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Amyloid-liposome composites as hybrid platforms for doxorubicin delivery 淀粉样蛋白-脂质体复合材料作为阿霉素递送的混合平台
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-23 DOI: 10.1016/j.bbamem.2025.184426
Valeriya Trusova, Uliana Malovytsia, Kateryna Vus, Olga Zhytniakivska, Galyna Gorbenko
The feasibility of engineering the sophisticated hybrid drug delivery platforms through the integration of phospholipid vesicles within a matrix of amyloid suspensions has been evaluated. Utilizing the equilibrium dialysis methodology and spectrofluorometric technique, the quantitative analysis of doxorubicin (DOX) encapsulation capacity of diverse phospholipid assemblies, amyloid suspensions, and their corresponding composite systems has been performed. Our findings revealed that the incorporation of negatively charged cardiolipin (CL) into phosphatidylcholine (PC) lipid vesicles significantly enhances DOX encapsulation and retention, while the addition of amyloid fibrils to charged liposomes has minimal impact on the drug binding. The neutral PC liposomes modified with insulin and lysozyme fibrillar suspensions exhibited improved doxorubicin encapsulation and retention compared to unmodified liposomes, thereby displaying a potential for reduced toxicity and prolonged drug action in vivo. Notably, amyloid fibrils alone were found to demonstrate the lower degree of DOX encapsulation and retention as compared to liposomes. Fluorimetric analysis suggests that the presence of insulin and lysozyme fibrils alters the microenvironment of DOX towards a more hydrophobic which is consistent with deeper bilayer penetration. Cumulative data from release kinetics and retention studies along with fluorescence measurements suggest that PC liposome-insulin fibril composites represent the most promising DOX nanocarriers, combining enhanced drug encapsulation, structural stability, and optimal drug location within the bilayer. The results obtained provide valuable insights into the design of protein-lipid nanomaterials for enhanced drug delivery, offering promising avenues for the development of more effective and targeted therapeutic strategies.
通过在淀粉样蛋白悬浮液基质中整合磷脂囊泡来设计复杂的混合药物输送平台的可行性已经进行了评估。利用平衡透析方法和荧光光谱技术,定量分析了多柔比星(DOX)在不同磷脂组装体、淀粉样蛋白悬浮液及其相应复合体系中的包封能力。我们的研究结果表明,将带负电荷的心磷脂(CL)掺入磷脂酰胆碱(PC)脂质囊泡可显著增强DOX的包封和保留,而将淀粉样蛋白原纤维添加到带电荷的脂质体中对药物结合的影响最小。与未经修饰的脂质体相比,经胰岛素和溶菌酶纤原悬浮液修饰的中性PC脂质体表现出更好的阿霉素包封和滞留性,从而在体内显示出降低毒性和延长药物作用的潜力。值得注意的是,与脂质体相比,淀粉样蛋白原纤维单独显示出较低程度的DOX包封和保留。荧光分析表明,胰岛素和溶菌酶原纤维的存在改变了DOX的微环境,使其更加疏水,这与更深的双分子层渗透一致。释放动力学和保留研究的累积数据以及荧光测量表明,PC脂质体-胰岛素原纤维复合材料是最有前途的DOX纳米载体,具有增强的药物包封性、结构稳定性和在双分子层内的最佳药物定位。研究结果为设计蛋白质-脂质纳米材料以增强药物传递提供了有价值的见解,为开发更有效和更有针对性的治疗策略提供了有希望的途径。
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引用次数: 0
Influence of lipid saturation on the structural properties of styrene maleic acid lipid nanoparticles (SMALPs) 脂质饱和度对苯乙烯马来酸脂质纳米颗粒(SMALPs)结构性能的影响。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-22 DOI: 10.1016/j.bbamem.2025.184424
Evelyn A. Okorafor , Emma A. Gordon , Indra D. Sahu , Muhammad Zeeshan Shah , Dominik Konkolewicz , Gary A. Lorigan
Membrane bilayers are complex three-dimensional structures whose molecular events in the deep dimensions of membrane lipids are crucial for understanding membrane function. This study investigates the interaction of coexisting membrane domains in terms of hydrophobicity, alkyl chain order, and fluidity using Styrene Maleic Acid (SMA) copolymers as membrane mimics. We employed continuous wave electron paramagnetic resonance spectroscopy (CW-EPR) to characterize the structural dynamic properties of membrane domains without separation. Lipid-spin probe vesicles were prepared using phospholipids with varying degrees of saturation (DOPC, POPC, DMPC, and DSPC) and doxyl spin-labeled phospholipids at different depths (5, 12, and 16-doxyl PC) as membrane probes. These vesicles were titrated with two SMA polymers of different hydrophobic tail lengths. Dynamic light scattering (DLS) confirmed the formation of Styrene Maleic Acid lipid nanoparticles (SMALPs). CW-EPR spectroscopy was used to characterize the dynamic properties of vesicles incorporated into the SMALP systems. Analysis of the CW-EPR spectral line shape data revealed that the hydrophobic tail of SMA, the degree of lipid saturation, and the length of phospholipids significantly affect membrane fluidity and alkyl chain ordering, as well as lipid interactions. Notably, samples containing DSPC, a fully saturated longer-chain phospholipid, and those containing SMA exhibited increased rigidity of motion, reduced fluidity, and improved ordering of the alkyl chain in the membrane. This study provides crucial insights into the molecular dynamics of membrane bilayers and the impact of SMA copolymers on membrane properties, contributing to our understanding of fundamental membrane functions such as lateral movement of proteins and lipids.
膜双分子层是复杂的三维结构,其深层膜脂分子事件对理解膜功能至关重要。本研究利用苯乙烯-马来酸(SMA)共聚物作为膜模拟物,研究了共存膜结构域在疏水性、烷基链序和流动性方面的相互作用。我们采用连续波电子顺磁共振波谱(CW-EPR)来表征无分离膜结构域的结构动力学特性。采用不同饱和度的磷脂(DOPC、POPC、DMPC和dsc)和不同深度的羟基自旋标记磷脂(5、12和16-羟基PC)作为膜探针制备脂质自旋探针囊泡。用两种不同疏水尾长度的SMA聚合物滴定这些囊泡。动态光散射(DLS)证实了苯乙烯马来酸脂质纳米颗粒(SMALPs)的形成。采用CW-EPR光谱法表征了加入到smallp系统中的囊泡的动态特性。w - epr谱线形状数据分析表明,SMA疏水尾部、脂质饱和程度和磷脂长度显著影响膜流动性、烷基链排序以及脂质相互作用。值得注意的是,含有dsc(一种完全饱和的长链磷脂)的样品和含有SMA的样品表现出运动刚性增加,流动性降低,并改善了膜中烷基链的有序性。这项研究为膜双层的分子动力学和SMA共聚物对膜性能的影响提供了重要的见解,有助于我们理解基本的膜功能,如蛋白质和脂质的横向运动。
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引用次数: 0
Evaluation of aquaporin Z water permeability in bilayers using droplet interface systems with internal-pressure–defined membrane tension 利用内压定义膜张力的液滴界面系统评价双层水通道蛋白Z的透水性
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-21 DOI: 10.1016/j.bbamem.2025.184425
Misuzu Ueki , Takahisa Maki , Masayuki Iwamoto
Cell membranes regulate water flow to maintain homeostasis, cell volume, and osmotic balance. Aquaporins (AQPs) enable selective water transport, making precise permeability measurements essential for understanding their function. The current methods have limitations, including high resource demands and poor control over membrane properties like bilayer tension. In this study, the droplet interface bilayer (DIB) system was used to measure aquaporin water channel activity. Unlike conventional water permeability assays, this method uniquely quantifies lipid bilayer tension by determining droplet internal pressure. This pressure-determined DIB (PDIB) method was used to investigate the water permeability of a lipid bilayer reconstituted with Escherichia coli aquaporin Z (AqpZ). Water permeability increased in an AqpZ concentration-dependent manner at bilayer tensions of 2.2–3.0 mN/m and was inhibited by mercury (IC50, 340 μM). Fluorescence microscopy was performed to visualize and quantify AqpZ molecules, thereby allowing us to derive an approximate estimate of the unitary water permeability. Although this study established the PDIB method and demonstrated its applicability to AqpZ, this technique may also facilitate future investigations on the effects of lipid bilayer tension on aquaporin function and the fundamental mechanisms of water transport across biological membranes.
细胞膜调节水流以维持体内平衡、细胞体积和渗透平衡。水通道蛋白(AQPs)能够选择性地进行水运输,因此精确的渗透率测量对于了解其功能至关重要。目前的方法有局限性,包括高资源需求和对双层张力等膜特性的控制较差。本研究采用液滴界面双层(DIB)系统测量水通道蛋白活性。与传统的水渗透性测定不同,该方法通过测定液滴内部压力来定量脂质双分子层张力。采用压力测定DIB (PDIB)方法研究了用大肠杆菌水通道蛋白Z (AqpZ)重组的脂质双分子层的透水性。在2.2 ~ 3.0 mN/m的双层张力下,水渗透性以AqpZ浓度依赖性的方式增加,并被汞(IC50, 340 μM)抑制。荧光显微镜进行可视化和量化AqpZ分子,从而使我们能够得出一个近似估计的单一水渗透率。虽然本研究建立了PDIB方法并证明了其对AqpZ的适用性,但该技术也可能有助于未来研究脂质双分子层张力对水通道蛋白功能的影响以及水跨生物膜运输的基本机制。
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引用次数: 0
Interactions of hinokitiol with fungal membrane lipids in model systems 模型系统中扁柏酚与真菌膜脂的相互作用
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-05 DOI: 10.1016/j.bbamem.2025.184423
Beata Wyżga , Magdalena Skóra , Karolina Olechowska , Katarzyna Hąc-Wydro
Hinokitiol (β-thujaplicin) is a naturally occurring substance of antimicrobial properties, which can be used e.g. as a cosmetic preservative. In this work the influence of hinokitiol on the monolayers and bilayers formed from fungal membrane lipids (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine – POPE; 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine – POPC and ergosterol) was investigated. These studies aimed to investigate the effect of hinokitiol on fungal membranes, being indicated as a target for this compound. In this context, the affinity of hinokitiol for ergosterol-containing membranes was of particular interest. The in vitro antifungal activity of hinokitiol was also determined. The results showed that hinokitiol is active against the Candida species tested and exhibits stronger antifungal than antibacterial activity. Moreover, hinokitiol alters the properties of model membranes and the observed effects correlated with ergosterol content in the system. Namely, the higher the ergosterol content, the greater the fluidizing and destabilising effect of hinokitiol and its removal from the model. Moreover, hinokitiol is not able to penetrate into ergosterol membranes; instead, causes strong destabilization of the film and dragging the monolayer material into the subphase. Thus, hinokitiol changes properties of model membrane by the exclusion of the molecules from the interface. The results evidenced differences in the interactions of hinokitiol with ergosterol vs phospholipids, and the interactions of hinokitiol with the membrane depend on the presence and levels of ergosterol. Thus, ergosterol can be a molecular target for this compound. Moreover, the presence of ergosterol in fungal membranes and its lack in bacteria membranes may explain stronger antifungal vs antibacterial effect of hinokitiol.
扁柏醇是一种天然存在的具有抗菌特性的物质,可以用作化妆品防腐剂等。本文研究了扁柏醇对真菌膜脂(1-棕榈酰-2-油酰- n-甘油-3-磷酸乙醇胺- POPE)形成的单分子和双分子膜的影响;研究了1-棕榈酰-2-油酰-sn-甘油-3-磷脂胆碱- POPC和麦角甾醇。这些研究旨在研究桧木醇对真菌膜的影响,被认为是该化合物的靶点。在这种情况下,扁柏醇对麦角甾醇膜的亲和力是特别感兴趣的。测定了桧木醇的体外抗真菌活性。结果表明,桧木醇对所测念珠菌具有较强的抗真菌活性。此外,扁柏醇改变了模型膜的性质,所观察到的影响与系统中麦角甾醇的含量有关。也就是说,麦角甾醇含量越高,扁桃木醇的流化和不稳定作用越大,并从模型中去除它。此外,扁柏醇不能渗透到麦角甾醇膜中;相反,它会引起薄膜的强烈不稳定,并将单层材料拖入亚相。因此,扁柏醇通过从界面中排除分子来改变模型膜的性质。结果证明,在与麦角甾醇和磷脂的相互作用的差异,以及与膜的相互作用,仰赖麦角甾醇的存在和水平。因此,麦角甾醇可以作为该化合物的分子靶标。此外,真菌膜中麦角甾醇的存在和细菌膜中麦角甾醇的缺乏可能解释了桧木醇具有较强的抗真菌和抗菌作用。
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引用次数: 0
Effect of glucosylation for the vertical movement of cholesterol in bilayer membranes 糖基化对胆固醇在双层膜中垂直运动的影响
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-01 DOI: 10.1016/j.bbamem.2025.184422
Shinya Hanashima , Takafumi Asahina , Raymond Malabed , Katsuaki Sasaki , Michio Murata
Cholesterol (Chol) in mammalian cell membranes facilitates the assembly of dynamic membrane domains that are involved in vital biological processes through lateral and transbilayer movements in the membranes. In the cell membranes, Chol undergoes glucose transglycosylation to produce cholesteryl-β-d-glucoside (ChoGlc). ChoGlc is involved in neurodegenerative diseases and accumulates in lysosomal storage disorders. However, the effects of glucosylation on membrane properties of Chol remain unclear. We investigated the membrane interaction of ChoGlc and its subsequent translocation between leaflets using fluorescent probes, such as 4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) and the newly synthesized 7-nitro-2,1,3-benzoxadiazole-labeled ChoGlc (NBD-ChoGlc) in dioleoylphosphatidylcholine (DOPC) membranes. The fluorescence of TMA-DPH, which selectively reported the order of the outer leaflet of the bilayer, indicated that ChoGlc added to the external solution, was mostly incorporated into the membranes and increased the DOPC membrane ordering. Furthermore, the anisotropy values reached a level similar to that of the ChoGlc-preloaded symmetric vesicle within approximately 5 min owing to the rapid distribution of ChoGlc in both leaflets. This was further confirmed by the selective fluorescence quenching of NBD-ChoGlc in the outer leaflet through irreversible quenching by dithionite. The similarity of the fluorescence decay curves of NBD-ChoGlc and NBD-Chol indicated that the glucosylation had little impact on the flip-flops of Chol in the DOPC bilayers. Our data demonstrates that some of the important membrane properties of Chol, such as fast flip-flop between leaflets and increased membrane order, were mostly maintained in ChoGlc despite hydrophilic glucose modification.
哺乳动物细胞膜中的胆固醇(Chol)促进动态膜结构域的组装,这些结构域通过膜的横向和跨双分子层运动参与重要的生物过程。在细胞膜中,Chol经过葡萄糖转糖基化产生胆固醇-β-d-葡萄糖苷(ChoGlc)。ChoGlc参与神经退行性疾病,并在溶酶体贮积性疾病中积累。然而,糖基化对Chol膜性质的影响尚不清楚。我们利用荧光探针,如4-三甲基氨苯)-6-苯基-1,3,5-己三烯(TMA-DPH)和新合成的7-硝基-2,1,3-苯并恶二唑标记的ChoGlc (NBD-ChoGlc),在二油酰基磷脂酰胆碱(DOPC)膜上研究了ChoGlc的膜相互作用及其随后在小叶之间的易位。TMA-DPH的荧光选择性地报告了双分子层外小叶的顺序,表明加入外溶液的ChoGlc大部分被纳入膜中,并增加了DOPC膜的有序度。此外,由于ChoGlc在两个小叶中的快速分布,各向异性值在大约5分钟内达到与预加载ChoGlc的对称囊泡相似的水平。这进一步证实了NBD-ChoGlc在外小叶中通过二亚铁不可逆猝灭而选择性荧光猝灭。NBD-ChoGlc和NBD-Chol的荧光衰减曲线相似,表明糖基化对DOPC双层中Chol的“翻转”影响不大。我们的数据表明,尽管在ChoGlc中进行了亲水性葡萄糖修饰,但Chol的一些重要的膜特性,如小叶之间的快速翻转和膜秩序的增加,大多保持不变。
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引用次数: 0
Elucidating the interactions of endocannabinoid-like neurotransmitters, N-acyltaurines and bovine serum albumin: Spectroscopic and computational approaches 阐明内源性大麻素样神经递质、n -酰基牛磺酸和牛血清白蛋白的相互作用:光谱和计算方法
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-01 DOI: 10.1016/j.bbamem.2025.184421
Martin Luther John , Sivaramakrishna Akella , Ravi Kanth Kamlekar
N-Acyltaurines (NATs) are endogenous neurotransmitters, structurally similar to endocannabinoids, and have anti-inflammatory and anti-proliferative effects. In response to NATs, TRP channels, TRPV1, TRPV4 and the peptide hormone, GLP-1 are activated. Serum albumin proteins act as transporters for a variety of substances in blood plasma (i.e., hormones, fatty acids, bilirubin, ions, and medications). Due to the structural closeness of Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA), a study into NAT-BSA interactions is crucial. To study interactions of NATs (n = 10–18) with BSA, spectroscopic and computational techniques were used. From the steady-state fluorescence measurements, observed binding constants are in the range of 1.57 × 105 M−1 to 2.85 × 105 M−1. Due to the binding of NATs, the fluorescence of BSA is quenched (∼24.77 %). The negative enthalpy and entropy change and Gibbs free energy values, obtained from van't Hoff plot indicate that the interactions between NATs and BSA are spontaneous and primarily driven by hydrogen bonding. Competitive site-binding assays with warfarin and ibuprofen show that NATs bind to both the drug-binding sites in BSA concurrently. The CD spectroscopic and FT-IR analysis indicates relatively marginal changes in the secondary structure of BSA. Molecular docking analyses are done to identify binding locations and molecular-level interactions. The negative free energy values indicate that NATs have a positive binding relationship with BSA. These findings are congruent with the findings of site-binding studies, which reveal that NATs have a higher proclivity for interacting with sites I and II at the same time.
n -酰基牛磺酸(NATs)是内源性神经递质,结构类似内源性大麻素,具有抗炎和抗增殖作用。在NATs的作用下,TRP通道、TRPV1、TRPV4和肽激素GLP-1被激活。血清白蛋白作为血浆中多种物质(如激素、脂肪酸、胆红素、离子和药物)的转运体。由于牛血清白蛋白(BSA)和人血清白蛋白(HSA)在结构上的紧密性,研究它们之间的相互作用是至关重要的。为了研究NATs (n = 10-18)与BSA的相互作用,使用了光谱和计算技术。从稳态荧光测量中,观察到的结合常数在1.57 × 105 M−1至2.85 × 105 M−1之间。由于NATs的结合,BSA的荧光被猝灭(~ 24.77%)。由van't Hoff图得到的负焓变、负熵变和Gibbs自由能值表明NATs与BSA之间的相互作用是自发的,主要由氢键驱动。与华法林和布洛芬的竞争性位点结合试验表明,NATs同时结合BSA中的两个药物结合位点。CD光谱和FT-IR分析表明,BSA的二级结构变化相对较小。分子对接分析用于确定结合位置和分子水平的相互作用。负自由能值表明NATs与BSA有正结合关系。这些发现与位点结合研究的结果一致,表明NATs同时与位点I和II相互作用的倾向更高。
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引用次数: 0
Effect of osmolytes on the conformational stability of Aβ(25–35): A circular dichroism analysis 渗透物对Aβ(25-35)构象稳定性的影响:圆二色分析。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-01 DOI: 10.1016/j.bbamem.2025.184420
Angelo Santoro , Michela Buonocore , Anna Maria D'Ursi
Alzheimer's (AD) is a neurodegenerative disease characterized by the onset and progression of mental decline. AD aetiopathogenesis is still questioned; however, according to one of the most accredited hypotheses, the accumulation of amyloid plaques formed by aggregated Aβ peptides is the primary cause of neuronal function loss. Accordingly, hundreds of molecules have been screened for their possible action to prevent or destroy amyloid aggregates. Following this track, osmolytes, naturally occurring small molecules produced by several organisms in response to external stressors, were recently evaluated as modulators of Aβ aggregation. In this study, we examined the conformational stability of Aβ(25–35) when exposed to the osmolytes acetylcholine (ACh), succinylcholine (SCh), and betaine (Bet). Aβ(25–35) is the shortest fragment known for replicating the aggregation process seen in Aβ peptides. By collecting circular dichroism (CD) spectra in water and different membrane-mimicking systems, we investigated the potential of the mentioned osmolytes to stabilize the soluble conformations of Aβ(25–35) and preserve them from denaturing conditions. Our data suggest that Bet is a promising small molecule that can safeguard the soluble form of Aβ peptide and is effective in counteracting environmental conditions by favoring the amyloid aggregation associated with pathology progression.
阿尔茨海默病(AD)是一种神经退行性疾病,其特征是智力衰退的发生和发展。阿尔茨海默病的发病机制仍有疑问;然而,根据最受认可的假设之一,由聚集的Aβ肽形成的淀粉样斑块的积累是神经元功能丧失的主要原因。因此,数百种分子已经被筛选出来,以寻找它们可能阻止或破坏淀粉样蛋白聚集体的作用。随着这一趋势的发展,渗透物,一种自然产生的小分子,由一些生物体响应外部压力,最近被评估为Aβ聚集的调节剂。在这项研究中,我们检测了Aβ(25-35)暴露于渗透物乙酰胆碱(Ach)、琥珀胆碱(SCh)和甜菜碱(Bet)时的构象稳定性。Aβ(25-35)是已知用于复制Aβ肽中所见聚集过程的最短片段。通过收集水和不同膜模拟系统中的圆二色性(CD)光谱,我们研究了上述渗透剂稳定Aβ(25-35)的可溶性构象并防止其变性的潜力。我们的数据表明,Bet是一种很有前途的小分子,它可以保护a β肽的可溶性形式,并通过促进与病理进展相关的淀粉样蛋白聚集来有效地抵消环境条件。
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引用次数: 0
Corrigendum to “Structural analysis of the NK-lysin-derived peptide NK-2 upon interaction with bacterial membrane mimetics consisting of phosphatidylethanolamine and phosphatidylglycerol” [BBA – Biomembr. 1866 (2024) 184267] “nk -裂解素衍生肽NK-2与由磷脂酰乙醇胺和磷脂酰甘油组成的细菌膜模拟物相互作用的结构分析”[BBA - Biomembranes 1866(2024) 184267]的更正。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-01 DOI: 10.1016/j.bbamem.2025.184416
Jörg Andrä , Christopher Aisenbrey , U.S. Sudheendra , Marc Prudhon , Gerald Brezesinski , Evgeniy S. Salnikov , Claudia Zschech , Regine Willumeit-Römer , Matthias Leippe , Thomas Gutsmann , Burkhard Bechinger
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引用次数: 0
Long-chain cationic gemini surfactants as drug retention adjuvant on liposomes. A methodological approach with atorvastatin 长链阳离子双子表面活性剂作为脂质体上的药物保留佐剂。使用阿托伐他汀的方法。
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-01 DOI: 10.1016/j.bbamem.2025.184419
Yago Radziunas-Salinas , Vicente Domínguez-Arca , Alberto Pardo , Adriana Cambón , Pablo Taboada , Gerardo Prieto
This study delves into the development and characterization of dipalmitoyl phosphatidylcholine (DPPC) liposomes incorporated with gemini surfactant (tetradecamethylene-1,14 bis(dimethyl tetradecyl ammonium bromide); 14-14-14) and atorvastatin, aimed at enhancing drug delivery efficiency for cardiovascular diseases. The integration of gemini surfactants into liposomes is investigated for its potential to improve atorvastatin encapsulation and retention, addressing the drug's poor water solubility and the limitations of conventional liposomal systems. Through a combination of dynamic light scattering (DLS), differential scanning calorimetry (DSC), and molecular dynamics (MD) simulations, the study reveals that the presence of gemini surfactants significantly reduces liposome size and polydispersity, indicative of a more uniform and potentially unilamellar structure. DSC analysis highlights a decrease in transition temperatures and an alteration in transition symmetry, suggesting enhanced stability and a favourable drug release profile at physiological temperatures. MD simulations provide insight into the internalization mechanism of gemini surfactants and atorvastatin within the liposomal bilayer, demonstrating their mutual incorporation facilitated by polar interactions. Spectrophotometry-based retention studies further confirmed that liposomes containing gemini surfactants exhibit superior atorvastatin retention capabilities, nearly doubling the encapsulation efficiency compared to conventional liposomes. This research highlights the promising role of gemini surfactant-incorporated liposomes as an efficient drug delivery platform for cardiovascular therapeutics, offering insights into the molecular interactions and structural dynamics underlying their enhanced performance.
本研究研究了双棕榈酰磷脂酰胆碱(DPPC)脂质体与gemini表面活性剂(十四甲基亚甲基-1,14二甲基十四烷基溴化铵)的结合;14-14-14)和阿托伐他汀,旨在提高心血管疾病的药物递送效率。将gemini表面活性剂整合到脂质体中,研究其改善阿托伐他汀包封和保留的潜力,解决药物的水溶性差和传统脂质体系统的局限性。通过动态光散射(DLS)、差示扫描量热法(DSC)和分子动力学(MD)模拟的结合,研究表明gemini表面活性剂的存在显著降低了脂质体的尺寸和多分散性,表明脂质体的结构更均匀,可能是单层结构。DSC分析强调了转变温度的降低和转变对称性的改变,表明在生理温度下稳定性增强和有利的药物释放谱。MD模拟揭示了gemini表面活性剂和阿托伐他汀在脂质体双分子层内的内化机制,证明了它们在极性相互作用下的相互结合。基于分光光度法的保留研究进一步证实,含有gemini表面活性剂的脂质体具有优越的阿托伐他汀保留能力,与常规脂质体相比,其包封效率几乎翻了一番。这项研究强调了gemini表面活性剂结合脂质体作为心血管治疗有效药物传递平台的前景,为其增强性能的分子相互作用和结构动力学提供了见解。
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引用次数: 0
Replacement of phenyl substituents at phosphorus by hexyl ones in 2-(2-hydroxyaryl)vinylphosphonium salts can tune the nature of the induced proton transport through lipid membranes 在2-(2-羟乙基)乙烯基磷酸盐中用己基取代磷上的苯基取代基可以调节诱导质子通过脂质膜转运的性质
IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-19 DOI: 10.1016/j.bbamem.2025.184417
Tatyana I. Rokitskaya , Ljudmila S. Khailova , Anna G. Strelnik , Elena A. Kotova , Vladimir F. Mironov , Dmitry A. Tatarinov , Yuri N. Antonenko
2-(2-hydroxyaryl)vinylphosphonium salts are zwitterionic protonophores previously shown to induce proton transport across lipid membranes via cyclic deprotonation and protonation of the hydroxyl group. Here, we examine the impact of the kind of substituents at phosphorus on the protonophoric activity of these compounds. In particular, replacement of all the three phenyl groups at the phosphorus atom of the 2-(2-hydroxyaryl)vinyl(triphenyl)phosphonium salt (2HVPPh3) by hexyl chains (2HVPHex3) led to a tremendous increase in electric current induced by the phosphonium salt across planar bilayer lipid membranes (BLM). Remarkably, the BLM conductance quadratically increased with increasing 2HVPHex3 concentration, whereas a linear concentration dependence of the BLM current was observed for 2HVPPh3, 2HVPHexPh2 ((hexyl)diphenyl) and 2HVPHex2Ph ((dihexyl)phenyl), i.e., in the presence of at least one phenyl substituent at the phosphorus atom. Proton selectivity of the 2HVPHex3-induced electric current was close to perfect in membranes formed of diphytanylphosphatidylcholine with the decreased dipole potential, but rather low in membranes formed of the usual synthetic lipid – diphytanoylphosphatidylcholine. We hypothesize that the proton transport across BLM is carried out by 2HVPHex3 dimers. By contrast, the uncoupling activity of 2HVPHex3 in isolated rat liver mitochondria was observed at similar concentrations, as found for the compounds with phenyl substituents, thereby indicating that dimers do not play a key role in the uncoupling process. At the same time, the rate of 2HVPHex3-induced mitochondrial swelling under the deenergized conditions in potassium acetate medium, reflecting the protonophoric activity of the compound in mitochondria, significantly exceeded that for other compounds.
2-(2-羟酰基)乙烯基磷酸盐是两性离子质子载体,先前证明可以通过羟基的环去质子化和质子化诱导质子在脂质膜上的转运。在这里,我们研究了磷取代基的种类对这些化合物的亲质子活性的影响。特别是,2-(2-羟基)乙烯基(三苯基)磷盐(2HVPPh3)磷原子上的三个苯基被己基链(2HVPHex3)取代,导致磷盐在平面双层脂质膜(BLM)上产生的电流急剧增加。值得注意的是,随着2HVPHex3浓度的增加,BLM电导呈二次增长,而对于2HVPPh3、2HVPHexPh2((己基)二苯基)和2HVPHex2Ph((二己基)苯基),即在磷原子上存在至少一个苯基取代基时,BLM电流呈线性依赖关系。在偶极电势降低的二植烷酰磷脂酰胆碱膜中,2hvphex3诱导电流的质子选择性接近完美,而在通常的合成脂质-二植烷酰磷脂酰胆碱膜中,质子选择性较低。我们假设质子通过BLM的输运是由2HVPHex3二聚体进行的。相比之下,2HVPHex3在离体大鼠肝脏线粒体中具有相似浓度的解偶联活性,与苯基取代基化合物相似,这表明二聚体在解偶联过程中不起关键作用。同时,在醋酸钾培养基中失电条件下,2hvphex3诱导的线粒体肿胀率明显超过其他化合物,反映了该化合物在线粒体中的亲原活性。
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Biochimica et biophysica acta. Biomembranes
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