Micelles Research Articles

Synthesis and research on pH and redox dual responsive UV-cross-linked micelle

Synthesis and research on pH and redox dual responsive UV-cross-linked micelle

Structural Stabilization and Functional Enhancement of Miceller Protein α-Crystallin by ATP and Zn2+

α-Crystallin is the most abundant protein of the eye lens. It has a micelle like associated structure and has a special chaperone- like property to prevent aggregation of other proteins. This function of α-crystallin plays a crucial role in maintaining the transparency of eye lens. Because of the absence of protein turn over in the lens, the proteins in the lens must survive the entire lifetime of the living species. This requires high structural stability of α-crystallin. In this article we present a brief review of our work on the mechanism of stabilization of α-crystallin by Zn. We have shown that some metal ions, Zn in particular play a very important role in enhancing the function of α-crystallin by enhancing its exposed hydrophobic surface. We have also characterized the Zn binding to α-crystallin by MALDI mass spectrometry and have shown that the structural stabilization occurs through intersubunit bridging by Zn. The binding region in the α-crystallin sequence has also been identified. The physiological relevance of enhanced chaperone function and structural stability is discussed.

BSA can form Micelle in Aqueous Solution

Protein aggregation is pathogenic and plays significant role in causing neurodegenerative diseases in biological system. Although the evolution of different types of protein aggregation mediated diseases are well-known, the origin and molecular mechanism of these aggregates remain unclear. In the present investigation, self-assembling characteristics of BSA is discussed by evaluating its critical micelle concentration (cmc) and aggregation number using surface tension and various spectroscopic techniques. The cmc of BSA is estimated to be 0.65-0.69 μM in solution. Steady state and time resolved fluorescence methods are employed to determine the aggregation number of the BSA micelles, which is found to be ~ 44. The accessibility of the fluorophore to the CPC quencher in the BSA micelle is assessed using Lehrer’s plot. Furthermore, the morphology and size of the aggregates are studied using HRTEM, Scanning Electron Microscopy, Confocal microscopy and Dynamic light scattering methods. The present study helps in understanding the physicochemical properties of BSA protein aggregation and also provides the mechanistic details of the phenomenon.

Fabrication and Multi-antitumor Effect of Novel Dextran-hemin Crosslinked Micelles Triggered by Photo Conditions†

Fabrication and Multi-antitumor Effect of Novel Dextran-hemin Crosslinked Micelles Triggered by Photo Conditions†

The oral bioavailability of curcuminoids in healthy humans is markedly enhanced by micellar solubilisation but not further improved by simultaneous ingestion of sesamin, ferulic acid, naringenin and xanthohumol

Curcuminoids (curcumin, demethoxycurcumin and bis-demethoxycurcumin) are poorly absorbed and rapidly metabolised and excreted. We investigated in healthy young and aged women and men if co-administration of adjuvants (sesamin, ferulic acid, naringenin, and xanthohumol) alone or in combination with micellar solubilisation improves the bioavailability of curcuminoids. A single oral dose of 98 mg curcuminoids was administered as native curcuminoids (NC), native curcuminoids plus phytochemicals (NCP), curcuminoid micelles (MC) or curcuminoid plus phytochemical micelles (MCP). Total curcuminoids were quantified in blood samples collected over 24 h. Based on the area under the curve, NCP, MC, and MCP increased the bioavailability of the major curcuminoid curcumin 8-, 88-, and 73-fold, respectively, compared to NC. No sex or age differences were observed. Thus, simultaneous ingestion of phytochemicals does modestly increase curcuminoid bioavailability, but does not enhance the large increase in bioavailability observed with micellar curcuminoids.

Synthetic of pH-Sensitive PEG-b-PHEMA(His) Polymers andthe Study of Micelle

通过点击化学(Click chemistry)与原子转移自由基聚合(ATRP)一锅法合成AB型嵌段聚合物聚乙二醇嵌段聚甲基丙烯酸羟乙酯(PEG-b-PHEMA),之后对所得聚合物进行组氨酸(His)修饰得到p H敏感型聚合物PEG-b-PHEMA(His),运用核磁共振(1H NMR)及凝胶渗透色谱(GPC)表征了该嵌段聚合物及组氨酸修饰后的产物的结构和分子量分布(Mn=8.2×103~13.0×103 g/mol,PDI=1.27~1.51),说明聚合物被成功地合成且具有较小的多分散系数.之后对嵌段聚合物PEG-b-PHEMA(His)进行了动态光散射(DLS)、透射电镜(TEM)和临界胶束浓度(CMC)的测试,结果表明,聚合物胶束呈球形且粒径分布均匀,并且粒径随组氨酸接枝率增大而减小.最后我们做不同接枝比的PEG-b-PHEMA(His)的酸碱滴定曲线,结果表明,组氨酸的接入使聚合物具备明显的p H响应能力,进一步的释药试验也证明了这一结果.

Polymeric 3D nano-architectures for transport and delivery of therapeutically relevant biomacromolecules.

A promising approach for addressing a range of diseases lies in the delivery of functional biomacromolecules such as nucleic acids or proteins to cells. Polymers, peptides and the different shapes accessible through self-assembly of polymeric and peptidic amphiphiles have been widely explored as carriers and as containers for reactions on the nanoscale. These building blocks are particularly interesting, because several essential parameters such as physical characteristics, conditions for degradation or biocompatibility can be tuned to suit specific requirements. In this review, different three-dimensional architectures ranging from dendrimers and hyperbranched molecules to micelles, vesicles and nanoparticles assembled from synthetic polymers and peptides are discussed. It is focused on their function as a carrier for biologically active macromolecules, highlighting seminal examples from the current literature and pointing out the remaining and upcoming challenges in this important area of research.

Beta-amyloid-acetylcholine structural interaction: evidence for neuroprotective effects of acetylcholine in neural cells

Alzheimer’s disease (AD) is regarded as a multifactorial disease characterized by a complex pathogenesis including a cholinergic deficit - due to degeneration of cholinergic projections from the basal forebrain - and the extracellular accumulation of amyloid beta (Aβ) peptide. Aβ containing 39 to 42 amino acids is the predominant component of the senile plaques that, together with neurofibrillary tangles, are regarded as the neuropathological hallmarks of AD (Sorrentino et al. 2014). Aβ may assume different conformations changing from random coil or α-helical monomers to β-sheet structures forming toxic oligomers and/or β-sheet mature fibrils. In this framework, we studied the effect of acetylcholine (ACh) on the conformation of Aβ by circular dichroism analysis. Moreover we investigated the ability of ACh to protect neuronal cells from the toxic action of amyloid peptide and to modulate the neuroinflammatory response occurring via the phospholipase A2 (PLA2). Results show that the amount of Aβ(25-35) β-strand raised linearly in absence of ACh, whereas it remained almost constant in presence of ACh. In addition, in a micelle solution mimicking the membrane environment ACh was found effective in increasing and stabilizing the soluble and not toxic helical content of Aβ(25-35) suggesting that ACh is capable to preserve the soluble form of Aβ(25-35), reducing the incipit of Aβ aggregation. In order to assess the neuro-protective ability of ACh against toxic Aβ(25-35) accumulation, we used neural cell (NCC) cultures containing both astrocytes and glial cells prepared from brains embryos from timed pregnant Wistar rats and infused ACh for 48h. By immunostaining, we observed that ACh reduced Aβ(25-35)-induced cell death. Then, we tested the protective effect of ACh on inflammation induced by Aβ administration. NCC were challenged with Aβ(25-35) in the presence and absence of ACh and immunostained for astroglial and neuronal markers: results showed a reduction of the morphological features of astrogliosys in ACh treated cells. PLA2 expression analysis corroborated these data also underlying that ACh can negatively regulate inflammation pathways in glial cells.

Progesterone-Induced Maturation and Down Regulation of Membrane Bound Na +, K+-ATPase

Progesterone induces maturation by releasing oocyte from G2 of MI cell cycle arrest. This process is rate limiting as it produces fertilizable eggs. Therefore, it draws a lot of attention. Na+, K+-ATPase is a membrane bound enzyme molecule that has known to have various functions. One of these functions is to act as receptor for Progesterone. In oocyte maturation to egg entirely depends on progesterone, a hormone that is known to reduce risk of cancer. Using EM Histo-cytochemical novel technique, we have shown that membrane bound Na+, K+-ATPase are gradually down-regulated following Progesterone-induced maturation. By Germinal Vesicle Break down, Na+, K+-ATPase is completely down-regulated from oolemma and only present in the narrow region of Germinal Vesicle Break Down. This is an important phenonmena as this down-regulation coincides with cell entering M-phase. Here, I also briefly introduce you to a technique that only localizes phosphate cleaving membrane bound Na+, K+-ATPase.

Interaction of Nickel-Dipeptide Complex with Ninhydrin in Aqueous and Micellar Media

Ninhydrin reactions using manual and automated techniques as well as ninhydrin spray reagents are wide ly used to analyze and characterize amino acids, peptides, and proteins as well as numerous other ninhydrin po sitive compounds in biomedical, clinical, food, forensic, histochemical , microbiological, and nutritional and plant studie s. Ninhydrin in aqueous solution reacts with α-amino acids to give a compound known as Ruhemann's purple (diketohydrindylidenediketohydrindamine, DYDA). In order to elucidate the mechanism of the reactions o f ninhydrin with (Ni(II)-Gly-Leu) + complexes, systematic kinetic studies were perform ed by following appearance of the respective colore d condensation products at different (surfactant), (r eactant), (salt) and temperature. The rates of the reaction were determined in both water and surfactant micelles in the absence and presence of various org anic and inorganic salts at 70 °C and pH 5.0. The result shows that the reaction follows the same fir st-order and fractional-order kinetics with respect to (Ni(II)-Gly-Leu) + and (ninhydrin), respectively, in both aqueous and mice llar medium. Quantitative kinetic analysis of k ψ(CTAB) data was performed on the basis of the pseudo-phase model of the micelles. + , CTAB

Optimizing Ultralow Interfacial Tension by Altering Surfactant Concentration Through Emulsion Test

Objectives : To select a specific concentration of surfactant, that could optimize Ultralow Interfacial tension between oil and Water. Formation of micro emulsion through Emulsion Test. Methodology : This work has been done through conductivity measurement of eight different surfactant concentrations to determine stable Critical Micelle Concentration (CMC). This concentration has been tested with different concentrations of electrolyte and alkali for middle layer micro emulsion. Results and Observations : Sodium Dodecyle Sulphate has been chosen for conductivity test. Through conductivity test CMC has been determined at 500ppm concentration. It has been tested with different concentrations of electrolyte and alkali for middle layer micro emulsion. Third layer have been appeared at NaCl 1.0 wt% and Alakli 0.5 wt%. At this particular concentration IFT between Oil and Water have been reduced.

Fluorescent Color Tuning of Conjugated Polymer Materials: Mechanisms and Methods

Conjugated polymers have received ever-increasing attention as fluorescent materials. They have many advantages compared w ith small-molecular fluorescent materials. As materials,conjugated polymers can be fabricated into different forms,such as thin films by spinning coating or drop casting,nano-/microfibers by electrospinning,nano-/microspheres,and micelle / vesicle /microtubule / nanoparticles by self-assembly . The great flexibility of conjugated polymers in processing makes it possible for them to meet the demands of different applications. With regard to the photophysics,the broader absorption allow s conjugated polymers to be excited by different light sources. In addition,the high resistance to the photobleaching,or photostability,guarantees a long lifetime when conjugated polymers in real applications. These advantages allow conjugated polymers to be used in different fields,ranging from fluorescent bioimaging and sensors,to optical encoding and photoelectric displays. Some applications,such as encoding and display,require that the fluorescent materials have various emission colors. Thus fluorescent color tuning is very important and also very challenging for realization of these applications. This article gives some detailed discussion about the main mechanisms for the color tuning,based

Structural insights of TM domain of LAMP-2A in DPC micelles

Structural insights of TM domain of LAMP-2A in DPC micelles

Hemocompatibility and cytocompatibility of diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-based micelles

合成的二嵌段共聚物聚（2-乙基-2-噁唑啉）-聚乳酸（PEOz-PLA）可自组装形成胶束，其在药物输送领域的应用与口俱增。然而，其与血液和细胞之间的相互作用迄今未知。本研究拟对PEOz-PLA胶束的血液相容性和细胞相容性进行评价，为PEOz-PLA胶束的潜在应用提供数据支持。通过溶血、凝血时间、血小板激活以及与白蛋白的相互作用评价了PEOz-PLA胶束的血液相容性。结果表明，PEOz-PLA胶束的血液相容性良好。SRB的实验结果表明，PEOz-PLA胶束与KBv细胞孵育后并未出现明显的细胞毒性，显示出良好的细胞相容性。总之，PEOz-PLA胶束是血液和细胞相容的药物载体，可用于静脉给药。

Unlocking Chain Exchange in Highly Amphiphilic Block Polymer Micellar Systems: Influence of Agitation.

Chain exchange between block polymer micelles in highly selective solvents, such as water, is well-known to be arrested under quiescent conditions, yet this work demonstrates that simple agitation methods can induce rapid chain exchange in these solvents. Aqueous solutions containing either pure poly(butadiene-b-ethylene oxide) or pure poly(butadiene-b-ethylene oxide-d4) micelles were combined and then subjected to agitation by vortex mixing, concentric cylinder Couette flow, or nitrogen gas sparging. Subsequently, the extent of chain exchange between micelles was quantified using small angle neutron scattering. Rapid vortex mixing induced chain exchange within minutes, as evidenced by a monotonic decrease in scattered intensity, whereas Couette flow and sparging did not lead to measurable chain exchange over the examined time scale of hours. The linear kinetics with respect to agitation time suggested a surface-limited exchange process at the air–water interface. These findings demonstrate the strong influence of processing conditions on block polymer solution assemblies.

Dual Role of Photosensitizer and Carrier Material of Fullerene in Micelles for Chemo–Photodynamic Therapy of Cancer

Derivatives of fullerene (C60) as photosensitizers have rarely been studied as delivery carrier materials. The focus of this study was to explore the potential advantages of diadduct malonic acid-fullerene (DMA-C60) as delivery carrier materials and combination of chemo-phototherapy of some tumors. In this study, DMA-C60 and docetaxel (DTX) were coentrapped in micelles (MCs) (DMA-C60/DTX-MC). The addition of DMA-C60 could obviously improve static stability and decrease critical MC concentration of DTX-MC without hemolysis. The sustained release of DTX and DMA-C60 could be achieved, following Higuichi and first-order model, respectively. DMA-C60 could still produce reactive oxygen species efficiently in HeLa cells after encapsulation in MC. The addition of DMA-C60 under irradiation caused DTX-MC more stronger cytotoxicity, cell cycle changes, and more early apoptotic cells in vitro. More importantly, after intravenous injection, the addition of DMA-C60 in DTX-MC could result in 2.25-fold and 4.57-fold longer mean residence time compared with DTX-MC and Duopafei(®) , increase drug intratumoral distribution and decrease drug distribution in heart and kidney, and enhance antitumor effect under irradiation without body weight loss. These results suggested tremendous promise of DMA-C60 as carrier materials of MC and significant advantages in combination of chemo-phototherapy of some tumors. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3225-3234, 2014.

Optimization of lipase extraction/recovery produced by the psychrotrophic yeast Leucosporidium scottii L117 using aqueous two-phase micellar systems

Universidade Estadual Paulista, Departamento de Bioquimica e Microbiologia, Instituto de Biociencias de Rio Claro

Synthesis and Self-assembly Behaviors of the ABC Miktoarm Star Terpolymer

The ABC miktoarm star terpolymer MPEG-PTHF (-PDMA) was synthesized by the combination of click chemistry, atom transfer radical polymerization (ATRP) and cationic ring opening polymerization (CROP). A block copolymer of poly(ethylene glycol) (PEG) and poly(N,N-dimethylaminoethyl methacrylate) (PDMA) which bears an azido at diblock junction (MPEG-N3 (-PDMA)) was first prepared by atom transfer radical polymerization. Then, an alkynyl-terminated narrow distributed polytetrahydrofuran (PTHF-Alk) was synthesized as another building block via cationic ring opening polymerization. The well-defined ABC miktoarm star shaped terpolymer was afforded by clicking MPEG-N, (-PDMA) onto the chain end of PTHF-Alk. The structure of the star terpolymer was characterized by the FTIR,NMR and SEC/MALLS. The self-assembly behavior of the polymer were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). This star shaped terpolymer consists of a hydrophobic PTHF chain, a hydrophiphilic PEG chain and another stimuli-responsive PDMA chain. It can self-assemble into micelles with different sizes and morphologies at various pH values, such as 5. 0,7. 4 and 9. 5. The micellar size also exhibits temperature-dependence at pH 7. 4 and 9. 5. The variation of size and morphology of the micelles with the solution pH and temperature is ascribed to the pH- and thermo-responsive properties of the PDMA block.

Surfactants solubility, concentration and the other formulations effects on the drug release rate from a controlled-release matrix

Surfactant effects on the drug release from controlled release systems have been widely studied. These effects are dependent on the surfactant physical properties such as structure, charge, solubility and concentration. In addition, presence of excipients in the matrices can modify the surfactants effects. Here we investigated the effects of surfactant solubility and concentration of excipients on the drug release. Two cationic surfactants (cetrimide and cetylpyridinium chloride), two anionic surfactants (sodium lauryl sulfate and sodium taurcholate) and the amphoteric surfactant betaine were used. The used dissolution medium was simulated gastric fluid pH 1.2. The results revealed that surfactants of the same charge with the drug showed increase of drug release rate in concentration below the surfactant critical micelle concentration (CMC), while the increase in the drug release was to a less extent in surfactant concentration above its CMC. On the other hand, drug release rate was increased with surfactant solubility and vice versa. Surfactants of different charges with that of the drug resulted in a decrease in the drug release rate, depending on surfactant solubility and the excipients. The amphoteric surfactant increased the drug release rate depending on surfactant solubility and concentrations. Key words: Propranolol hydrochloride, surfactant solubility, controlled-release, surfactant concentration, drug release rate.

Micellization and Adsolubilization of Amphilic Invertible Polyesters

Micellization and Adsolubilization of Amphilic Invertible Polyesters