol for the experimental conditions of our study and the interaction with Ca<sup>2+</sup> and Mg<sup>2+</sup> was not influenced by the presence of cholesterol.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"264 ","pages":"Article 105424"},"PeriodicalIF":3.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887840","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":"Nanoscale Perturbations of Lipid Bilayers Induced by Magainin 2: Insights from AFM Imaging and Force Spectroscopy","authors":"Yasith Indigahawela Gamage, Jianjun Pan","doi":"10.1016/j.chemphyslip.2024.105421","DOIUrl":"10.1016/j.chemphyslip.2024.105421","url":null,"abstract":"<div><p>This study explores the impact of the antimicrobial peptide magainin 2 (Mag2) on lipid bilayers with varying compositions. We employed high-resolution atomic force microscopy (AFM) to reveal a dynamic spectrum of structural changes induced by Mag2. Our AFM imaging unveiled distinct structural alterations in zwitterionic POPC bilayers upon Mag2 exposure, notably the formation of nanoscale depressions within the bilayer surface, which we term as \"surface pores\" to differentiate them from transmembrane pores. These surface pores are characterized by a limited depth that does not appear to fully traverse the bilayer and reach the opposing leaflet. Additionally, our AFM-based force spectroscopy investigation on POPC bilayers revealed a reduction in bilayer puncture force (F<sub>P</sub>) and Young's modulus (E) upon Mag2 interaction, indicating a weakening of bilayer stability and increased flexibility, which may facilitate peptide insertion. The inclusion of anionic POPG into POPC bilayers elucidated its modulatory effects on Mag2 activity, highlighting the role of lipid composition in peptide-bilayer interactions. In contrast to surface pores, Mag2 treatment of <em>E. coli</em> total lipid extract bilayers resulted in increased surface roughness, which we describe as a fluctuation-like morphology. We speculate that the weaker cohesive interactions between heterogeneous lipids in <em>E. coli</em> bilayers may render them more susceptible to Mag2-induced perturbations. This could lead to widespread disruptions manifested as surface fluctuations throughout the bilayer, rather than the formation of well-defined pores. Together, our findings of nanoscale bilayer perturbations provide useful insights into the molecular mechanisms governing Mag2-membrane interactions.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"263 ","pages":"Article 105421"},"PeriodicalIF":3.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786752","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}
Martina Moggio, Marcella La Noce, Virginia Tirino, Gianpaolo Papaccio, Maria Lepore, Nadia Diano
{"title":"Sphingolipidomic profiling of human Dental Pulp Stem Cells undergoing osteogenic differentiation","authors":"Martina Moggio, Marcella La Noce, Virginia Tirino, Gianpaolo Papaccio, Maria Lepore, Nadia Diano","doi":"10.1016/j.chemphyslip.2024.105420","DOIUrl":"10.1016/j.chemphyslip.2024.105420","url":null,"abstract":"<div><p>It is now recognized that sphingolipids are involved in the regulation and pathophysiology of several cellular processes such as proliferation, migration, and survival. Growing evidence also implicates them in regulating the behaviour of stem cells, the use of which is increasingly finding application in regenerative medicine. A shotgun lipidomic study was undertaken to determine whether sphingolipid biomarkers exist that can regulate the proliferation and osteogenic differentiation of human Dental Pulp Stem Cells (hDPSCs). Sphingolipids were extracted and identified by direct infusion into an electrospray mass spectrometer. By using cells cultured in osteogenic medium and in medium free of osteogenic stimuli, as a control, we analyzed and compared the SPLs profiles. Both cellular systems were treated at different times (72 hours, 7 days, and 14 days) to highlight any changes in the sphingolipidomic profiles in the subsequent phases of the differentiation process. Signals from sphingolipid species demonstrating clear differences were selected, their relative abundance was determined, and statistical differences were analyzed. Thus, our work suggests a connection between sphingolipid metabolism and hDPSC osteogenic differentiation and provides new biomarkers for improving hDPSC-based orthopaedic regenerative medicine.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"263 ","pages":"Article 105420"},"PeriodicalIF":3.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308424000458/pdfft?md5=42cc6de6007f08d6dad5967e3a8ea212&pid=1-s2.0-S0009308424000458-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756035","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}
Devansh Kaushik , Prashant Hitaishi , Ashwani Kumar , Debasis Sen , Syed M. Kamil , Sajal K. Ghosh
{"title":"Modulating a model membrane of sphingomyelin by a tricyclic antidepressant drug","authors":"Devansh Kaushik , Prashant Hitaishi , Ashwani Kumar , Debasis Sen , Syed M. Kamil , Sajal K. Ghosh","doi":"10.1016/j.chemphyslip.2024.105419","DOIUrl":"10.1016/j.chemphyslip.2024.105419","url":null,"abstract":"<div><p>Tricyclic medicine such as amitriptyline (AMT) hydrochloride, initially developed to treat depression, is also used to treat neuropathic pain, anxiety disorder, and migraines. The mechanism of functioning of this type of drugs is ambiguous. Understanding the mechanism is important for designing new drug molecules with higher pharmacological efficiency. Hence, in the present study, biophysical approaches have been taken to shed light on their interactions with a model cellular membrane of brain sphingomyelin in the form of monolayer and multi-lamellar vesicles. The surface pressure-area isotherm infers the partitioning of a drug molecule into the lipid monolayer at the air water interface, providing a higher surface area per molecule and reducing the in-plane elasticity. Further, the surface electrostatic potential of the lipid monolayer is found to increase due to the insertion of drug molecule. The interfacial rheology revealed a reduction of the in-plane viscoelasticity of the lipid film, which, depends on the adsorption of the drug molecule onto the film. Small-angle X-ray scattering (SAXS) measurements on multilamellar vesicles (MLVs) have revealed that the AMT molecules partition into the hydrophobic core of the lipid membrane, modifying the organization of lipids in the membrane. The modified physical state of less rigid membrane and the transformed electrostatics of the membrane could influence its interaction with synaptic vesicles and neurotransmitters making higher availability of the neurotransmitters in the synaptic cleft.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"263 ","pages":"Article 105419"},"PeriodicalIF":3.4,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533048","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}
Grzegorz Łazarski, Natan Rajtar, Agata Żak, Dorota Jamróz, Mariusz Kepczynski
{"title":"Interaction of chondroitin sulfate with zwitterionic lipid membranes","authors":"Grzegorz Łazarski, Natan Rajtar, Agata Żak, Dorota Jamróz, Mariusz Kepczynski","doi":"10.1016/j.chemphyslip.2024.105417","DOIUrl":"10.1016/j.chemphyslip.2024.105417","url":null,"abstract":"<div><p>Chondroitin sulfates (CSs) are important components of the extracellular matrix and side chains of membrane proteoglycans. These polysaccharides are, therefore, likely to interact with plasma membranes and play a significant role in modulating cellular functions. So far, the details of the processes occurring at the interface between the extracellular matrix and cellular membranes are not fully understood. In this study, we used experimental methods and atomic-scale molecular dynamics (MD) simulations to reveal the molecular picture of the interactions between CS and phosphocholine (PC) membranes, used as a simplified model of cell membranes. MD simulations reveal that the polysaccharide associates to the PC bilayer as a result of electrostatic interactions between the positively charged quaternary ammonium groups of choline and the negatively charged sulfate groups of CS. Compared to an aqueous medium, the adsorbed polysaccharide chains adopt more elongated conformations, which facilitates the electrostatic interactions with the membrane, and have a high degree of freedom to change their conformations and to adhere to and detach from the membrane surface. Penetrating slightly between the polar groups of the bilayer, they form a loosely anchored layer, but do not intrude into the hydrophobic region of the PC bilayer. The CS adsorption spread the PC headgroups apart, which is manifested by an increase in the value of the area pre lipid. The expansion of the lipid polar groups weakens the dispersion interactions between the lipid acyl chains. As a result, the lipid membrane in the membrane-polysaccharide contact areas becomes more fluid. Our outcomes may help to understand in detail the interaction of chondroitin sulfate with zwitterionic membranes at the molecular level, which is of biological interest since many biological processes depend on lipid-CS interactions.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"263 ","pages":"Article 105417"},"PeriodicalIF":3.4,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308424000422/pdfft?md5=6c214d56ef7378c3385ccefcd230de0e&pid=1-s2.0-S0009308424000422-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475559","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}
Aline S. Perez , Aleksandra T. Morikawa , Raul C. Maranhão , Antônio M. Figueiredo Neto
{"title":"Structural characterization of cholesterol-rich nanoemulsion (LDE)","authors":"Aline S. Perez , Aleksandra T. Morikawa , Raul C. Maranhão , Antônio M. Figueiredo Neto","doi":"10.1016/j.chemphyslip.2024.105418","DOIUrl":"10.1016/j.chemphyslip.2024.105418","url":null,"abstract":"<div><p>Cholesterol-rich nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and can concentrate those agents in the neoplastic and inflammatory tissues. This method improves the biodistribution of the drug and reduces toxicity. However, the structural stability of LDE particles, without or with associated drugs, has not been extensively investigated. The aim of the present study is to investigate the structural stability of LDE and LDE associated to paclitaxel, etoposide or methotrexate in aqueous solution over time by small-angle X-ray scattering (SAXS and Ultra SAXS) and dynamic light scattering (DLS). The results show that LDE and LDE associated with those chemotherapeutic agents had reproducible and stable particle diameter, physical structure, and aggregation behavior over 3-month observation period. As estimated from both DLS and Ultra-SAXS methods, performed at pre-established intervals, the average particle diameter of LDE alone was approx. 32 nm, of LDE-paclitaxel was 31 nm, of LDE-methotrexate was 35 nm and of LDE-etoposide was 36 nm. Ultra-SAXS analysis showed that LDE nanoparticles were quasi-spherical, and SAXS showed that drug molecules inside the particles showed a layered-like organization. Formulations of LDE with associated PTX, ETO or MTX were successfully tested in animal experiments and in patients with cancer or with cardiovascular disease, showing markedly low toxicity, good tolerability and possible superior pharmacological action. Our results may be useful for ensuing clinical trials of this novel Nanomedicine tool, by strengthening the knowledge of the structural aspects of those LDE formulations.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"263 ","pages":"Article 105418"},"PeriodicalIF":3.4,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464797","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}
Rong-zu Nie , Huo-min Luo , Jing-yu Chen , Li-heng Sun , Zi-bo Wang , Zhen-ping Zhang , Ya-ru Bao
{"title":"Molecular insights into the interactions of theaflavin and epicatechin with different lipid bilayer membranes by molecular dynamics simulation","authors":"Rong-zu Nie , Huo-min Luo , Jing-yu Chen , Li-heng Sun , Zi-bo Wang , Zhen-ping Zhang , Ya-ru Bao","doi":"10.1016/j.chemphyslip.2024.105405","DOIUrl":"https://doi.org/10.1016/j.chemphyslip.2024.105405","url":null,"abstract":"<div><p>At present, consumers increasingly favored the natural food preservatives with fewer side-effects on health. The green tea catechins and black tea theaflavins attracted considerable interest, and their antibacterial effects were extensively reported in the literature. Epicatechin (EC), a green tea catechin without a gallate moiety, showed no bactericidal activity, whereas the theaflavin (TF), also lacking a gallate moiety, exhibited potent bactericidal activity, and the antibacterial effects of green tea catechins and black tea theaflavins were closely correlated with their abilities to disrupt the bacterial cell membrane. In our present study, the mechanisms of membrane interaction modes and behaviors of TF and EC were explored by molecular dynamics simulations. It was demonstrated that TF exhibited markedly stronger affinity for the POPG bilayer compared to EC. Additionally, the hydrophobic interactions of tropolone/catechol rings with the acyl chain part could significantly contribute to the penetration of TF into the POPG bilayer. It was also found that the resorcinol/pyran rings were the key functional groups in TF for forming hydrogen bonds with the POPG bilayer. We believed that the findings from our current study could offer useful insights to better understand the stronger antibacterial effects of TF compared to EC.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"262 ","pages":"Article 105405"},"PeriodicalIF":3.4,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090869","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}
Jacob J. Kinnun , Jan Michael Y. Carrillo , C. Patrick Collier , Micholas Dean Smith , John Katsaras
{"title":"Amantadine interactions with phase separated lipid membranes","authors":"Jacob J. Kinnun , Jan Michael Y. Carrillo , C. Patrick Collier , Micholas Dean Smith , John Katsaras","doi":"10.1016/j.chemphyslip.2024.105397","DOIUrl":"10.1016/j.chemphyslip.2024.105397","url":null,"abstract":"<div><p>Amantadine, a small amphilphic organic compound that consists of an adamantane backbone and an amino group, was first recognized as an antiviral in 1963 and received approval for prophylaxis against the type A influenza virus in 1976. Since then, it has also been used to treat Parkinson’s disease-related dyskinesia and is being considered as a treatment for corona viruses. Since amantadine usually targets membrane-bound proteins, its interactions with the membrane are also thought to be important. Biological membranes are now widely understood to be laterally heterogeneous and certain proteins are known to preferentially co-localize within specific lipid domains. Does amantadine, therefore, preferentially localize in certain lipid composition domains? To address this question, we studied amantadine’s interactions with phase separating membranes composed of cholesterol, DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), POPC (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine), and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), as well as single-phase DPhPC (1,2-diphytanoyl-sn-glycero-3-phos-phocholine) membranes. From Langmuir trough and differential scanning calorimetry (DSC) measurements, we determined, respectively, that amantadine preferentially binds to disordered lipids, such as POPC, and lowers the phase transition temperature of POPC/DSPC/cholesterol mixtures, implying that amantadine increases membrane disorder. Further, using droplet interface bilayers (DIBs), we observed that amantadine disrupts DPhPC membranes, consistent with its disordering properties. Finally, we carried out molecular dynamics (MD) simulations on POPC/DSPC/cholesterol membranes with varying amounts of amantadine. Consistent with experiment, MD simulations showed that amantadine prefers to associate with disordered POPC-rich domains, domain boundaries, and lipid glycerol backbones. Since different proteins co-localize with different lipid domains, our results have possible implications as to which classes of proteins may be better targets for amantadine.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"262 ","pages":"Article 105397"},"PeriodicalIF":3.4,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915426","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":"The impact of phospholipids with high transition temperature to enhance redox-sensitive liposomal doxorubicin efficacy in colon carcinoma model","authors":"Elaheh Mirhadi , Anis Askarizadeh , Leila Farhoudi , Mohammad Mashreghi , Saeed Behboodifar , Seyedeh Hoda Alavizadeh , Leila Arabi , Mahmoud Reza Jaafari","doi":"10.1016/j.chemphyslip.2024.105396","DOIUrl":"https://doi.org/10.1016/j.chemphyslip.2024.105396","url":null,"abstract":"<div><p>In this study, we have developed a redox-sensitive (RS) liposomal doxorubicin formulation by incorporating 10,10′-diselanediylbis decanoic acid (DDA) organoselenium compound as the RS moiety. Hence, several RS liposomal formulations were prepared by using DOPE, HSPC, DDA, mPEG<sub>2000</sub>-DSPE, and cholesterol. <em>In situ</em> drug loading using a pH gradient and citrate complex yielded high drug to lipid ratio and encapsulation efficiency (100<!--> <!-->%) for RS liposomes. Liposomal formulations were characterized in terms of size, surface charge and morphology, drug loading, release properties, cell uptake and cytotoxicity, as well as therapeutic efficacy in BALB/c mice bearing C26 tumor cells. The formulations showed an average particle size of 200 nm with narrow size distributions (PDI < 0.3), and negative surface charges varying from −6 mV to −18.6 mV. Our study confirms that the presence of the DDA compound in liposomes is highly sensitive to hydrogen peroxide at 0.1<!--> <!-->% w/v, resulting in a significant burst release of up to 40<!--> <!-->%. The <em>in vivo</em> therapeutic efficacy study in BALB/c mice bearing C26 colon carcinoma confirmed the promising function of RS liposomes in the tumor microenvironment which led to a prolonged median survival time (MST). The addition of hydrogenated soy phosphatidylcholine (HSPC) with a high transition temperature (Tm: 52–53.5<!--> <!-->°C) extended the MST of our 3-component formulation of F14 (DOPE/HSPC/DDA) to 60 days in comparison to Caelyx (PEGylated liposomal Dox), which is not RS-sensitive (39 days). Overall, HSPC liposomes bearing RS-sensitive moiety enhanced therapeutic efficacy against colon cancer <em>in vitro</em> and <em>in vivo</em>. This achievement unequivocally underscores the criticality of high-TM phospholipids, particularly HSPC, in significantly enhancing liposome stability within the bloodstream. In addition, RS liposomes enable the on-demand release of drugs, leveraging the redox environment of tumor cells, thereby augmenting the efficacy of the formulation.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"261 ","pages":"Article 105396"},"PeriodicalIF":3.4,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644349","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}
Andreas H. Franz, Nataliya M. Samoshina, Vyacheslav V. Samoshin
{"title":"A convenient method for the relative and absolute quantification of lipid components in liposomes by 1H- and 31P NMR-spectroscopy","authors":"Andreas H. Franz, Nataliya M. Samoshina, Vyacheslav V. Samoshin","doi":"10.1016/j.chemphyslip.2024.105395","DOIUrl":"https://doi.org/10.1016/j.chemphyslip.2024.105395","url":null,"abstract":"<div><h3>Objective</h3><p>Liposomes are promising delivery systems for pharmaceutical applications and have been used in medicine in the recent past. Preparation of liposomes requires reliable characterization and quantification of the phospholipid components for which the traditional cumbersome molybdate method is used frequently. The objective was to improve relative and absolute quantification of lipid components from liposomes.</p></div><div><h3>Methods</h3><p>A reliable method for quantification of lipid composition in liposome formulations in the 1–10 μmol range with <sup>1</sup>H- and <sup>31</sup>P NMR spectroscopy at 600 MHz has been developed. The method is based on three crystalline small-molecule standards (Ph<sub>3</sub>PO<sub>4</sub>, (Tol)<sub>3</sub>PO<sub>4</sub>, and Ph<sub>3</sub>PO) in CDCl<sub>3</sub>.</p></div><div><h3>Results</h3><p>Excellent calibration linearity and chemical stability of the standards was observed. The method was tested in blind fashion on liposomes containing POPC, PEG-ceramide and a pH-sensitive <em>trans</em>-aminocyclohexanol-based amphiphile (TACH).<span><sup>1</sup></span> Relative quantification (percentage of components) as well as determination of absolute lipid amount was possible with excellent reproducibility with an average error of 5<!--> <!-->%. Quantification (triplicate) was accomplished in 15 min based on <sup>1</sup>H NMR and in 1 h based on <sup>31</sup>P NMR. Very little change in mixture composition was observed over multiple preparative steps.</p></div><div><h3>Conclusion</h3><p>Liposome preparations containing POPC, POPE, DOPC, DPPC, TACH, and PEG-ceramide can be reliably characterized and quantified by <sup>1</sup>H NMR and <sup>31</sup>P NMR spectroscopy at 600 MHz in the μmol range.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"261 ","pages":"Article 105395"},"PeriodicalIF":3.4,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140554674","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}