Sample records for chlorophyll micelles models

  1. Characterisation of chlorophyll a solubilised in sodium lauryl sulphate micelles

    NASA Astrophysics Data System (ADS)

    Mukherjee, T.; Sapre, A. V.; Mittal, Jai P.

    1980-01-01

    Poisson statistics has been applied to the problem of solubilisation of chlorophyll a in sodium lauryl sulphate micelles. Dilution experiments have been carried out to support the finding that each unit of chlorophyll a contributing to the 740 nm band contains just one chlorophyll a molecule.

  2. Characterization of chlorophyll derivatives in micelles of polymeric surfactants aiming photodynamic applications

    NASA Astrophysics Data System (ADS)

    Gerola, Adriana Passarella; de Morais, Flavia Amanda Pedroso; Costa, Paulo Fernando A.; Kimura, Elza; Caetano, Wilker; Hioka, Noboru

    2017-02-01

    The spectrophotometric properties of chlorophylls' derivatives (Chls) formulated in the Pluronics® F-127 and P-123 were evaluated and the results have shown that the Chls were efficiently solubilized in these drug delivery systems as monomers. The relative location of the Chls in the Pluronics® was estimated from the Stokes shift and micropolarity of the micellar environment. Chls with phytyl chain were located in the micellar core, where the micropolarity is similar to ethanol, while phorbides' derivatives (without phytyl chain) were located in the outer shell of the micelle, i.e., more polar environment. In addition, the thermal stability of the micellar formulations was evaluated through electronic absorption, fluorescence emission and resonance light scattering with lowering the temperature. The Chls promote the stability of the micelles at temperatures below the Critical Micellar Temperature (CMT) of these surfactants. For F-127 formulations, the water molecules drive through inside the nano-structure at temperatures below the CMT, which increased the polarity of this microenvironment and directly affected the spectrophotometric properties of the Chls with phytyl chain. The properties of the micellar microenvironment of P-123, with more hydrophobic core due to the small PEO/PPO fraction, were less affected by lowering the temperature than for F-127. These results enable us to better understand the Chls behavior in micellar copolymers and allowed us to design new drug delivery system that maintains the photosensitizer's properties for photodynamic applications.

  3. Characterization of chlorophyll binding to LIL3.

    PubMed

    Mork-Jansson, Astrid Elisabeth; Eichacker, Lutz Andreas

    2018-01-01

    The light harvesting like protein 3 (LIL 3) from higher plants, has been linked to functions in chlorophyll and tocopherol biosynthesis, photo-protection and chlorophyll transfer. However, the binding of chlorophyll to LIL3 is unclear. We present a reconstitution protocol for chlorophyll binding to LIL3 in DDM micelles. It is shown in the absence of lipids and carotenoids that reconstitution of chlorophyll binding to in vitro expressed LIL3 requires pre-incubation of reaction partners at room temperature. We show chlorophyll a but not chlorophyll b binding to LIL3 at a molar ratio of 1:1. Neither dynamic light scattering nor native PAGE, enabled a discrimination between binding of chlorophyll a and/or b to LIL3.

  4. Characterization of chlorophyll binding to LIL3

    PubMed Central

    Mork-Jansson, Astrid Elisabeth

    2018-01-01

    The light harvesting like protein 3 (LIL 3) from higher plants, has been linked to functions in chlorophyll and tocopherol biosynthesis, photo-protection and chlorophyll transfer. However, the binding of chlorophyll to LIL3 is unclear. We present a reconstitution protocol for chlorophyll binding to LIL3 in DDM micelles. It is shown in the absence of lipids and carotenoids that reconstitution of chlorophyll binding to in vitro expressed LIL3 requires pre-incubation of reaction partners at room temperature. We show chlorophyll a but not chlorophyll b binding to LIL3 at a molar ratio of 1:1. Neither dynamic light scattering nor native PAGE, enabled a discrimination between binding of chlorophyll a and/or b to LIL3. PMID:29390011

  5. An extended PROSPECT: Advance in the leaf optical properties model separating total chlorophylls into chlorophyll a and b.

    PubMed

    Zhang, Yao; Huang, Jingfeng; Wang, Fumin; Blackburn, George Alan; Zhang, Hankui K; Wang, Xiuzhen; Wei, Chuanwen; Zhang, Kangyu; Wei, Chen

    2017-07-25

    The PROSPECT leaf optical model has, to date, well-separated the effects of total chlorophyll and carotenoids on leaf reflectance and transmittance in the 400-800 nm. Considering variations in chlorophyll a:b ratio with leaf age and physiological stress, a further separation of total plant-based chlorophylls into chlorophyll a and chlorophyll b is necessary for advanced monitoring of plant growth. In this study, we present an extended version of PROSPECT model (hereafter referred to as PROSPECT-MP) that can combine the effects of chlorophyll a, chlorophyll b and carotenoids on leaf directional hemispherical reflectance and transmittance (DHR and DHT) in the 400-800 nm. The LOPEX93 dataset was used to evaluate the capabilities of PROSPECT-MP for spectra modelling and pigment retrieval. The results show that PROSPECT-MP can both simultaneously retrieve leaf chlorophyll a and b, and also performs better than PROSPECT-5 in retrieving carotenoids concentrations. As for the simulation of DHR and DHT, the performances of PROSPECT-MP are similar to that of PROSPECT-5. This study demonstrates the potential of PROSPECT-MP for improving capabilities of remote sensing of leaf photosynthetic pigments (chlorophyll a, chlorophyll b and carotenoids) and for providing a framework for future refinements in the modelling of leaf optical properties.

  6. Multiscale Molecular Dynamics Simulations of Model Hydrophobically Modified Ethylene Oxide Urethane Micelles.

    PubMed

    Yuan, Fang; Larson, Ronald G

    2015-09-24

    The flower-like micelles of various aggregation numbers of a model hydrophobically modified ethylene oxide urethane (HEUR) molecule, C16E45C16, and their corresponding starlike micelles, containing the surfactants C16E22 and C16E23, were studied by atomistic and coarse-grained molecular dynamic (MD) simulations. We used free energies from umbrella sampling to calculate the size distribution of micelle sizes and the average time for escape of a hydrophobic group from the micelle. Using the coarse-grained MARTINI force field, the most probable size of the model HEUR molecule was thereby determined to be about 80 hydrophobes per micelle and the average hydrophobe escape time to be about 0.1 s, both of which are consistent with previous experimental studies. Atomistic simulations reveal that hydrogen bond formation and the mean lifetime of hydration waters of the poly(ethylene oxide) (or PEO) groups are location-dependent in the HEUR micelle, with PEO groups immediately adjacent to the C16 groups forming the fewest hydrogen bonds with water and having hydration waters with longer lifetimes than those of the PEO groups located further away from the C16 groups.

  7. [Estimation of forest canopy chlorophyll content based on PROSPECT and SAIL models].

    PubMed

    Yang, Xi-guang; Fan, Wen-yi; Yu, Ying

    2010-11-01

    The forest canopy chlorophyll content directly reflects the health and stress of forest. The accurate estimation of the forest canopy chlorophyll content is a significant foundation for researching forest ecosystem cycle models. In the present paper, the inversion of the forest canopy chlorophyll content was based on PROSPECT and SAIL models from the physical mechanism angle. First, leaf spectrum and canopy spectrum were simulated by PROSPECT and SAIL models respectively. And leaf chlorophyll content look-up-table was established for leaf chlorophyll content retrieval. Then leaf chlorophyll content was converted into canopy chlorophyll content by Leaf Area Index (LAD). Finally, canopy chlorophyll content was estimated from Hyperion image. The results indicated that the main effect bands of chlorophyll content were 400-900 nm, the simulation of leaf and canopy spectrum by PROSPECT and SAIL models fit better with the measured spectrum with 7.06% and 16.49% relative error respectively, the RMSE of LAI inversion was 0. 542 6 and the forest canopy chlorophyll content was estimated better by PROSPECT and SAIL models with precision = 77.02%.

  8. A review of ocean chlorophyll algorithms and primary production models

    NASA Astrophysics Data System (ADS)

    Li, Jingwen; Zhou, Song; Lv, Nan

    2015-12-01

    This paper mainly introduces the five ocean chlorophyll concentration inversion algorithm and 3 main models for computing ocean primary production based on ocean chlorophyll concentration. Through the comparison of five ocean chlorophyll inversion algorithm, sums up the advantages and disadvantages of these algorithm,and briefly analyzes the trend of ocean primary production model.

  9. "Non-equilibrium" block copolymer micelles with glassy cores: a predictive approach based on theory of equilibrium micelles.

    PubMed

    Nagarajan, Ramanathan

    2015-07-01

    Micelles generated in water from most amphiphilic block copolymers are widely recognized to be non-equilibrium structures. Typically, the micelles are prepared by a kinetic process, first allowing molecular scale dissolution of the block copolymer in a common solvent that likes both the blocks and then gradually replacing the common solvent by water to promote the hydrophobic blocks to aggregate and create the micelles. The non-equilibrium nature of the micelle originates from the fact that dynamic exchange between the block copolymer molecules in the micelle and the singly dispersed block copolymer molecules in water is suppressed, because of the glassy nature of the core forming polymer block and/or its very large hydrophobicity. Although most amphiphilic block copolymers generate such non-equilibrium micelles, no theoretical approach to a priori predict the micelle characteristics currently exists. In this work, we propose a predictive approach for non-equilibrium micelles with glassy cores by applying the equilibrium theory of micelles in two steps. In the first, we calculate the properties of micelles formed in the mixed solvent while true equilibrium prevails, until the micelle core becomes glassy. In the second step, we freeze the micelle aggregation number at this glassy state and calculate the corona dimension from the equilibrium theory of micelles. The condition when the micelle core becomes glassy is independently determined from a statistical thermodynamic treatment of diluent effect on polymer glass transition temperature. The predictions based on this "non-equilibrium" model compare reasonably well with experimental data for polystyrene-polyethylene oxide diblock copolymer, which is the most extensively studied system in the literature. In contrast, the application of the equilibrium model to describe such a system significantly overpredicts the micelle core and corona dimensions and the aggregation number. The non-equilibrium model suggests ways to

  10. Quantitative structure-property relationship (QSPR) modeling of drug-loaded polymeric micelles via genetic function approximation.

    PubMed

    Wu, Wensheng; Zhang, Canyang; Lin, Wenjing; Chen, Quan; Guo, Xindong; Qian, Yu; Zhang, Lijuan

    2015-01-01

    Self-assembled nano-micelles of amphiphilic polymers represent a novel anticancer drug delivery system. However, their full clinical utilization remains challenging because the quantitative structure-property relationship (QSPR) between the polymer structure and the efficacy of micelles as a drug carrier is poorly understood. Here, we developed a series of QSPR models to account for the drug loading capacity of polymeric micelles using the genetic function approximation (GFA) algorithm. These models were further evaluated by internal and external validation and a Y-randomization test in terms of stability and generalization, yielding an optimization model that is applicable to an expanded materials regime. As confirmed by experimental data, the relationship between microstructure and drug loading capacity can be well-simulated, suggesting that our models are readily applicable to the quantitative evaluation of the drug-loading capacity of polymeric micelles. Our work may offer a pathway to the design of formulation experiments.

  11. Quantitative Structure-Property Relationship (QSPR) Modeling of Drug-Loaded Polymeric Micelles via Genetic Function Approximation

    PubMed Central

    Lin, Wenjing; Chen, Quan; Guo, Xindong; Qian, Yu; Zhang, Lijuan

    2015-01-01

    Self-assembled nano-micelles of amphiphilic polymers represent a novel anticancer drug delivery system. However, their full clinical utilization remains challenging because the quantitative structure-property relationship (QSPR) between the polymer structure and the efficacy of micelles as a drug carrier is poorly understood. Here, we developed a series of QSPR models to account for the drug loading capacity of polymeric micelles using the genetic function approximation (GFA) algorithm. These models were further evaluated by internal and external validation and a Y-randomization test in terms of stability and generalization, yielding an optimization model that is applicable to an expanded materials regime. As confirmed by experimental data, the relationship between microstructure and drug loading capacity can be well-simulated, suggesting that our models are readily applicable to the quantitative evaluation of the drug-loading capacity of polymeric micelles. Our work may offer a pathway to the design of formulation experiments. PMID:25780923

  12. Remote sensing of oligotrophic waters: model divergence at low chlorophyll concentrations.

    PubMed

    Mehrtens, Hela; Martin, Thomas

    2002-11-20

    The performance of the OC2 Sea-viewing Wide Field-of-view Sensor (SeaWiFS) algorithm based on 490- and 555-nm water-leaving radiances at low chlorophyll contents is compared with those of semianalytical models and a Monte Carlo radiative transfer model. We introduce our model, which uses two particle phase functions and scattering coefficient parameterizations to achieve a backscattering ratio that varies with chlorophyll concentration. We discuss the various parameterizations and compare them with existent measurements. The SeaWiFS algorithm could be confirmed within an accuracy of 35% over a chlorophyll range from 0.1 to 1 mg m(-3), whereas for lower chlorophyll concentrations we found a significant overestimation of the OC2 algorithm.

  13. Modeling micelle formation and interfacial properties with iSAFT classical density functional theory

    NASA Astrophysics Data System (ADS)

    Wang, Le; Haghmoradi, Amin; Liu, Jinlu; Xi, Shun; Hirasaki, George J.; Miller, Clarence A.; Chapman, Walter G.

    2017-03-01

    Surfactants reduce the interfacial tension between phases, making them an important additive in a number of industrial and commercial applications from enhanced oil recovery to personal care products (e.g., shampoo and detergents). To help obtain a better understanding of the dependence of surfactant properties on molecular structure, a classical density functional theory, also known as interfacial statistical associating fluid theory, has been applied to study the effects of surfactant architecture on micelle formation and interfacial properties for model nonionic surfactant/water/oil systems. In this approach, hydrogen bonding is explicitly included. To minimize the free energy, the system minimizes interactions between hydrophobic components and hydrophilic components with water molecules hydrating the surfactant head group. The theory predicts micellar structure, effects of surfactant architecture on critical micelle concentration, aggregation number, and interfacial tension isotherm of surfactant/water systems in qualitative agreement with experimental data. Furthermore, this model is applied to study swollen micelles and reverse swollen micelles that are necessary to understand the formation of a middle-phase microemulsion.

  14. Modeling of estuarne chlorophyll a from an airborne scanner

    USGS Publications Warehouse

    Khorram, Siamak; Catts, Glenn P.; Cloern, James E.; Knight, Allen W.

    1987-01-01

    Near simultaneous collection of 34 surface water samples and airborne multispectral scanner data provided input for regression models developed to predict surface concentrations of estuarine chlorophyll a. Two wavelength ratios were employed in model development. The ratios werechosen to capitalize on the spectral characteristics of chlorophyll a, while minimizing atmospheric influences. Models were then applied to data previously acquired over the study area thre years earlier. Results are in the form of color-coded displays of predicted chlorophyll a concentrations and comparisons of the agreement among measured surface samples and predictions basedon coincident remotely sensed data. The influence of large variations in fresh-water inflow to the estuary are clearly apparent in the results. The synoptic view provided by remote sensing is another method of examining important estuarine dynamics difficult to observe from in situ sampling alone.

  15. Intravitreal injection of rapamycin-loaded polymeric micelles for inhibition of ocular inflammation in rat model.

    PubMed

    Wu, Wei; He, Zhifen; Zhang, Zhaoliang; Yu, Xinxin; Song, Zongming; Li, Xingyi

    2016-11-20

    The therapeutic efficacy of rapamycin conjugated monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles (rapamycin micelles) was evaluated in a rat experimental autoimmune uveitis (EAU) model. Rapamycin micelles exhibited spherical morphology and had a mean particle size of 40nm and a zeta-potential of -0.89mv. The water solubility of rapamycin improved by more than 1000-fold in a micellar formulation. Intravitreal injection of MPEG-PCL micelles did not result in vitreous hemorrhage or retinal detachment. Fluorescence microscopy demonstrated that labeled micelles localized to the retinal pigment epithelium for at least 14 days following injection and the drug concentration of rapamycin micelles in the retinal tissue was significantly higher than unconjugated rapamycin over this period. At the optimal concentration of rapamycin micelles (9μg/eye), clinical signs of EAU were abolished via the downregulation of the Th1 and Th17 response. There were no significant difference in T cell proliferation and delayed-type hypersensitivity between the treatment and control groups, suggesting that the therapeutic effect of rapamycin manifested locally in the eye and not systemically. These results indicate that intravitreal injection of rapamycin micelles is a promising therapy for controlling sterile intraocular inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Patterns and Variability in Global Ocean Chlorophyll: Satellite Observations and Modeling

    NASA Technical Reports Server (NTRS)

    Gregg, Watson

    2004-01-01

    Recent analyses of SeaWiFS data have shown that global ocean chlorophyll has increased more than 4% since 1998. The North Pacific ocean basin has increased nearly 19%. These trend analyses follow earlier results showing decadal declines in global ocean chlorophyll and primary production. To understand the causes of these changes and trends we have applied the newly developed NASA Ocean Biogeochemical Assimilation Model (OBAM), which is driven in mechanistic fashion by surface winds, sea surface temperature, atmospheric iron deposition, sea ice, and surface irradiance. The model utilizes chlorophyll from SeaWiFS in a daily assimilation. The model has in place many of the climatic variables that can be expected to produce the changes observed in SeaWiFS data. This enables us to diagnose the model performance, the assimilation performance, and possible causes for the increase in chlorophyll. A full discussion of the changes and trends, possible causes, modeling approaches, and data assimilation will be the focus of the seminar.

  17. Casein micelles and their internal structure.

    PubMed

    de Kruif, Cornelis G; Huppertz, Thom; Urban, Volker S; Petukhov, Andrei V

    2012-01-01

    The internal structure of casein micelles was studied by calculating the small-angle neutron and X-ray scattering and static light scattering spectrum (SANS, SAXS, SLS) as a function of the scattering contrast and composition. We predicted experimental SANS, SAXS, SLS spectra self consistently using independently determined parameters for composition size, polydispersity, density and voluminosity. The internal structure of the casein micelles, i.e. how the various components are distributed within the casein micelle, was modeled according to three different models advocated in the literature; i.e. the classical sub-micelle model, the nanocluster model and the dual binding model. In this paper we present the essential features of these models and combine new and old experimental SANS, SAXS, SLS and DLS scattering data with new calculations that predict the spectra. Further evidence on micellar substructure was obtained by internally cross linking the casein micelles using transglutaminase, which led to casein nanogel particles. In contrast to native casein micelles, the nanogel particles were stable in 6M urea and after sequestering the calcium using trisodium citrate. The changed scattering properties were again predicted self consistently. An important result is that the radius of gyration is independent of contrast, indicating that the mass distribution within a casein micelle is homogeneous. Experimental contrast is predicted quite well leading to a match point at a D(2)O volume fraction of 0.41 ratio in SANS. Using SANS and SAXS model calculations it is concluded that only the nanocluster model is capable of accounting for the experimental scattering contrast variation data. All features and trends are predicted self consistently, among which the 'famous' shoulder at a wave vector value Q=0.35 nm(-1) In the nanocluster model, the casein micelle is considered as a (homogeneous) matrix of caseins in which the colloidal calcium phosphate (CCP) nanoclusters are

  18. Casein micelles and their internal structure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    De Kruif, Cornelis G; Huppertz, Thom; Urban, Volker S

    2012-01-01

    The internal structure of casein micelles was studied by calculating the small-angle neutron and X-ray scattering and static light scattering spectrum (SANS, SAXS, SLS) as a function of the scattering contrast and composition. We predicted experimental SANS, SAXS, SLS spectra self consistently using independently determined parameters for composition size, polydispersity, density and voluminosity. The internal structure of the casein micelles, i.e. how the various components are distributed within the casein micelle, was modeled according to three different models advocated in the literature; i.e. the classical sub-micelle model, the nanocluster model and the dual binding model. In this paper we presentmore » the essential features of these models and combine new and old experimental SANS, SAXS, SLS and DLS scattering data with new calculations that predict the spectra. Further evidence on micellar substructure was obtained by internally cross linking the casein micelles using transglutaminase, which led to casein nanogel particles. In contrast to native casein micelles, the nanogel particles were stable in 6 M urea and after sequestering the calcium using trisodium citrate. The changed scattering properties were again predicted self consistently. An important result is that the radius of gyration is independent of contrast, indicating that the mass distribution within a casein micelle is homogeneous. Experimental contrast is predicted quite well leading to a match point at a D{sub 2}O volume fraction of 0.41 ratio in SANS. Using SANS and SAXS model calculations it is concluded that only the nanocluster model is capable of accounting for the experimental scattering contrast variation data. All features and trends are predicted self consistently, among which the 'famous' shoulder at a wave vector value Q = 0.35 nm{sup -1}. In the nanocluster model, the casein micelle is considered as a (homogeneous) matrix of caseins in which the colloidal calcium phosphate (CCP

  19. Curcumin-loaded chitosan-cholesterol micelles: evaluation in monolayers and 3D cancer spheroid model.

    PubMed

    Muddineti, Omkara Swami; Kumari, Preeti; Ray, Eupa; Ghosh, Balaram; Biswas, Swati

    2017-06-02

    To improve the bioavailability and anticancer potential of curcumin by using a cholesterol-conjugated chitosan micelle. Methods & methods: Cholesterol was conjugated to chitosan (15 kDa) to form self-assembled micelles, which loaded curcumin. Physicochemical characterization and formulation optimization of the drug-loaded micelles (curcumin-loaded chitosan-cholesterol micelles [C-CCM]) were performed. In vitro cellular uptake and viability of C-CCM were investigated in melanoma and breast cancer cell lines. The antitumor efficacy was evaluated in 3D lung cancer spheroid model. The optimized C-CCM had size of approximately 162 nm with loading efficiency of approximately 36%. C-CCM was taken up efficiently by the cells, and it reduced cancer cell viability significantly compared with free curcumin. C-CCM enhanced the antitumor efficacy in spheroids, suggesting that C-CCM could be used as an effective chemotherapy in cancer.

  20. Photo-responsive polymeric micelles.

    PubMed

    Huang, Yu; Dong, Ruijiao; Zhu, Xinyuan; Yan, Deyue

    2014-09-07

    Photo-responsive polymeric micelles have received increasing attention in both academic and industrial fields due to their efficient photo-sensitive nature and unique nanostructure. In view of the photo-reaction mechanism, photo-responsive polymeric micelles can be divided into five major types: (1) photoisomerization polymeric micelles, (2) photo-induced rearrangement polymeric micelles, (3) photocleavage polymeric micelles, (4) photo-induced crosslinkable polymeric micelles, and (5) photo-induced energy conversion polymeric micelles. This review highlights the recent advances of photo-responsive polymeric micelles, including the design, synthesis and applications in various biomedical fields. Especially, the influence of different photo-reaction mechanisms on the morphology, structure and properties of the polymeric micelles is emphasized. Finally, the possible future directions and perspectives in this emerging area are briefly discussed.

  1. Ocean Chlorophyll as a Precursor of ENSO: An Earth System Modeling Study

    NASA Astrophysics Data System (ADS)

    Park, Jong-Yeon; Dunne, John P.; Stock, Charles A.

    2018-02-01

    Ocean chlorophyll concentration, a proxy for phytoplankton, is strongly influenced by internal ocean dynamics such as those associated with El Niño-Southern Oscillation (ENSO). Observations show that ocean chlorophyll responses to ENSO generally lead sea surface temperature (SST) responses in the equatorial Pacific. A long-term global Earth system model simulation incorporating marine biogeochemical processes also exhibits a preceding chlorophyll response. In contrast to simulated SST anomalies, which significantly lag the wind-driven subsurface heat response to ENSO, chlorophyll anomalies respond rapidly. Iron was found to be the key factor connecting the simulated surface chlorophyll anomalies to the subsurface ocean response. Westerly wind bursts decrease central Pacific chlorophyll by reducing iron supply through wind-driven thermocline deepening but increase western Pacific chlorophyll by enhancing the influx of coastal iron from the maritime continent. Our results mechanistically support the potential for chlorophyll-based indices to inform seasonal ENSO forecasts beyond previously identified SST-based indices.

  2. Iron Oxide Nanoparticle-Micelles (ION-Micelles) for Sensitive (Molecular) Magnetic Particle Imaging and Magnetic Resonance Imaging

    PubMed Central

    Starmans, Lucas W. E.; Burdinski, Dirk; Haex, Nicole P. M.; Moonen, Rik P. M.; Strijkers, Gustav J.; Nicolay, Klaas; Grüll, Holger

    2013-01-01

    Background Iron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. Methods and Results IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots. Conclusions The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for

  3. Iron oxide nanoparticle-micelles (ION-micelles) for sensitive (molecular) magnetic particle imaging and magnetic resonance imaging.

    PubMed

    Starmans, Lucas W E; Burdinski, Dirk; Haex, Nicole P M; Moonen, Rik P M; Strijkers, Gustav J; Nicolay, Klaas; Grüll, Holger

    2013-01-01

    Iron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots. The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in

  4. The Evaluation Of Therapeutic Efficacy and Safety Profile of Simvastatin Prodrug Micelles in a Closed Fracture Mouse Model

    PubMed Central

    Zhang, Yijia; Jia, Zhenshan; Yuan, Hongjiang; Dusad, Anand; Ren, Ke; Wei, Xin; Fehringer, Edward V.; Purdue, P. Edward; Daluiski, Aaron; Goldring, Steven R.; Wang, Dong

    2016-01-01

    Purpose To evaluate the therapeutic efficiency of a micellar prodrug formulation of simvastatin (SIM/SIM-mPEG) and explore its safety in a closed femoral fracture mouse model. Methods The amphiphilic macromolecular prodrug of simvastatin (SIM-mPEG) was synthesized and formulated together with free simvastatin into micelles. It was also labeled with a near infrared dye for in vivo imaging purpose. A closed femoral fracture mouse model was established using a three-point bending device. The mice with established closed femoral fracture were treated with SIM/SIM-mPEG micelle, using free simvastatin and saline as controls. The therapeutic efficacy of the micelles was evaluated using a high-resolution micro-CT. Serum biochemistry and histology analyses were performed to explore the potential toxicity of the micelle formulation. Results Near Infrared Fluorescence (NIRF) imaging confirmed the passive targeting of SIM/SIM-mPEG micelles to the bone lesion of the mice with closed femoral fracture. The micelle was found to promote fracture healing with an excellent safety profile. In addition, the accelerated healing of the femoral fracture also helped to prevent disuse-associated same-side tibia bone loss accompanying the femur fracture. Conclusion SIM/SIM-mPEG micelle was found to be an effective and safe treatment for closed femoral fracture repair in mice. The evidence obtained in this study suggests that it may have the potential to be translated into a novel therapy for clinical management of skeletal fractures and non-union. PMID:27164897

  5. Casein micelle dispersions under osmotic stress.

    PubMed

    Bouchoux, Antoine; Cayemitte, Pierre-Emerson; Jardin, Julien; Gésan-Guiziou, Geneviève; Cabane, Bernard

    2009-01-01

    Casein micelles dispersions have been concentrated and equilibrated at different osmotic pressures using equilibrium dialysis. This technique measured an equation of state of the dispersions over a wide range of pressures and concentrations and at different ionic strengths. Three regimes were found. i), A dilute regime in which the osmotic pressure is proportional to the casein concentration. In this regime, the casein micelles are well separated and rarely interact, whereas the osmotic pressure is dominated by the contribution from small residual peptides that are dissolved in the aqueous phase. ii), A transition range that starts when the casein micelles begin to interact through their kappa-casein brushes and ends when the micelles are forced to get into contact with each other. At the end of this regime, the dispersions behave as coherent solids that do not fully redisperse when osmotic stress is released. iii), A concentrated regime in which compression removes water from within the micelles, and increases the fraction of micelles that are irreversibly linked to each other. In this regime the osmotic pressure profile is a power law of the residual free volume. It is well described by a simple model that considers the micelle to be made of dense regions separated by a continuous phase. The amount of water in the dense regions matches the usual hydration of proteins.

  6. Casein Micelle Dispersions under Osmotic Stress

    PubMed Central

    Bouchoux, Antoine; Cayemitte, Pierre-Emerson; Jardin, Julien; Gésan-Guiziou, Geneviève; Cabane, Bernard

    2009-01-01

    Abstract Casein micelles dispersions have been concentrated and equilibrated at different osmotic pressures using equilibrium dialysis. This technique measured an equation of state of the dispersions over a wide range of pressures and concentrations and at different ionic strengths. Three regimes were found. i), A dilute regime in which the osmotic pressure is proportional to the casein concentration. In this regime, the casein micelles are well separated and rarely interact, whereas the osmotic pressure is dominated by the contribution from small residual peptides that are dissolved in the aqueous phase. ii), A transition range that starts when the casein micelles begin to interact through their κ-casein brushes and ends when the micelles are forced to get into contact with each other. At the end of this regime, the dispersions behave as coherent solids that do not fully redisperse when osmotic stress is released. iii), A concentrated regime in which compression removes water from within the micelles, and increases the fraction of micelles that are irreversibly linked to each other. In this regime the osmotic pressure profile is a power law of the residual free volume. It is well described by a simple model that considers the micelle to be made of dense regions separated by a continuous phase. The amount of water in the dense regions matches the usual hydration of proteins. PMID:19167314

  7. Supramolecular structure of the casein micelle.

    PubMed

    McMahon, D J; Oommen, B S

    2008-05-01

    The supramolecular structure of colloidal casein micelles in milk was investigated by using a sample preparation protocol based on adsorption of proteins onto a poly-l-lysine and parlodion-coated copper grid, staining of proteins and calcium phosphate by uranyl oxalate, instantaneous freezing, and drying under a high vacuum. High-resolution transmission electron microscopy stereo-images were obtained showing the interior structure of casein micelles. On the basis of our interpretation of these images, an interlocked lattice model was developed in which both casein-calcium phosphate aggregates and casein polymer chains act together to maintain casein micelle integrity. The caseins form linear and branched chains (2 to 5 proteins long) interlocked by the casein-stabilized calcium phosphate nanoclusters. This model suggests that stabilization of calcium phosphate nanoclusters by phosphoserine domains of alpha(s1)-, alpha(s2)-, or beta-casein, or their combination, would orient their hydrophobic domains outward, allowing interaction and binding to other casein molecules. Other interactions between the caseins, such as calcium bridging, could also occur and further stabilize the supramolecule. The combination of having an interlocked lattice structure and multiple interactions results in an open, sponge-like colloidal supramolecule that is resistant to spatial changes and disintegration. Hydrophobic interactions between caseins surrounding a calcium phosphate nanocluster would prevent complete dissociation of casein micelles when the calcium phosphate nanoclusters are solubilized. Likewise, calcium bridging and other electrostatic interactions between caseins would prevent dissociation of the casein micelles into casein-calcium phosphate nanocluster aggregates when milk is cooled or urea is added to milk, and hydrophobic interactions are reduced. The appearance of both polymer chains and small aggregate particles during milk synthesis would also be expected based on

  8. Treating acute cystitis with biodegradable micelle-encapsulated quercetin

    PubMed Central

    Wang, Bi Lan; Gao, Xiang; Men, Ke; Qiu, Jinfeng; Yang, Bowen; Gou, Ma Ling; Huang, Mei Juan; Huang, Ning; Qian, Zhi Yong; Zhao, Xia; Wei, Yu Quan

    2012-01-01

    Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These QU/MPEG-PCL micelles with DL of 7% had a mean particle size of <34 nm, and could release QU for an extended period in vitro. The in vivo study indicated that intravesical application of MPEG-PCL micelles did not induce any toxicity to the bladder, and could efficiently deliver cargo to the bladder. Moreover, the therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle treatment efficiently reduced the edema and inflammatory cell infiltration of the bladder in an Escherichia coli-induced acute cystitis model. These data suggested that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL micelles may have potential application in acute cystitis therapy. PMID:22661886

  9. Impact of chlorophyll bias on the tropical Pacific mean climate in an earth system model

    NASA Astrophysics Data System (ADS)

    Lim, Hyung-Gyu; Park, Jong-Yeon; Kug, Jong-Seong

    2017-12-01

    Climate modeling groups nowadays develop earth system models (ESMs) by incorporating biogeochemical processes in their climate models. The ESMs, however, often show substantial bias in simulated marine biogeochemistry which can potentially introduce an undesirable bias in physical ocean fields through biogeophysical interactions. This study examines how and how much the chlorophyll bias in a state-of-the-art ESM affects the mean and seasonal cycle of tropical Pacific sea-surface temperature (SST). The ESM used in the present study shows a sizeable positive bias in the simulated tropical chlorophyll. We found that the correction of the chlorophyll bias can reduce the ESM's intrinsic cold SST mean bias in the equatorial Pacific. The biologically-induced cold SST bias is strongly affected by seasonally-dependent air-sea coupling strength. In addition, the correction of chlorophyll bias can improve the annual cycle of SST by up to 25%. This result suggests a possible modeling approach in understanding the two-way interactions between physical and chlorophyll biases by biogeophysical effects.

  10. Effect of hydrostatic pressure on gas solubilization in micelles.

    PubMed

    Meng, Bin; Ashbaugh, Henry S

    2015-03-24

    Molecular dynamics simulations of anionic sodium decylsulfate and nonionic pentaethylene glycol monodecyl ether micelles in water have been performed to examine the impact of hydrostatic pressure on argon solubilization as a function of pressure. The potential-of-mean force between the micelles and argon demonstrates that nonpolar gases are attracted to the interiors of both micelles. The affinity of argon for micelle interiors, however, decreases with increasing pressure as a result of the comparatively higher molar volume of argon inside assemblies. We evaluate solubility enhancement coefficients, which describe the drop in the solute chemical potential as a function of the micellized surfactant concentration, to quantify the impact of micellization on gas solubilization. While argon is similarly attracted to the hydrophobic cores of both micelles, the gas is more effectively sequestered within nonionic micelles compared with anionic micelles as a result of salting out by charged head groups and accompanying counterions. The solubility enhancement coefficients of both micelles decrease with increasing pressure, reflecting the changing forces observed in the potentials-of-mean force. An analytical liquid drop model is proposed to describe the pressure dependence of argon solubilization within micelles that captures the simulation solubility enhancement coefficients after fitting an effective micelle radius for each surfactant.

  11. Rennet-induced coagulation properties of yak casein micelles: A comparison with cow casein micelles.

    PubMed

    Zhang, Yan; Li, Yuan; Wang, Pengjie; Tian, Yanbao; Liang, Qi; Ren, Fazheng

    2017-12-01

    It is essential for yak cheese processing to understand the rennet-induced coagulation properties of gel formation from casein micelles. We have previously discovered that yak milk requires a longer incubation time but forms stronger gels compared with cow milk. In this study, we are aiming to understand the rennet-induced coagulation properties of yak casein micelles comparing with cow casein micelles. Rheological analyses revealed that the gelling times of yak and cow casein micelles were 11.6±0.5 and 8.7±0.4min (P<0.05) respectively, but yak casein gel had a higher elastic modulus G' (6.5±0.2Pa) than cow casein gel (2.5±0.2Pa; P<0.05). This is consistent with the results obtained by micro-rheology. Confocal laser scanning microscopic images (CLSM) and cryo-scanning electron microscopic images (cryo-SEM) showed that yak casein gel was more homogeneous and had smaller pore size than cow casein gels. Yak casein micelles had higher calcium (26.00mM), phosphate (19.90mM) and β-casein (relative 32%) concentrations. In addition, yak casein micelles were larger (Z-average 218.6nm) than cow casein micelles, and contained lower κ-casein (relative 13%). By comparison with cow casein micelles, yak casein micelle composition corresponding to their micellar calcium phosphate and κ-casein content may greatly contribute to the longer coagulation time and denser gel structure. An initial slower caseinomacropeptide (CMP) release rate and the slower rate of aggregation between para-casein micelles contributed to a more homogeneous yak gel network. Higher colloidal calcium phosphate is crucial for yak casein micelle aggregation and gel firmness because sufficient colloidal calcium phosphates can firmly glue sub-micelles and links casein micelles. This study provides valuable information for yak cheese production. Copyright © 2017. Published by Elsevier Ltd.

  12. Influence of succinylation on the conformation of yak casein micelles.

    PubMed

    Yang, Min; Cui, Na; Fang, Yan; Shi, Ying; Yang, Jitao; Wang, Jiangyu

    2015-07-15

    Succinylation modifies the physicochemical characteristics and improves the functional properties of proteins. This study assessed the effects of succinylation on the conformation of yak casein micelles with seven degree of modification. The results revealed that succinylation contributed to the dissociation of casein micelles. With the increase of succinylated degree, soluble nitrogen and minerals content increased, while casein micelle size and polydispersity index of micelles decreased. Succinylation affected the spatial conformation of yak casein micelles: turn decreased, ß-sheet and α-helix increased, and irregular structure were non-significantly affected. The intrinsic and ANS fluorescence intensity decreased and the maximum emission wavelength shifted red with increasing succinylation. Based on the results, the structure of yak casein micelles was characteristic of the sub-micelle model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Responsive micellar films of amphiphilic block copolymer micelles: control on micelle opening and closing.

    PubMed

    Chen, Zhiquan; He, Changcheng; Li, Fengbin; Tong, Ling; Liao, Xingzhi; Wang, Yong

    2010-06-01

    We reported the deliberate control on the micelle opening and closing of amphiphilic polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) micellar films by exposing them to selective solvents. We first treated the micellar films with polar solvents including ethanol and water (pH = 4, 8, and 12) that have different affinities to P2VP. We observed opening of the micelles in all the cases. Both the size of opened pores and the opening rate are dependent on the solvency of different solvents for P2VP. We then explored the closing behavior of the opened micelles using solvents having different affinities to PS. We found that the opened micelles were recovered to their initial closed micelle forms. The recovery was accompanied by a slow micelle disassociation process which gradually reduced the micelle size. The rates of the micelle closing and disassociation are also dependent on the solvency of different solvents for PS.

  14. The efficacy of nimodipine drug delivery using mPEG-PLA micelles and mPEG-PLA/TPGS mixed micelles.

    PubMed

    Huang, Shuling; Yu, Xiaohong; Yang, Linlin; Song, Fenglan; Chen, Gang; Lv, Zhufen; Li, Tiao; Chen, De; Zhu, Wanhua; Yu, Anan; Zhang, Yongming; Yang, Fan

    2014-10-15

    In order to develop and compare mPEG-PLA micelles and mPEG-PLA/TPGS mixed micelles, with the intention to develop a highly efficient formulation for nimodipine (NIM), NIM-loaded micelles and mixed micelles were made and their pharmacokinetics were studied. Single factor experiments and orthogonal experiments were designed to optimize the final preparation process, characterizations and drug release behaviors were studied. Pharmacokinetics of NIM micelles, NIM mixed micelles were researched and were compared to NIM solution. Micelles and mixed micelles were prepared by solvent evaporation method, with relatively high drug loading efficiency and within nano-particle size range. The CMC value of mPEG-PLA was lower than that of mPEG-PLA/TPGS. The results of FTIR and TEM confirmed the spherical core-shell structure of micelles as well as mixed micelles, and the encapsulation of NIM inside the cores. In vitro release showed that micelles and mixed micelles had sustained release effect in the forms of passive diffusion and dissolution process, respectively. Following intraperitoneal administration (5mg/kg), micelles and mixed micelles were absorbed faster than solution, and with larger MRT(0-t), smaller CLz and larger AUC(0-t) as compared to that of solution, which showed micelles and mixed micelles had higher retention, slower elimination and higher bioavailability. This experiment also showed that mixed micelles released NIM more stably than micelles. By evaluate the bioequivalence, NIM micelles and NIM mixed micelles were testified non-bioequivalent to NIM solution. Micelles and mixed micelles could sustain the NIM concentrations more efficiently in plasma as compared to solution. Mixed micelles were the best ones since they had high loading content and released more stably. Thus, apprehending micelles and mixed micelles were suited as poor aqueous solubility drug carriers, and mixed micelles were better due to their high loading content and more stable release

  15. Enhancing curcumin anticancer efficacy through di-block copolymer micelle encapsulation.

    PubMed

    Lv, Li; Shen, Yuanyuan; Liu, Jieying; Wang, Feihu; Li, Min; Li, Min; Guo, Aijie; Wang, Yun; Zhou, Dejian; Guo, Shengrong

    2014-02-01

    We report herein the development of a novel aqueous formulation and improved antitumor activity for curcumin by encapsulating it into a biocompatible and biodegradable poly(L-lactic acid) based poly(anhydride-ester)-b-poly(ethylene glycol) (PAE-b-PEG) micelle. The resulting curcumin loaded micelles were completely water-dispersible, overcoming the problem of poor water solubility that limited its efficacy and bioavailability. In vitro cellular studies revealed that the curcumin-loaded micelles were taken up mainly via endocytosis route and exhibited higher cytotoxicities toward model cancer cell lines (HeLa and EMT6) than free curcumin. An in vivo biodistribution study revealed that the curcumin-loaded micelles displayed significantly enhanced accumulation inside the tumor of EMT6 breast tumor-bearing mice. More impressively, the curcumin-loaded micelles showed stronger antitumor activity, higher anti-angiogenesis effects and induced apoptosis on the EMT6 breast tumor model bearing mice than free curcumin. Furthermore, the curcumin-loaded micelles showed no significant toxicity towards hemotological system, major organs or tissues in mice. Combined with a high antitumor activity and low toxic side-effects, the curcumin-loaded micelles developed here thus appear to be a highly attractive nanomedicine for effective, targeted cancer therapy.

  16. Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells

    NASA Astrophysics Data System (ADS)

    Deng, Senyi; Wu, Qinjie; Zhao, Yuwei; Zheng, Xin; Wu, Ni; Pang, Jing; Li, Xuejing; Bi, Cheng; Liu, Xinyu; Yang, Li; Liu, Lei; Su, Weijun; Wei, Yuquan; Gong, Changyang

    2015-03-01

    Circulating tumor cells (CTCs) play a crucial role in tumor metastasis, but it is rare for any chemotherapy regimen to focus on killing CTCs. Herein, we describe doxorubicin (Dox) micelles that showed anti-metastatic activity by killing CTCs. Dox micelles with a small particle size and high encapsulation efficiency were obtained using a pH-induced self-assembly method. Compared with free Dox, Dox micelles exhibited improved cytotoxicity, apoptosis induction, and cellular uptake. In addition, Dox micelles showed a sustained release behavior in vitro, and in a transgenic zebrafish model, Dox micelles exhibited a longer circulation time and lower extravasation from blood vessels into surrounding tissues. Anti-tumor and anti-metastatic activities of Dox micelles were investigated in transgenic zebrafish and mouse models. In transgenic zebrafish, Dox micelles inhibited tumor growth and prolonged the survival of tumor-bearing zebrafish. Furthermore, Dox micelles suppressed tumor metastasis by killing CTCs. In addition, improved anti-tumor and anti-metastatic activities were also confirmed in mouse tumor models, where immunofluorescent staining of tumors indicated that Dox micelles induced more apoptosis and showed fewer proliferation-positive cells. There were decreased side effects in transgenic zebrafish and mice after administration of Dox micelles. In conclusion, Dox micelles showed stronger anti-tumor and anti-metastatic activities and decreased side effects both in vitro and in vivo, which may have potential applications in cancer therapy.

  17. Inversion of chlorophyll contents by use of hyperspectral CHRIS data based on radiative transfer model

    NASA Astrophysics Data System (ADS)

    Wang, M. C.; Niu, X. F.; Chen, S. B.; Guo, P. J.; Yang, Q.; Wang, Z. J.

    2014-03-01

    Chlorophyll content, the most important pigment related to photosynthesis, is the key parameter for vegetation growth. The continuous spectrum characteristics of ground objects can be captured through hyperspectral remotely sensed data. In this study, based on the coniferous forest radiative transfer model, chlorophyll contents were inverted by use of hyperspectral CHRIS data in the coniferous forest coverage of Changbai Mountain Area. In addition, the sensitivity of LIBERTY model was analyzed. The experimental results validated that the reflectance simulation of different chlorophyll contents was coincided with that of the field measurement, and hyperspectral vegetation indices applied to the quantitative inversion of chlorophyll contents was feasible and accurate. This study presents a reasonable method of chlorophyll inversion for the coniferous forest, promotes the inversion precision, is of significance in coniferous forest monitoring.

  18. Predicting critical micelle concentration and micelle molecular weight of polysorbate 80 using compendial methods.

    PubMed

    Braun, Alexandra C; Ilko, David; Merget, Benjamin; Gieseler, Henning; Germershaus, Oliver; Holzgrabe, Ulrike; Meinel, Lorenz

    2015-08-01

    This manuscript addresses the capability of compendial methods in controlling polysorbate 80 (PS80) functionality. Based on the analysis of sixteen batches, functionality related characteristics (FRC) including critical micelle concentration (CMC), cloud point, hydrophilic-lipophilic balance (HLB) value and micelle molecular weight were correlated to chemical composition including fatty acids before and after hydrolysis, content of non-esterified polyethylene glycols and sorbitan polyethoxylates, sorbitan- and isosorbide polyethoxylate fatty acid mono- and diesters, polyoxyethylene diesters, and peroxide values. Batches from some suppliers had a high variability in functionality related characteristic (FRC), questioning the ability of the current monograph in controlling these. Interestingly, the combined use of the input parameters oleic acid content and peroxide value - both of which being monographed methods - resulted in a model adequately predicting CMC. Confining the batches to those complying with specifications for peroxide value proved oleic acid content alone as being predictive for CMC. Similarly, a four parameter model based on chemical analyses alone was instrumental in predicting the molecular weight of PS80 micelles. Improved models based on analytical outcome from fingerprint analyses are also presented. A road map controlling PS80 batches with respect to FRC and based on chemical analyses alone is provided for the formulator. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Vegetation chlorophyll estimates in the Amazon from multi-angle MODIS observations and canopy reflectance model

    NASA Astrophysics Data System (ADS)

    Hilker, Thomas; Galvão, Lênio Soares; Aragão, Luiz E. O. C.; de Moura, Yhasmin M.; do Amaral, Cibele H.; Lyapustin, Alexei I.; Wu, Jin; Albert, Loren P.; Ferreira, Marciel José; Anderson, Liana O.; dos Santos, Victor A. H. F.; Prohaska, Neill; Tribuzy, Edgard; Barbosa Ceron, João Vitor; Saleska, Scott R.; Wang, Yujie; de Carvalho Gonçalves, José Francisco; de Oliveira Junior, Raimundo Cosme; Cardoso Rodrigues, João Victor Figueiredo; Garcia, Maquelle Neves

    2017-06-01

    As a preparatory study for future hyperspectral missions that can measure canopy chemistry, we introduce a novel approach to investigate whether multi-angle Moderate Resolution Imaging Spectroradiometer (MODIS) data can be used to generate a preliminary database with long-term estimates of chlorophyll. MODIS monthly chlorophyll estimates between 2000 and 2015, derived from a fully coupled canopy reflectance model (ProSAIL), were inspected for consistency with eddy covariance fluxes, tower-based hyperspectral images and chlorophyll measurements. MODIS chlorophyll estimates from the inverse model showed strong seasonal variations across two flux-tower sites in central and eastern Amazon. Marked increases in chlorophyll concentrations were observed during the early dry season. Remotely sensed chlorophyll concentrations were correlated to field measurements (r2 = 0.73 and r2 = 0.98) but the data deviated from the 1:1 line with root mean square errors (RMSE) ranging from 0.355 μg cm-2 (Tapajós tower) to 0.470 μg cm-2 (Manaus tower). The chlorophyll estimates were consistent with flux tower measurements of photosynthetically active radiation (PAR) and net ecosystem productivity (NEP). We also applied ProSAIL to mono-angle hyperspectral observations from a camera installed on a tower to scale modeled chlorophyll pigments to MODIS observations (r2 = 0.73). Chlorophyll pigment concentrations (ChlA+B) were correlated to changes in the amount of young and mature leaf area per month (0.59 ≤ r2 ≤ 0.64). Increases in MODIS observed ChlA+B were preceded by increased PAR during the dry season (0.61 ≤ r2 ≤ 0.62) and followed by changes in net carbon uptake. We conclude that, at these two sites, changes in LAI, coupled with changes in leaf chlorophyll, are comparable with seasonality of plant productivity. Our results allowed the preliminary development of a 15-year time series of chlorophyll estimates over the Amazon to support canopy chemistry studies using future

  20. Micelle depletion-induced vs. micelle-mediated aggregation in nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ray, D., E-mail: debes.phys@gmail.com; Aswal, V. K.

    2015-06-24

    The phase behavior anionic silica nanoparticle (Ludox LS30) with non-ionic surfactants decaethylene glycol monododecylether (C12E10) and cationic dodecyltrimethyl ammonium bromide (DTAB) in aqueous electrolyte solution has been studied by small-angle neutron scattering (SANS). The measurements have been carried out for fixed concentrations of nanoparticle (1 wt%), surfactants (1 wt%) and electrolyte (0.1 M NaCl). Each of these nanoparticle–surfactant systems has been examined for different contrast conditions where individual components (nanoparticle or surfactant) are made visible. It is observed that the nanoparticle-micelle system in both the cases lead to the aggregation of nanoparticles. The aggregation is found to be micelle depletion-inducedmore » for C12E10 whereas micelle-mediated aggregation for DTAB. Interestingly, it is also found that phase behavior of mixed surfactant (C12E10 + DTAB) system is similar to that of C12E10 (unlike DTAB) micelles with nanoparticles.« less

  1. Polymer nano-particle hybrid micelles: Encapsulation of POSS into semi-fluorinated polymer micelles

    NASA Astrophysics Data System (ADS)

    Ratnaweera, Dilru; Perahia, Dvora; Iacono, Scott; Mabry, Joseph; Smith, Dennis

    2012-02-01

    Self-assembly of block copolymers in selective solvents was used to form a nanoparticle (NP)/polymer hybrid micelles. These micelles can be used as a cargo vehicle for other substances such as drug delivery, and as building blocks for polymer-nanocomposites with controlled NP distribution. Association of NPs into specific blocks of the copolymer depends on the compatibility between the NPs and the block as well as their preference to the solvent that micellization takes place. The current work introduces a small angle neutron scattering study of association of Polyhedral Oligomeric Silsesquioxane (POSS) NPs into micelles of a highly segregating random copolymer, Biphenyl Perfluorocyclobutane (BPh-PFCB), in toluene, which is a good solvent for BPh. Incompatibility between the blocks drives copolymer into micelles with PFCB in the core and BPh in swollen corona. Modification of NPs with polymer chains drives POSS cages into the micelle core and prevents the micelle dissociation at higher temperatures.

  2. Gradient structure-induced temperature responsiveness in styrene/methyl methacrylate gradient copolymers micelles.

    PubMed

    Zheng, Chao; Huang, Haiying; He, Tianbai

    2014-02-01

    In this work, micelles are formed by gradient copolymer of styrene and methyl methacrylate in acetone-water mixture and their temperature responsiveness is investigated in a narrow range near room temperature. Three different kinds of structural transitions could be induced by temperature: unimers to micelle transition, shrinkage/stretching of micelles, and morphological transition from spherical micelles to vesicles. In addition, a model analysis on the interface of gradient copolymer micelle is made to better understand these phenomena. It is found that both position and composition of the interface could alter in response to the change in temperature. According to the experiments and model analysis, it is proposed that temperature responsiveness might be an intrinsic and universal property of gradient copolymer micelles, which only originates from the gradient structure. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Cationizable lipid micelles as vehicles for intraarterial glioma treatment.

    PubMed

    Nguyen, Juliane; Cooke, Johann R N; Ellis, Jason A; Deci, Michael; Emala, Charles W; Bruce, Jeffrey N; Bigio, Irving J; Straubinger, Robert M; Joshi, Shailendra

    2016-05-01

    The relative abundance of anionic lipids on the surface of endothelia and on glioma cells suggests a workable strategy for selective drug delivery by utilizing cationic nanoparticles. Furthermore, the extracellular pH of gliomas is relatively acidic suggesting that tumor selectivity could be further enhanced if nanoparticles can be designed to cationize in such an environment. With these motivating hypotheses the objective of this study was to determine whether nanoparticulate (20 nm) micelles could be designed to improve their deposition within gliomas in an animal model. To test this, we performed intra-arterial injection of micelles labeled with an optically quantifiable dye. We observed significantly greater deposition (end-tissue concentration) of cationizable micelles as compared to non-ionizable micelles in the ipsilateral hemisphere of normal brains. More importantly, we noted enhanced deposition of cationizable as compared to non-ionizable micelles in glioma tissue as judged by semiquantitative fluorescence analysis. Micelles were generally able to penetrate to the core of the gliomas tested. Thus we conclude that cationizable micelles may be constructed as vehicles for facilitating glioma-selective delivery of compounds after intraarterial injection.

  4. Growth of wormlike micelles in nonionic surfactant solutions: Quantitative theory vs. experiment.

    PubMed

    Danov, Krassimir D; Kralchevsky, Peter A; Stoyanov, Simeon D; Cook, Joanne L; Stott, Ian P; Pelan, Eddie G

    2018-06-01

    Despite the considerable advances of molecular-thermodynamic theory of micelle growth, agreement between theory and experiment has been achieved only in isolated cases. A general theory that can provide self-consistent quantitative description of the growth of wormlike micelles in mixed surfactant solutions, including the experimentally observed high peaks in viscosity and aggregation number, is still missing. As a step toward the creation of such theory, here we consider the simplest system - nonionic wormlike surfactant micelles from polyoxyethylene alkyl ethers, C i E j . Our goal is to construct a molecular-thermodynamic model that is in agreement with the available experimental data. For this goal, we systematized data for the micelle mean mass aggregation number, from which the micelle growth parameter was determined at various temperatures. None of the available models can give a quantitative description of these data. We constructed a new model, which is based on theoretical expressions for the interfacial-tension, headgroup-steric and chain-conformation components of micelle free energy, along with appropriate expressions for the parameters of the model, including their temperature and curvature dependencies. Special attention was paid to the surfactant chain-conformation free energy, for which a new more general formula was derived. As a result, relatively simple theoretical expressions are obtained. All parameters that enter these expressions are known, which facilitates the theoretical modeling of micelle growth for various nonionic surfactants in excellent agreement with the experiment. The constructed model can serve as a basis that can be further upgraded to obtain quantitative description of micelle growth in more complicated systems, including binary and ternary mixtures of nonionic, ionic and zwitterionic surfactants, which determines the viscosity and stability of various formulations in personal-care and house-hold detergency. Copyright © 2018

  5. Effect of styrene maleic acid WIN55,212-2 micelles on neuropathic pain in a rat model.

    PubMed

    Linsell, Oliver; Brownjohn, Philip W; Nehoff, Hayley; Greish, Khaled; Ashton, John C

    2015-05-01

    Cannabinoid receptor agonists are moderately effective at reducing neuropathic pain but are limited by psychoactivity. We developed a styrene maleic acid (SMA) based on the cannabinoid WIN 55,212-2 (WIN) and tested in a rat model of neuropathic pain and in the rotarod test. We hypothesized that miceller preparation can ensure prolonged plasma half-life being above the renal threshold of excretion. Furthermore, SMA-WIN could potentially reduce the central nervous system effects of encapsulated WIN by limiting its transport across the blood-brain barrier. Using the chronic constriction injury model of sciatic neuropathy, the SMA-WIN micelles were efficacious in the treatment of neuropathic pain for a prolonged period compared to control (base WIN). Attenuation of chronic constriction injury-induced mechanical allodynia occurred for up to 8 h at a dose of 11.5 mg/kg of SMA-WIN micelles. To evaluate central effects on motor function, the rotarod assessment was utilized. Results showed initial impairment caused by SMA-WIN micelles to be identical to WIN control for up to 1.5 h. Despite this, the SMA-WIN micelle formulation was able to produce prolonged analgesia over a time when there was decreased impairment in the rotarod test compared with base WIN.

  6. The Use of Dodecylphosphocholine Micelles in Solution NMR

    NASA Astrophysics Data System (ADS)

    Kallick, D. A.; Tessmer, M. R.; Watts, C. R.; Li, C. Y.

    Dodecylphosphocholine (DPC) micelles are useful as a model membrane system for solution NMR. Several new observations on dodecylphosphocholine micelles and their interactions with opioid peptides are described. The optimal lipid concentration has been investigated for small peptide NMR studies in DPC micelles for two opioid peptides, a 5-mer and a 17-mer. In contrast to reports in the literature, identical 2D spectra have been observed at low and high lipid concentrations. The chemical shift of resolved peptide proton resonances has been followed as a function of added lipid and indicates that there are changes in the chemical shifts above the critical micelle concentration and up to a ratio of 7:1 (lipid:peptide) for the 17-mer, and 9.6:1 for the 5-mer. These results suggest that conformational changes occur in the peptide significantly above the critical micelle concentration, up to a lipid:peptide ratio which is dependent upon the peptide, here ranging from 7:1 to 9.6:1. To address the stoichiometry more directly, the diffusion coefficients of the lipid alone and the lipid with peptide have been measured using pulsed-field gradient spin-echo NMR experiments. These data have been used to calculate the hydrodynamic radius and the aggregation number of the micelle with and without peptide and show that the aggregation number of the peptide-lipid complex increases at high lipid concentrations without a concomitant change in the peptide conformation. Last, several protonated impurities have been observed in the commercial preparation of DPC which resonate in the amide proton region of the NMR spectrum. These results are significant for researchers using DPC micelles and illustrate that both care in sample preparation and the stoichiometry are important issues with the use of DPC as a model membrane.

  7. Self-assembly of star micelle into vesicle in solvents of variable quality: the star micelle retains its core-shell nanostructure in the vesicle.

    PubMed

    Liu, Nijuan; He, Qun; Bu, Weifeng

    2015-03-03

    Intra- and intermolecular interactions of star polymers in dilute solutions are of fundamental importance for both theoretical interest and hierarchical self-assembly into functional nanostructures. Here, star micelles with a polystyrene corona and a small ionic core bearing platinum(II) complexes have been regarded as a model of star polymers to mimic their intra- and interstar interactions and self-assembled behaviors in solvents of weakening quality. In the chloroform/methanol mixture solvents, the star micelles can self-assemble to form vesicles, in which the star micelles shrink significantly and are homogeneously distributed on the vesicle surface. Unlike the morphological evolution of conventional amphiphiles from micellar to vesicular, during which the amphiphilic molecules are commonly reorganized, the star micelles still retain their core-shell nanostructures in the vesicles and the coronal chains of the star micelle between the ionic cores are fully interpenetrated.

  8. Aggregation work at polydisperse micellization: ideal solution and "dressed micelle" models comparing to molecular dynamics simulations.

    PubMed

    Burov, S V; Shchekin, A K

    2010-12-28

    General thermodynamic relations for the work of polydisperse micelle formation in the model of ideal solution of molecular aggregates in nonionic surfactant solution and the model of "dressed micelles" in ionic solution have been considered. In particular, the dependence of the aggregation work on the total concentration of nonionic surfactant has been analyzed. The analogous dependence for the work of formation of ionic aggregates has been examined with regard to existence of two variables of a state of an ionic aggregate, the aggregation numbers of surface active ions and counterions. To verify the thermodynamic models, the molecular dynamics simulations of micellization in nonionic and ionic surfactant solutions at two total surfactant concentrations have been performed. It was shown that for nonionic surfactants, even at relatively high total surfactant concentrations, the shape and behavior of the work of polydisperse micelle formation found within the model of the ideal solution at different total surfactant concentrations agrees fairly well with the numerical experiment. For ionic surfactant solutions, the numerical results indicate a strong screening of ionic aggregates by the bound counterions. This fact as well as independence of the coefficient in the law of mass action for ionic aggregates on total surfactant concentration and predictable behavior of the "waterfall" lines of surfaces of the aggregation work upholds the model of "dressed" ionic aggregates.

  9. Structure and dynamics of ionic micelles: MD simulation and neutron scattering study.

    PubMed

    Aoun, B; Sharma, V K; Pellegrini, E; Mitra, S; Johnson, M; Mukhopadhyay, R

    2015-04-16

    Fully atomistic molecular dynamics (MD) simulations have been carried out on sodium dodecyl sulfate (SDS), an anionic micelle, and three cationic (CnTAB; n = 12, 14, 16) micelles, investigating the effects of size, the form of the headgroup, and chain length. They have been used to analyze neutron scattering data. MD simulations confirm the dynamical model of global motion of the whole micelle, segmental motion (headgroup and alkyl chain), and fast torsional motion associated with the surfactants that is used to analyze the experimental data. It is found that the solvent surrounding the headgroups results in their significant mobility, which exceeds that of the tails on the nanosecond time scale. The middle of the chain is found to be least mobile, consolidating the micellar configuration. This dynamical feature is similar for all the ionic micelles investigated and therefore independent of headgroup form and charge and chain length. Diffusion constants for global and segmental motion of the different micelles are consistent with experimentally obtained values as well as known structural features. This work provides a more realistic model of micelle dynamics and offers new insight into the strongly fluctuating surface of micelles which is important in understanding micelle dispersion and related functionality, like drug delivery.

  10. Polymerization of anionic wormlike micelles.

    PubMed

    Zhu, Zhiyuan; González, Yamaira I; Xu, Hangxun; Kaler, Eric W; Liu, Shiyong

    2006-01-31

    Polymerizable anionic wormlike micelles are obtained upon mixing the hydrotropic salt p-toluidine hydrochloride (PTHC) with the reactive anionic surfactant sodium 4-(8-methacryloyloxyoctyl)oxybenzene sulfonate (MOBS). Polymerization captures the cross-sectional radius of the micelles (approximately 2 nm), induces micellar growth, and leads to the formation of a stable single-phase dispersion of wormlike micellar polymers. The unpolymerized and polymerized micelles were characterized using static and dynamic laser light scattering, small-angle neutron scattering, 1H NMR, and stopped-flow light scattering. Stopped-flow light scattering was also used to measure the average lifetime of the unpolymerized wormlike micelles. A comparison of the average lifetime of unpolymerized wormlike micelles with the surfactant monomer propagation rate was used to elucidate the mechanism of polymerization. There is a significant correlation between the ratio of the average lifetime to the monomer propagation rate and the average aggregation number of the polymerized wormlike micelles.

  11. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, John L.; Smith, Richard D.

    1993-01-01

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W.sub.o that determines the maximum size of the reverse micelles. The maximum ratio W.sub.o of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions.

  12. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  13. Development of transferrin targeted NCL-240 micelles and their evaluation using in-vitro 3D cancer cell culture (spheroid) models

    NASA Astrophysics Data System (ADS)

    Nagelli, Srikar Goud

    The main objective of this project was to develop targeted micellar delivery systems of a novel cytotoxic drug (NCL-240; a second generation DM-PIT-1 analog) and to evaluate their efficacy using optimized 3D cell culture spheroid models. Spheroids were optimized for several cancer cell lines using a range of techniques such as non-adhesive liquid overlay method, hanging drop method, and co-culturing. Transferrin (Tf)-conjugated NCL-240 micelles were prepared with varying Tf amounts and their cytotoxicities were evaluated using the optimized spheroid models. The uptake and penetration of the formulations were also studied using confocal microscopy. The results indicated that the concentration of NCL-240 micelles required to achieve the same cytotoxicity was relatively higher in spheroids compared to the monolayers. Also, In NCI-ADR-RES, Tf-targeted NCL-240 micelles were shown to have a significant increase in cytotoxicity compared to untargeted NCL-240 micelles. Even the penetration and uptake studies indicated that targeting improves the uptake and penetration of formulations. However, in U87-MG spheroids, there was a significant difference in cell viability among micelles compared to free drug but no significant benefit due to targeting was observed. The same formulations penetrated lesser in U87-MG spheroids compared to NCI-ADR-RES spheroids. This study thereby emphasizes the importance of drug screening in spheroid models as the penetration dynamics are varying from cell line to cell line because of the 3D structure.

  14. Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model

    PubMed Central

    Kim, Tae Hee; Mount, Christopher W; Dulken, Benjamin W; Ramos, Jenelyn; Fu, Caroline J; Khant, Htet A; Chiu, Wah; Gombotz, Wayne R; Pun, Suzie H

    2012-01-01

    Polymeric micelles formed by the self-assembly of amphiphilic block copolymers can be used to encapsulate hydrophobic drugs for tumor-delivery applications. Filamentous carriers with high aspect ratios offer potential advantages over spherical carriers, including prolonged circulation times. In this work, mixed micelles comprised of poly (ethylene oxide)-poly-[(R)-3-hydroxybutyrate]-poly (ethylene oxide) (PEO-PHB-PEO) and Pluronic F-127 (PF-127) were used to encapsulate a near-infrared fluorophore. The micelle formulations were assessed for tumor accumulation after tail vein injection to xenograft tumor-bearing mice by non-invasive optical imaging. The mixed micelle formulation that facilitated the highest tumor accumulation was shown by cryo-electron microscopy to be filamentous in structure compared to spherical structures of pure PF-127 micelles. In addition, increased dye loading efficiency and dye stability was attained in this mixed micelle formulation compared to pure PEO-PHB-PEO micelles. Therefore, the optimized PEO-PHB-PEO/PF-127 mixed micelle formulation offers advantages for cancer delivery over micelles formed from the individual copolymer components. PMID:22118658

  15. Antimicrobial activity of topically-applied soyaethyl morpholinium ethosulfate micelles against Staphylococcus species.

    PubMed

    Yang, Shih-Chun; Aljuffali, Ibrahim A; Sung, Calvin T; Lin, Chwan-Fwu; Fang, Jia-You

    2016-03-01

    Here we evaluated the antibacterial efficacy of soyaethyl morpholinium ethosulfate (SME) micelles as an inherent bactericide against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The antimicrobial activity was examined by in vitro culture model and murine model of skin infection. Cationic micelles formed by benzalkonium chloride or cetylpyridinium chloride were used for comparison. The minimum inhibitory concentration and minimum bactericidal concentration against S. aureus and MRSA were 1.71-3.42 and 1.71-6.84 μg/ml, respectively. Topical administration of SME micelles significantly decreased the cutaneous infection and MRSA load in mice. The killing of bacteria was caused by direct cell wall/membrane rupture. SME micelles also penetrated into the bacteria to elicit a Fenton reaction and oxidative stress. SME micelles have potential as antimicrobial agents due to their lethal effect against S. aureus and MRSA with a low toxicity to mammalian cells.

  16. Reflectance model for quantifying chlorophyll a in the presence of productivity degradation products

    NASA Technical Reports Server (NTRS)

    Carder, K. L.; Hawes, S. K.; Steward, R. G.; Baker, K. A.; Smith, R. C.; Mitchell, B. G.

    1991-01-01

    A reflectance model developed to estimate chlorophyll a concentrations in the presence of marine colored dissolved organic matter, pheopigments, detritus, and bacteria is presented. Nomograms and lookup tables are generated to describe the effects of different mixtures of chlorophyll a and these degradation products on the R(412):R(443) and R(443):R(565) remote-sensing reflectance or irradiance reflectance ratios. These are used to simulate the accuracy of potential ocean color satellite algorithms, assuming that atmospheric effects have been removed. For the California Current upwelling and offshore regions, with chlorophyll a not greater than 1.3 mg/cu m, the average error for chlorophyll a retrievals derived from irradiance reflectance data for degradation product-rich areas was reduced from +/-61 percent to +/-23 percent by application of an algorithm using two reflectance ratios rather than the commonly used algorithm applying a single reflectance ratio.

  17. Assessment of predictive models for chlorophyll-a concentration of a tropical lake

    PubMed Central

    2011-01-01

    Background This study assesses four predictive ecological models; Fuzzy Logic (FL), Recurrent Artificial Neural Network (RANN), Hybrid Evolutionary Algorithm (HEA) and multiple linear regressions (MLR) to forecast chlorophyll- a concentration using limnological data from 2001 through 2004 of unstratified shallow, oligotrophic to mesotrophic tropical Putrajaya Lake (Malaysia). Performances of the models are assessed using Root Mean Square Error (RMSE), correlation coefficient (r), and Area under the Receiving Operating Characteristic (ROC) curve (AUC). Chlorophyll-a have been used to estimate algal biomass in aquatic ecosystem as it is common in most algae. Algal biomass indicates of the trophic status of a water body. Chlorophyll- a therefore, is an effective indicator for monitoring eutrophication which is a common problem of lakes and reservoirs all over the world. Assessments of these predictive models are necessary towards developing a reliable algorithm to estimate chlorophyll- a concentration for eutrophication management of tropical lakes. Results Same data set was used for models development and the data was divided into two sets; training and testing to avoid biasness in results. FL and RANN models were developed using parameters selected through sensitivity analysis. The selected variables were water temperature, pH, dissolved oxygen, ammonia nitrogen, nitrate nitrogen and Secchi depth. Dissolved oxygen, selected through stepwise procedure, was used to develop the MLR model. HEA model used parameters selected using genetic algorithm (GA). The selected parameters were pH, Secchi depth, dissolved oxygen and nitrate nitrogen. RMSE, r, and AUC values for MLR model were (4.60, 0.5, and 0.76), FL model were (4.49, 0.6, and 0.84), RANN model were (4.28, 0.7, and 0.79) and HEA model were (4.27, 0.7, and 0.82) respectively. Performance inconsistencies between four models in terms of performance criteria in this study resulted from the methodology used in measuring

  18. Musk Oxen and Micelles

    NASA Astrophysics Data System (ADS)

    Hill, John W.

    1996-09-01

    Musk oxen behavior provides an analogy to micelle formation by amphipathic substances. Mature male musk oxen protect their young and females from wolves by forming a protective circle around them. The males stand with their tails to the inside and their heads facing outward. Amphipathic substances such as soap form micelles. The hydrophobic hydrocarbon tails of the soap are turned to the inside of the micelle and the hydrophilic carboxylate heads are on the outside at the interface with the polar water molecules.

  19. Apparent voluminosity of casein micelles determined by rheometry.

    PubMed

    Nöbel, Stefan; Weidendorfer, Konrad; Hinrichs, Jörg

    2012-11-15

    The voluminosity of casein micelles was studied by means of static rheometry. In concentrated casein micelle suspensions with fluid-like flow properties to random-close packing, the reduced viscosity was obtained and linked via the Krieger-Dougherty model of volume fraction effect. The temperature dependency of hydration was fitted in a wide temperature (5°C≤θ≤35°C) and mass fraction range (0.01≤w≤0.16). The results of our study suggested that the voluminosity of casein micelles decreased with increasing temperature and asymptotically reached a plateau (θ>30°C) as a consequence of the protein swelling and decreasing water immobilization. The obtained apparent voluminosity of native casein micelles dispersed in UF permeate was 5.0 ml g(-1) at 5°C, 4.1 ml g(-1) at 20°C, and 3.7 ml g(-1) at 35°C. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Hydration behavior of casein micelles in thin film geometry: a GISANS study?

    PubMed

    Metwalli, E; Moulin, J F; Gebhardt, R; Cubitt, R; Tolkach, A; Kulozik, U; Müller-Buschbaum, P

    2009-04-07

    The water content of casein micelle films in water vapor atmosphere is investigated using time-resolved grazing incidence small-angle neutron scattering (GISANS). Initial dry casein films are prepared with a spin-coating method. At 30 degrees C, the formation of a water-equilibrated casein protein film is reached after 11 min with a total content of 0.36 g of water/g of protein. With increasing water vapor temperature up to 70 degrees C, an increase in the water content is found. With GISANS, lateral structures on the nanometer scale are resolved during the swelling experiment at different temperatures and modeled using two types of spheres: micelles and mini-micelles. Upon water uptake, molecular assemblies in the size range of 15 nm (mini-micelles) are attributed to the formation of a high-contrast D2O outer shell on the small objects that already exist in the protein film. For large objects (>100 nm), the mean size increases at high D2O vapor temperature because of possible aggregation between hydrated micelles. These results are discussed and compared with various proposed models for casein micelle structures.

  1. Light Scattering Characterization of Elastin-Like Polypeptide Trimer Micelles

    NASA Astrophysics Data System (ADS)

    Tsuper, Ilona; Terrano, Daniel; Maraschky, Adam; Holland, Nolan; Streletzky, Kiril

    The elastin-like polypeptides (ELP) nanoparticles are composed of three-armed star polypeptides connected by a negatively charged foldon. Each of the three arms extending from the foldon domain includes 20 repeats of the (GVGVP) amino acid sequence. The ELP polymer chains are soluble at room temperature and become insoluble at the transition temperature (close to 50 ° C), forming micelles. The size and shape of the micelle are dependent on the temperature and the pH of the solution, and on the concentration of the phosphate buffered saline (PBS). The depolarized dynamic light scattering (DDLS) was employed to study the structure and dynamics of micelles at 62 ° C. The solution was maintained at an approximate pH level of 7.3 - 7.5, while varying PBS concentration. At low salt concentrations (<15 mM), the micelle radius was about 10nm but not very reproducible on account of unstable pH levels arising from low buffer concentrations. At intermediate salt concentrations (15 - 60 mM), the system formed spherically-shaped micelles, exhibiting a steady growth in the hydrodynamic radius (Rh) from 10 to 21 nm, with increasing PBS concentration. Interestingly, higher salt concentrations (>60 mM) displayed an apparent elongation of the micelles evident by a significant VH signal, along with a surge in the apparent Rh. A model of micelle growth (and potential elongation) with increase in salt concentration is considered.

  2. Simvastatin Prodrug Micelles Target Fracture and Improve Healing

    PubMed Central

    Dusad, Anand; Yuan, Hongjiang; Ren, Ke; Li, Fei; Fehringer, Edward V.; Purdue, P. Edward; Goldring, Steven R.; Daluiski, Aaron; Wang, Dong

    2014-01-01

    Simvastatin (SIM), a widely used anti-lipidaemic drug, has been identified as a bone anabolic agent. Its poor water solubility and the lack of distribution to the skeleton, however, have limited its application in the treatment of bone metabolic diseases. In this study, an amphiphilic macromolecular prodrug of SIM was designed and synthesized to overcome these limitations. The polyethylene glycol (PEG)-based prodrug can spontaneously self-assemble to form micelles. The use of SIM trimer as the prodrug’s hydrophobic segment allows easy encapsulation of additional free SIM. The in vitro studies showed that SIM/SIM-mPEG micelles were internalized by MC3T3 cells via lysosomal trafficking and consistently induced expression of both BMP2 and DKK1 mRNA, suggesting that the prodrug micelle retains the biological functions of SIM. After systemic administration, optical imaging suggests that the micelles would passively target to bone fracture sites associated with hematoma and inflammation. Furthermore, flow cytometry study revealed that SIM/SIM-mPEG micelles had preferred cellular uptake by inflammatory and resident cells within the fracture callus tissue. The treatment study using a mouse osteotomy model validated the micelles’ therapeutic efficacy in promoting bone fracture healing as demonstrated by micro-CT and histological analyses. Collectively, these data suggest that the macromolecular prodrug-based micelle formulation of SIM may have great potential for clinical management of impaired fracture healing. PMID:25542644

  3. Nanoscale elastic modulus variation in loaded polymeric micelle reactors.

    PubMed

    Solmaz, Alim; Aytun, Taner; Deuschle, Julia K; Ow-Yang, Cleva W

    2012-07-17

    Tapping mode atomic force microscopy (TM-AFM) enables mapping of chemical composition at the nanoscale by taking advantage of the variation in phase angle shift arising from an embedded second phase. We demonstrate that phase contrast can be attributed to the variation in elastic modulus during the imaging of zinc acetate (ZnAc)-loaded reverse polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) diblock co-polymer micelles less than 100 nm in diameter. Three sample configurations were characterized: (i) a 31.6 μm thick polystyrene (PS) support film for eliminating the substrate contribution, (ii) an unfilled PS-b-P2VP micelle supported by the same PS film, and (iii) a ZnAc-loaded PS-b-P2VP micelle supported by the same PS film. Force-indentation (F-I) curves were measured over unloaded micelles on the PS film and over loaded micelles on the PS film, using standard tapping mode probes of three different spring constants, the same cantilevers used for imaging of the samples before and after loading. For calibration of the tip geometry, nanoindentation was performed on the bare PS film. The resulting elastic modulus values extracted by applying the Hertz model were 8.26 ± 3.43 GPa over the loaded micelles and 4.17 ± 1.65 GPa over the unloaded micelles, confirming that phase contrast images of a monolayer of loaded micelles represent maps of the nanoscale chemical and mechanical variation. By calibrating the tip geometry indirectly using a known soft material, we are able to use the same standard tapping mode cantilevers for both imaging and indentation.

  4. Modeling chlorophyll-a and dissolved oxygen concentration in tropical floodplain lakes (Paraná River, Brazil).

    PubMed

    Rocha, R R A; Thomaz, S M; Carvalho, P; Gomes, L C

    2009-06-01

    The need for prediction is widely recognized in limnology. In this study, data from 25 lakes of the Upper Paraná River floodplain were used to build models to predict chlorophyll-a and dissolved oxygen concentrations. Akaike's information criterion (AIC) was used as a criterion for model selection. Models were validated with independent data obtained in the same lakes in 2001. Predictor variables that significantly explained chlorophyll-a concentration were pH, electrical conductivity, total seston (positive correlation) and nitrate (negative correlation). This model explained 52% of chlorophyll variability. Variables that significantly explained dissolved oxygen concentration were pH, lake area and nitrate (all positive correlations); water temperature and electrical conductivity were negatively correlated with oxygen. This model explained 54% of oxygen variability. Validation with independent data showed that both models had the potential to predict algal biomass and dissolved oxygen concentration in these lakes. These findings suggest that multiple regression models are valuable and practical tools for understanding the dynamics of ecosystems and that predictive limnology may still be considered a powerful approach in aquatic ecology.

  5. Phase separation in solution of worm-like micelles: a dilute ? spin-vector model

    NASA Astrophysics Data System (ADS)

    Panizza, Pascal; Cristobal, Galder; Curély, Jacques

    1998-12-01

    We show how the dilute 0953-8984/10/50/006/img2 spin vector model introduced originally by Wheeler and co-workers for describing the polymerization phenomenon in solutions of liquid sulphur and of living polymers may be conveniently adapted for studying phase separation in systems containing long flexible micelles. We draw an isomorphism between the coupling constant appearing in the exchange Hamiltonian and the surfactant energies in the micellar problem. We solve this problem within the mean-field approximation and compare the main results we have obtained with respect to polymer theory and previous theories of phase separation in micellar solutions. We show that the attractive interaction term 0953-8984/10/50/006/img3 between monomers renormalizes the aggregation energy and subsequently the corresponding size distribution. Under these conditions, we observe that the general aspect of the phase diagram in the 0953-8984/10/50/006/img4 plane (where 0953-8984/10/50/006/img5 is the surfactant concentration) is different from previous results. The spinodal line shows a re-entrant behaviour and, at low concentrations, we point out the possibility of specific nucleation phenomena related to the existence of a metastable transition line between a region composed of spherical micelles and another one corresponding to a dilute solution of long flexible micelles.

  6. Crafting threads of diblock copolymer micelles via flow-enabled self-assembly.

    PubMed

    Li, Bo; Han, Wei; Jiang, Beibei; Lin, Zhiqun

    2014-03-25

    Hierarchically assembled amphiphilic diblock copolymer micelles were exquisitely crafted over large areas by capitalizing on two concurrent self-assembling processes at different length scales, namely, the periodic threads composed of a monolayer or a bilayer of diblock copolymer micelles precisely positioned by flow-enabled self-assembly (FESA) on the microscopic scale and the self-assembly of amphiphilic diblock copolymer micelles into ordered arrays within an individual thread on the nanometer scale. A minimum spacing between two adjacent threads λmin was observed. A model was proposed to rationalize the relationship between the thread width and λmin. Such FESA of diblock copolymer micelles is remarkably controllable and easy to implement. It opens up possibilities for lithography-free positioning and patterning of diblock copolymer micelles for various applications in template fabrication of periodic inorganic nanostructures, nanoelectronics, optoelectronics, magnetic devices, and biotechnology.

  7. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    NASA Astrophysics Data System (ADS)

    Gou, MaLing; Shi, HuaShan; Guo, Gang; Men, Ke; Zhang, Juan; Zheng, Lan; Li, ZhiYong; Luo, Feng; Qian, ZhiYong; Zhao, Xia; Wei, YuQuan

    2011-03-01

    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ~ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  8. Self-assembled penetratin-deferasirox micelles as potential carriers for hydrophobic drug delivery.

    PubMed

    Goswami, Dibakar; Vitorino, Hector Aguilar; Machini, M Teresa; Espósito, Breno P

    2015-11-01

    There has been a growing interest in the use of micelles with nanofiber geometry as nanocarriers for hydrophobic drugs. Here we show that the conjugate of penetratin, a cell-penetrating peptide (CPP) with blood-brain barrier (BBB) permeability, and deferasirox (DFX), a hydrophobic iron chelator, self-assembles to form micelles at a very low concentration (∼15 mg/L). The critical micelle concentration (CMC) was determined, and the micelles were used for solubilizing curcumin, a hydrophobic anti-neurodegenerative drug, for successful delivery across RBE4 cells, a BBB model. Transmission Electron Microscope images of the curcumin-loaded micelles confirmed the formation of nanofibers. These results indicate the potential of CPP-drug conjugates for use as nanocarriers. © 2015 Wiley Periodicals, Inc.

  9. Bioinspired Coordination Micelles Integrating High Stability, Triggered Cargo Release, and Magnetic Resonance Imaging.

    PubMed

    Xin, Keting; Li, Man; Lu, Di; Meng, Xuan; Deng, Jun; Kong, Deling; Ding, Dan; Wang, Zheng; Zhao, Yanjun

    2017-01-11

    Catechol-Fe 3+ coordinated micelles show the potential for achieving on-demand drug delivery and magnetic resonance imaging in a single nanoplatform. Herein, we developed bioinspired coordination-cross-linked amphiphilic polymeric micelles loaded with a model anticancer agent, doxorubicin (Dox). The nanoscale micelles could tolerate substantial dilution to a condition below the critical micelle concentration (9.4 ± 0.3 μg/mL) without sacrificing the nanocarrier integrity due to the catechol-Fe 3+ coordinated core cross-linking. Under acidic conditions (pH 5.0), the release rate of Dox was significantly faster compared to that at pH 7.4 as a consequence of coordination collapse and particle de-cross-linking. The cell viability study in 4T1 cells showed no toxicity regarding placebo cross-linked micelles. The micelles with improved stability showed a dramatically increased Dox accumulation in tumors and hence the enhanced suppression of tumor growth in a 4T1 tumor-bearing mouse model. The presence of Fe 3+ endowed the micelles T 1 -weighted MRI capability both in vitro and in vivo without the incorporation of traditional toxic paramagnetic contrast agents. The current work presented a simple "three birds with one stone" approach to engineer the robust theranostic nanomedicine platform.

  10. Excited and ionic states of dimeric chlorophyll derivatives. Biomimetic modelling of the primary events of photosynthesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wasielewski, M. R.

    1978-01-01

    The following topics are discussed: preparation of covalently bound dimeric species of chlorophyll; molecular structure of bis(bacteriochlorophyllide a) ethylene glycol diester; /sup 1/H spectra of BChl, a covalent dimer, dissolved in various solvents; chemical shift changes in proton resonances; C/sub 2/ symmetric folded configuration of covalently linked BChl; electronic transition spectrum of Chl a covalent dimer in dry CCl/sub 4/ and in water-saturated CCl/sub 4/; special pair models of bis(chlorophyll) cyclophanes; synthetic pathway for preparation of bis(chlorophyll) cyclophane 8; proton magnetic resonance data; redox potentials of chlorophyll; and optical and EPR properties of special pairs. (HLW)

  11. The Effects of Chlorophyll Assimilation on Carbon Fluxes in a Global Biogeochemical Model. [Technical Report Series on Global Modeling and Data Assimilation

    NASA Technical Reports Server (NTRS)

    Koster, Randal D. (Editor); Rousseaux, Cecile Severine; Gregg, Watson W.

    2014-01-01

    In this paper, we investigated whether the assimilation of remotely-sensed chlorophyll data can improve the estimates of air-sea carbon dioxide fluxes (FCO2). Using a global, established biogeochemical model (NASA Ocean Biogeochemical Model, NOBM) for the period 2003-2010, we found that the global FCO2 values produced in the free-run and after assimilation were within -0.6 mol C m(sup -2) y(sup -1) of the observations. The effect of satellite chlorophyll assimilation was assessed in 12 major oceanographic regions. The region with the highest bias was the North Atlantic. Here the model underestimated the fluxes by 1.4 mol C m(sup -2) y(sup -1) whereas all the other regions were within 1 mol C m(sup -2) y(sup -1) of the data. The FCO2 values were not strongly impacted by the assimilation, and the uncertainty in FCO2 was not decreased, despite the decrease in the uncertainty in chlorophyll concentration. Chlorophyll concentrations were within approximately 25% of the database in 7 out of the 12 regions, and the assimilation improved the chlorophyll concentration in the regions with the highest bias by 10-20%. These results suggest that the assimilation of chlorophyll data does not considerably improve FCO2 estimates and that other components of the carbon cycle play a role that could further improve our FCO2 estimates.

  12. Glycation Reactions of Casein Micelles.

    PubMed

    Moeckel, Ulrike; Duerasch, Anja; Weiz, Alexander; Ruck, Michael; Henle, Thomas

    2016-04-13

    After suspensions of micellar casein or nonmicellar sodium caseinate had been heated, respectively, in the presence and absence of glucose for 0-4 h at 100 °C, glycation compounds were quantitated. The formation of Amadori products as indicators for the "early" Maillard reaction were in the same range for both micellar and nonmicellar caseins, indicating that reactive amino acid side chains within the micelles are accessible for glucose in a comparable way as in nonmicellar casein. Significant differences, however, were observed concerning the formation of the advanced glycation end products (AGEs), namely, N(ε)-carboxymethyllysine (CML), pyrraline, pentosidine, and glyoxal-lysine dimer (GOLD). CML could be observerd in higher amounts in nonmicellar casein, whereas in the micelles the pyrraline formation was increased. Pentosidine and GOLD were formed in comparable amounts. Furthermore, the extent of protein cross-linking was significantly higher in the glycated casein micelles than in the nonmicellar casein samples. Dynamic light scattering and scanning electron microscopy showed that glycation has no influence on the size of the casein micelles, indicating that cross-linking occurs only in the interior of the micelles, but altered the surface morphology. Studies on glycation and nonenzymatic cross-linking can contribute to the understanding of the structure of casein micelles.

  13. Association of denatured whey proteins with casein micelles in heated reconstituted skim milk and its effect on casein micelle size.

    PubMed

    Anema, Skelte G; Li, Yuming

    2003-02-01

    When skim milk at pH 6.55 was heated (75 to 100 degrees C for up to 60 min), the casein micelle size, as monitored by photon correlation spectroscopy, was found to increase during the initial stages of heating and tended to plateau on prolonged heating. At any particular temperature, the casein micelle size increased with longer holding times, and, at any particular holding time, the casein micelle size increased with increasing temperature. The maximum increase in casein micelle size was about 30-35 nm. The changes in casein micelle size were poorly correlated with the level of whey protein denaturation. However, the changes in casein micelle size were highly correlated with the levels of denatured whey proteins that were associated with the casein micelles. The rate of association of the denatured whey proteins with the casein micelles was considerably slower than the rate of denaturation of the whey proteins. Removal of the whey proteins from the skim milk resulted in only small changes in casein micelle size during heating. Re-addition of beta-lactoglobulin to the whey-protein-depleted milk caused the casein micelle size to increase markedly on heat treatment. The changes in casein micelle size induced by the heat treatment of skim milk may be a consequence of the whey proteins associating with the casein micelles. However, these associated whey proteins would need to occlude a large amount of serum to account for the particle size changes. Separate experiments showed that the viscosity changes of heated milk and the estimated volume fraction changes were consistent with the particle size changes observed. Further studies are needed to determine whether the changes in size are due to the specific association of whey proteins with the micelles or whether a low level of aggregation of the casein micelles accompanies this association behaviour. Preliminary studies indicated lower levels of denatured whey proteins associated with the casein micelles and smaller

  14. Recent Trends in Global Ocean Chlorophyll

    NASA Technical Reports Server (NTRS)

    Gregg, Watson; Casey, Nancy

    2004-01-01

    Recent analyses of SeaWiFS data have shown that global ocean chlorophyll has increased more than 5% since 1998. The North Pacific ocean basin has increased nearly 19%. To understand the causes of these trends we have applied the newly developed NASA Ocean Biogeochemical Assimilation Model (OBAM), which is driven in mechanistic fashion by surface winds, sea surface temperature, atmospheric iron deposition, sea ice, and surface irradiance. The mode1 utilizes chlorophyll from SeaWiFS in a daily assimilation. The model has in place many of the climatic variables that can be expected to produce the changes observed in SeaWiFS data. Ths enables us to diagnose the model performance, the assimilation performance, and possible causes for the increase in chlorophyll.

  15. Synthesis and characterization of chitosan-grafted-polycaprolactone micelles for modulate intestinal paclitaxel delivery.

    PubMed

    Almeida, Andreia; Silva, Daniella; Gonçalves, Virginia; Sarmento, Bruno

    2018-04-01

    In this work, self-assembled amphiphilic micelles based on chitosan (CS) and polycaprolactone (PCL) were produced and used as carriers of paclitaxel (PTX) to improve its intestinal pharmacokinetic profile. Chitosan-grafted-polycaprolactone (CS-g-PCL) was synthesized through a carbodiimide reaction by amidation and confirmed by Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance analysis ( 1 H NMR), and contact angle evaluation. Micelles were produced by solvent evaporation method, and the critical micelle concentration was investigated by conductimetry. The obtained micelles were of 408-nm mean particle size, narrow size distribution (polydispersity index of 0.335) and presented positive surface charge around 30 mV. The morphology of micelles assessed by transmission electron microscopy (TEM) revealed round and smooth surface, in agreement with dynamic light scattering measurements. The association efficiency determined by high-performance liquid chromatography (HPLC) was as high as 82%. The in vitro cytotoxicity of the unloaded and PTX-loaded micelles was tested against Caco-2 and HT29-MTX intestinal epithelial cells, resulting in the absence of cell toxicity for all formulations. Moreover, the permeability of PTX-loaded micelles in Caco-2 monolayer and Caco-2/HT29-MTX co-culture model was determined. Results showed that the permeability of PTX was higher in Caco-2/HT29-MTX co-culture model compared with Caco-2 monolayer due to the mucoadhesive character of micelles, acting as a platform to deliver PTX at the sites of absorption. Therefore, it can be concluded that the PTX-loaded CS-g-PCL micelles, employed for the first time as PTX carriers, may be a potential drug carrier for the intestinal delivery of hydrophobic drugs, particularly anticancer agents.

  16. Stabilized micelles as delivery vehicles for paclitaxel.

    PubMed

    Yoncheva, Krassimira; Calleja, Patricia; Agüeros, Maite; Petrov, Petar; Miladinova, Ivanka; Tsvetanov, Christo; Irache, Juan M

    2012-10-15

    Paclitaxel is an antineoplastic drug used against a variety of tumors, but its low aqueous solubility and active removal caused by P-glycoprotein in the intestinal cells hinder its oral administration. In our study, new type of stabilized Pluronic micelles were developed and evaluated as carriers for paclitaxel delivery via oral or intravenous route. The pre-stabilized micelles were loaded with paclitaxel by simple solvent/evaporation technique achieving high encapsulation efficiency of approximately 70%. Gastrointestinal transit of the developed micelles was evaluated by oral administration of rhodamine-labeled micelles in rats. Our results showed prolonged gastrointestinal residence of the marker encapsulated into micelles, compared to a solution containing free marker. Further, the oral administration of micelles in mice showed high area under curve of micellar paclitaxel (similar to the area of i.v. Taxol(®)), longer mean residence time (9-times longer than i.v. Taxol(®)) and high distribution volume (2-fold higher than i.v. Taxol(®)) indicating an efficient oral absorption of paclitaxel delivered by micelles. Intravenous administration of micelles also showed a significant improvement of pharmacokinetic parameters of micellar paclitaxel vs. Taxol(®), in particular higher area under curve (1.2-fold), 5-times longer mean residence time and lower clearance, indicating longer systemic circulation of the micelles. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Structural heterogeneity of milk casein micelles: a SANS contrast variation study.

    PubMed

    Bouchoux, Antoine; Ventureira, Jorge; Gésan-Guiziou, Geneviève; Garnier-Lambrouin, Fabienne; Qu, Peng; Pasquier, Coralie; Pézennec, Stéphane; Schweins, Ralf; Cabane, Bernard

    2015-01-14

    We examine the internal structure of milk casein micelles using the contrast variation method in Small-Angle Neutron Scattering (SANS). Experiments were performed with casein dispersions of different origins (i.e., milk powder or fresh milk) and extended to very low q-values (∼9 × 10(-4) Å(-1)), thus making it possible to precisely determine the apparent gyration radius Rg at each contrast. From the variation of I(q → 0) with contrast, we determine the distribution of composition of all the particles in the dispersions. As expected, most of these particles are micelles, made of casein and calcium phosphate, with a narrow distribution in compositions. These micelles always coexist with a very small fraction of fat droplets, with sizes in the range of 20-400 nm. For the dispersions prepared from fresh milk, which were purified under particularly stringent conditions, the number ratio of fat droplets to casein micelles is as low as 1 to 10(6). In that case, we are able to subtract from the total intensity the contribution of the fat droplets and in this way obtain the contribution of the micelles only. We then analyze the variation of this contribution with contrast using the approach pioneered by H. B. Stuhrmann. We model the casein micelle as a core-shell spherical object, in which the local scattering length density is determined by the ratio of calcium phosphate nanoclusters to proteins. We find that models in which the shell has a lower concentration of calcium phosphate than the core give a better agreement than models in which the shell has a higher density than the core.

  18. Structural changes of casein micelles in a calcium gradient film.

    PubMed

    Gebhardt, Ronald; Burghammer, Manfred; Riekel, Christian; Roth, Stephan Volkher; Müller-Buschbaum, Peter

    2008-04-09

    Calcium gradients are prepared by sequentially filling a micropipette with casein solutions of varying calcium concentration and spreading them on glass slides. The casein film is formed by a solution casting process, which results in a macroscopically rough surface. Microbeam grazing incidence small-angle X-ray scattering (microGISAXS) is used to investigate the lateral size distribution of three main components in casein films: casein micelles, casein mini-micelles, and micellar calcium phosphate. At length scales within the beam size the film surface is flat and detection of size distribution in a macroscopic casein gradient becomes accessible. The model used to analyze the data is based on a set of three log-normal distributed particle sizes. Increasing calcium concentration causes a decrease in casein micelle diameter while the size of casein mini-micelles increases and micellar calcium phosphate particles remain unchanged.

  19. Sampling the kinetic pathways of a micelle fusion and fission transition.

    PubMed

    Pool, René; Bolhuis, Peter G

    2007-06-28

    The mechanism and kinetics of micellar breakup and fusion in a dilute solution of a model surfactant are investigated by path sampling techniques. Analysis of the path ensemble gives insight in the mechanism of the transition. For larger, less stable micelles the fission/fusion occurs via a clear neck formation, while for smaller micelles the mechanism is more direct. In addition, path analysis yields an appropriate order parameter to evaluate the fusion and fission rate constants using stochastic transition interface sampling. For the small, stable micelle (50 surfactants) the computed fission rate constant is a factor of 10 lower than the fusion rate constant. The procedure opens the way for accurate calculation of free energy and kinetics for, e.g., membrane fusion, and wormlike micelle endcap formation.

  20. Pluronic®-bile salt mixed micelles.

    PubMed

    Patel, Vijay; Ray, Debes; Bahadur, Anita; Ma, Junhe; Aswal, V K; Bahadur, Pratap

    2018-06-01

    The present study was aimed to examine the interaction of two bile salts viz. sodium cholate (NaC) and sodium deoxycholate (NaDC) with three ethylene polyoxide-polypropylene polyoxide (PEO-PPO-PEO) triblock copolymers with similar PPO but varying PEO micelles with a focus on the effect of pH on mixed micelles. Mixed micelles of moderately hydrophobic Pluronic ® P123 were examined in the presence of two bile salts and compared with those from very hydrophobic L121 and very hydrophilic F127. Both the bile salts increase the cloud point (CP) of copolymer solution and decreased apparent micelle hydrodynamic diameter (D h ). SANS study revealed that P123 forms small spherical micelles showing a decrease in size on progressive addition of bile salts. The negatively charged mixed micelles contained fewer P123 molecules but progressively rich in bile salt. NaDC being more hydrophobic displays more pronounced effect than NaC. Interestingly, NaC shows micellar growth in acidic media which has been attributed to the formation of bile acids by protonation of carboxylate ion and subsequent solubilization. In contrast, NaDC showed phase separation at higher concentration. Nuclear Overhauser effect spectroscopy (NOESY) experiments provided information on interaction and location of bile salts in micelles. Results are discussed in terms of hydrophobicity of bile salts and Pluronics ® and the site of bile salt in polymer micelles. Proposed molecular interactions are useful to understand more about bile salts which play important role in physiological processes. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Statistical thermodynamics of amphiphile chains in micelles

    PubMed Central

    Ben-Shaul, A.; Szleifer, I.; Gelbart, W. M.

    1984-01-01

    The probability distribution of amphiphile chain conformations in micelles of different geometries is derived through maximization of their packing entropy. A lattice model, first suggested by Dill and Flory, is used to represent the possible chain conformations in the micellar core. The polar heads of the chains are assumed to be anchored to the micellar surface, with the other chain segments occupying all lattice sites in the interior of the micelle. This “volume-filling” requirement, the connectivity of the chains, and the geometry of the micelle define constraints on the possible probability distributions of chain conformations. The actual distribution is derived by maximizing the chain's entropy subject to these constraints; “reversals” of the chains back towards the micellar surface are explicitly included. Results are presented for amphiphiles organized in planar bilayers and in cylindrical and spherical micelles of different sizes. It is found that, for all three geometries, the bond order parameters decrease as a function of the bond distance from the polar head, in accordance with recent experimental data. The entropy differences associated with geometrical changes are shown to be significant, suggesting thereby the need to include curvature (environmental)-dependent “tail” contributions in statistical thermodynamic treatments of micellization. PMID:16593492

  2. Interaction of lactoferrin and lysozyme with casein micelles.

    PubMed

    Anema, Skelte G; de Kruif, C G Kees

    2011-11-14

    On addition of lactoferrin (LF) to skim milk, the turbidity decreases. The basic protein binds to the caseins in the casein micelles, which is then followed by a (partial) disintegration of the casein micelles. The amount of LF initially binding to casein micelles follows a Langmuir adsorption isotherm. The kinetics of the binding of LF could be described by first-order kinetics and similarly the disintegration kinetics. The disintegration was, however, about 10 times slower than the initial adsorption, which allowed investigating both phenomena. Kinetic data were also obtained from turbidity measurements, and all data could be described with one equation. The disintegration of the casein micelles was further characterized by an activation energy of 52 kJ/mol. The initial increase in hydrodynamic size of the casein micelles could be accounted for by assuming that it would go as the cube root of the mass using the adsorption and disintegration kinetics as determined from gel electrophoresis. The results show that LF binds to casein micelles and that subsequently the casein micelles partly disintegrate. All micelles behave in a similar manner as average particle size decreases. Lysozyme also bound to the casein micelles, and this binding followed a Langmuir adsorption isotherm. However, lysozyme did not cause the disintegration of the casein micelles.

  3. Chemical reactions in reverse micelle systems

    DOEpatents

    Matson, Dean W.; Fulton, John L.; Smith, Richard D.; Consani, Keith A.

    1993-08-24

    This invention is directed to conducting chemical reactions in reverse micelle or microemulsion systems comprising a substantially discontinuous phase including a polar fluid, typically an aqueous fluid, and a microemulsion promoter, typically a surfactant, for facilitating the formation of reverse micelles in the system. The system further includes a substantially continuous phase including a non-polar or low-polarity fluid material which is a gas under standard temperature and pressure and has a critical density, and which is generally a water-insoluble fluid in a near critical or supercritical state. Thus, the microemulsion system is maintained at a pressure and temperature such that the density of the non-polar or low-polarity fluid exceeds the critical density thereof. The method of carrying out chemical reactions generally comprises forming a first reverse micelle system including an aqueous fluid including reverse micelles in a water-insoluble fluid in the supercritical state. Then, a first reactant is introduced into the first reverse micelle system, and a chemical reaction is carried out with the first reactant to form a reaction product. In general, the first reactant can be incorporated into, and the product formed in, the reverse micelles. A second reactant can also be incorporated in the first reverse micelle system which is capable of reacting with the first reactant to form a product.

  4. Inhibition of atherosclerosis-promoting microRNAs via targeted polyelectrolyte complex micelles

    PubMed Central

    Kuo, Cheng-Hsiang; Leon, Lorraine; Chung, Eun Ji; Huang, Ru-Ting; Sontag, Timothy J.; Reardon, Catherine A.; Getz, Godfrey S.; Tirrell, Matthew; Fang, Yun

    2015-01-01

    Polyelectrolyte complex micelles have great potential as gene delivery vehicles because of their ability to encapsulate charged nucleic acids forming a core by neutralizing their charge, while simultaneously protecting the nucleic acids from non-specific interactions and enzymatic degradation. Furthermore, to enhance specificity and transfection efficiency, polyelectrolyte complex micelles can be modified to include targeting capabilities. Here, we describe the design of targeted polyelectrolyte complex micelles containing inhibitors against dys-regulated microRNAs (miRNAs) that promote atherosclerosis, a leading cause of human mortality and morbidity. Inhibition of dys-regulated miRNAs in diseased cells associated with atherosclerosis has resulted in therapeutic efficacy in animal models and has been proposed to treat human diseases. However, the non-specific targeting of microRNA inhibitors via systemic delivery has remained an issue that may cause unwanted side effects. For this reason, we incorporated two different peptide sequences to our miRNA inhibitor containing polyelectrolyte complex micelles. One of the peptides (Arginine-Glutamic Acid-Lysine-Alanine or REKA) was used in another micellar system that demonstrated lesion-specific targeting in a mouse model of atherosclerosis. The other peptide (Valine-Histidine-Proline-Lysine-Glutamine-Histidine-Arginine or VHPKQHR) was identified via phage display and targets vascular endothelial cells through the vascular cell adhesion molecule-1 (VCAM-1). In this study we have tested the in vitro efficacy and efficiency of lesion- and cell-specific delivery of microRNA inhibitors to the cells associated with atherosclerotic lesions via peptide-targeted polyelectrolyte complex micelles. Our results show that REKA-containing micelles (fibrin-targeting) and VHPKQHR-containing micelles (VCAM-1 targeting) can be used to carry and deliver microRNA inhibitors into macrophages and human endothelial cells, respectively

  5. Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway

    NASA Astrophysics Data System (ADS)

    Zhang, Nannan; Liu, Shichang; Wang, Ning; Deng, Senyi; Song, Linjiang; Wu, Qinjie; Liu, Lei; Su, Weijun; Wei, Yuquan; Xie, Yongmei; Gong, Changyang

    2015-01-01

    JK184 can specially inhibit Gli in the Hedgehog (Hh) pathway, which showed great promise for cancer therapeutics. For developing aqueous formulation and improving anti-tumor activity of JK184, we prepared JK184 encapsulated MPEG-PCL micelles by the solid dispersion method without using surfactants or toxic organic solvents. The cytotoxicity and cellular uptake of JK184 micelles were both increased compared with the free drug. JK184 micelles induced more apoptosis and blocked proliferation of Panc-1 and BxPC-3 tumor cells. In addition, JK184 micelles exerted a sustained in vitro release behavior and had a stronger inhibitory effect on proliferation, migration and invasion of HUVECs than free JK184. Furthermore, JK184 micelles had stronger tumor growth inhibiting effects in subcutaneous Panc-1 and BxPC-3 tumor models. Histological analysis showed that JK184 micelles improved anti-tumor activity by inducing more apoptosis, decreasing microvessel density and reducing expression of CD31, Ki67, and VEGF in tumor tissues. JK184 micelles showed a stronger inhibition of Gli expression in Hh signaling, which played an important role in pancreatic carcinoma. Furthermore, circulation time of JK184 in blood was prolonged after entrapment in polymeric micelles. Our results suggested that JK184 micelles are a promising drug candidate for treating pancreatic tumors with a highly inhibitory effect on Hh activity.JK184 can specially inhibit Gli in the Hedgehog (Hh) pathway, which showed great promise for cancer therapeutics. For developing aqueous formulation and improving anti-tumor activity of JK184, we prepared JK184 encapsulated MPEG-PCL micelles by the solid dispersion method without using surfactants or toxic organic solvents. The cytotoxicity and cellular uptake of JK184 micelles were both increased compared with the free drug. JK184 micelles induced more apoptosis and blocked proliferation of Panc-1 and BxPC-3 tumor cells. In addition, JK184 micelles exerted a sustained in

  6. Unique chlorophylls in picoplankton Prochlorococcus sp. "Physicochemical properties of divinyl chlorophylls, and the discovery of monovinyl chlorophyll b as well as divinyl chlorophyll b in the species Prochlorococcus NIES-2086".

    PubMed

    Komatsu, Hirohisa; Wada, Katsuhiro; Kanjoh, Terumitsu; Miyashita, Hideaki; Sato, Mayumi; Kawachi, Masanobu; Kobayashi, Masami

    2016-12-01

    In this review, we introduce our recent studies on divinyl chlorophylls functioning in unique marine picoplankton Prochlorococcus sp. (1) Essential physicochemical properties of divinyl chlorophylls are compared with those of monovinyl chlorophylls; separation by normal-phase and reversed-phase high-performance liquid chromatography with isocratic eluent mode, absorption spectra in four organic solvents, fluorescence information (emission spectra, quantum yields, and life time), circular dichroism spectra, mass spectra, nuclear magnetic resonance spectra, and redox potentials. The presence of a mass difference of 278 in the mass spectra between [M+H] + and the ions indicates the presence of a phytyl tail in all the chlorophylls. (2) Precise high-performance liquid chromatography analyses show divinyl chlorophyll a' and divinyl pheophytin a as the minor key components in four kinds of Prochlorococcus sp.; neither monovinyl chlorophyll a' nor monovinyl pheophytin a is detected, suggesting that the special pair in photosystem I and the primary electron acceptor in photosystem II are not monovinyl but divinyl-type chlorophylls. (3) Only Prochlorococcus sp. NIES-2086 possesses both monovinyl chlorophyll b and divinyl chlorophyll b, while any other monovinyl-type chlorophylls are absent in this strain. Monovinyl chlorophyll b is not detected at all in the other three strains. Prochlorococcus sp. NIES-2086 is the first example that has both monovinyl chlorophyll b as well as divinyl chlorophylls a/b as major chlorophylls.

  7. Chlorophyll content retrieval from hyperspectral remote sensing imagery.

    PubMed

    Yang, Xiguang; Yu, Ying; Fan, Wenyi

    2015-07-01

    Chlorophyll content is the essential parameter in the photosynthetic process determining leaf spectral variation in visible bands. Therefore, the accurate estimation of the forest canopy chlorophyll content is a significant foundation in assessing forest growth and stress affected by diseases. Hyperspectral remote sensing with high spatial resolution can be used for estimating chlorophyll content. In this study, the chlorophyll content was retrieved step by step using Hyperion imagery. Firstly, the spectral curve of the leaf was analyzed, 25 spectral characteristic parameters were identified through the correlation coefficient matrix, and a leaf chlorophyll content inversion model was established using a stepwise regression method. Secondly, the pixel reflectance was converted into leaf reflectance by a geometrical-optical model (4-scale). The three most important parameters of reflectance conversion, including the multiple scattering factor (M 0 ), and the probability of viewing the sunlit tree crown (P T ) and the background (P G ), were estimated by leaf area index (LAI), respectively. The results indicated that M 0 , P T , and P G could be described as a logarithmic function of LAI, with all R (2) values above 0.9. Finally, leaf chlorophyll content was retrieved with RMSE = 7.3574 μg/cm(2), and canopy chlorophyll content per unit ground surface area was estimated based on leaf chlorophyll content and LAI. Chlorophyll content mapping can be useful for the assessment of forest growth stage and diseases.

  8. Identification of the 7-Hydroxymethyl Chlorophyll a Reductase of the Chlorophyll Cycle in Arabidopsis[W

    PubMed Central

    Meguro, Miki; Ito, Hisashi; Takabayashi, Atsushi; Tanaka, Ryouichi; Tanaka, Ayumi

    2011-01-01

    The interconversion of chlorophyll a and chlorophyll b, referred to as the chlorophyll cycle, plays a crucial role in the processes of greening, acclimation to light intensity, and senescence. The chlorophyll cycle consists of three reactions: the conversions of chlorophyll a to chlorophyll b by chlorophyllide a oxygenase, chlorophyll b to 7-hydroxymethyl chlorophyll a by chlorophyll b reductase, and 7-hydroxymethyl chlorophyll a to chlorophyll a by 7-hydroxymethyl chlorophyll a reductase. We identified 7-hydroxymethyl chlorophyll a reductase, which is the last remaining unidentified enzyme of the chlorophyll cycle, from Arabidopsis thaliana by genetic and biochemical methods. Recombinant 7-hydroxymethyl chlorophyll a reductase converted 7-hydroxymethyl chlorophyll a to chlorophyll a using ferredoxin. Both sequence and biochemical analyses showed that 7-hydroxymethyl chlorophyll a reductase contains flavin adenine dinucleotide and an iron-sulfur center. In addition, a phylogenetic analysis elucidated the evolution of 7-hydroxymethyl chlorophyll a reductase from divinyl chlorophyllide vinyl reductase. A mutant lacking 7-hydroxymethyl chlorophyll a reductase was found to accumulate 7-hydroxymethyl chlorophyll a and pheophorbide a. Furthermore, this accumulation of pheophorbide a in the mutant was rescued by the inactivation of the chlorophyll b reductase gene. The downregulation of pheophorbide a oxygenase activity is discussed in relation to 7-hydroxymethyl chlorophyll a accumulation. PMID:21934147

  9. Polymeric micelles for potentiated antiulcer and anticancer activities of naringin.

    PubMed

    Mohamed, Elham Abdelmonem; Abu Hashim, Irhan Ibrahim; Yusif, Rehab Mohammad; Shaaban, Ahmed Abdel Aziz; El-Sheakh, Ahmed Ramadan; Hamed, Mohammed Fawzy; Badria, Farid Abd Elreheem

    2018-01-01

    Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin-PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities.

  10. Polymeric micelles for potentiated antiulcer and anticancer activities of naringin

    PubMed Central

    Mohamed, Elham Abdelmonem; Abu Hashim, Irhan Ibrahim; Yusif, Rehab Mohammad; Shaaban, Ahmed Abdel Aziz; El-Sheakh, Ahmed Ramadan; Hamed, Mohammed Fawzy; Badria, Farid Abd Elreheem

    2018-01-01

    Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin–PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities. PMID:29497294

  11. The structure of the casein micelle of milk and its changes during processing.

    PubMed

    Dalgleish, Douglas G; Corredig, Milena

    2012-01-01

    The majority of the protein in cow's milk is contained in the particles known as casein micelles. This review describes the main structural features of these particles and the different models that have been used to define the interior structures. The reactions of the micelles during processing operations are described in terms of the structural models.

  12. Lecithin in mixed micelles attenuates the cytotoxicity of bile salts in Caco-2 cells.

    PubMed

    Tan, Ya'nan; Qi, Jianping; Lu, Yi; Hu, Fuqiang; Yin, Zongning; Wu, Wei

    2013-03-01

    This study was designed to investigate the cytotoxicity of bile salt-lecithin mixed micelles on the Caco-2 cell model. Cell viability and proliferation after mixed micelles treatments were evaluated with the MTT assay, and the integrity of Caco-2 cell monolayer was determined by quantitating the transepithelial electrical resistance and the flux of tracer, FITC-dextran 4400. The apoptosis induced by mixed micelles treatments was investigated with the annexin V/PI protocol. The particle size of mixed micelles was all smaller than 100 nm. The mixed micelles with lower than 0.2mM sodium deoxycholate (SDC) had no significant effects on cell viability and proliferation. When the level of SDC was higher than 0.4mM and the lecithin/SDC ratio was lower than 2:1, the mixed micelles caused significant changes in cell viability and proliferation. Furthermore, the mixed micelles affected tight junctions in a composition-dependent manner. Specifically, the tight junctions were transiently opened rather than damaged by the mixed micelles with SDC of between 0.2 and 0.6mM. The mixed micelles with more lecithin also induced less apoptosis. These results demonstrate that relatively higher concentrations of mixed micelles are toxic to Caco-2 cells, while phospholipids can attenuate the toxicity of the bile salts. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  13. Chain exchange in triblock copolymer micelles

    NASA Astrophysics Data System (ADS)

    Lu, Jie; Lodge, Timothy; Bates, Frank

    2015-03-01

    Block polymer micelles offer a host of technological applications including drug delivery, viscosity modification, toughening of plastics, and colloidal stabilization. Molecular exchange between micelles directly influences the stability, structure and access to an equilibrium state in such systems and this property recently has been shown to be extraordinarily sensitive to the core block molecular weight in diblock copolymers. The dependence of micelle chain exchange dynamics on molecular architecture has not been reported. The present work conclusively addresses this issue using time-resolved small-angle neutron scattering (TR-SANS) applied to complimentary S-EP-S and EP-S-EP triblock copolymers dissolved in squalane, a selective solvent for the EP blocks, where S and EP refer to poly(styrene) and poly(ethylenepropylene), respectively. Following the overall SANS intensity as a function of time from judiciously deuterium labelled polymer and solvent mixtures directly probes the rate of molecular exchange. Remarkably, the two triblocks display exchange rates that differ by approximately ten orders of magnitude, even though the solvophobic S blocks are of comparable size. This discovery is considered in the context of a model that successfully explains S-EP diblock exchange dynamics.

  14. Structure and rheological behavior of casein micelle suspensions during ultrafiltration process

    NASA Astrophysics Data System (ADS)

    Pignon, F.; Belina, G.; Narayanan, T.; Paubel, X.; Magnin, A.; Gésan-Guiziou, G.

    2004-10-01

    The stability and mechanism underlying the formation of deposits of casein micelles during ultrafiltration process were investigated by small-angle and ultra small-angle x-ray scattering (SAXS and USAXS). The casein micelle dispersions consisted of phospho-caseinate model powders and the measurements probed length scales ranging from 1 to 2000 nm. Rheometric and frontal filtration measurements were combined with SAXS to establish the relationship between the rheological behavior of deposits (shear and/or compression) and the corresponding microstructure. The results revealed two characteristic length scales for the equilibrium structure with radius of gyrations Rg, about 100 and 5.6 nm pertaining to the globular micelles and their non-globular internal structure, respectively. The SAXS measurements further indicated that the increase of temperature from 20 to 70 °C or the decrease of pH from 6.6 to 6 lead to agglomeration of the globular micelles. In situ scattering measurements showed that the decrease of permeation flows is directly related to the deformation and compression of the micelles in the immediate vicinity of the membrane.

  15. Indicators: Chlorophyll a

    EPA Pesticide Factsheets

    Chlorophyll allows plants (including algae) to photosynthesize, i.e., use sunlight to convert simple molecules into organic compounds. Chlorophyll a is the predominant type of chlorophyll found in green plants and algae.

  16. Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG-PLA micelle

    NASA Astrophysics Data System (ADS)

    Shi, Yanan; Sun, Fengying; Wang, Dan; Zhang, Renyu; Dou, Changlin; Liu, Wanhui; Sun, Kaoxiang; Li, Youxin

    2013-10-01

    A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly( d, l-lactide) (PEG-PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs < 0.3). Only a trace amount of protein was in aggregate form. The zeta potential of the spherical micelles was ranging from -0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG-PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system.

  17. Assimilation of SeaWiFS Ocean Chlorophyll Data into a Three-Dimensional Global Ocean Model

    NASA Technical Reports Server (NTRS)

    Gregg, Watson W.

    2005-01-01

    Assimilation of satellite ocean color data is a relatively new phenomenon in ocean sciences. However, with routine observations from the Sea-viewing Wide Field-of-view Sensor (SeaWiFS), launched in late 1997, and now with new data from the Moderate Resolution Imaging Spectroradometer (MODIS) Aqua, there is increasing interest in ocean color data assimilation. Here SeaWiFS chlorophyll data were assimilated with an established thre-dimentional global ocean model. The assimilation improved estimates of hlorophyll and primary production relative to a free-run (no assimilation) model. This represents the first attempt at ocean color data assimilation using NASA satellites in a global model. The results suggest the potential of assimilation of satellite ocean chlorophyll data for improving models.

  18. Cellular uptake and trafficking of polydiacetylene micelles

    NASA Astrophysics Data System (ADS)

    Gravel, Edmond; Thézé, Benoit; Jacques, Isabelle; Anilkumar, Parambath; Gombert, Karine; Ducongé, Frédéric; Doris, Eric

    2013-02-01

    Polydiacetylene (PDA) micelles coated with either carboxylate-, ammonium-, or methoxy-polyethyleneglycol (PEG) chains were assembled and loaded with a fluorescent dye (DiO). Their interaction with MCF-7 human breast tumor cells was investigated by epi-fluorescence microscopy and fluorescence-activated cell sorting (FACS) to determine their internalization pathway and intracellular fate. It was found that the ionic character of the micelles influenced their internalization kinetics through a caveolae-mediated pathway and that all micelle types behaved somewhat similarly inside cells.Polydiacetylene (PDA) micelles coated with either carboxylate-, ammonium-, or methoxy-polyethyleneglycol (PEG) chains were assembled and loaded with a fluorescent dye (DiO). Their interaction with MCF-7 human breast tumor cells was investigated by epi-fluorescence microscopy and fluorescence-activated cell sorting (FACS) to determine their internalization pathway and intracellular fate. It was found that the ionic character of the micelles influenced their internalization kinetics through a caveolae-mediated pathway and that all micelle types behaved somewhat similarly inside cells. Electronic supplementary information (ESI) available: Detailed synthetic procedures and supplementary figures. See DOI: 10.1039/c2nr34149b

  19. Size And Shape of Detergent Micelles Determined By Small-Angle X-Ray Scattering

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lipfert, Jan; Columbus, Linda; Chu, Vincent B.

    2009-04-29

    We present a systematic analysis of the aggregation number and shape of micelles formed by nine detergents commonly used in the study of membrane proteins. Small-angle X-ray scattering measurements are reported for glucosides with 8 and 9 alkyl carbons (OG/NG), maltosides and phosphocholines with 10 and 12 alkyl carbons (DM/DDM and FC-10/FC-12), 1,2-dihexanoyl-sn-glycero-phosphocholine (DHPC), 1-palmitoyl-2-hydroxy-sn-glycero-3-[phospho-rac-(1-glycerol)] (LPPG), and 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS). The SAXS intensities are well described by two-component ellipsoid models, with a dense outer shell corresponding to the detergent head groups and a less electron dense hydrophobic core. These models provide an intermediate resolution view of micelle size and shape.more » In addition, we show that Guinier analysis of the forward scattering intensity can be used to obtain an independent and model-free measurement of the micelle aggregation number and radius of gyration. This approach has the advantage of being easily generalizable to protein-detergent complexes, where simple geometric models are inapplicable. Furthermore, we have discovered that the position of the second maximum in the scattering intensity provides a direct measurement of the characteristic head group-head group spacing across the micelle core. Our results for the micellar aggregation numbers and dimensions agree favorably with literature values as far as they are available. We de novo determine the shape of FC-10, FC-12, DM, LPPG, and CHAPS micelles and the aggregation numbers of FC-10 and OG to be ca. 50 and 250, respectively. Combined, these data provide a comprehensive view of the determinants of micelle formation and serve as a starting point to correlate detergent properties with detergent-protein interactions.« less

  20. Effectiveness of Losartan-Loaded Hyaluronic Acid (HA) Micelles for the Reduction of Advanced Hepatic Fibrosis in C3H/HeN Mice Model

    PubMed Central

    Thomas, Reju George; Moon, Myeong Ju; Kim, Jo Heon; Lee, Jae Hyuk; Jeong, Yong Yeon

    2015-01-01

    Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis. PMID:26714035

  1. Effectiveness of Losartan-Loaded Hyaluronic Acid (HA) Micelles for the Reduction of Advanced Hepatic Fibrosis in C3H/HeN Mice Model.

    PubMed

    Thomas, Reju George; Moon, Myeong Ju; Kim, Jo Heon; Lee, Jae Hyuk; Jeong, Yong Yeon

    2015-01-01

    Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis.

  2. RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells.

    PubMed

    Cai, Li-Li; Liu, Ping; Li, Xi; Huang, Xuan; Ye, Yi-Qing; Chen, Feng-Ying; Yuan, Hong; Hu, Fu-Qiang; Du, Yong-Zhong

    2011-01-01

    Solid tumors need new blood vessels to feed and nourish them as well as to allow tumor cells to escape into the circulation and lodge in other organs, which is termed "angiogenesis." Some tumor cells within solid tumors can overexpress integrins α(v)β(3) and α(v)β(5), which can specifically recognize the peptide motif Arg-Gly-Asp (RGD). Thus, the targeting of RGD-modified micelles to tumor vasculature is a promising strategy for tumor-targeting treatment. RGD peptide (GSSSGRGDSPA) was coupled to poly(ethylene glycol)-modified stearic acid-grafted chitosan (PEG-CS-SA) micelles via chemical reaction in the presence of N,N'-Disuccinimidyl carbonate. The critical micelle concentration of the polymeric micelles was determined by measuring the fluorescence intensity of pyrene as a fluorescent probe. The micelle size, size distribution, and zeta potential were measured by light scattering and electrophoretic mobility. Doxorubicin (DOX) was chosen as a model anticancer drug to investigate the drug entrapment efficiency, in vitro drug-release profile, and in vitro antitumor activities of drug-loaded RGD-PEG-CS-SA micelles in cells that overexpress integrins (α(ν)β(3) and α(ν)β(5)) and integrin-deficient cells. Using DOX as a model drug, the drug encapsulation efficiency could reach 90%, and the in vitro drug-release profiles suggested that the micelles could be used as a controlled-release carrier for the hydrophobic drug. Qualitative and quantitative analysis of cellular uptake indicated that RGD-modified micelles could significantly increase the DOX concentration in integrin-overexpressing human hepatocellular carcinoma cell line (BEL-7402), but not in human epithelial carcinoma cell line (Hela). The competitive cellular-uptake test showed that the cellular uptake of RGD-modified micelles in BEL-7402 cells was significantly inhibited in the presence of excess free RGD peptides. In vitro cytotoxicity tests demonstrated DOX-loaded RGD-modified micelles could

  3. Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

    PubMed Central

    Singleton, WG; Collins, AM; Bienemann, AS; Killick-Cole, CL; Haynes, HR; Asby, DJ; Butts, CP; Wyatt, MJ; Barua, NU; Gill, SS

    2017-01-01

    Background The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood–brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). Materials and methods The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Results Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P<0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. Conclusion CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic. PMID:28260886

  4. Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model.

    PubMed

    Singleton, W G; Collins, A M; Bienemann, A S; Killick-Cole, C L; Haynes, H R; Asby, D J; Butts, C P; Wyatt, M J; Barua, N U; Gill, S S

    2017-01-01

    The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P <0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic.

  5. Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery

    NASA Astrophysics Data System (ADS)

    Cao, Yanwu; Gao, Min; Chen, Chao; Fan, Aiping; Zhang, Ju; Kong, Deling; Wang, Zheng; Peer, Dan; Zhao, Yanjun

    2015-03-01

    Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6 ± 5.9 (nm) with a zeta potential of -10.6 ± 0.7 (mV). The critical micelle concentration was determined at 6.7 ± 0.4 (μg mL-1). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in HeLa cells at 18.5 ± 1.4 (μg mL-1), whereas the IC50 of control micelles was 41.0 ± 2.4 (μg mL-1). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice.

  6. Disruption and reassociation of casein micelles under high pressure: influence of milk serum composition and casein micelle concentration.

    PubMed

    Huppertz, Thom; de Kruif, Cornelis G

    2006-08-09

    In this study, factors influencing the disruption and aggregation of casein micelles during high-pressure (HP) treatment at 250 MPa for 40 min were studied in situ in serum protein-free casein micelle suspensions. In control milk, light transmission increased with treatment time for approximately 15 min, after which a progressive partial reversal of the HP-induced increase in light transmission occurred, indicating initial HP-induced disruption of casein micelles, followed by reformation of casein aggregates from micellar fragments. The extent of HP-induced micellar disruption was negatively correlated with the concentration of casein micelles, milk pH, and levels of added ethanol, calcium chloride, or sodium chloride and positively correlated with the level of added sodium phosphate. The reformation of casein aggregates during prolonged HP treatment did not occur when HP-induced disruption of casein micelles was limited (<60%) or very extensive (>95%) and was promoted by a low initial milk pH or added sodium phosphate, sodium chloride, or ethanol. On the basis of these findings, a mechanism for HP-induced disruption of casein micelles and subsequent aggregation of micellar fragments is proposed, in which the main element appears to be HP-induced solubilization of micellar calcium phosphate.

  7. Stimuli-sensitive polymeric micelles as anticancer drug carriers.

    PubMed

    Na, Kun; Sethuraman, Vijay T; Bae, You Han

    2006-11-01

    Amphiphilic block copolymers often form core-shell type micelles by self-organization of the blocks in an aqueous medium or under specific experimental conditions. Polymeric micelles constructed from these polymers that contain a segment whose physical or chemical properties respond to small changes in environmental conditions are collectively called 'stimuli-sensitive' micelles. This class of nano-scaled constructs has been investigated as a promising anti-cancer drug carrier because the micelles are able to utilize small environmental changes and modify drug release kinetics, biodistribution and the interactions with tissues and cells. This review summarizes the recent progress in stimuli-sensitive micelles for tumor chemotherapy, particularly for those responding to hyperthermic conditions, tumor pH and endosomal/lysosomal pH.

  8. Polysaccharide-Based Micelles for Drug Delivery

    PubMed Central

    Zhang, Nan; Wardwell, Patricia R.; Bader, Rebecca A.

    2013-01-01

    Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date. PMID:24300453

  9. Micelle Morphology and Mechanical Response of Triblock Gels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Seitz, Michelle E.; Burghardt, Wesley R.; Shull, Kenneth R.

    2010-01-12

    The effect of polymer concentration on mechanical response and micelle morphology of ABA and AB copolymers in B-selective solvents has been systematically studied. Micelle morphology was determined using a combination of small-angle X-ray scattering, shear, and birefringence while mechanical response at low and high strains was determined using indentation techniques. Self-consistent field theory calculations were used to determine micelle volume fraction profiles and to construct an equilibrium phase map. The transition from spherical to cylindrical micelles increases the triblock gel modulus and energy dissipation. Combining knowledge of gel relaxation time, which determines the rate at which the gel can equilibratemore » its micelle structure, with the equilibrium phase map allows estimation of the experimental temperatures and time scales over which kinetic trapping will arrest micelle structure evolution. Kinetic trapping enables cylindrical morphologies to be obtained at significantly lower polymer fractions than is possible in equilibrated systems.« less

  10. Dynamics of micelle-nanoparticle systems undergoing shear. A coarse-grained molecular dynamics approach

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rolfe, Bryan A.; Chun, Jaehun; Joo, Yong L.

    2013-09-05

    Recent experimental work has shown that polymeric micelles can template nanoparticles via interstitial sites in shear-ordered micelle solutions. In the current study, we report simulation results based on a coarse-grained molecular dynamics (CGMD) model of a solvent/polymer/nanoparticle system. Our results demonstrate the importance of polymer concentration and the micelle corona length in 2D shear-ordering of neat block copolymer solutions. Although our results do not show strong 3D ordering during shear, we find that cessation of shear allows the system to relax into a 3D configuration of greater order than without shear. It is further shown that this post-shear relaxation ismore » strongly dependent on the length of the micelle corona. For the first time, we demonstrate the presence and importance of a flow disturbance surrounding micelles in simple shear flow at moderate Péclet numbers. This disturbance is similar to what is observed around simulated star polymers and ellipsoids. The extent of the flow disturbance increases as expected with a longer micelle corona length. It is further suggested that without proper consideration of these dynamics, a stable nanoparticle configuration would be difficult to obtain.« less

  11. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo.

    PubMed

    Gou, MaLing; Men, Ke; Shi, HuaShan; Xiang, MingLi; Zhang, Juan; Song, Jia; Long, JianLin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, ZhiYong

    2011-04-01

    Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 ± 0.011) with a mean particle size of 27.3 ± 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 ± 1.02%, and drug loading of 12.95 ± 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t(1/2) and AUC of curcumin in vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesis in vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cells in vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg(-1) curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

  12. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Gou, Maling; Men, Ke; Shi, Huashan; Xiang, Mingli; Zhang, Juan; Song, Jia; Long, Jianlin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, Zhiyong

    2011-04-01

    Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 +/- 0.011) with a mean particle size of 27.3 +/- 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 +/- 1.02%, and drug loading of 12.95 +/- 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t1/2 and AUC of curcuminin vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesisin vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cellsin vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg-1curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

  13. Block Copolymer Micelles as Nanocontainers for Controlled Release of Proteins from Biocompatible Oil Phases

    PubMed Central

    2009-01-01

    Biocompatible oils are used in a variety of medical applications ranging from vaccine adjuvants to vehicles for oral drug delivery. To enable such nonpolar organic phases to serve as reservoirs for delivery of hydrophilic compounds, we explored the ability of block copolymer micelles in organic solvents to sequester proteins for sustained release across an oil−water interface. Self-assembly of the block copolymer, poly(ϵ-caprolactone)-block-poly(2-vinyl pyridine) (PCL-b-P2VP), was investigated in toluene and oleic acid, a biocompatible naturally occurring fatty acid. Micelle formation in toluene was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM) imaging of micelles cast onto silicon substrates. Cryogenic transmission electron microscopy confirmed a spherical morphology in oleic acid. Studies of homopolymer solubility implied that micelles in oleic acid consist of a P2VP corona and a PCL core, while P2VP formed the core of micelles assembled in toluene. The loading of two model proteins (ovalbumin (ova) and bovine serum albumin (BSA)) into micelles was demonstrated with loadings as high as 7.8% wt of protein per wt of P2VP in oleic acid. Characterization of block copolymer morphology in the two solvents after protein loading revealed spherical particles with similar size distributions to the as-assembled micelles. Release of ova from micelles in oleic acid was sustained for 12−30 h upon placing the oil phase in contact with an aqueous bath. Unique to the situation of micelle assembly in an oily phase, the data suggest protein is sequestered in the P2VP corona block of PCL-b-P2VP micelles in oleic acid. More conventionally, protein loading occurs in the P2VP core of micelles assembled in toluene. PMID:19235932

  14. Chlorophyll b degradation by chlorophyll b reductase under high-light conditions.

    PubMed

    Sato, Rei; Ito, Hisashi; Tanaka, Ayumi

    2015-12-01

    The light-harvesting chlorophyll a/b binding protein complex of photosystem II (LHCII) is the main antenna complex of photosystem II (PSII). Plants change their LHCII content depending on the light environment. Under high-light conditions, the content of LHCII should decrease because over-excitation damages the photosystem. Chlorophyll b is indispensable for accumulating LHCII, and chlorophyll b degradation induces LHCII degradation. Chlorophyll b degradation is initiated by chlorophyll b reductase (CBR). In land plants, NON-YELLOW COLORING 1 (NYC1) and NYC1-Like (NOL) are isozymes of CBR. We analyzed these mutants to determine their functions under high-light conditions. During high-light treatment, the chlorophyll a/b ratio was stable in the wild-type (WT) and nol plants, and the LHCII content decreased in WT plants. The chlorophyll a/b ratio decreased in the nyc1 and nyc1/nol plants, and a substantial degree of LHCII was retained in nyc1/nol plants after the high-light treatment. These results demonstrate that NYC1 degrades the chlorophyll b on LHCII under high-light conditions, thus decreasing the LHCII content. After the high-light treatment, the maximum quantum efficiency of the PSII photochemistry was lower in nyc1 and nyc1/nol plants than in WT and nol plants. A larger light-harvesting system would damage PSII in nyc1 and nyc1/nol plants. The fluorescence spectroscopy of the leaves indicated that photosystem I was also damaged by the excess LHCII in nyc1/nol plants. These observations suggest that chlorophyll b degradation by NYC1 is the initial reaction for the optimization of the light-harvesting capacity under high-light conditions.

  15. Reformation of casein particles from alkaline-disrupted casein micelles.

    PubMed

    Huppertz, Thom; Vaia, Betsy; Smiddy, Mary A

    2008-02-01

    In this study, the properties of casein particles reformed from alkaline disrupted casein micelles were studied. For this purpose, micelles were disrupted completely by increasing milk pH to 10.0, and subsequently reformed by decreasing milk pH to 6.6. Reformed casein particles were smaller than native micelles and had a slightly lower zeta-potential. Levels of ionic and serum calcium, as well as rennet coagulation time did not differ between milk containing native micelles or reformed casein particles. Ethanol stability and heat stability, >pH 7.0, were lower for reformed casein particles than native micelles. Differences in heat stability, ethanol stability and zeta-potential can be explained in terms of the influence of increased concentrations of sodium and chloride ions in milk containing reformed casein particles. Hence, these results indicate that, if performed in a controlled manner, casein particles with properties closely similar to those of native micelles can be reformed from alkaline disrupted casein micelles.

  16. Mesoscale crystallization of calcium phosphate nanostructures in protein (casein) micelles

    NASA Astrophysics Data System (ADS)

    Thachepan, Surachai; Li, Mei; Mann, Stephen

    2010-11-01

    Aqueous micelles of the multi-protein calcium phosphate complex, casein, were treated at 60 °C and pH 7 over several months. Although partial dissociation of the micelles into 12 nm sized amorphous calcium phosphate (ACP)/protein nanoparticles occurred within a period of 14 days, crystallization of the ACP nanoclusters into bundles of hydroxyapatite (HAP) nanofilaments was not observed until after 12 weeks. The HAP nanofilaments were formed specifically within the partially disrupted protein micelles suggesting a micelle-mediated pathway of mesoscale crystallization. Similar experiments using ACP-containing synthetic micelles prepared from β-casein protein alone indicated that co-aligned bundles of HAP nanofilaments were produced within the protein micelle interior after 24 hours at temperatures as low as 35 °C. The presence of Mg2+ ions in the casein micelles, as well as a possible synergistic effect associated with the multi-protein nature of the native aggregates, could account for the marked inhibition in mesoscale crystallization observed in the casein micelles compared with the single-component β-casein constructs.Aqueous micelles of the multi-protein calcium phosphate complex, casein, were treated at 60 °C and pH 7 over several months. Although partial dissociation of the micelles into 12 nm sized amorphous calcium phosphate (ACP)/protein nanoparticles occurred within a period of 14 days, crystallization of the ACP nanoclusters into bundles of hydroxyapatite (HAP) nanofilaments was not observed until after 12 weeks. The HAP nanofilaments were formed specifically within the partially disrupted protein micelles suggesting a micelle-mediated pathway of mesoscale crystallization. Similar experiments using ACP-containing synthetic micelles prepared from β-casein protein alone indicated that co-aligned bundles of HAP nanofilaments were produced within the protein micelle interior after 24 hours at temperatures as low as 35 °C. The presence of Mg2+ ions in

  17. [Algorithm for estimating chlorophyll-a concentration in case II water body based on bio-optical model].

    PubMed

    Yang, Wei; Chen, Jin; Mausushita, Bunki

    2009-01-01

    In the present study, a novel retrieval method for estimating chlorophyll-a concentration in case II waters based on bio-optical model was proposed and was tested with the data measured in the laboratory. A series of reflectance spectra, with which the concentration of each sample constituent (for example chlorophyll-a, NPSS etc.) was obtained from accurate experiments, were used to calculate the absorption and backscattering coefficients of the constituents of the case II waters. Then non-negative least square method was applied to calculate the concentration of chlorophyll-a and non-phytoplankton suspended sediments (NPSS). Green algae was firstly collected from the Kasumigaura lake in Japan and then cultured in the laboratory. The reflectance spectra of waters with different amounts of phytoplankton and NPSS were measured in the dark room using FieldSpec Pro VNIR (Analytical Spectral Devises Inc. , Boulder, CO, USA). In order to validate whether this method can be applied in multispectral data (for example Landsat TM), the spectra measured in the laboratory were resampled with Landsat TM bands 1, 2, 3 and 4. Different combinations of TM bands were compared to derive the most appropriate wavelength for detecting chlorophyll-a in case II water for green algae. The results indicated that the combination of TM bands 2, 3 and 4 achieved much better accuracy than other combinations, and the estimated concentration of chlorophyll-a was significantly more accurate than empirical methods. It is expected that this method can be directly applied to the real remotely sensed image because it is based on bio-optical model.

  18. In situ electron-beam polymerization stabilized quantum dot micelles.

    PubMed

    Travert-Branger, Nathalie; Dubois, Fabien; Renault, Jean-Philippe; Pin, Serge; Mahler, Benoit; Gravel, Edmond; Dubertret, Benoit; Doris, Eric

    2011-04-19

    A polymerizable amphiphile polymer containing PEG was synthesized and used to encapsulate quantum dots in micelles. The quantum dot micelles were then polymerized using a "clean" electron beam process that did not require any post-irradiation purification. Fluorescence spectroscopy revealed that the polymerized micelles provided an organic coating that preserved the quantum dot fluorescence better than nonpolymerized micelles, even under harsh conditions. © 2011 American Chemical Society

  19. Determination and importance of temperature dependence of retention coefficient (RPHPLC) in QSAR model of nitrazepams' partition coefficient in bile acid micelles.

    PubMed

    Posa, Mihalj; Pilipović, Ana; Lalić, Mladena; Popović, Jovan

    2011-02-15

    Linear dependence between temperature (t) and retention coefficient (k, reversed phase HPLC) of bile acids is obtained. Parameters (a, intercept and b, slope) of the linear function k=f(t) highly correlate with bile acids' structures. Investigated bile acids form linear congeneric groups on a principal component (calculated from k=f(t)) score plot that are in accordance with conformations of the hydroxyl and oxo groups in a bile acid steroid skeleton. Partition coefficient (K(p)) of nitrazepam in bile acids' micelles is investigated. Nitrazepam molecules incorporated in micelles show modified bioavailability (depo effect, higher permeability, etc.). Using multiple linear regression method QSAR models of nitrazepams' partition coefficient, K(p) are derived on the temperatures of 25°C and 37°C. For deriving linear regression models on both temperatures experimentally obtained lipophilicity parameters are included (PC1 from data k=f(t)) and in silico descriptors of the shape of a molecule while on the higher temperature molecular polarisation is introduced. This indicates the fact that the incorporation mechanism of nitrazepam in BA micelles changes on the higher temperatures. QSAR models are derived using partial least squares method as well. Experimental parameters k=f(t) are shown to be significant predictive variables. Both QSAR models are validated using cross validation and internal validation method. PLS models have slightly higher predictive capability than MLR models. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Micelle Delivery of Parthenolide to Acute Myeloid Leukemia Cells

    PubMed Central

    Baranello, Michael P.; Bauer, Louisa; Jordan, Craig T.; Benoit, Danielle S. W.

    2018-01-01

    Parthenolide (PTL) has shown great promise as a novel anti-leukemia agent as it selectively eliminates acute myeloid leukemia (AML) blast cells and leukemia stem cells (LSCs) while sparing normal hematopoietic cells. This success has not yet translated to the clinical setting because PTL is rapidly cleared from blood due to its hydrophobicity. To increase the aqueous solubility of PTL, we previously developed micelles formed from predominantly hydrophobic amphiphilic diblock copolymers of poly(styrene-alt-maleic anhydride)-b-poly(styrene) (e.g., PSMA100-b-PS258) that exhibit robust PTL loading (75%efficiency, 11% w/w capacity) and release PTL over 24 h. Here, PTL-loaded PSMA-b-PS micelles were thoroughly characterized in vitro for PTL delivery to MV4-11 AML cells. Additionally, the mechanisms governing micelle-mediated cytotoxicity were examined in comparison to free PTL. PSMA-b-PS micelles were taken up by MV4-11 cells as evidenced by transmission electron microscopy and flow cytometry. Specifically, MV4-11 cells relied on clathrin-mediated endocytosis, rather than caveolae-mediated endocytosis and macropinocytosis. In addition, PTL-loaded PSMA-b-PS micelles exhibited a dose-dependent cytotoxicity towards AML cells and were capable of reducing cell viability by 75% at 10 μM PTL, while unloaded micelles were nontoxic. At 10 μM PTL, the cytotoxicity of PTL-loaded micelles increased gradually over 24 h while free PTL achieved maximal cytotoxicity between 2 and 4 h, demonstrating micelle-mediated delivery of PTL to AML cells and stability of the drug-loaded micelle even in the presence of cells. Both free PTL and PTL-loaded micelles induced NF-κB inhibition at 10 μM PTL doses, demonstrating some mechanistic similarities in cytotoxicity. However, free PTL relied more heavily on exofacial free thiol interactions to induce cytotoxicity than PTL-loaded micelles; free PTL cytotoxicity was reduced by over twofold when cell surface free thiols were depleted, where PTL

  1. Fibrin-binding, peptide amphiphile micelles for targeting glioblastoma☆

    PubMed Central

    Chung, Eun Ji; Cheng, Yu; Morshed, Ramin; Nord, Kathryn; Han, Yu; Wegscheid, Michelle L.; Auffinger, Brenda; Wainwright, Derek A.; Lesniak, Maciej S.; Tirrell, Matthew V.

    2013-01-01

    Glioblastoma-targeted drug delivery systems facilitate efficient delivery of chemotherapeutic agents to malignant gliomas, while minimizing systemic toxicity and side effects. Taking advantage of the fibrin deposition that is characteristic of tumors, we constructed spherical, Cy7-labeled, targeting micelles to glioblastoma through the addition of the fibrin-binding pentapeptide, cysteine–arginine–glutamic acid–lysine–alanine, or CREKA. Conjugation of the CREKA peptide to Cy7-micelles increased the average particle size and zeta potential. Upon intravenous administration to GL261 glioma bearing mice, Cy7-micelles passively accumulated at the brain tumor site via the enhanced permeability and retention (EPR) effect, and Cy7-CREKA-micelles displayed enhanced tumor homing via active targeting as early as 1 h after administration, as confirmed via in vivo and ex vivo imaging and immunohistochemistry. Biodistribution of micelles showed an accumulation within the liver and kidneys, leading to micelle elimination via renal clearance and the reticuloendothelial system (RES). Histological evaluation showed no signs of cytotoxicity or tissue damage, confirming the safety and utility of this nanoparticle system for delivery to glioblastoma. Our findings offer strong evidence for the glioblastoma-targeting potential of CREKA-micelles and provide the foundation for CREKA-mediated, targeted therapy of glioma. PMID:24211079

  2. Performance of a two-leaf light use efficiency model for mapping gross primary productivity against remotely sensed sun-induced chlorophyll fluorescence data.

    PubMed

    Zan, Mei; Zhou, Yanlian; Ju, Weimin; Zhang, Yongguang; Zhang, Leiming; Liu, Yibo

    2018-02-01

    Estimating terrestrial gross primary production is an important task when studying the carbon cycle. In this study, the ability of a two-leaf light use efficiency model to simulate regional gross primary production in China was validated using satellite Global Ozone Monitoring Instrument - 2 sun-induced chlorophyll fluorescence data. The two-leaf light use efficiency model was used to estimate daily gross primary production in China's terrestrial ecosystems with 500-m resolution for the period from 2007 to 2014. Gross primary production simulated with the two-leaf light use efficiency model was resampled to a spatial resolution of 0.5° and then compared with sun-induced chlorophyll fluorescence. During the study period, sun-induced chlorophyll fluorescence and gross primary production simulated by the two-leaf light use efficiency model exhibited similar spatial and temporal patterns in China. The correlation coefficient between sun-induced chlorophyll fluorescence and monthly gross primary production simulated by the two-leaf light use efficiency model was significant (p<0.05, n=96) in 88.9% of vegetated areas in China (average value 0.78) and varied among vegetation types. The interannual variations in monthly sun-induced chlorophyll fluorescence and gross primary production simulated by the two-leaf light use efficiency model were similar in spring and autumn in most vegetated regions, but dissimilar in winter and summer. The spatial variability of sun-induced chlorophyll fluorescence and gross primary production simulated by the two-leaf light use efficiency model was similar in spring, summer, and autumn. The proportion of spatial variations of sun-induced chlorophyll fluorescence and annual gross primary production simulated by the two-leaf light use efficiency model explained by ranged from 0.76 (2011) to 0.80 (2013) during the study period. Overall, the two-leaf light use efficiency model was capable of capturing spatial and temporal variations in gross

  3. Mixed micelles of 7,12-dioxolithocholic acid and selected hydrophobic bile acids: interaction parameter, partition coefficient of nitrazepam and mixed micelles haemolytic potential.

    PubMed

    Poša, Mihalj; Tepavčević, Vesna

    2011-09-01

    The formation of mixed micelles built of 7,12-dioxolithocholic and the following hydrophobic bile acids was examined by conductometric method: cholic (C), deoxycholic (D), chenodeoxycholic (CD), 12-oxolithocholic (12-oxoL), 7-oxolithocholic (7-oxoL), ursodeoxycholic (UD) and hiodeoxycholic (HD). Interaction parameter (β) in the studied binary mixed micelles had negative value, suggesting synergism between micelle building units. Based on β value, the hydrophobic bile acids formed two groups: group I (C, D and CD) and group II (12-oxoL, 7-oxoL, UD and HD). Bile acids from group II had more negative β values than bile acids from group I. Also, bile acids from group II formed intermolecular hydrogen bonds in aggregates with both smaller (2) and higher (4) aggregation numbers, according to the analysis of their stereochemical (conformational) structures and possible structures of mixed micelles built of these bile acids and 7,12-dioxolithocholic acid. Haemolytic potential and partition coefficient of nitrazepam were higher in mixed micelles built of the more hydrophobic bile acids (C, D, CD) and 7,12-dioxolithocholic acid than in micelles built only of 7,12-dioxolithocholic acid. On the other hand, these mixed micelles still had lower values of haemolytic potential than micelles built of C, D or CD. The mixed micelles that included bile acids: 12-oxoL, 7-oxoL, UD or HD did not significantly differ from the micelles of 7,12-dioxolithocholic acid, observing the values of their haemolytic potential. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma

    PubMed Central

    Shih, Ying-Hsia; Peng, Cheng-Liang; Chiang, Ping-Fang; Lin, Wuu-Jyh; Luo, Tsai-Yueh; Shieh, Ming-Jium

    2015-01-01

    This study evaluated a multifunctional micelle simultaneously loaded with doxorubicin (Dox) and labeled with radionuclide rhenium-188 (188Re) as a combined radiotherapy and chemotherapy treatment for hepatocellular carcinoma. We investigated the single photon emission computed tomography, biodistribution, antitumor efficacy, and pathology of 188Re-Dox micelles in a murine orthotopic luciferase-transfected BNL tumor cells hepatocellular carcinoma model. The single photon emission computed tomography and computed tomography images showed high radioactivity in the liver and tumor, which was in agreement with the biodistribution measured by γ-counting. In vivo bioluminescence images showed the smallest size tumor (P<0.05) in mice treated with the combined micelles throughout the experimental period. In addition, the combined 188Re-Dox micelles group had significantly longer survival compared with the control, 188ReO4 alone (P<0.005), and Dox micelles alone (P<0.01) groups. Pathohistological analysis revealed that tumors treated with 188Re-Dox micelles had more necrotic features and decreased cell proliferation. Therefore, 188Re-Dox micelles may enable combined radiotherapy and chemotherapy to maximize the effectiveness of treatment for hepatocellular carcinoma. PMID:26719687

  5. Neutral Polymeric Micelles for RNA Delivery

    PubMed Central

    Lundy, Brittany B.; Convertine, Anthony; Miteva, Martina; Stayton, Patrick S.

    2013-01-01

    RNA interference (RNAi) drugs have significant therapeutic potential but delivery systems with appropriate efficacy and toxicity profiles are still needed. Here, we describe a neutral, ampholytic polymeric delivery system based on conjugatable diblock polymer micelles. The diblock copolymer contains a hydrophilic poly[N-(2-hydroxypropyl) methacrylamide-co-N-(2-(pyridin-2- yldisulfanyl)ethyl)methacrylamide) (poly[HPMA-co-PDSMA]) segment to promote aqueous stability and facilitate thiol-disulfide exchange reactions, and a second ampholytic block composed of propyl acrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The poly[(HPMA-co-PDSMA)-b-(PAA-co-DMAEMA-co-BMA)] was synthesized using Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization with an overall molecular weight of 22,000 g/mol and a PDI of 1.88. Dynamic light scattering and fluorescence measurements indicated that the diblock copolymers self-assemble under aqueous conditions to form polymeric micelles with a hydrodynamic radius and critical micelle concentration of 25 nm and 25 μg/mL respectively. Red blood cell hemolysis experiments show that the neutral hydrophilic micelles have potent membrane destabilizing activity at endosomal pH values. Thiolated siRNA targeting glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was directly conjugated to the polymeric micelles via thiol exchange reactions with the pyridal disulfide groups present in the micelle corona. Maximum silencing activity in HeLa cells was observed at a 1:10 molar ratio of siRNA to polymer following a 48 h incubation period. Under these conditions 90 % mRNA knockdown and 65 % and protein knockdown of at 48 h was achieved with negligible toxicity. In contrast the polymeric micelles lacking a pH-responsive endosomalytic segment demonstrated negligible mRNA and protein knockdown under these conditions. The potent mRNA knockdown and excellent biocompatibility of the neutral siRNA conjugates

  6. Reduction-sensitive micelles self-assembled from amphiphilic chondroitin sulfate A-deoxycholic acid conjugate for triggered release of doxorubicin.

    PubMed

    Liu, Hongxia; Wu, Shuqin; Yu, Jingmou; Fan, Dun; Ren, Jin; Zhang, Lei; Zhao, Jianguo

    2017-06-01

    Reduction-sensitive chondroitin sulfate A (CSA)-based micelles were developed. CSA was conjugated with deoxycholic acid (DOCA) via a disulfide linkage. The bioreducible conjugate (CSA-ss-DOCA) can form self-assembled micelles in aqueous medium. The critical micelle concentration (CMC) of CSA-ss-DOCA conjugate is 0.047mg/mL, and its mean diameter is 387nm. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the micelles with high loading efficiency. Reduction-sensitive micelles and reduction-insensitive control micelles displayed similar DOX release behavior in phosphate buffered saline (PBS, pH7.4). Notably, DOX release from the reduction-sensitive micelles in vitro was accelerated in the presence of 20mM glutathione-containing PBS environment. Moreover, DOX-loaded CSA-ss-DOCA (CSA-ss-DOCA/DOX) micelles exhibited intracellular reduction-responsive characteristics in human gastric cancer HGC-27 cells determined by confocal laser scanning microscopy (CLSM). Furthermore, CSA-ss-DOCA/DOX micelles demonstrated higher antitumor efficacy than reduction-insensitive control micelles in HGC-27 cells. These results suggested that reduction-sensitive CSA-ss-DOCA micelles had the potential as intracellular targeted carriers of anticancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Gadolinium-Functionalized Peptide Amphiphile Micelles for Multimodal Imaging of Atherosclerotic Lesions

    PubMed Central

    2016-01-01

    The leading causes of morbidity and mortality globally are cardiovascular diseases, and nanomedicine can provide many improvements including disease-specific targeting, early detection, and local delivery of diagnostic agents. To this end, we designed fibrin-binding, peptide amphiphile micelles (PAMs), achieved by incorporating the targeting peptide cysteine-arginine-glutamic acid-lysine-alanine (CREKA), with two types of amphiphilic molecules containing the gadoliniuim (Gd) chelator diethylenetriaminepentaacetic acid (DTPA), DTPA-bis(stearylamide)(Gd), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(poly(ethylene glycol) (PEG))-2000]-DTPA(Gd) (DSPE-PEG2000-DTPA(Gd)). The material characteristics of the resulting nanoparticle diagnostic probes, clot-binding properties in vitro, and contrast enhancement and safety for dual, optical imaging–magnetic resonance imaging (MRI) were evaluated in the atherosclerotic mouse model. Transmission electron micrographs showed a homogenous population of spherical micelles for formulations containing DSPE-PEG2000-DTPA(Gd), whereas both spherical and cylindrical micelles were formed upon mixing DTPA-BSA(Gd) and CREKA amphiphiles. Clot-binding assays confirmed DSPE-PEG2000-DTPA(Gd)-based CREKA micelles targeted clots over 8-fold higher than nontargeting (NT) counterpart micelles, whereas no difference was found between CREKA and NT, DTPA-BSA(Gd) micelles. However, in vivo MRI and optical imaging studies of the aortas and hearts showed fibrin specificity was conferred by the peptide ligand without much difference between the nanoparticle formulations or shapes. Biodistribution studies confirmed that all micelles were cleared through both the reticuloendothelial system and renal clearance, and histology showed no signs of necrosis. In summary, these studies demonstrate the successful synthesis, and the molecular imaging capabilities of two types of CREKA-Gd PAMs for atherosclerosis. Moreover, we demonstrate the differences in

  8. Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery.

    PubMed

    Cao, Yanwu; Gao, Min; Chen, Chao; Fan, Aiping; Zhang, Ju; Kong, Deling; Wang, Zheng; Peer, Dan; Zhao, Yanjun

    2015-03-20

    Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6 ± 5.9 (nm) with a zeta potential of -10.6 ± 0.7 (mV). The critical micelle concentration was determined at 6.7 ± 0.4 (μg mL(-1)). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in HeLa cells at 18.5 ± 1.4 (μg mL(-1)), whereas the IC50 of control micelles was 41.0 ± 2.4 (μg mL(-1)). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice.

  9. Structural changes in block copolymer micelles induced by cosolvent mixtures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kelley, Elizabeth G.; Smart, Thomas P.; Jackson, Andrew J.

    2012-11-26

    We investigated the influence of tetrahydrofuran (THF) addition on the structure of poly(1,2-butadiene-b-ethylene oxide) [PB-PEO] micelles in aqueous solution. Our studies showed that while the micelles remained starlike, the micelle core-corona interfacial tension and micelle size decreased upon THF addition. The detailed effects of the reduction in interfacial tension were probed using contrast variations in small angle neutron scattering (SANS) experiments. At low THF contents (high interfacial tensions), the SANS data were fit to a micelle form factor that incorporated a radial density distribution of corona chains to account for the starlike micelle profile. However, at higher THF contents (lowmore » interfacial tensions), the presence of free chains in solution affected the scattering at high q and required the implementation of a linear combination of micelle and Gaussian coil form factors. These SANS data fits indicated that the reduction in interfacial tension led to broadening of the core-corona interface, which increased the PB chain solvent accessibility at intermediate THF solvent fractions. We also noted that the micelle cores swelled with increasing THF addition, suggesting that previous assumptions of the micelle core solvent content in cosolvent mixtures may not be accurate. Control over the size, corona thickness, and extent of solvent accessible PB in these micelles can be a powerful tool in the development of targeting delivery vehicles.« less

  10. Structural changes in block copolymer micelles induced by cosolvent mixtures†

    PubMed Central

    Kelley, Elizabeth G.; Smart, Thomas P.; Jackson, Andrew J.; Sullivan, Millicent O.

    2013-01-01

    We investigated the influence of tetrahydrofuran (THF) addition on the structure of poly(1,2-butadiene-b-ethylene oxide) [PB-PEO] micelles in aqueous solution. Our studies showed that while the micelles remained starlike, the micelle core-corona interfacial tension and micelle size decreased upon THF addition. The detailed effects of the reduction in interfacial tension were probed using contrast variations in small angle neutron scattering (SANS) experiments. At low THF contents (high interfacial tensions), the SANS data were fit to a micelle form factor that incorporated a radial density distribution of corona chains to account for the starlike micelle profile. However, at higher THF contents (low interfacial tensions), the presence of free chains in solution affected the scattering at high q and required the implementation of a linear combination of micelle and Gaussian coil form factors. These SANS data fits indicated that the reduction in interfacial tension led to broadening of the core-corona interface, which increased the PB chain solvent accessibility at intermediate THF solvent fractions. We also noted that the micelle cores swelled with increasing THF addition, suggesting that previous assumptions of the micelle core solvent content in cosolvent mixtures may not be accurate. Control over the size, corona thickness, and extent of solvent accessible PB in these micelles can be a powerful tool in the development of targeting delivery vehicles. PMID:24282441

  11. Identification of a Chlorophyll Dephytylase Involved in Chlorophyll Turnover in Arabidopsis.

    PubMed

    Lin, Yao-Pin; Wu, Meng-Chen; Charng, Yee-Yung

    2016-12-01

    Chlorophyll turns over in green organs during photosystem repair and is salvaged via de- and rephytylation, but the enzyme involved in dephytylation is unknown. We have identified an Arabidopsis thaliana thylakoid protein with a putative hydrolase domain that can dephytylate chlorophyll in vitro and in vivo. The corresponding locus, CHLOROPHYLL DEPHYTYLASE1 (CLD1), was identified by mapping a semidominant, heat-sensitive, missense allele (cld1-1). CLD1 is conserved in oxygenic photosynthetic organisms, sharing structural similarity with pheophytinase, which functions in chlorophyll breakdown during leaf senescence. Unlike pheophytinase, CLD1 is predominantly expressed in green organs and can dephytylate chlorophyll in vitro. The specific activity is significantly higher for the mutant protein encoded by cld1-1 than the wild-type enzyme, consistent with the semidominant nature of the cld1-1 mutation. Supraoptimal CLD1 activities in cld1-1 mutants and transgenic seedlings led to the proportional accumulation of chlorophyllides derived from chlorophyll dephytylation after heat shock, which resulted in light-dependent cotyledon bleaching. Reducing CLD1 expression diminished thermotolerance and the photochemical efficiency of photosystem II under prolonged moderate heat stress. Taken together, our results suggest that CLD1 is the long-sought enzyme for removing the phytol chain from chlorophyll during its turnover at steady state within the chloroplast. © 2016 American Society of Plant Biologists. All rights reserved.

  12. Glutathione-responsive core cross-linked micelles for controlled cabazitaxel delivery

    NASA Astrophysics Data System (ADS)

    Han, Xiaoxiong; Gong, Feirong; Sun, Jing; Li, Yueqi; Liu, XiaoFei; Chen, Dan; Liu, Jianwen; Shen, Yaling

    2018-02-01

    Stimulus-responsive polymeric micelles (PMs) have recently received attention due to the controlled delivery of drug or gene for application in cancer diagnosis and treatment. In this work, novel glutathione-responsive PMs were prepared to encapsulate hydrophobic antineoplastic drug, cabazitaxel (CTX), to improve its solubility and toxicity. These CTX-loaded micelles core cross-linked by disulfide bonds (DCL-CTX micelles) were prepared by a novel copolymer, lipoic acid grafted mPEG-PLA. These micelles had regular spherical shape, homogeneous diameter of 18.97 ± 0.23 nm, and a narrow size distribution. The DCL-CTX micelles showed high encapsulation efficiency of 98.65 ± 1.77%, and the aqueous solubility of CTX was improved by a factor of 1:1200. In vitro release investigation showed that DCL-CTX micelles were stable in the medium without glutathione (GSH), whereas the micelles had burst CTX release in the medium with 10 mM GSH. Cell uptake results implied that DCL-CTX micelles were internalized into MCF-7 cells through clathrin-mediated endocytosis and released cargo more effectively than Jevtana (commercially available CTX) owing to GSH-stimulated degradation. In MTT assay against MCF-7 cells, these micelles inhibited tumor cell proliferation more effectively than Jevtana due to their GSH-responsive CTX release. All results revealed the potency of GSH-responsive DCL-CTX micelles for stable delivery in blood circulation and for intracellular GSH-trigged release of CTX. Therefore, DCL-CTX micelles show potential as safe and effective CTX delivery carriers and as a cancer chemotherapy formulation.

  13. Fibrin-binding, peptide amphiphile micelles for targeting glioblastoma.

    PubMed

    Chung, Eun Ji; Cheng, Yu; Morshed, Ramin; Nord, Kathryn; Han, Yu; Wegscheid, Michelle L; Auffinger, Brenda; Wainwright, Derek A; Lesniak, Maciej S; Tirrell, Matthew V

    2014-01-01

    Glioblastoma-targeted drug delivery systems facilitate efficient delivery of chemotherapeutic agents to malignant gliomas, while minimizing systemic toxicity and side effects. Taking advantage of the fibrin deposition that is characteristic of tumors, we constructed spherical, Cy7-labeled, targeting micelles to glioblastoma through the addition of the fibrin-binding pentapeptide, cysteine-arginine-glutamic acid-lysine-alanine, or CREKA. Conjugation of the CREKA peptide to Cy7-micelles increased the average particle size and zeta potential. Upon intravenous administration to GL261 glioma bearing mice, Cy7-micelles passively accumulated at the brain tumor site via the enhanced permeability and retention (EPR) effect, and Cy7-CREKA-micelles displayed enhanced tumor homing via active targeting as early as 1 h after administration, as confirmed via in vivo and ex vivo imaging and immunohistochemistry. Biodistribution of micelles showed an accumulation within the liver and kidneys, leading to micelle elimination via renal clearance and the reticuloendothelial system (RES). Histological evaluation showed no signs of cytotoxicity or tissue damage, confirming the safety and utility of this nanoparticle system for delivery to glioblastoma. Our findings offer strong evidence for the glioblastoma-targeting potential of CREKA-micelles and provide the foundation for CREKA-mediated, targeted therapy of glioma. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Mesoscale crystallization of calcium phosphate nanostructures in protein (casein) micelles.

    PubMed

    Thachepan, Surachai; Li, Mei; Mann, Stephen

    2010-11-01

    Aqueous micelles of the multi-protein calcium phosphate complex, casein, were treated at 60°C and pH 7 over several months. Although partial dissociation of the micelles into 12 nm sized amorphous calcium phosphate (ACP)/protein nanoparticles occurred within a period of 14 days, crystallization of the ACP nanoclusters into bundles of hydroxyapatite (HAP) nanofilaments was not observed until after 12 weeks. The HAP nanofilaments were formed specifically within the partially disrupted protein micelles suggesting a micelle-mediated pathway of mesoscale crystallization. Similar experiments using ACP-containing synthetic micelles prepared from ß-casein protein alone indicated that co-aligned bundles of HAP nanofilaments were produced within the protein micelle interior after 24 hours at temperatures as low as 35°C. The presence of Mg²(+) ions in the casein micelles, as well as a possible synergistic effect associated with the multi-protein nature of the native aggregates, could account for the marked inhibition in mesoscale crystallization observed in the casein micelles compared with the single-component b-casein constructs.

  15. Peptide-conjugated micelles as a targeting nanocarrier for gene delivery

    NASA Astrophysics Data System (ADS)

    Lin, Wen Jen; Chien, Wei Hsuan

    2015-09-01

    The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly( d,l-lactide- co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells.

  16. Preventing Small Molecule Nucleation and Crystallization by Sequestering in a Micelle Corona

    NASA Astrophysics Data System (ADS)

    Li, Ziang; Johnson, Lindsay; Ricarte, Ralm; Yao, Letitia; Hillmyer, Marc; Bates, Frank; Lodge, Timothy

    We exploited a blend of hydroxypropyl methylcellulose acetate succinate and poly(N-isopropylacrylamide) (PNIPAm) to improve the solubility and dissolution of a rapidly crystallizing model drug molecule phenytoin and observed synergistic effect in vitro at constant drug loading by varying the blending ratio. Dynamic and static light scattering experiments showed that PNIPAm self-assembled into micelles in aqueous solution. We believe that adding these PNIPAm micelles inhibited both nucleation and crystal growth of phenytoin based on the polarized light micrographs taken from the dissolution media. The drug-polymer intermolecular interaction was revealed by nuclear Overhauser effect spectroscopy and further quantified by diffusion ordered spectroscopy. We found that the phenytoin molecules were sequestered in aqueous solution by partitioning into the corona of the micelle. The blend strategy through the use of self-assembled micelles showcased in this study offers a new platform for designing advanced excipients for oral drug delivery. This study was funded by The Dow Chemical Company through Agreement 224249AT with the University of Minnesota.

  17. Satellite retrievals of leaf chlorophyll and photosynthetic capacity for improved modeling of GPP

    USDA-ARS?s Scientific Manuscript database

    This study investigates the utility of in-situ and satellite-based leaf chlorophyll (Chl) estimates for quantifying leaf photosynthetic capacity and for constraining model simulations of Gross Primary Productivity (GPP) over a corn field in Maryland, U.S.A. The maximum rate of carboxylation (Vmax) r...

  18. Smart wormlike micelles.

    PubMed

    Chu, Zonglin; Dreiss, Cécile A; Feng, Yujun

    2013-09-07

    A major scientific challenge of the past decade pertaining to the field of soft matter has been to craft 'adaptable' materials, inspired by nature, which can dynamically alter their structure and functionality on demand, in response to triggers produced by environmental changes. Amongst these, 'smart' surfactant wormlike micelles, responsive to external stimuli, are a particularly recent area of development, yet highly promising, given the versatility of the materials but simplicity of the design-relying on small amphiphilic molecules and their spontaneous self-assembly. The switching 'on' and 'off' of the micellar assembly structures has been reported using electrical, optical, thermal or pH triggers and is now envisaged for multiple stimuli. The structural changes, in turn, can induce major variations in the macroscopic characteristics, affecting properties such as viscosity and elasticity and sometimes even leading to a spontaneous and effective 'sol-gel' transition. These original smart materials based on wormlike micelles have been successfully used in the oil industry, and offer a significant potential in a wide range of other technological applications, including biomedicine, cleaning processes, drag reduction, template synthesis, to name but a few. This review will report results in this field published over the last few years, describe the potential and practical applications of stimuli-responsive wormlike micelles and point out future challenges.

  19. Reduction-Degradable Polymeric Micelles Decorated with PArg for Improving Anticancer Drug Delivery Efficacy.

    PubMed

    Cui, Yani; Sui, Junhui; He, Mengmeng; Xu, Zhiyi; Sun, Yong; Liang, Jie; Fan, Yujiang; Zhang, Xingdong

    2016-01-27

    In this study, five kinds of reduction-degradable polyamide amine-g-polyethylene glycol/polyarginine (PAA-g-PEG/PArg) micelles with different proportions of hydrophilic and hydrophobic segments were synthesized as novel drug delivery vehicles. Polyarginine not only acted as a hydrophilic segment but also possessed a cell-penetrating function to carry out a rapid transduction into target cells. Polyamide amine-g-polyethylene glycol (PAA-g-PEG) was prepared for comparison. The characterization and antitumor effect of the DOX-incorporated PAA-g-PEG/PArg cationic polymeric micelles were investigated in vitro and in vivo. The cytotoxicity experiments demonstrated that the PAA-g-PEG/PArg micelles have good biocompatibility. Compared with DOX-incorporated PAA-g-PEG micelles, the DOX-incorporated PAA-g-PEG/PArg micelles were more efficiently internalized into human hepatocellular carcinoma (HepG2) cells and more rapidly released DOX into the cytoplasm to inhibit cell proliferation. In the 4T1-bearing nude mouse tumor models, the DOX-incorporated PAA-g-PEG/PArg micelles could efficiently accumulate in the tumor site and had a longer accumulation time and more significant aggregation concentration than those of PAA-g-PEG micelles. Meanwhile, it excellently inhibited the solid tumor growth and extended the survival period of the tumor-bearing Balb/c mice. These results could be attributed to their appropriate nanosize and the cell-penetrating peculiarity of polyarginine as a surface layer. The PAA-g-PEG/PArg polymeric micelles as a safe and high efficiency drug delivery system were expected to be a promising delivery carrier that targeted hydrophobic chemotherapy drugs to tumors and significantly enhanced antitumor effects.

  20. Premicellar and micelle formation behavior of dye surfactant ion pairs in aqueous solutions: deprotonation of dye in ion pair micelles.

    PubMed

    Gohain, Biren; Dutta, Robin K

    2008-07-15

    The premicellar and micelle formation behavior of dye surfactant ion pairs in aqueous solutions monitored by surface tension and spectroscopic measurements has been described. The measurements have been made for three anionic sulfonephthalein dyes and cationic surfactants of different chain lengths, head groups, and counterions. The observations have been attributed to the formation of closely packed dye surfactant ion pairs which is similar to nonionic surfactants in very dilute concentrations of the surfactant. These ion pairs dominate in the monolayer at the air-water interface of the aqueous dye surfactant solutions below the CMC of the pure surfactant. It has been shown that the dye in the ion pair deprotonates on micelle formation by the ion pair surfactants at near CMC but submicellar surfactant concentrations. The results of an equilibrium study at varying pH agree with the model of deprotonated 1:1 dye-surfactant ion pair formation in the near CMC submicellar solutions. At concentrations above the CMC of the cationic surfactant the dye is solubilized in normal micelles and the monolayer at the air-water interface consists of the cationic surfactant alone even in the presence of the dyes.

  1. Evaluation of Doxorubicin-loaded 3-Helix Micelles as Nanocarriers

    PubMed Central

    Dube, Nikhil; Shu, Jessica Y.; Dong, He; Seo, Jai W.; Ingham, Elizabeth; Kheirolomoom, Azadeh; Chen, Pin-Yuan; Forsayeth, John; Bankiewicz, Krystof; Ferrara, Katherine W.; Xu, Ting

    2013-01-01

    Designing stable drug nanocarriers, 10-30 nm in size, would have significant impact on their transport in circulation, tumor penetration and therapeutic efficacy. In the present study, biological properties of 3-helix micelles loaded with 8 wt% doxorubicin (DOX), ~15 nm in size, were characterized to validate their potential as a nanocarrier platform. DOX-loaded micelles exhibited high stability in terms of size and drug retention in concentrated protein environments similar to conditions after intravenous injections. DOX-loaded micelles were cytotoxic to PPC-1 and 4T1 cancer cells at levels comparable to free DOX. 3-helix micelles can be disassembled by proteolytic degradation of peptide shell to enable drug release and clearance to minimize long-term accumulation. Local administration to normal rat striatum by convection enhanced delivery (CED) showed greater extent of drug distribution and reduced toxicity relative to free drug. Intravenous administration of DOX-loaded 3-helix micelles demonstrated improved tumor half-life and reduced toxicity to healthy tissues in comparison to free DOX. In vivo delivery of DOX-loaded 3-helix micelles through two different routes clearly indicates the potential of 3-helix micelles as safe and effective nanocarriers for cancer therapeutics. PMID:24050265

  2. Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs.

    PubMed

    Lukyanov, Anatoly N; Torchilin, Vladimir P

    2004-05-07

    Polymeric micelles have a whole set of unique characteristics, which make them very promising drug carriers, in particular, for poorly soluble drugs. Our review article focuses on micelles prepared from conjugates of water-soluble polymers, such as polyethylene glycol (PEG) or polyvinyl pyrrolidone (PVP), with phospholipids or long-chain fatty acids. The preparation of micelles from certain polymer-lipid conjugates and the loading of these micelles with various poorly soluble anticancer agents are discussed. The data on the characterization of micellar preparations in terms of their morphology, stability, longevity in circulation, and ability to spontaneously accumulate in experimental tumors via the enhanced permeability and retention (EPR) effect are presented. The review also considers the preparation of targeted immunomicelles with specific antibodies attached to their surface. Available in vivo results on the efficiency of anticancer drugs incorporated into plain micelles and immunomicelles in animal models are also discussed.

  3. Novel Redox-Responsive Amphiphilic Copolymer Micelles for Drug Delivery: Synthesis and Characterization.

    PubMed

    Bae, Jungeun; Maurya, Abhijeet; Shariat-Madar, Zia; Murthy, S Narasimha; Jo, Seongbong

    2015-11-01

    A novel redox-responsive amphiphilic polymer was synthesized with bioreductive trimethyl-locked quinone propionic acid for a potential triggered drug delivery application. The aim of this study was to synthesize and characterize the redox-responsive amphiphilic block copolymer micelles containing pendant bioreductive quinone propionic acid (QPA) switches. The redox-responsive hydrophobic block (polyQPA), synthesized from QPA-serinol and adipoyl chloride, was end-capped with methoxy poly(ethylene glycol) of molecular weight 750 (mPEG750) to achieve a redox-responsive amphiphilic block copolymer, polyQPA-mPEG750. PolyQPA-mPEG750 was able to self-assemble as micelles to show a critical micelle concentration (CMC) of 0.039% w/v (0.39 mg/ml, 0.107 mM) determined by a dye solubilization method using 1,6-diphenyl-1,3,5-hexatriene (DPH) in phosphate-buffered saline (PBS). The mean diameter of polymeric micelles was found to be 27.50 nm (PI = 0.064) by dynamic light scattering. Furthermore, redox-triggered destabilization of the polymeric micelles was confirmed by (1)H-NMR spectroscopy and particle size measurements in a simulated redox state. PolyQPA-mPEG750 underwent triggered reduction to shed pendant redox-responsive QPA groups and its polymeric micelles were swollen to be dissembled in the presence of a reducing agent, thereby enabling the release of loaded model drug, paclitaxel. The redox-responsive polyQPA-mPEG750 polymer micelles would be useful as a drug delivery system allowing triggered drug release in an altered redox state such as tumor microenvironments with an altered redox potential and/or redox enzyme upregulation.

  4. Micelles As Delivery System for Cancer Treatment.

    PubMed

    Keskin, Dilek; Tezcaner, Aysen

    2017-01-01

    Micelles are nanoparticles formed by the self-assembly of amphiphilic block copolymers in certain solvents above concentrations called critical micelle concentration (CMC). Micelles are used in different fields like food, cosmetics, medicine, etc. These nanosized delivery systems are under spotlight in the recent years with new achievements in terms of their in vivo stability, ability to protect entrapped drug, release kinetics, ease of cellular penetration and thereby increased therapeutic efficacy. Drug loaded micelles can be prepared by dialysis, oil-in-water method, solid dispersion, freezing, spray drying, etc. The aim of this review is to give an overview of the research on micelles (in vitro, in vivo and clinical) as delivery system for cancer treatment. Passive targeting is one route for accumulation of nanosized micellar drug formulations. Many research groups from both academia and industry focus on developing new strategies for improving the therapeutic efficacy of micellar systems (active targeting to the tumor site, designing multidrug delivery systems for overcoming multidrug resistance or micelles formed by prodrug conjugates, etc). There is only one micellar drug formulation in South Korea that has reached clinical practice. However, there are many untargeted anticancer drug loaded micellar formulations in clinical trials, which have potential for use in clinics. Many more products are expected to be on the market in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Disulphide bonds in casein micelle from milk.

    PubMed

    Bouguyon, Edwige; Beauvallet, Christian; Huet, Jean-Claude; Chanat, Eric

    2006-05-05

    Mammary epithelial cells synthesised and secreted caseins, the major milk proteins in most mammals, as large aggregates called micelles into the alveolar lumen they surround. We investigated the implication of the highly conserved cysteine(s) of kappa-casein in disulphide bond formation in casein micelles from several species. Dimers were found in all milks studied, confirming previous observation in ruminants. More importantly, the study of interchain disulphide bridges in mouse and rat casein micelles revealed that any casein possessing a cysteine is engaged in disulphide bond interchange; these species express four or five cysteine-containing caseins, respectively. We found that the main rodent caseins form both homo- and heterodimers. Additionally, disulphide bond formation among milk proteins was specific since the interaction of the caseins with cysteine-containing whey proteins was not observed in native casein micelles.

  6. A nondestructive method to estimate the chlorophyll content of Arabidopsis seedlings

    DOE PAGES

    Liang, Ying; Urano, Daisuke; Liao, Kang-Ling; ...

    2017-04-14

    Chlorophyll content decreases in plants under stress conditions, therefore it is used commonly as an indicator of plant health. Arabidopsis thaliana offers a convenient and fast way to test physiological phenotypes of mutations and treatments. But, chlorophyll measurements with conventional solvent extraction are not applicable to Arabidopsis leaves due to their small size, especially when grown on culture dishes. We provide a nondestructive method for chlorophyll measurement whereby the red, green and blue (RGB) values of a color leaf image is used to estimate the chlorophyll content from Arabidopsis leaves. The method accommodates different profiles of digital cameras by incorporatingmore » the ColorChecker chart to make the digital negative profiles, to adjust the white balance, and to calibrate the exposure rate differences caused by the environment so that this method is applicable in any environment. We chose an exponential function model to estimate chlorophyll content from the RGB values, and fitted the model parameters with physical measurements of chlorophyll contents. As further proof of utility, this method was used to estimate chlorophyll content of G protein mutants grown on different sugar to nitrogen ratios. Our method is a simple, fast, inexpensive, and nondestructive estimation of chlorophyll content of Arabidopsis seedlings. This method lead to the discovery that G proteins are important in sensing the C/N balance to control chlorophyll content in Arabidopsis.« less

  7. Relationship between chlorophyll density and SPAD chlorophyll meter reading for Jerusalem artichoke (Helianthus tuberosus L.)

    USDA-ARS?s Scientific Manuscript database

    Chlorophyll is an indicator of crop health and productivity. Measuring chlorophyll is usually done directly and requires significant time and resources. Indirect measurement of chlorophyll density using a handheld portable chlorophyll meter can reduce time. However, this information is very limit...

  8. Block copolymer micelles for controlled delivery of glycolytic enzyme inhibitors.

    PubMed

    Akter, Shanjida; Clem, Brian F; Lee, Hyun Jin; Chesney, Jason; Bae, Younsoo

    2012-03-01

    To develop block copolymer micelles as an aqueous dosage form for a potent glycolytic enzyme inhibitor, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO). The micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) [PEG-p(HYD)] block copolymers to which 3PO was conjugated through an acid-labile hydrazone bond. The optimal micelle formulation was determined following the screening of block copolymer library modified with various aromatic and aliphatic pendant groups. Both physical drug entrapment and chemical drug conjugation methods were tested to maximize 3PO loading in the micelles during the screening. Particulate characterization showed that the PEG-p(HYD) block copolymers conjugated with 3PO (2.08∼2.21 wt.%) appeared the optimal polymer micelles. Block copolymer compositions greatly affected the micelle size, which was 38 nm and 259 nm when 5 kDa and 12 kDa PEG chains were used, respectively. 3PO release from the micelles was accelerated at pH 5.0, potentiating effective drug release in acidic tumor environments. The micelles retained biological activity of 3PO, inhibiting various cancer cells (Jurkat, He-La and LLC) in concentration ranges similar to free 3PO. A novel micelle formulation for controlled delivery of 3PO was successfully prepared.

  9. Information content of in situ and remotely sensed chlorophyll-a: Learning from size-structured phytoplankton model

    NASA Astrophysics Data System (ADS)

    Laiolo, Leonardo; Matear, Richard; Baird, Mark E.; Soja-Woźniak, Monika; Doblin, Martina A.

    2018-07-01

    Chlorophyll-a measurements in the form of in situ observations and satellite ocean colour products are commonly used in data assimilation to calibrate marine biogeochemical models. Here, a two size-class phytoplankton biogeochemical model, with a 0D configuration, was used to simulate the surface chlorophyll-a dynamics (simulated surface Chl-a) for cyclonic and anticyclonic eddies off East Australia. An optical model was then used to calculate the inherent optical properties from the simulation and convert them into remote-sensing reflectance (Rrs). Subsequently, Rrs was used to produce a satellite-like estimate of the simulated surface Chl-a concentrations through the MODIS OC3M algorithm (simulated OC3M Chl-a). Identical parameter optimisation experiments were performed through the assimilation of the two separate datasets (simulated surface Chl-a and simulated OC3M Chl-a), with the purpose of investigating the contrasting information content of simulated surface Chl-a and remotely-sensed data sources. The results we present are based on the analysis of the distribution of a cost function, varying four parameters of the biogeochemical model. In our idealized experiments the simulated OC3M Chl-a product is a poor proxy for the total simulated surface Chl-a concentration. Furthermore, our result show the OC3M algorithm can underestimate the simulated chlorophyll-a concentration in offshore eddies off East Australia (Case I waters), because of the weak relationship between large-sized phytoplankton and remote-sensing reflectance. Although Case I waters are usually characteristic of oligotrophic environments, with a photosynthetic community typically represented by relatively small-sized phytoplankton, mesoscale features such as eddies can generate seasonally favourable conditions for a photosynthetic community with a greater proportion of large phytoplankton cells. Furthermore, our results show that in mesoscale features such as eddies, in situ chlorophyll

  10. Simulated laser fluorosensor signals from subsurface chlorophyll distributions

    NASA Technical Reports Server (NTRS)

    Venable, D. D.; Khatun, S.; Punjabi, A.; Poole, L.

    1986-01-01

    A semianalytic Monte Carlo model has been used to simulate laser fluorosensor signals returned from subsurface distributions of chlorophyll. This study assumes the only constituent of the ocean medium is the common coastal zone dinoflagellate Prorocentrum minimum. The concentration is represented by Gaussian distributions in which the location of the distribution maximum and the standard deviation are variable. Most of the qualitative features observed in the fluorescence signal for total chlorophyll concentrations up to 1.0 microg/liter can be accounted for with a simple analytic solution assuming a rectangular chlorophyll distribution function.

  11. Targeting Mast Cells and Basophils with Anti-FcεRIα Fab-Conjugated Celastrol-Loaded Micelles Suppresses Allergic Inflammation.

    PubMed

    Peng, Xia; Wang, Juan; Li, Xianyang; Lin, Lihui; Xie, Guogang; Cui, Zelin; Li, Jia; Wang, Yuping; Li, Li

    2015-12-01

    Mast cells and basophils are effector cells in the pathophysiology of allergic diseases. Targeted elimination of these cells may be a promising strategy for the treatment of allergic disorders. Our present study aims at targeted delivery of anti-FcεRIα Fab-conjugated celastrol-loaded micelles toward FcεRIα receptors expressed on mast cells and basophils to have enhanced anti-allergic effect. To achieve this aim, we prepared celastrol-loaded (PEO-block-PPO-block-PEO, Pluronic) polymeric nanomicelles using thin-film hydration method. The anti-FcεRIα Fab Fragment was then conjugated to carboxyl groups on drug-loaded micelles via EDC amidation reaction. The anti-FcεRIα Fab-conjugated celastrol-loaded micelles revealed uniform particle size (93.43 ± 12.93 nm) with high loading percentage (21.2 ± 1.5% w/w). The image of micelles showed oval and rod like. The anti-FcεRIα Fab-conjugated micelles demonstrated enhanced cellular uptake and cytotoxity toward target KU812 cells than non-conjugated micelles in vitro. Furthermore, diffusion of the drug into the cells allowed an efficient induction of cell apoptosis. In mouse model of allergic asthma, treatment with anti-FcεRIα Fab-conjugated micelles increased lung accumulation of micelles, and significantly reduced OVA-sIgE, histamine and Th2 cytokines (IL-4, IL-5, TNF-α) levels, eosinophils infiltration and mucus production. In addition, in mouse model of passive cutaneous anaphylaxis, anti-FcεRIα Fab-conjugated celastrol-loaded micelles treatment significantly decreased extravasated evan's in the ear. These results indicate that anti-FcεRIα Fab-conjugated celastrol-loaded micelles can target and selectively kill mast cells and basophils which express FcεRIα, and may be efficient reagents for the treatment of allergic disorders and mast cell related diseases.

  12. Multifunctional SPIO/DOX-loaded A54 Homing Peptide Functionalized Dextran-g-PLGA Micelles for Tumor Therapy and MR Imaging

    NASA Astrophysics Data System (ADS)

    Situ, Jun-Qing; Wang, Xiao-Juan; Zhu, Xiu-Liang; Xu, Xiao-Ling; Kang, Xu-Qi; Hu, Jing-Bo; Lu, Chen-Ying; Ying, Xiao-Ying; Yu, Ri-Sheng; You, Jian; Du, Yong-Zhong

    2016-10-01

    Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL-1 and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI. The drug-encapsulation efficiency was about 80% and the in vitro DOX release was prolonged to 72 hours. The DOX/SPIO-loaded micelles could specifically target BEL-7402 cell line. In vitro MRI results also proved the specific binding ability of A54-Dex-PLGA/DOX/SPIO micelles to hepatoma cell BEL-7402. The in vivo MR imaging experiments using a BEL-7402 orthotopic implantation model further validated the targeting effect of DOX/SPIO-loaded micelles. In vitro and in vivo anti-tumor activities results showed that A54-Dex-PLGA/DOX/SPIO micelles revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles and reduced toxicity compared with commercial adriamycin injection.

  13. Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo

    PubMed Central

    Zheng, Songping; Gao, Xiang; Liu, Xiaoxiao; Yu, Ting; Zheng, Tianying; Wang, Yi; You, Chao

    2016-01-01

    Curcumin (Cur), a natural polyphenol of Curcuma longa, has been recently reported to possess antitumor activities. However, due to its poor aqueous solubility and low biological availability, the clinical application of Cur is quite limited. The encapsulation of hydrophobic drugs into nanoparticles is an effective way to improve their pharmaceutical activities. In this research, nanomicelles loaded with Cur were formulated by a self-assembly method with biodegradable monomethoxy poly(ethylene glycol)-poly(lactide) copolymers (MPEG-PLAs). After encapsulation, the cellular uptake was increased and Cur could be released from MPEG-PLA micelles in a sustained manner. The Cur-loaded MPEG-PLA micelles (Cur/MPEG-PLA micelles) exhibited an enhanced toxicity on C6 and U251 glioma cells and induced more apoptosis on C6 glioma cells compared with free Cur. Moreover, the therapy efficiency of Cur/MPEG-PLA micelles was evaluated at length on a nude mouse model bearing glioma. The Cur/MPEG-PLA micelles were more effective on suppressing tumor growth compared with free Cur, which indicated that Cur/MPEG-PLA micelles improved the antiglioma activity of Cur in vivo. The results of immunohistochemical and immunofluorescent analysis indicated that the induction of apoptosis, antiangiogenesis, and inhibition of cell proliferation may contribute to the improvement in antiglioma effects. Our data suggested that Cur/MPEG-PLA may have potential clinic applications in glioma therapy. PMID:27354801

  14. Bowel perforation detection using metabolic fluorescent chlorophylls

    NASA Astrophysics Data System (ADS)

    Han, Jung Hyun; Jo, Young Goun; Kim, Jung Chul; Choi, Sujeong; Kang, Hoonsoo; Kim, Yong-Chul; Hwang, In-Wook

    2016-03-01

    Thus far, there have been tries of detection of disease using fluorescent materials. We introduce the chlorophyll derivatives from food plants, which have longer-wavelength emissions (at >650 nm) than those of fluorescence of tissues and organs, for detection of bowel perforation. To figure out the possibility of fluorescence spectroscopy as a monitoring sensor of bowel perforation, fluorescence from organs of rodent models, intestinal and peritoneal fluids of rodent models and human were analyzed. In IVIS fluorescence image of rodent abdominal organ, visualization of perforated area only was possible when threshold of image is extremely finely controlled. Generally, both perforated area of bowel and normal bowel which filled with large amount of chlorophyll derivatives were visualized with fluorescence. The fluorescence from chlorophyll derivatives penetrated through the normal bowel wall makes difficult to distinguish perforation area from normal bowel with direct visualization of fluorescence. However, intestinal fluids containing chlorophyll derivatives from food contents can leak from perforation sites in situation of bowel perforation. It may show brighter and longer-wavelength regime emissions of chlorophyll derivatives than those of pure peritoneal fluid or bioorgans. Peritoneal fluid mixed with intestinal fluids show much brighter emissions in longer wavelength (at>650 nm) than those of pure peritoneal fluid. In addition, irrigation fluid, which is used for the cleansing of organ and peritoneal cavity, made of mixed intestinal and peritoneal fluid diluted with physiologic saline also can be monitored bowel perforation during surgery.

  15. Forecasting Ocean Chlorophyll in the Equatorial Pacific.

    PubMed

    Rousseaux, Cecile S; Gregg, Watson W

    2017-01-01

    Using a global ocean biogeochemical model combined with a forecast of physical oceanic and atmospheric variables from the NASA Global Modeling and Assimilation Office, we assess the skill of a chlorophyll concentrations forecast in the Equatorial Pacific for the period 2012-2015 with a focus on the forecast of the onset of the 2015 El Niño event. Using a series of retrospective 9-month hindcasts, we assess the uncertainties of the forecasted chlorophyll by comparing the monthly total chlorophyll concentration from the forecast with the corresponding monthly ocean chlorophyll data from the Suomi-National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (S-NPP VIIRS) satellite. The forecast was able to reproduce the phasing of the variability in chlorophyll concentration in the Equatorial Pacific, including the beginning of the 2015-2016 El Niño. The anomaly correlation coefficient (ACC) was significant ( p < 0.05) for forecast at 1-month ( R = 0.33), 8-month ( R = 0.42) and 9-month ( R = 0.41) lead times. The root mean square error (RMSE) increased from 0.0399 μg chl L -1 for the 1-month lead forecast to a maximum of 0.0472 μg chl L -1 for the 9-month lead forecast indicating that the forecast of the amplitude of chlorophyll concentration variability was getting worse. Forecasts with a 3-month lead time were on average the closest to the S-NPP VIIRS data (23% or 0.033 μg chl L -1 ) while the forecast with a 9-month lead time were the furthest (31% or 0.042 μg chl L -1 ). These results indicate the potential for forecasting chlorophyll concentration in this region but also highlights various deficiencies and suggestions for improvements to the current biogeochemical forecasting system. This system provides an initial basis for future applications including the effects of El Niño events on fisheries and other ocean resources given improvements identified in the analysis of these results.

  16. Thermoresponsive complex amphiphilic block copolymer micelles investigated by laser light scattering.

    PubMed

    Zhao, Fang; Xie, Dinghai; Zhang, Guangzhao; Pispas, Stergios

    2008-05-22

    Poly(isoprene)-block-poly(ethylene oxide) (PI-b-PEO) diblock copolymers form micelles in water. The introduction of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-b-PPO-b-PEO) triblock copolymer leads to the formation of mixed micelles through hydrophobic interaction. The dimension of the mixed micelles varies with the weight ratio (r) of PEO-b-PPO-b-PEO to PI-b-PEO. By use of laser light scattering, we have investigated the temperature dependence of the structural evolution of the micelles at different r. At r<10, the size of the mixed micelles decreases with temperature. At r>10, due to the excessive PEO-b-PPO-b-PEO chains in solution, as temperature increases, the mixed micelles aggregate into larger micelle clusters.

  17. Identification of a Chlorophyll Dephytylase Involved in Chlorophyll Turnover in Arabidopsis[OPEN

    PubMed Central

    2016-01-01

    Chlorophyll turns over in green organs during photosystem repair and is salvaged via de- and rephytylation, but the enzyme involved in dephytylation is unknown. We have identified an Arabidopsis thaliana thylakoid protein with a putative hydrolase domain that can dephytylate chlorophyll in vitro and in vivo. The corresponding locus, CHLOROPHYLL DEPHYTYLASE1 (CLD1), was identified by mapping a semidominant, heat-sensitive, missense allele (cld1-1). CLD1 is conserved in oxygenic photosynthetic organisms, sharing structural similarity with pheophytinase, which functions in chlorophyll breakdown during leaf senescence. Unlike pheophytinase, CLD1 is predominantly expressed in green organs and can dephytylate chlorophyll in vitro. The specific activity is significantly higher for the mutant protein encoded by cld1-1 than the wild-type enzyme, consistent with the semidominant nature of the cld1-1 mutation. Supraoptimal CLD1 activities in cld1-1 mutants and transgenic seedlings led to the proportional accumulation of chlorophyllides derived from chlorophyll dephytylation after heat shock, which resulted in light-dependent cotyledon bleaching. Reducing CLD1 expression diminished thermotolerance and the photochemical efficiency of photosystem II under prolonged moderate heat stress. Taken together, our results suggest that CLD1 is the long-sought enzyme for removing the phytol chain from chlorophyll during its turnover at steady state within the chloroplast. PMID:27920339

  18. Histopathological and biochemical changes following fat embolism with administration of corn oil micelles: a new animal model for fat embolism syndrome.

    PubMed

    Liu, D D; Hsieh, N-K; Chen, H I

    2008-11-01

    Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight. Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A(2), nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid. This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome.

  19. Targeted polymeric micelles for delivery of poorly soluble drugs.

    PubMed

    Torchilin, V P

    2004-10-01

    Polymeric micelles (micelles formed by amphiphilic block copolymers) demonstrate a series of attractive properties as drug carriers, such as high stability both in vitro and in vivo and good biocompatibility, and can be successfully used for the solubilization of various poorly soluble pharmaceuticals. These micelles can also be used as targeted drug delivery systems. The targeting can be achieved via the enhanced permeability and retention effect (into the areas with the compromised vasculature), by making micelles of stimuli-responsive amphiphilic block copolymers, or by attaching specific targeting ligand molecules to the micelle surface. Immunomicelles prepared by coupling monoclonal antibody molecules to p-nitrophenylcarbonyl groups on the water-exposed termini of the micelle corona-forming blocks demonstrate high binding specificity and targetability. Immunomicelles prepared with cancer-specific monoclonal antibody 2C5 specifically bind to different cancer cells in vitro and demonstrate increased therapeutic activity in vivo. This new family of pharmaceutical carriers can be used for the solubilization and targeted delivery of poorly soluble drugs to various pathological sites in the body.

  20. A Graphical User Interface for Parameterizing Biochemical Models of Photosynthesis and Chlorophyll Fluorescence

    NASA Astrophysics Data System (ADS)

    Kornfeld, A.; Van der Tol, C.; Berry, J. A.

    2015-12-01

    Recent advances in optical remote sensing of photosynthesis offer great promise for estimating gross primary productivity (GPP) at leaf, canopy and even global scale. These methods -including solar-induced chlorophyll fluorescence (SIF) emission, fluorescence spectra, and hyperspectral features such as the red edge and the photochemical reflectance index (PRI) - can be used to greatly enhance the predictive power of global circulation models (GCMs) by providing better constraints on GPP. The way to use measured optical data to parameterize existing models such as SCOPE (Soil Canopy Observation, Photochemistry and Energy fluxes) is not trivial, however. We have therefore extended a biochemical model to include fluorescence and other parameters in a coupled treatment. To help parameterize the model, we then use nonlinear curve-fitting routines to determine the parameter set that enables model results to best fit leaf-level gas exchange and optical data measurements. To make the tool more accessible to all practitioners, we have further designed a graphical user interface (GUI) based front-end to allow researchers to analyze data with a minimum of effort while, at the same time, allowing them to change parameters interactively to visualize how variation in model parameters affect predicted outcomes such as photosynthetic rates, electron transport, and chlorophyll fluorescence. Here we discuss the tool and its effectiveness, using recently-gathered leaf-level data.

  1. Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia.

    PubMed

    Gong, Feirong; Chen, Dan; Teng, Xin; Ge, Junhua; Ning, Xianfeng; Shen, Ya-Ling; Li, Jian; Wang, Shanfeng

    2017-08-07

    Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG-PCL (mPEG-PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG-PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague-Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.

  2. Engineering single-polymer micelle shape using nonuniform spontaneous surface curvature

    NASA Astrophysics Data System (ADS)

    Moths, Brian; Witten, T. A.

    2018-03-01

    Conventional micelles, composed of simple amphiphiles, exhibit only a few standard morphologies, each characterized by its mean surface curvature set by the amphiphiles. Here we demonstrate a rational design scheme to construct micelles of more general shape from polymeric amphiphiles. We replace the many amphiphiles of a conventional micelle by a single flexible, linear, block copolymer chain containing two incompatible species arranged in multiple alternating segments. With suitable segment lengths, the chain exhibits a condensed spherical configuration in solution, similar to conventional micelles. Our design scheme posits that further shapes are attained by altering the segment lengths. As a first study of the power of this scheme, we demonstrate the capacity to produce long-lived micelles of horseshoe form using conventional bead-spring simulations in two dimensions. Modest changes in the segment lengths produce smooth changes in the micelle's shape and stability.

  3. Naproxen conjugated mPEG-PCL micelles for dual triggered drug delivery.

    PubMed

    Karami, Zahra; Sadighian, Somayeh; Rostamizadeh, Kobra; Parsa, Maliheh; Rezaee, Saeed

    2016-04-01

    A conjugate of the NSAIDs drug, naproxen, with diblock methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) copolymer was synthesized by the reaction of copolymer with naproxen in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The naproxen conjugated copolymers were characterized with different techniques including (1)HNMR, FTIR, and DSC. The naproxen conjugated mPEG-PCL copolymers were self-assembled into micelles in aqueous solution. The TEM analysis revealed that the micelles had the average size of about 80 nm. The release behavior of conjugated copolymer was investigated in two different media with the pH values of 7.4 and 5.2. In vitro release study showed that the drug release rate was dependant on pH as it was higher at lower pH compared to neutral pH. Another feature of the conjugated micelles was a more sustained release profile compared to the conjugated copolymer. The kinetic of the drug release from naproxen conjugated micelles under different values of pH was also investigated by different kinetic models such as first-order, Makoid-Banakar, Weibull, Logistic, and Gompertz. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Chlorophyll a + b content and chlorophyll fluorescence in avocado

    USDA-ARS?s Scientific Manuscript database

    One Tonnage (T) and one Simmonds (S) avocado tree and four TxS crosses were evaluated for differences in chlorophyll content and maximal quantum yield of photosystem II in sun and shade-type leaves. Total chlorophyll content by area (Chl a+bar) ranged from 981 mg m-2 in TxS240 to 4339 mg m-2 in Simm...

  5. Dustfall Effect on Hyperspectral Inversion of Chlorophyll Content - a Laboratory Experiment

    NASA Astrophysics Data System (ADS)

    Chen, Yuteng; Ma, Baodong; Li, Xuexin; Zhang, Song; Wu, Lixin

    2018-04-01

    Dust pollution is serious in many areas of China. It is of great significance to estimate chlorophyll content of vegetation accurately by hyperspectral remote sensing for assessing the vegetation growth status and monitoring the ecological environment in dusty areas. By using selected vegetation indices including Medium Resolution Imaging Spectrometer Terrestrial Chlorophyll Index (MTCI) Double Difference Index (DD) and Red Edge Position Index (REP), chlorophyll inversion models were built to study the accuracy of hyperspectral inversion of chlorophyll content based on a laboratory experiment. The results show that: (1) REP exponential model has the most stable accuracy for inversion of chlorophyll content in dusty environment. When dustfall amount is less than 80 g/m2, the inversion accuracy based on REP is stable with the variation of dustfall amount. When dustfall amount is greater than 80 g/m2, the inversion accuracy is slightly fluctuation. (2) Inversion accuracy of DD is worst among three models. (3) MTCI logarithm model has high inversion accuracy when dustfall amount is less than 80 g/m2; When dustfall amount is greater than 80 g/m2, inversion accuracy decreases regularly and inversion accuracy of modified MTCI (mMTCI) increases significantly. The results provide experimental basis and theoretical reference for hyperspectral remote sensing inversion of chlorophyll content.

  6. Rheology and phase behavior of dense casein micelle dispersions

    NASA Astrophysics Data System (ADS)

    Bouchoux, A.; Debbou, B.; Gésan-Guiziou, G.; Famelart, M.-H.; Doublier, J.-L.; Cabane, B.

    2009-10-01

    Casein micelle dispersions have been concentrated through osmotic stress and examined through rheological experiments. In conditions where the casein micelles are separated from each other, i.e., below random-close packing, the dispersions have exactly the flow and dynamic properties of the polydisperse hard-sphere fluid, demonstrating that the micelles interact only through excluded volume effects in this regime. These interactions cause the viscosity and the elastic modulus to increase by three orders of magnitude approaching the concentration of random-close packing estimated at Cmax≈178 g/l. Above Cmax, the dispersions progressively turn into "gels" (i.e., soft solids) as C increases, with elastic moduli G' that are nearly frequency independent. In this second regime, the micelles deform and/or deswell as C increases, and the resistance to deformation results from the formation of bonds between micelles combined with the intrinsic mechanical resistance of the micelles. The variation in G' with C is then very similar to that observed with concentrated emulsions where the resistance to deformation originates from a set of membranes that separate the droplets. As in the case of emulsions, the G' values at high frequency are also nearly identical to the osmotic pressures required to compress the casein dispersions. The rheology of sodium caseinate dispersions in which the caseins are not structured into micelles is also reported. Such dispersions have the behavior of associative polymer solutions at all the concentrations investigated, further confirming the importance of structure in determining the rheological properties of casein micelle systems.

  7. Rheology and phase behavior of dense casein micelle dispersions.

    PubMed

    Bouchoux, A; Debbou, B; Gésan-Guiziou, G; Famelart, M-H; Doublier, J-L; Cabane, B

    2009-10-28

    Casein micelle dispersions have been concentrated through osmotic stress and examined through rheological experiments. In conditions where the casein micelles are separated from each other, i.e., below random-close packing, the dispersions have exactly the flow and dynamic properties of the polydisperse hard-sphere fluid, demonstrating that the micelles interact only through excluded volume effects in this regime. These interactions cause the viscosity and the elastic modulus to increase by three orders of magnitude approaching the concentration of random-close packing estimated at C(max) approximately 178 g/l. Above C(max), the dispersions progressively turn into "gels" (i.e., soft solids) as C increases, with elastic moduli G(') that are nearly frequency independent. In this second regime, the micelles deform and/or deswell as C increases, and the resistance to deformation results from the formation of bonds between micelles combined with the intrinsic mechanical resistance of the micelles. The variation in G(') with C is then very similar to that observed with concentrated emulsions where the resistance to deformation originates from a set of membranes that separate the droplets. As in the case of emulsions, the G(') values at high frequency are also nearly identical to the osmotic pressures required to compress the casein dispersions. The rheology of sodium caseinate dispersions in which the caseins are not structured into micelles is also reported. Such dispersions have the behavior of associative polymer solutions at all the concentrations investigated, further confirming the importance of structure in determining the rheological properties of casein micelle systems.

  8. Intelligent polymeric micelles: development and application as drug delivery for docetaxel.

    PubMed

    Li, Yimu; Zhang, Hui; Zhai, Guang-Xi

    2017-04-01

    Recent years, docetaxel (DTX)-loaded intelligent polymeric micelles have been regarded as a promising vehicle for DTX for the reason that compared with conventional DTX-loaded micelles, DTX-loaded intelligent micelles not only preserve the basic functions of micelles such as DTX solubilization, enhanced accumulation in tumor tissue, and improved bioavailability and biocompatibility of DTX, but also possess other new properties, for instance, tumor-specific DTX delivery and series of responses to endogenous or exogenous stimulations. In this paper, basic theories and action mechanism of intelligent polymeric micelles are discussed in detail, especially the related theories of DTX-loaded stimuli-responsive micelles. The relevant examples of stimuli-responsive DTX-loaded micelles are also provided in this paper to sufficiently illustrate the advantages of relevant technology for the clinical application of anticancer drug, especially for the medical application of DTX.

  9. pH and redox-responsive mixed micelles for enhanced intracellular drug release.

    PubMed

    Cai, Mengtan; Zhu, Kun; Qiu, Yongbin; Liu, Xinrong; Chen, Yuanwei; Luo, Xianglin

    2014-04-01

    In order to prepare pH and redox sensitive micelles, amphiphilic copolymers of poly (epsilon-caprolactone)-b-poly(2-(diethylamino) ethyl methacrylate) (PCL-PDEA) and disulfide-linked poly(ethyl glycol)-poly(epsilon-caprolactone) (mPEG-SS-PCL) were synthesized. The double-sensitive micelles were prepared simply by solvent-evaporating method with the mixed two copolymers. The pH sensitivity of the mixed micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic lighting scattering (DLS) and the redox sensitivity of the mixed micelles was testified by the change of micellar morphous observed by scanning electron microscope (SEM). In vitro drug release showed that drug-loaded mixed micelles (mass ratio 5:5) could achieve above 90% of drug release under low pH and reducing condition within 10h. Moreover, the drug-loaded mixed micelles (mass ratio 5:5) showed the largest cellular toxicity compared with other drug-loaded micelles, while blank mixed micelles exhibited no toxicity. These results meant that the mixed micelles composed by the two amphiphilic copolymers can enhance intracellular drug release. It is concluded that the newly developed mixed micelles can serve as a potential drug delivery system for anticancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. A Coupled Ocean General Circulation, Biogeochemical, and Radiative Model of the Global Oceans: Seasonal Distributions of Ocean Chlorophyll and Nutrients

    NASA Technical Reports Server (NTRS)

    Gregg, Watson W.; Busalacchi, Antonio (Technical Monitor)

    2000-01-01

    A coupled ocean general circulation, biogeochemical, and radiative model was constructed to evaluate and understand the nature of seasonal variability of chlorophyll and nutrients in the global oceans. Biogeochemical processes in the model are determined from the influences of circulation and turbulence dynamics, irradiance availability. and the interactions among three functional phytoplankton groups (diatoms. chlorophytes, and picoplankton) and three nutrients (nitrate, ammonium, and silicate). Basin scale (greater than 1000 km) model chlorophyll results are in overall agreement with CZCS pigments in many global regions. Seasonal variability observed in the CZCS is also represented in the model. Synoptic scale (100-1000 km) comparisons of imagery are generally in conformance although occasional departures are apparent. Model nitrate distributions agree with in situ data, including seasonal dynamics, except for the equatorial Atlantic. The overall agreement of the model with satellite and in situ data sources indicates that the model dynamics offer a reasonably realistic simulation of phytoplankton and nutrient dynamics on synoptic scales. This is especially true given that initial conditions are homogenous chlorophyll fields. The success of the model in producing a reasonable representation of chlorophyll and nutrient distributions and seasonal variability in the global oceans is attributed to the application of a generalized, processes-driven approach as opposed to regional parameterization and the existence of multiple phytoplankton groups with different physiological and physical properties. These factors enable the model to simultaneously represent many aspects of the great diversity of physical, biological, chemical, and radiative environments encountered in the global oceans.

  11. Micelle-templated composite quantum dots for super-resolution imaging.

    PubMed

    Xu, Jianquan; Fan, Qirui; Mahajan, Kalpesh D; Ruan, Gang; Herrington, Andrew; Tehrani, Kayvan F; Kner, Peter; Winter, Jessica O

    2014-05-16

    Quantum dots (QDs) have tremendous potential for biomedical imaging, including super-resolution techniques that permit imaging below the diffraction limit. However, most QDs are produced via organic methods, and hence require surface treatment to render them water-soluble for biological applications. Previously, we reported a micelle-templating method that yields nanocomposites containing multiple core/shell ZnS-CdSe QDs within the same nanocarrier, increasing overall particle brightness and virtually eliminating QD blinking. Here, this technique is extended to the encapsulation of Mn-doped ZnSe QDs (Mn-ZnSe QDs), which have potential applications in super-resolution imaging as a result of the introduction of Mn(2+) dopant energy levels. The size, shape and fluorescence characteristics of these doped QD-micelles were compared to those of micelles created using core/shell ZnS-CdSe QDs (ZnS-CdSe QD-micelles). Additionally, the stability of both types of particles to photo-oxidation was investigated. Compared to commercial QDs, micelle-templated QDs demonstrated superior fluorescence intensity, higher signal-to-noise ratios, and greater stability against photo-oxidization,while reducing blinking. Additionally, the fluorescence of doped QD-micelles could be modulated from a bright 'on' state to a dark 'off' state, with a modulation depth of up to 76%, suggesting the potential of doped QD-micelles for applications in super-resolution imaging.

  12. Optofluidic chlorophyll lasers.

    PubMed

    Chen, Yu-Cheng; Chen, Qiushu; Fan, Xudong

    2016-06-21

    Chlorophylls are essential for photosynthesis and also one of the most abundant pigments on earth. Using an optofluidic ring resonator of extremely high Q-factors (>10(7)), we investigated the unique characteristics and underlying mechanism of chlorophyll lasers. Chlorophyll lasers with dual lasing bands at 680 nm and 730 nm were observed for the first time in isolated chlorophyll a (Chla). Particularly, a laser at the 730 nm band was realized in 0.1 mM Chla with a lasing threshold of only 8 μJ mm(-2). Additionally, we observed lasing competition between the two lasing bands. The presence of laser emission at the 680 nm band can lead to quenching or significant reduction of laser emission at the 730 nm band, effectively increasing the lasing threshold for the 730 nm band. Further concentration-dependent studies, along with theoretical analysis, elucidated the mechanism that determines when and why the laser emission band appears at one of the two bands, or concomitantly at both bands. Finally, Chla was exploited as the donor in fluorescence resonance energy transfer to extend the laser emission to the near infrared regime with an unprecedented wavelength shift as large as 380 nm. Our work will open a door to the development of novel biocompatible and biodegradable chlorophyll-based lasers for various applications such as miniaturized tunable coherent light sources and in vitro/in vivo biosensing. It will also provide important insight into the chlorophyll fluorescence and photosynthesis processes inside plants.

  13. Detection of hydrogen peroxide with chemiluminescent micelles

    PubMed Central

    Lee, Dongwon; Erigala, Venkata R; Dasari, Madhuri; Yu, Junhua; Dickson, Robert M; Murthy, Niren

    2008-01-01

    The overproduction of hydrogen peroxide is implicated in the progress of numerous life-threatening diseases and there is a great need for the development of contrast agents that can detect hydrogen peroxide in vivo. In this communication, we present a new contrast agent for hydrogen peroxide, termed peroxalate micelles, which detect hydrogen peroxide through chemiluminescence, and have the physical/chemical properties needed for in vivo imaging applications. The peroxalate micelles are composed of amphiphilic peroxalate based copolymers and the fluorescent dye rubrene, they have a ‘stealth’ polyethylene glycol (PEG) corona to evade macrophage phagocytosis, and a diameter of 33 nm to enhance extravasation into permeable tissues. The peroxalate micelles can detect nanomolar concentrations of hydrogen peroxide (>50 nM) and thus have the sensitivity needed to detect physiological concentrations of hydrogen peroxide. We anticipate numerous applications of the peroxalate micelles for in vivo imaging of hydrogen peroxide, given their high sensitivity, small size, and biocompatible PEG corona. PMID:19337415

  14. Casein polymorphism heterogeneity influences casein micelle size in milk of individual cows.

    PubMed

    Day, L; Williams, R P W; Otter, D; Augustin, M A

    2015-06-01

    Milk samples from individual cows producing small (148-155 nm) or large (177-222 nm) casein micelles were selected to investigate the relationship between the individual casein proteins, specifically κ- and β-casein phenotypes, and casein micelle size. Only κ-casein AA and β-casein A1A1, A1A2 and A2A2 phenotypes were found in the large casein micelle group. Among the small micelle group, both κ-casein and β-casein phenotypes were more diverse. κ-Casein AB was the dominant phenotype, and 3 combinations (AA, AB, and BB) were present in the small casein micelle group. A considerable mix of β-casein phenotypes was found, including B and I variants, which were only found in the small casein micelle group. The relative amount of κ-casein to total casein was significantly higher in the small micelle group, and the nonglycosylated and glycosylated κ-casein contents were higher in the milks with small casein micelles (primarily with κ-casein AB and BB variants) compared with the large micelle group. The ratio of glycosylated to nonglycosylated κ-casein was higher in the milks with small casein micelles compared with the milks with large casein micelles. This suggests that although the amount of κ-casein (both glycosylated and nonglycosylated) is associated with micelle size, an increased proportion of glycosylated κ-casein could be a more important and favorable factor for small micelle size. This suggests that the increased spatial requirement due to addition of the glycosyl group with increasing extent of glycosylation of κ-casein is one mechanism that controls casein micelle assembly and growth. In addition, increased electrostatic repulsion due to the sialyl residues on the glycosyl group could be a contributory factor. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release

    PubMed Central

    Bult, Wouter; Bos, Mariska; Storm, Gert; Nijsen, J. Frank W.; Hennink, Wim E.

    2010-01-01

    ABSTRACT Micelles are colloidal particles with a size around 5–100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a ‘magic bullet’ a major step forward. PMID:20725771

  16. Soluplus/TPGS mixed micelles for dioscin delivery in cancer therapy.

    PubMed

    Zhao, Jing; Xu, Youwei; Wang, Changyuan; Ding, Yanfang; Chen, Manyu; Wang, Yifei; Peng, Jinyong; Li, Lei; Lv, Li

    2017-07-01

    Dioscin has shown cytotoxicity against cancer cells, but its poor solubility and stability have limited its clinical application. In this study, we designed mixed micelles composed of TPGS and Soluplus ® copolymers entrapping the poorly soluble anticancer drug dioscin. In order to improve the aqueous solubility and bioactivity of dioscin, TPGS/Soluplus ® mixed micelles with an optimal ratio were prepared using a thin-film hydration method, and their physicochemical properties were characterized. Cellular cytotoxicity and uptake of the dioscin-loaded TPGS/Soluplus ® mixed micelles were studied in MCF-7 breast cancer cells and A2780s ovarian cancer cells. The pharmacokinetics of free dioscin and dioscin-loaded TPGS/Soluplus ® mixed micelles was studied in vivo in male Sprague-Dawley rats via a single intravenous injection in the tail vein. The average size of the optimized mixed micelle was 67.15 nm, with 92.59% drug encapsulation efficiency and 4.63% drug loading efficiency. The in vitro release profile showed that the mixed micelles presented sustained release behavior compared to the anhydrous ethanol solution of dioscin. In vitro cytotoxicity assays were conducted on human cancer cell lines including A2780s ovarian cancer cells and MCF-7 breast cancer cells. The mixed micelles exhibited better antitumor activity compared to free dioscin against all cell lines, which may benefit from the significant increase in the cellular uptake of dioscin from mixed micelles compared to free dioscin. The pharmacokinetic study showed that the mixed micelle formulation achieved a 1.3 times longer mean residual time (MRT) in circulation and a 2.16 times larger area under the plasma concentration-time curve (AUC) than the free dioscin solution. Our results suggest that the dioscin-loaded mixed micelles developed in this study might be a potential nano drug-delivery system for cancer chemotherapy.

  17. Modeling Primary Productivity in the Margin Ice Zone from Glider-Based Measurements of Chlorophyll and Light during the 2014 Miz Program

    NASA Astrophysics Data System (ADS)

    Perry, M. J.; Lee, C.; Rainville, L.; Cetinic, I.; Yang, E. J.; Kang, S. H.

    2016-02-01

    In late summer 2014 during the Marginal Ice Zone (MIZ) Experiment, an international project sponsored by ONR, four Seagliders transited open water, through the marginal ice zone, and under ice-covered regions in the Beaufort Sea, penetrating as far as 100 km into the ice pack. The gliders navigated either by GPS in open water or, when under the ice, by acoustics from sound sources embedded in the MIZ autonomous observing array. The glider sensor suite included temperature, temperature microstructure, salinity, oxygen, chlorophyll fluorescence, optical backscatter, and multi-spectral downwelling irradiance. Cruises on the IBRV Araon operating in the open Beaufort Sea and on the R/V Ukpik and Norseman operating in continental shelf waters off Alaska's north slope allowed us to construct proxy libraries for converting chlorophyll fluorescence to chlorophyll concentration and optical backscatter to particulate organic carbon concentration. Water samples were collected for chlorophyll and particulate organic carbon analysis on the cruises and aligned with optical profiles of fluorescence and backscatter using sensors that were factory calibrated at the same time as the glider sensors. Fields of chlorophyll, particulate organic carbon, light, and primary productivity are constructed from the glider data. Productivity is modeled as a function of chlorophyll and light, using photosynthesis-light (PE) models with available PE parameters from Arctic measurements. During August the region under the ice was characterized by a deep chlorophyll maximum layer with low rates of production in overlying waters. A phytoplankton bloom developed in open water at the end of September, preceding the rapid reformation of ice, despite shorter days and reduce irradiation.

  18. Structural model of the SARS coronavirus E channel in LMPG micelles.

    PubMed

    Surya, Wahyu; Li, Yan; Torres, Jaume

    2018-06-01

    Coronaviruses (CoV) cause common colds in humans, but are also responsible for the recent Severe Acute, and Middle East, respiratory syndromes (SARS and MERS, respectively). A promising approach for prevention are live attenuated vaccines (LAVs), some of which target the envelope (E) protein, which is a small membrane protein that forms ion channels. Unfortunately, detailed structural information is still limited for SARS-CoV E, and non-existent for other CoV E proteins. Herein, we report a structural model of a SARS-CoV E construct in LMPG micelles with, for the first time, unequivocal intermolecular NOEs. The model corresponding to the detergent-embedded region is consistent with previously obtained orientational restraints obtained in lipid bilayers and in vivo escape mutants. The C-terminal domain is mostly α-helical, and extramembrane intermolecular NOEs suggest interactions that may affect the TM channel conformation. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Enhanced solubility and targeted delivery of curcumin by lipopeptide micelles.

    PubMed

    Liang, Ju; Wu, Wenlan; Lai, Danyu; Li, Junbo; Fang, Cailin

    2015-01-01

    A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 10(3) times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.

  20. Stereocomplex micelle from nonlinear enantiomeric copolymers efficiently transports antineoplastic drug

    NASA Astrophysics Data System (ADS)

    Wang, Jixue; Shen, Kexin; Xu, Weiguo; Ding, Jianxun; Wang, Xiaoqing; Liu, Tongjun; Wang, Chunxi; Chen, Xuesi

    2015-05-01

    Nanoscale polymeric micelles have attracted more and more attention as a promising nanocarrier for controlled delivery of antineoplastic drugs. Herein, the doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric four-armed poly(ethylene glycol)-polylactide (PEG-PLA) copolymers were successfully fabricated. In phosphate-buffered saline (PBS) at pH 7.4, SCM/DOX exhibited the smallest hydrodynamic diameter ( D h) of 90 ± 4.2 nm and the slowest DOX release compared with PDM/DOX and PLM/DOX. Moreover, PDM/DOX, PLM/DOX, and SCM/DOX exhibited almost stable D hs of around 115, 105, and 90 nm at above normal physiological condition, respectively, which endowed them with great potential in controlled drug delivery. The intracellular DOX fluorescence intensity after the incubation with the laden micelles was different degrees weaker than that incubated with free DOX · HCl within 12 h, probably due to the slow DOX release from micelles. As the incubation time reached to 24 h, all the cells incubated with the laden micelles, especially SCM/DOX, demonstrated a stronger intracellular DOX fluorescence intensity than free DOX · HCl-cultured ones. More importantly, all the DOX-loaded micelles, especially SCM/DOX, exhibited potent antineoplastic efficacy in vitro, excellent serum albumin-tolerance stability, and satisfactory hemocompatibility. These encouraging data indicated that the loading micelles from nonlinear enantiomeric copolymers, especially SCM/DOX, might be promising in clinical systemic chemotherapy through intravenous injection.

  1. E-selectin-targeted Sialic Acid-PEG-dexamethasone Micelles for Enhanced Anti-Inflammatory Efficacy for Acute Kidney Injury.

    PubMed

    Hu, Jing-Bo; Kang, Xu-Qi; Liang, Jing; Wang, Xiao-Juan; Xu, Xiao-Ling; Yang, Ping; Ying, Xiao-Ying; Jiang, Sai-Ping; Du, Yong-Zhong

    2017-01-01

    The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewis x antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65.6 µg/mL critical micelle concentration. Free DXM is incorporated into the micelles with 6.28 ± 0.21% drug loading content. In vitro DXM release from SA-PEG-DXM/DXM micelles can be prolonged to 48h. Much more SA-PEG-DXM micelles can be internalized by lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs) in comparison to PEG-DXM micelles due to specific interaction between SA and E-selectin expressed on HUVECs, and consequently more SA-PEG-DXM micelles are accumulated in the kidney of AKI murine model. Furthermore, SA in SA-PEG-DXM conjugates can significantly ameliorate LPS-induced production of pro-inflammatory cytokines via suppressing LPS-activated Beclin-1/Atg5-Atg12-mediated autophagy to attenuate toxicity. Compared with free DXM and PEG-DXM/DXM micelles, SA-PEG-DXM/DXM micelles show better therapeutical effects, as reflected by the improved renal function, histopathological changes, pro-inflammatory cytokines, oxidative stress and expression of apoptotic related proteins.

  2. Revisiting chlorophyll extraction methods in biological soil crusts - methodology for determination of chlorophyll a and chlorophyll a + b as compared to previous methods

    NASA Astrophysics Data System (ADS)

    Caesar, Jennifer; Tamm, Alexandra; Ruckteschler, Nina; Lena Leifke, Anna; Weber, Bettina

    2018-03-01

    Chlorophyll concentrations of biological soil crust (biocrust) samples are commonly determined to quantify the relevance of photosynthetically active organisms within these surface soil communities. Whereas chlorophyll extraction methods for freshwater algae and leaf tissues of vascular plants are well established, there is still some uncertainty regarding the optimal extraction method for biocrusts, where organism composition is highly variable and samples comprise major amounts of soil. In this study we analyzed the efficiency of two different chlorophyll extraction solvents, the effect of grinding the soil samples prior to the extraction procedure, and the impact of shaking as an intermediate step during extraction. The analyses were conducted on four different types of biocrusts. Our results show that for all biocrust types chlorophyll contents obtained with ethanol were significantly lower than those obtained using dimethyl sulfoxide (DMSO) as a solvent. Grinding of biocrust samples prior to analysis caused a highly significant decrease in chlorophyll content for green algal lichen- and cyanolichen-dominated biocrusts, and a tendency towards lower values for moss- and algae-dominated biocrusts. Shaking of the samples after each extraction step had a significant positive effect on the chlorophyll content of green algal lichen- and cyanolichen-dominated biocrusts. Based on our results we confirm a DMSO-based chlorophyll extraction method without grinding pretreatment and suggest the addition of an intermediate shaking step for complete chlorophyll extraction (see Supplement S6 for detailed manual). Determination of a universal chlorophyll extraction method for biocrusts is essential for the inter-comparability of publications conducted across all continents.

  3. Evaluation of the MERIS terrestrial Chlorophyll Index

    NASA Astrophysics Data System (ADS)

    Dash, J.; Curran, P.

    The MEdium Resolution Imaging Spectrometer (MERIS), one of the payloads on Envisat, has fine spectral resolution, moderate spatial resolution and a three day repeat cycle. This makes MERIS a potentially valuable sensor for the measurement and monitoring of terrestrial environments at regional to global scales. The red edge, which results from an abrupt change in reflectance in red and near-infrared wavelengths has a location that is related directly to the chlorophyll content of vegetation. A new index called the MERIS terrestrial chlorophyll index (MTCI) uses data in three red and NIR wavebands centred at 681.25nm, 705nm and 753.75nm (bands 8, 9 and 10 in the MERIS standard band setting). The MTCI is easy to calculate and can be automated. Preliminary indirect evaluation using model, field and MERIS data suggested its sensitivity, notably to high values of chlorophyll content and its limited sensitivity to spatial resolution and atmospheric effects. As a result this index is now a standard level-2 product of the European Space Agency. For direct MTCI evaluation two different approaches were used. First, the MTCI/chlorophyll content relationship were determined using a surrogate of chlorophyll content for sites in southern Vietnam and second, the MTCI/chlorophyll relationship was determined using actual chlorophyll content for sites in the New Forest, UK and for plots in a greenhouse. Forests in southern Vietnam were contaminated heavily with Agent Orange during the Vietnam War. The contamination levels were so high that it led to a long term decrease in chlorophyll content within forests that have long since regained full canopy cover. In this approach the amount of Agent Orange dropped onto the forest between 1965 and 1971 was used as a surrogate for contemporary chlorophyll content and was related to current MTCI at selected forest sites. The resulting relationship was positive. Further per pixel investigation of the MTCI/Agent Orange concentration relationship

  4. Glycopolymer micelles with reducible ionic cores for hepatocytes-targeting delivery of DOX.

    PubMed

    Wang, Yanxia; Zhang, Xinge; Yu, Peien; Li, Chaoxing

    2013-01-30

    A novel galactose-decorated cross-linked micelles (cl-micelles) with ionic cores using cystamine (Cys) as a biodegradable cross-linker was prepared by using block ionomer complexes of poly(ethylene glycol)-b-poly(2-acryloxyethyl-galactose)-b-poly(acrylic acid) (PEG-b-PAEG-b-PAA) and Ca(2+) (PEG-b-PAEG-b-PAA cl-micelles/Cys). Doxorubicin (DOX) was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. Proton nuclear magnetic resonance spectrum and Fourier transform infrared spectrometer indicated galactose ligands were exposed at the micellar surface. The micelles were spherical in shape, with an average size of 100nm. The in vitro release studies confirmed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys accomplished rapid drug release under reducing condition. Remarkably, PEG-b-PAEG-b-PAA cl-micelles/Cys efficiently delivered and released DOX into the cell nucleus of HepG2 cells, and the intensity of fluorescence observed in HepG2 cells was stronger than that incubated with the micelles without galactose ligands. In contrast, little fluorescence was observed in NIH3T3 cells after incubation with PEG-b-PAEG-b-PAA cl-micelles/Cys. Interestingly, cytotoxicity assays showed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys retained higher cell inhibition efficiency in HepG2 cells as compared with NIH3T3 cells, and were more potent than the micelles without galactose ligands and the micelles with non degradable cross-links. These results indicate that PEG-b-PAEG-b-PAA cl-micelles/Cys have great potential in liver tumor-targeted chemotherapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Hydrolytic degradation of poly(ethylene oxide)-block-polycaprolactone worm micelles.

    PubMed

    Geng, Yan; Discher, Dennis E

    2005-09-21

    Spherical micelles and nanoparticles made with degradable polymers have been of great interest for therapeutic application, but degradation-induced changes in a spherical morphology can be subtle and mechanism/kinetics appears poorly understood. Here, we report the first preparation of giant and flexible worm micelles self-assembled from degradable copolymer poly(ethylene oxide)-block-polycaprolactone. Such worm micelles spontaneously shorten to generate spherical micelles, triggered by polycaprolactone hydrolysis, with distinct mechanism and kinetics from that which occurs in bulk material.

  6. Seasonal Distributions of Global Ocean Chlorophyll and Nutrients: Analysis with a Coupled Ocean General Circulation Biogeochemical, and Radiative Model

    NASA Technical Reports Server (NTRS)

    Gregg, Watson W.

    1999-01-01

    A coupled general ocean circulation, biogeochemical, and radiative model was constructed to evaluate and understand the nature of seasonal variability of chlorophyll and nutrients in the global oceans. The model is driven by climatological meteorological conditions, cloud cover, and sea surface temperature. Biogeochemical processes in the model are determined from the influences of circulation and turbulence dynamics, irradiance availability, and the interactions among three functional phytoplankton groups (diatoms, chorophytes, and picoplankton) and three nutrient groups (nitrate, ammonium, and silicate). Phytoplankton groups are initialized as homogeneous fields horizontally and vertically, and allowed to distribute themselves according to the prevailing conditions. Basin-scale model chlorophyll results are in very good agreement with CZCS pigments in virtually every global region. Seasonal variability observed in the CZCS is also well represented in the model. Synoptic scale (100-1000 km) comparisons of imagery are also in good conformance, although occasional departures are apparent. Agreement of nitrate distributions with in situ data is even better, including seasonal dynamics, except for the equatorial Atlantic. The good agreement of the model with satellite and in situ data sources indicates that the model dynamics realistically simulate phytoplankton and nutrient dynamics on synoptic scales. This is especially true given that initial conditions are homogenous chlorophyll fields. The success of the model in producing a reasonable representation of chlorophyll and nutrient distributions and seasonal variability in the global oceans is attributed to the application of a generalized, processes-driven approach as opposed to regional parameterization, and the existence of multiple phytoplankton groups with different physiological and physical properties. These factors enable the model to simultaneously represent the great diversity of physical, biological

  7. Chlorophyll a reconstruction from in situ measurements: 1. Method description

    NASA Astrophysics Data System (ADS)

    Fründt, B.; Dippner, J. W.; Waniek, J. J.

    2015-02-01

    Understanding the development of primary production is essential for projections of the global carbon cycle in the context of climate change. A chlorophyll a hindcast that serves as a primary production indicator was obtained by fitting in situ measurements of nitrate, chlorophyll a, and temperature. The resulting fitting functions were adapted to a modeled temperature field. The method was applied to observations from the Madeira Basin, in the northeastern part of the oligotrophic North Atlantic Subtropical Gyre and yielded a chlorophyll a field from 1989 to 2008 with a monthly resolution validated with remotely measured surface chlorophyll a data by SeaWiFS. The chlorophyll a hindcast determined with our method resolved the seasonal and interannual variability in the phytoplankton biomass of the euphotic zone as well as the deep chlorophyll maximum. Moreover, it will allow estimation of carbon uptake over long time scales.

  8. Pulse amplitude modulated chlorophyll fluorometer

    DOEpatents

    Greenbaum, Elias; Wu, Jie

    2015-12-29

    Chlorophyll fluorometry may be used for detecting toxins in a sample because of changes in micro algae. A portable lab on a chip ("LOAC") based chlorophyll fluorometer may be used for toxin detection and environmental monitoring. In particular, the system may include a microfluidic pulse amplitude modulated ("PAM") chlorophyll fluorometer. The LOAC PAM chlorophyll fluorometer may analyze microalgae and cyanobacteria that grow naturally in source drinking water.

  9. pH-dependent structures and properties of casein micelles.

    PubMed

    Liu, Yan; Guo, Rong

    2008-08-01

    The association behavior of casein over a broad pH range has first been investigated by fluorescent technique together with DLS and turbidity measurements. Casein molecules can self-assemble into casein micelles in the pH ranges 2.0 to 3.0, and 5.5 to 12.0. The hydrophobic interaction, hydrogen bond and electrostatic action are the main interactions in the formation of casein micelles. The results show that the structure of casein micelles is more compact at low pH and looser at high pH. The casein micelle has the most compact structure at pH 5.5, when it has almost no electrostatic repulsion between casein molecules.

  10. Modeling of chemical reactions in micelle: water-mediated keto-enol interconversion as a case study.

    PubMed

    Marracino, Paolo; Amadei, Andrea; Apollonio, Francesca; d'Inzeo, Guglielmo; Liberti, Micaela; di Crescenzo, Antonello; Fontana, Antonella; Zappacosta, Romina; Aschi, Massimiliano

    2011-06-30

    The effect of a zwitterionic micelle environment on the efficiency of the keto-enol interconversion of 2-phenylacetylthiophene has been investigated by means of a joint application of experimental and theoretical/computational approaches. Results have revealed a reduction of the reaction rate constant if compared with bulk water essentially because of the different solvation conditions experienced by the reactant species, including water molecules, in the micelle environment. The slight inhibiting effect due to the application of a static electric field has also been theoretically investigated and presented.

  11. Inherent limitations of nondestructive chlorophyll meters: a comparison of two types of meters

    NASA Technical Reports Server (NTRS)

    Monje, O. A.; Bugbee, B.

    1992-01-01

    Two types of nondestructive chlorophyll meters were compared with a standard, destructive chlorophyll measurement technique. The nondestructive chlorophyll meters were 1) a custom built, single-wavelength meter, and 2) the recently introduced, dual-wavelengh, chlorophyll meter from Minolta (model SPAD-502). Data from both meters were closely correlated with destructive measurements of chlorophyll (r2 = 0.90 and 0.93; respectively) for leaves with chlorophyll concentrations ranging from 100 to 600 mg m-2, but both meters consistently overestimated chlorophyll outside this range. Although the dual-wavelength meter was slightly more accurate than the single-wavelength meter (higher r2), the light-scattering properties of leaf cells and the nonhomogeneous distribution of chlorophyll in leaves appear to limit the ability of all meters to estimate in vivo chlorophyll concentration.

  12. Antiproliferative activity of tea catechins associated with casein micelles, using HT29 colon cancer cells.

    PubMed

    Haratifar, S; Meckling, K A; Corredig, M

    2014-02-01

    Numerous studies have shown that green tea polyphenols display anticancer activities in many organ sites by using different experimental models in rodents and in cultured cell lines in vitro. The present study tested the ability of casein micelles to deliver biologically active concentrations of polyphenols to HT-29 colon cancer cells. Epigallocatechin gallate (EGCG), the major catechin found in green tea, was used as the model molecule, as it has been shown to have antiproliferative activity on colon cancer cells. In the present work, we hypothesized that due to the binding of caseins with EGCG, casein micelles may be an ideal platform for the delivery of this bioactive molecule and that the binding would not affect the bioaccessibility of EGCG. The cytotoxicity and proliferation behavior of HT-29 colon cancer cells when exposed to free EGCG was compared with that of nanoencapsulated EGCG in casein micelles of skim milk. Epigallocatechin gallate-casein complexes were able to decrease the proliferation of HT-29 cancer cells, demonstrating that bioavailability may not be reduced by the nanoencapsulation. As casein micelles may act as protective carriers for EGCG in foods, it was concluded that nanoencapsulation of tea catechins in casein micelles may not diminish their antiproliferative activity on colon cancer cells compared with free tea catechins. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Interaction between casein micelles and whey protein/κ-casein complexes during renneting of heat-treated reconstituted skim milk powder and casein micelle/serum mixtures.

    PubMed

    Kethireddipalli, Prashanti; Hill, Arthur R; Dalgleish, Douglas G

    2011-02-23

    Casein micelles were separated from unheated reconstituted skim milk powder (RSMP) and were resuspended in the serum of RSMP that had been heated, with and without dialysis of this serum against unheated RSMP. Using size-exclusion chromatography, it was found that the soluble complexes of whey protein (WP) with κ-casein in the serum of the heated milk bind progressively to unheated casein micelles during renneting, even prior to the onset of clotting. Similar trends were noted when casein micelles from RSMP heated at pH values of 6.7, 7.1, or 6.3, each with different amounts of WP coating the micelles, were renneted in the presence of soluble WP/κ-casein complexes. No matter what was the initial load of micelle-bound WP complexes, all micelle types were capable of binding additional serum protein complexes during renneting. However, it is not clear that this binding of WP/κ-casein complexes to the micellar surface is a direct cause of the impaired rennet clotting of the RSMP.

  14. Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading

    PubMed Central

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M

    2015-01-01

    Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. PMID:26005348

  15. Polymeric micelle for tumor pH and folate-mediated targeting.

    PubMed

    Lee, Eun Seong; Na, Kun; Bae, You Han

    2003-08-28

    Novel pH-sensitive polymeric mixed micelles composed of poly(L-histidine) (polyHis; M(w) 5000)/PEG (M(n) 2000) and poly(L-lactic acid) (PLLA) (M(n) 3000)/PEG (M(n) 2000) block copolymers with or without folate conjugation were prepared by diafiltration. The micelles were investigated for pH-dependent drug release, folate receptor-mediated internalization and cytotoxicity using MCF-7 cells in vitro. The polyHis/PEG micelles showed accelerated adriamycin release as the pH decreased from 8.0. When the cumulative release for 24 h was plotted as a function of pH, the gradual transition in release rate appeared in a pH range from 8.0 to 6.8. In order to tailor the triggering pH of the polymeric micelles to the more acidic extracellular pH of tumors, while improving the micelle stability at pH 7.4, the PLLA/PEG block copolymer was blended with polyHis/PEG to form mixed micelles. Blending shifted the triggering pH to a lower value. Depending on the amount of PLLA/PEG, the mixed micelles were destabilized in the pH range of 7.2-6.6 (triggering pH for adriamycin release). When the mixed micelles were conjugated with folic acid, the in vitro results demonstrated that the micelles were more effective in tumor cell kill due to accelerated drug release and folate receptor-mediated tumor uptake. In addition, after internalization polyHis was found to be effective for cytosolic ADR delivery by virtue of fusogenic activity. This approach is expected to be useful for treatment of solid tumors in vivo.

  16. Designing Dendrimers to Offer Micelle-Type Nanocontainers

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    The properties of a dendrimer with hydrophobic and hydrophilic substituents on an orthogonal plane is synthesized and studied. The resulting polymer contains one of the substituents in its concave interior and the other at the convex surface and the design promotes micelle-like behavior in polar solvent and inverted micelle arrangement in…

  17. Applications of polymeric micelles with tumor targeted in chemotherapy

    NASA Astrophysics Data System (ADS)

    Ding, Hui; Wang, Xiaojun; Zhang, Song; Liu, Xinli

    2012-11-01

    Polymeric micelles (PMs) have gained more progress as a carrier system with the quick development of biological and nanoparticle techniques. In particular, PMs with smart targeting can deliver anti-cancer drugs directly into tumor cells at a sustained rate. PMs with core-shell structure (with diameters of 10 100 nm) have been prepared by a variety of biodegradable and biocompatible polymers via a self-assembly process. The preparation of polymeric micelles with stimuli-responsive block copolymers or modification of target molecules on polymeric micelles' surface are able to significantly improve the efficiency of drug delivery. Polymeric micelles, which have been considered as a novel promising drug carrier for cancer therapeutics, are rapidly evolving and being introduced in an attempt to overcome several limitations of traditional chemotherapeutics, including water solubility, tumor-specific accumulation, anti-tumor efficacy, and non-specific toxicity. This review describes the preparation of polymeric micelles and the targeted modification which greatly enhance the effects of chemotherapeutic agents.

  18. Influence of race and crossbreeding on casein micelles size.

    PubMed

    Freitas, Denise R; Fonseca, Leorges M; Souza, Fernando N; Ladeira, Cristiane V G; Diniz, Soraia A; Haddad, João Paulo A; Ferreira, Diêgo S; Santoro, Marcelo M; Cerqueira, Mônica M O P

    2015-05-01

    Casein (CN) micelles are colloidal aggregates of protein dispersed in milk, the importance of which in the dairy industry is related to functionality and yield in dairy products. The objective of this work was to investigate the correlation of milk CN micelles diameter from Holstein and Zebu crossbreds with milk composition (protein, fat, lactose, total and nonfat solids and milk urea nitrogen), somatic cell count (SCC), age, lactation stage and production. Average casein micelles diameters of milk samples obtained from 200 cows were measured using photon correlation spectroscopy and multiple regression analysis was used to find relationship between variables. CN micelle diameter, SCC and nonfat solids were different between animals with different Holstein crossbreed ratios, which suggests influence of genetic factors, mammary gland health and milk composition. Overall, results indicate the potential use of CN micelle diameter as a tool to select animals to produce milk more suitable to cheese production. © 2014 Japanese Society of Animal Science.

  19. Polymeric micelles for multi-drug delivery in cancer.

    PubMed

    Cho, Hyunah; Lai, Tsz Chung; Tomoda, Keishiro; Kwon, Glen S

    2015-02-01

    Drug combinations are common in cancer treatment and are rapidly evolving, moving beyond chemotherapy combinations to combinations of signal transduction inhibitors. For the delivery of drug combinations, i.e., multi-drug delivery, major considerations are synergy, dose regimen (concurrent versus sequential), pharmacokinetics, toxicity, and safety. In this contribution, we review recent research on polymeric micelles for multi-drug delivery in cancer. In concurrent drug delivery, polymeric micelles deliver multi-poorly water-soluble anticancer agents, satisfying strict requirements in solubility, stability, and safety. In sequential drug delivery, polymeric micelles participate in pretreatment strategies that "prime" solid tumors and enhance the penetration of secondarily administered anticancer agent or nanocarrier. The improved delivery of multiple poorly water-soluble anticancer agents by polymeric micelles via concurrent or sequential regimens offers novel and interesting strategies for drug combinations in cancer treatment.

  20. Evaluation of the MERIS terrestrial chlorophyll index (MTCI)

    NASA Astrophysics Data System (ADS)

    Dash, J.; Curran, P. J.

    The Medium Resolution Imaging Spectrometer (MERIS), one of the payloads on Envisat, has fine spectral resolution, moderate spatial resolution and a 3-day repeat cycle. This makes MERIS a potentially valuable sensor for the measurement and monitoring of terrestrial environments at regional to global scales. The red edge, which results from an abrupt reflectance change in red and near-infrared (NIR) wavelengths has a location that is related directly to the chlorophyll content of vegetation. A new index called the MERIS terrestrial chlorophyll index (MTCI) uses data in three red/NIR wavebands centered at 681.25, 708.75 and 753.75 nm (bands 8, 9 and 10 in the MERIS standard band setting). The MTCI is easy to calculate and can be automated. Preliminary indirect evaluation using model, field and MERIS data suggested its sensitivity to chlorophyll content, notably at high values. As a result this index is now a standard level-2 product of the European Space Agency. For direct MTCI evaluation two approaches were used. First, MTCI/chlorophyll content relationships were determined using a chlorophyll content surrogate for sites in southern Vietnam and second, MTCI/chlorophyll relationships were determined using actual chlorophyll content for sites in the New Forest, UK and for plots in the greenhouse. Forests in southern Vietnam were contaminated heavily with herbicides during the Vietnam War. This led to a long term decrease in chlorophyll content within forests that have long since regained full canopy cover. The amount of herbicide dropped onto the forests between 1965 and 1971 was used as a surrogate (inverse) for contemporary chlorophyll content and was related to current MTCI at selected forest sites. The resulting relationship was both strong and negative. Further per-pixel investigation of the MTCI/herbicide concentration relationship is under way for large forest regions. In the second approach MTCI was related directly to chlorophyll content at two scales and the

  1. Assimilation of seasonal chlorophyll and nutrient data into an adjoint three-dimensional ocean carbon cycle model: Sensitivity analysis and ecosystem parameter optimization

    NASA Astrophysics Data System (ADS)

    Tjiputra, Jerry F.; Polzin, Dierk; Winguth, Arne M. E.

    2007-03-01

    An adjoint method is applied to a three-dimensional global ocean biogeochemical cycle model to optimize the ecosystem parameters on the basis of SeaWiFS surface chlorophyll observation. We showed with identical twin experiments that the model simulated chlorophyll concentration is sensitive to perturbation of phytoplankton and zooplankton exudation, herbivore egestion as fecal pellets, zooplankton grazing, and the assimilation efficiency parameters. The assimilation of SeaWiFS chlorophyll data significantly improved the prediction of chlorophyll concentration, especially in the high-latitude regions. Experiments that considered regional variations of parameters yielded a high seasonal variance of ecosystem parameters in the high latitudes, but a low variance in the tropical regions. These experiments indicate that the adjoint model is, despite the many uncertainties, generally capable to optimize sensitive parameters and carbon fluxes in the euphotic zone. The best fit regional parameters predict a global net primary production of 36 Pg C yr-1, which lies within the range suggested by Antoine et al. (1996). Additional constraints of nutrient data from the World Ocean Atlas showed further reduction in the model-data misfit and that assimilation with extensive data sets is necessary.

  2. Polymeric micelles encapsulating fisetin improve the therapeutic effect in colon cancer.

    PubMed

    Chen, Yishan; Wu, Qinjie; Song, Linjiang; He, Tao; Li, Yuchen; Li, Ling; Su, Weijun; Liu, Lei; Qian, Zhiyong; Gong, Changyang

    2015-01-14

    The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) was discovered to possess antitumor activity, revealing its potential value in future chemotherapy. However, its poor water solubility makes it difficult for intravenous administration. In this study, the monomethyl poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) copolymer was applied to prepare nanoassemblies of fisetin by a self-assembly procedure. The prepared fisetin micelles gained a mean particle size of 22 ± 3 nm, polydisperse index of 0.163 ± 0.032, drug loading of 9.88 ± 0.14%, and encapsulation efficiency of 98.53 ± 0.02%. Compared with free fisetin, fisetin micelles demonstrated a sustained and prolonged in vitro release behavior, as well as enhanced cytotoxicity, cellular uptake, and fisetin-induced apoptosis in CT26 cells. As for in vivo studies, fisetin micelles were more competent for suppressing tumor growth and prolonging survival time than free fisetin in the subcutaneous CT26 tumor model. Furthermore, histological analysis, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, immunohistochemical detection of Ki-67, and microvessel density detection were conducted, demonstrating that fisetin micelles gained increased tumor apoptosis induction, proliferation suppression, and antiangiogenesis activities. In conclusion, we have successfully produced a MPEG-PCL-based nanocarrier encapsulating fisetin with enhanced antitumor activity.

  3. The fabrication of nanopatterns with Au nanoparticles-embedded micelles via nanoimprint lithography.

    PubMed

    Lee, Jung-Pil; Kim, Eun-Uk; Koh, Haeng-Deog; Kang, Nam-Goo; Jung, Gun-Young; Lee, Jae-Suk

    2009-09-09

    We fabricated nanopatterns with Au nanoparticles-embedded micelles (Au-micelles) by self-assembly of block copolymers via nanoimprint lithography. The micelle structure prepared by self-assembled block copolymers was used as a template for the synthesis of Au nanoparticles (Au NPs). Au NPs were synthesized in situ inside the micelles of polystyrene-block-poly(2-vinylpyridine) (PS- b-P2VP). Au-micelles were arranged on the trenches of the polymer template, which was imprinted by nanoimprint lithography. The fabrication of line-type and dot-type nanopatterns was carried out by the combined method. In addition, multilayer nanopatterns of the Au-micelles were also proposed.

  4. A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

    2017-04-01

    Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of 25 nm and vertical distance of 1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.

  5. Redox-sensitive Pluronic F127-tocopherol micelles: synthesis, characterization, and cytotoxicity evaluation

    PubMed Central

    Liu, Yuling; Fu, Sai; Lin, Longfei; Cao, Yuhong; Xie, Xi; Yu, Hua; Chen, Meiwan; Li, Hui

    2017-01-01

    Pluronic F127 (F127), an amphiphilic triblock copolymer, has been shown to have significant potential for drug delivery, as it is able to incorporate hydrophobic drugs and self-assemble into nanosize micelles. However, it suffers from dissociation upon dilution owing to the relatively high critical micelle concentration and lack of stimuli-responsive behavior. Here, we synthesized the α-tocopherol (TOC) modified F127 polymer (F127-SS-TOC) via a redox-sensitive disulfide bond between F127 and TOC, which formed stable micelles at relatively low critical micelle concentration and was sensitive to the intracellular redox environment. The particle size and zeta potential of the F127-SS-TOC micelles were 51.87±6.39 nm and -8.43±2.27 mV, respectively, and little changes in both particle size and zeta potential were observed within 7 days at room temperature. With 10 mM dithiothreitol stimulation, the F127-SS-TOC micelles rapidly dissociated followed by a significant change in size, which demonstrated a high reduction sensitivity of the micelles. In addition, the micelles showed a high hemocompatibility even at a high micelle concentration (1,000 μg/mL). Low cytotoxicity of the F127-SS-TOC micelles at concentrations ranging from 12.5 μg/mL to 200 μg/mL was also found on both Bel 7402 and L02 cells. Overall, our results demonstrated F127-SS-TOC micelles as a stable and safe aqueous formulation with a considerable potential for drug delivery. PMID:28435248

  6. A novel chlorophyll solar cell

    NASA Astrophysics Data System (ADS)

    Ludlow, J. C.

    The photosynthetic process is reviewed in order to produce a design for a chlorophyll solar cell. In a leaf, antenna chlorophyll absorbs light energy and conducts it to an energy trap composed of a protein and two chlorophyll molecules, which perform the oxidation-reduction chemistry. The redox potential of the trap changes from 0.4 to -0.6 V, which is sufficient to reduce nearby molecules with redox potentials in that range. The reduction occurs by transfer of an electron, and a chlorophyll solar cell would direct the transferred electron to a current carrier. Chlorophyll antenna and traps are placed on a metallic support immersed in an electron acceptor solution, and resulting electrons from exposure to light are gathered by a metallic current collector. Spinach chlorophyll extracted, purified, and applied in a cell featuring a Pt collector and an octane water emulsion resulted in intensity independent voltages.

  7. Modeling the relationship between extractable chlorophyll and SPAD-502 readings for endangered plant species research

    Treesearch

    Tracy S. Hawkins; Emile S. Gardiner; Greg S. Comer

    2009-01-01

    Handheld chlorophyll meters have proven to be useful tools for rapid, nondestructive assessment of chlorophyll and nutrient status in various agricultural and arborescent plant species. We proposed that a SPAD-502 chlorophyll meter would provide valuable information when monitoring life cycle changes and intraspecific variation in...

  8. Chemical and biosynthetic studies of chlorophylls

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huster, M.S.

    1988-01-01

    Chlorophyll occurrence, structure, biosynthesis, and degradation are discussed. Degradation and ring cleavage of heme is also discussed. The author examines the formation of dihydrobiliverdins by alkaline hydrolysis of zinc(II) meso-trifluoroacetoxypheophoribides, as a possible model for chlorophyll catabolism. {sup 18}O{sub 2}-labelling experiments show that the dihydrobiliverdin terminal lactam oxygens are derived from two different dioxygen molecules, also analogous to the Two Oxygen Molecular mechanism observed in heme degradation. The initially obtained dihydrobiliverdin readily undergoes an isomeric structural transformation, which is proposed as a model for the P{sub R}-P{sub FR} interconversion of the light sensor pigment phytochrome. The generality of the ring-openingmore » reaction is demonstrated with various chlorophyll-derived zinc(II) trifluoroacetoxychlorins, and side reactions of the isocyclic ring are discussed. The synthesis and properties of a chlorophyll-derived meso-oxochlorin are described. Facile one-electron oxidation, and its inhibition by protonation, is demonstrated by NMR, ESR, and cyclic voltammetry studies. Cyclic voltammetry is also used to measure redox potentials of a range of pheophorbide and meso-trifluoroacetoxypheophorbide metal complexes, including an oxochlorin nickel(II) complex. The results are presented of biosynthetic feeding studies of green sulfur bacteria with {sup 13}C- and {sup 14}C-labelled glutamate, glycine, and methionine. This study examines an unusual oxidation of a bacteriomethylpheophorbide 5-ethyl substituent, and describes attempts to elucidate the mechanism by {sup 18}O-labelling studies. Attempts to similarily derivatize a pyropheophorbide 5-methyl substituent are discussed.« less

  9. Fluorescent supramolecular micelles for imaging-guided cancer therapy

    NASA Astrophysics Data System (ADS)

    Sun, Mengmeng; Yin, Wenyan; Dong, Xinghua; Yang, Wantai; Zhao, Yuliang; Yin, Meizhen

    2016-02-01

    A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy.A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth

  10. Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy.

    PubMed

    Jin, Rong; Guo, Xuelian; Dong, Lingli; Xie, Enyuan; Cao, Aoneng

    2017-10-01

    A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH 2 ) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH 2 . These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Completing the Feedback Loop: The Impact of Chlorophyll Data Assimilation on the Ocean State

    NASA Technical Reports Server (NTRS)

    Borovikov, Anna; Keppenne, Christian; Kovach, Robin

    2015-01-01

    In anticipation of the integration of a full biochemical model into the next generation GMAO coupled system, an intermediate solution has been implemented to estimate the penetration depth (1Kd_PAR) of ocean radiation based on the chlorophyll concentration. The chlorophyll is modeled as a tracer with sources-sinks coming from the assimilation of MODIS chlorophyll data. Two experiments were conducted with the coupled ocean-atmosphere model. In the first, climatological values of Kpar were used. In the second, retrieved daily chlorophyll concentrations were assimilated and Kd_PAR was derived according to Morel et al (2007). No other data was assimilated to isolate the effects of the time-evolving chlorophyll field. The daily MODIS Kd_PAR product was used to validate the skill of the penetration depth estimation and the MERRA-OCEAN re-analysis was used as a benchmark to study the sensitivity of the upper ocean heat content and vertical temperature distribution to the chlorophyll input. In the experiment with daily chlorophyll data assimilation, the penetration depth was estimated more accurately, especially in the tropics. As a result, the temperature bias of the model was reduced. A notably robust albeit small (2-5 percent) improvement was found across the equatorial Pacific ocean, which is a critical region for seasonal to inter-annual prediction.

  12. CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging.

    PubMed

    Chen, Guojun; Ma, Ben; Wang, Yuyuan; Xie, Ruosen; Li, Chun; Dou, Kefeng; Gong, Shaoqin

    2017-12-06

    Cancer remains a major threat to human health due to low therapeutic efficacies of currently available cancer treatment options. Nanotheranostics, capable of simultaneous therapy and diagnosis/monitoring of diseases, has attracted increasing amounts of attention, particularly for cancer treatment. In this study, CuS-based theranostic micelles capable of simultaneous combination chemotherapy and photothermal therapy (PTT), as well as photoacoustic imaging, were developed for targeted cancer therapy. The micelle was formed by a CuS nanoparticle (NP) functionalized by thermosensitive amphiphilic poly(acrylamide-acrylonitrile)-poly(ethylene glycol) block copolymers. CuS NPs under near-infrared (NIR) irradiation induced a significant temperature elevation, thereby enabling NIR-triggered PTT. Moreover, the hydrophobic core formed by poly(acrylamide-acrylonitrile) segments used for drug encapsulation exhibited an upper critical solution temperature (UCST; ∼38 °C), which underwent a hydrophobic-to-hydrophilic transition once the temperature rose above the UCST induced by NIR-irradiated CuS NPs, thereby triggering a rapid drug release and enabling NIR-controlled chemotherapy. The CuS-based micelles conjugated with GE11 peptides were tested in an epidermal growth factor receptor-overexpressing triple-negative breast cancer model. In both two-dimensional monolayer cell and three-dimensional multicellular tumor spheroid models, GE11-tagged CuS-based micelles under NIR irradiation, enabling the combination chemotherapy and PTT, exhibited the best therapeutic outcome due to a synergistic effect. These CuS-based micelles also displayed a good photoacoustic imaging ability under NIR illumination. Taken together, this multifunctional CuS-based micelle could be a promising nanoplatform for targeted cancer nanotheranostics.

  13. Interactions of casein micelles with calcium phosphate particles.

    PubMed

    Tercinier, Lucile; Ye, Aiqian; Anema, Skelte G; Singh, Anne; Singh, Harjinder

    2014-06-25

    Insoluble calcium phosphate particles, such as hydroxyapatite (HA), are often used in calcium-fortified milks as they are considered to be chemically unreactive. However, this study showed that there was an interaction between the casein micelles in milk and HA particles. The caseins in milk were shown to bind to the HA particles, with the relative proportions of bound β-casein, αS-casein, and κ-casein different from the proportions of the individual caseins present in milk. Transmission electron microscopy showed no evidence of intact casein micelles on the surface of the HA particles, which suggested that the casein micelles dissociated either before or during binding. The HA particles behaved as ion chelators, with the ability to bind the ions contained in the milk serum phase. Consequently, the depletion of the serum minerals disrupted the milk mineral equilibrium, resulting in dissociation of the casein micelles in milk.

  14. Dynamics of micelle formation from temperature-jump Monte Carlo simulations.

    PubMed

    Heinzelmann, G; Seide, P; Figueiredo, W

    2015-11-01

    In the present work we perform temperature jumps in a surfactant solution by means of Monte Carlo simulations, investigating the dynamics of micelle formation. We use a lattice model that allows orientational freedom and hydrogen bonding for solvent molecules, which can make a connection between the different time scales of hydrogen bond formation and amphiphilic aggregation. When we perform a large jump between a high-temperature nonmicellized state and a micellized state, there is strong hysteresis between the heating and cooling processes, the latter showing the formation of premicelles that act as nucleation centers for the assembly of larger aggregates and the former is a drive for dissociation of the existing aggregates. Hysteresis is not seen when we perform a small jump between two states that can be both micellized or nonmicellized. Looking for a more detailed analysis of the hydrophobic effect that drives aggregation, we compare the time evolution of the solvent hydrogen bonds in our system close and far from micelles and how that is affected by the formation of large clusters at low temperatures. We find a strong connection between them, with the total number of hydrogen bonds in the system always increasing when micelles are formed. To gain insights into the mechanism of premicellar formation and growth, we measure the lifetime of micellized amphiphiles as a function of the aggregate size and the stage of the aggregation process. Our results indicate that the premicelles are always unstable, quickly exchanging amphiphiles with the solution due to their low probabilty in equilibrium. Furthermore, we find that the stability of individual surfactants in micelles increases with the aggregate size, with the lifetime of amphiphiles in large micelles being as much as 35 times longer than in the case of the unstable premicellar region.

  15. On the binding of calcium by micelles composed of carboxy-modified pluronics measured by means of differential potentiometric titration and modeled with a self-consistent-field theory.

    PubMed

    Lauw, Y; Leermakers, F A M; Cohen Stuart, M A; Pinheiro, J P; Custers, J P A; van den Broeke, L J P; Keurentjes, J T F

    2006-12-19

    We perform differential potentiometric titration measurements for the binding of Ca2+ ions to micelles composed of the carboxylic acid end-standing Pluronic P85 block copolymer (i.e., CAE-85 (COOH-(EO)26-(PO)39-(EO)26-COOH)). Two different ion-selective electrodes (ISEs) are used to detect the free calcium concentration; the first ISE is an indicator electrode, and the second is a reference electrode. The titration is done by adding the block copolymers to a known solution of Ca2+ at neutral pH and high enough temperature (above the critical micellization temperature CMT) and various amount of added monovalent salt. By measuring the difference in the electromotive force between the two ISEs, the amount of Ca2+ that is bound by the micelles is calculated. This is then used to determine the binding constant of Ca2+ with the micelles, which is a missing parameter needed to perform molecular realistic self-consistent-field (SCF) calculations. It turns out that the micelles from block copolymer CAE-85 bind Ca2+ ions both electrostatically and specifically. The specific binding between Ca2+ and carboxylic groups in the corona of the micelles is modeled through the reaction equilibrium -COOCa+ <==> -COO- + Ca2+ with pKCa = 1.7 +/- 0.06.

  16. Regional variability among nonlinear chlorophyll-phosphorus relationships in lakes

    USGS Publications Warehouse

    Filstrup, Christopher T.; Wagner, Tyler; Soranno, Patricia A.; Stanley, Emily H.; Stow, Craig A.; Webster, Katherine E.; Downing, John A.

    2014-01-01

    The relationship between chlorophyll a (Chl a) and total phosphorus (TP) is a fundamental relationship in lakes that reflects multiple aspects of ecosystem function and is also used in the regulation and management of inland waters. The exact form of this relationship has substantial implications on its meaning and its use. We assembled a spatially extensive data set to examine whether nonlinear models are a better fit for Chl a—TP relationships than traditional log-linear models, whether there were regional differences in the form of the relationships, and, if so, which regional factors were related to these differences. We analyzed a data set from 2105 temperate lakes across 35 ecoregions by fitting and comparing two different nonlinear models and one log-linear model. The two nonlinear models fit the data better than the log-linear model. In addition, the parameters for the best-fitting model varied among regions: the maximum and lower Chl aasymptotes were positively and negatively related to percent regional pasture land use, respectively, and the rate at which chlorophyll increased with TP was negatively related to percent regional wetland cover. Lakes in regions with more pasture fields had higher maximum chlorophyll concentrations at high TP concentrations but lower minimum chlorophyll concentrations at low TP concentrations. Lakes in regions with less wetland cover showed a steeper Chl a—TP relationship than wetland-rich regions. Interpretation of Chl a—TP relationships depends on regional differences, and theory and management based on a monolithic relationship may be inaccurate.

  17. Analysis of Seasonal Chlorophyll-a Using An Adjoint Three-Dimensional Ocean Carbon Cycle Model

    NASA Astrophysics Data System (ADS)

    Tjiputra, J.; Winguth, A.; Polzin, D.

    2004-12-01

    The misfit between numerical ocean model and observations can be reduced using data assimilation. This can be achieved by optimizing the model parameter values using adjoint model. The adjoint model minimizes the model-data misfit by estimating the sensitivity or gradient of the cost function with respect to initial condition, boundary condition, or parameters. The adjoint technique was used to assimilate seasonal chlorophyll-a data from the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) satellite to a marine biogeochemical model HAMOCC5.1. An Identical Twin Experiment (ITE) was conducted to test the robustness of the model and the non-linearity level of the forward model. The ITE experiment successfully recovered most of the perturbed parameter to their initial values, and identified the most sensitive ecosystem parameters, which contribute significantly to model-data bias. The regional assimilations of SeaWiFS chlorophyll-a data into the model were able to reduce the model-data misfit (i.e. the cost function) significantly. The cost function reduction mostly occurred in the high latitudes (e.g. the model-data misfit in the northern region during summer season was reduced by 54%). On the other hand, the equatorial regions appear to be relatively stable with no strong reduction in cost function. The optimized parameter set is used to forecast the carbon fluxes between marine ecosystem compartments (e.g. Phytoplankton, Zooplankton, Nutrients, Particulate Organic Carbon, and Dissolved Organic Carbon). The a posteriori model run using the regional best-fit parameterization yields approximately 36 PgC/yr of global net primary productions in the euphotic zone.

  18. Self-assembly of micelles in organic solutions of lecithin and bile salt: Mesoscale computer simulation

    NASA Astrophysics Data System (ADS)

    Markina, A.; Ivanov, V.; Komarov, P.; Khokhlov, A.; Tung, S.-H.

    2016-11-01

    We propose a coarse-grained model for studying the effects of adding bile salt to lecithin organosols by means of computer simulation. This model allows us to reveal the mechanisms of experimentally observed increasing of viscosity upon increasing the bile salt concentration. We show that increasing the bile salt to lecithin molar ratio induces the growth of elongated micelles of ellipsoidal and cylindrical shape due to incorporation of disklike bile salt molecules. These wormlike micelles can entangle into transient network displaying perceptible viscoelastic properties.

  19. Revisiting the chlorophyll biosynthesis pathway using genome scale metabolic model of Oryza sativa japonica

    PubMed Central

    Chatterjee, Ankita; Kundu, Sudip

    2015-01-01

    Chlorophyll is one of the most important pigments present in green plants and rice is one of the major food crops consumed worldwide. We curated the existing genome scale metabolic model (GSM) of rice leaf by incorporating new compartment, reactions and transporters. We used this modified GSM to elucidate how the chlorophyll is synthesized in a leaf through a series of bio-chemical reactions spanned over different organelles using inorganic macronutrients and light energy. We predicted the essential reactions and the associated genes of chlorophyll synthesis and validated against the existing experimental evidences. Further, ammonia is known to be the preferred source of nitrogen in rice paddy fields. The ammonia entering into the plant is assimilated in the root and leaf. The focus of the present work is centered on rice leaf metabolism. We studied the relative importance of ammonia transporters through the chloroplast and the cytosol and their interlink with other intracellular transporters. Ammonia assimilation in the leaves takes place by the enzyme glutamine synthetase (GS) which is present in the cytosol (GS1) and chloroplast (GS2). Our results provided possible explanation why GS2 mutants show normal growth under minimum photorespiration and appear chlorotic when exposed to air. PMID:26443104

  20. RNA-based micelles: A novel platform for paclitaxel loading and delivery.

    PubMed

    Shu, Yi; Yin, Hongran; Rajabi, Mehdi; Li, Hui; Vieweger, Mario; Guo, Sijin; Shu, Dan; Guo, Peixuan

    2018-04-28

    RNA can serve as powerful building blocks for bottom-up fabrication of nanostructures for biotechnological and biomedical applications. In addition to current self-assembly strategies utilizing base pairing, motif piling and tertiary interactions, we reported for the first time the formation of RNA based micellar nanoconstruct with a cholesterol molecule conjugated onto one helical end of a branched pRNA three-way junction (3WJ) motif. The resulting amphiphilic RNA micelles consist of a hydrophilic RNA head and a covalently linked hydrophobic lipid tail that can spontaneously assemble in aqueous solution via hydrophobic interaction. Taking advantage of pRNA 3WJ branched structure, the assembled RNA micelles are capable of escorting multiple functional modules. As a proof of concept for delivery for therapeutics, Paclitaxel was loaded into the RNA micelles with significantly improved water solubility. The successful construction of the drug loaded RNA micelles was confirmed and characterized by agarose gel electrophoresis, atomic force microscopy (AFM), dynamic light scattering (DLS), and fluorescence Nile Red encapsulation assay. The estimate critical micelle formation concentration ranges from 39 nM to 78 nM. The Paclitaxel loaded RNA micelles can internalize into cancer cells and inhibit their proliferation. Further studies showed that the Paclitaxel loaded RNA micelles induced cancer cell apoptosis in a Caspase-3 dependent manner but RNA micelles alone exhibited low cytotoxicity. Finally, the Paclitaxel loaded RNA micelles targeted to tumor in vivo without accumulation in healthy tissues and organs. There is also no or very low induction of pro-inflammatory response. Therefore, multivalence, cancer cell permeability, combined with controllable assembly, low or non toxic nature, and tumor targeting are all promising features that make our pRNA micelles a suitable platform for potential drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Polymeric micelles: nanocarriers for cancer-targeted drug delivery.

    PubMed

    Zhang, Yifei; Huang, Yixian; Li, Song

    2014-08-01

    Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. With small size (10-100 nm) and hydrophilic shell of PEG, polymeric micelles exhibit prolonged circulation time in the blood and enhanced tumor accumulation. In this review, the importance of rational design was highlighted by summarizing the recent progress on the development of micellar formulations. Emphasis is placed on the new strategies to enhance the drug/carrier interaction for improved drug-loading capacity. In addition, the micelle-forming drug-polymer conjugates are also discussed which have both drug-loading function and antitumor activity.

  2. Quantum-Dot-Based Theranostic Micelles Conjugated with an Anti-EGFR Nanobody for Triple-Negative Breast Cancer Therapy.

    PubMed

    Wang, Yuyuan; Wang, Yidan; Chen, Guojun; Li, Yitong; Xu, Wei; Gong, Shaoqin

    2017-09-13

    A quantum-dot (QD)-based micelle conjugated with an anti-epidermal growth factor receptor (EGFR) nanobody (Nb) and loaded with an anticancer drug, aminoflavone (AF), has been engineered for EGFR-overexpressing cancer theranostics. The near-infrared (NIR) fluorescence of the indium phosphate core/zinc sulfide shell QDs (InP/ZnS QDs) allowed for in vivo nanoparticle biodistribution studies. The anti-EGFR nanobody 7D12 conjugation improved the cellular uptake and cytotoxicity of the QD-based micelles in EGFR-overexpressing MDA-MB-468 triple-negative breast cancer (TNBC) cells. In comparison with the AF-encapsulated nontargeted (i.e., without Nb conjugation) micelles, the AF-encapsulated Nb-conjugated (i.e., targeted) micelles accumulated in tumors at higher concentrations, leading to more effective tumor regression in an orthotopic triple-negative breast cancer xenograft mouse model. Furthermore, there was no systemic toxicity observed with the treatments. Thus, this QD-based Nb-conjugated micelle may serve as an effective theranostic nanoplatform for EGFR-overexpressing cancers such as TNBCs.

  3. Extracting Aggregation Free Energies of Mixed Clusters from Simulations of Small Systems: Application to Ionic Surfactant Micelles.

    PubMed

    Zhang, X; Patel, L A; Beckwith, O; Schneider, R; Weeden, C J; Kindt, J T

    2017-11-14

    Micelle cluster distributions from molecular dynamics simulations of a solvent-free coarse-grained model of sodium octyl sulfate (SOS) were analyzed using an improved method to extract equilibrium association constants from small-system simulations containing one or two micelle clusters at equilibrium with free surfactants and counterions. The statistical-thermodynamic and mathematical foundations of this partition-enabled analysis of cluster histograms (PEACH) approach are presented. A dramatic reduction in computational time for analysis was achieved through a strategy similar to the selector variable method to circumvent the need for exhaustive enumeration of the possible partitions of surfactants and counterions into clusters. Using statistics from a set of small-system (up to 60 SOS molecules) simulations as input, equilibrium association constants for micelle clusters were obtained as a function of both number of surfactants and number of associated counterions through a global fitting procedure. The resulting free energies were able to accurately predict micelle size and charge distributions in a large (560 molecule) system. The evolution of micelle size and charge with SOS concentration as predicted by the PEACH-derived free energies and by a phenomenological four-parameter model fit, along with the sensitivity of these predictions to variations in cluster definitions, are analyzed and discussed.

  4. Light Scattering Study of Mixed Micelles Made from Elastin-Like Polypeptide Linear Chains and Trimers

    NASA Astrophysics Data System (ADS)

    Terrano, Daniel; Tsuper, Ilona; Maraschky, Adam; Holland, Nolan; Streletzky, Kiril

    Temperature sensitive nanoparticles were generated from a construct (H20F) of three chains of elastin-like polypeptides (ELP) linked to a negatively charged foldon domain. This ELP system was mixed at different ratios with linear chains of ELP (H40L) which lacks the foldon domain. The mixed system is soluble at room temperature and at a transition temperature (Tt) will form swollen micelles with the hydrophobic linear chains hidden inside. This system was studied using depolarized dynamic light scattering (DDLS) and static light scattering (SLS) to determine the size, shape, and internal structure of the mixed micelles. The mixed micelle in equal parts of H20F and H40L show a constant apparent hydrodynamic radius of 40-45 nm at the concentration window from 25:25 to 60:60 uM (1:1 ratio). At a fixed 50 uM concentration of the H20F, varying H40L concentration from 5 to 80 uM resulted in a linear growth in the hydrodynamic radius from about 11 to about 62 nm, along with a 1000-fold increase in VH signal. A possible simple model explaining the growth of the swollen micelles is considered. Lastly, the VH signal can indicate elongation in the geometry of the particle or could possibly be a result from anisotropic properties from the core of the micelle. SLS was used to study the molecular weight, and the radius of gyration of the micelle to help identify the structure and morphology of mixed micelles and the tangible cause of the VH signal.

  5. Celecoxib Encapsulation in β-Casein Micelles: Structure, Interactions, and Conformation.

    PubMed

    Turovsky, Tanya; Khalfin, Rafail; Kababya, Shifi; Schmidt, Asher; Barenholz, Yechezkel; Danino, Dganit

    2015-07-07

    β-Casein is a 24 kDa natural protein that has an open conformation and almost no folded or secondary structure, and thus is classified as an intrinsically unstructured protein. At neutral pH, β-casein has an amphiphilic character. Therefore, in contrast to most unstructured proteins that remain monomeric in solution, β-casein self-assembles into well-defined core-shell micelles. We recently developed these micelles as potential carriers for oral administration of poorly water-soluble pharmaceuticals, using celecoxib as a model drug. Herein we present deep and precise insight into the physicochemical characteristics of the protein-drug formulation, both in bulk solution and in dry form, emphasizing drug conformation, packing properties and aggregation state. In addition, the formulation is extensively studied in terms of structure and morphology, protein/drug interactions and physical stability. Particularly, NMR measurements indicated strong drug-protein interactions and noncrystalline drug conformation, which is expected to improve drug solubility and bioavailability. Small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) were combined for nanostructural characterization, proving that drug-protein interactions lead to well-defined spheroidal micelles that become puffier and denser upon drug loading. Dynamice light scattering (DLS), turbidity measurements, and visual observations complemented the analysis for determining formulation structure, interactions, and stability. Additionally, it was shown that the loaded micelles retain their properties through freeze-drying and rehydration, providing long-term physical and chemical stability. Altogether, the formulation seems greatly promising for oral drug delivery.

  6. Thermodynamics of micelle formation in a water-alcohol solution of sodium tetradecyl sulfate

    NASA Astrophysics Data System (ADS)

    Shilova, S. V.; Tret'yakova, A. Ya.; Barabanov, V. P.

    2016-01-01

    The effects of addition of ethanol and propan-1-ol on sodium tetradecyl sulfate micelle formation in an aqueous solution are studied via microprobe fluorescence microscopy and conductometry. The critical micelle concentration, quantitative characteristics of micelles, and thermodynamic parameters of micelle formation are determined. Addition of 5-15 vol % of ethanol or 5-10 vol % of propan-1-ol is shown to result in a lower critical micelle concentration than in the aqueous solution, and in the formation of mixed spherical micelles whose sizes and aggregation numbers are less than those for the systems without alcohol. The contribution from the enthalpy factor to the free energy of sodium tetradecyl sulfate micelle formation is found to dominate in mixed solvents, in contrast to aqueous solutions.

  7. DNA-polymer micelles as nanoparticles with recognition ability.

    PubMed

    Talom, Renée Mayap; Fuks, Gad; Kaps, Leonard; Oberdisse, Julian; Cerclier, Christel; Gaillard, Cédric; Mingotaud, Christophe; Gauffre, Fabienne

    2011-11-25

    The Watson-Crick binding of DNA single strands is a powerful tool for the assembly of nanostructures. Our objective is to develop polymer nanoparticles equipped with DNA strands for surface-patterning applications, taking advantage of the DNA technology, in particular, recognition and reversibility. A hybrid DNA copolymer is synthesized through the conjugation of a ssDNA (22-mer) with a poly(ethylene oxide)-poly(caprolactone) diblock copolymer (PEO-b-PCl). It is shown that, in water, the PEO-b-PCl-ssDNA(22) polymer forms micelles with a PCl hydrophobic core and a hydrophilic corona made of PEO and DNA. The micelles are thoroughly characterized using electron microscopy (TEM and cryoTEM) and small-angle neutron scattering. The binding of these DNA micelles to a surface through DNA recognition is monitored using a quartz crystal microbalance and imaged by atomic force microscopy. The micelles can be released from the surface by a competitive displacement event. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. A Mixed Micelle Formulation for Oral Delivery of Vitamin K.

    PubMed

    Sun, Feilong; Jaspers, Tessa C C; van Hasselt, Peter M; Hennink, Wim E; van Nostrum, Cornelus F

    2016-09-01

    To develop a stable micellar formulation of vitamin K for oral delivery, because the commercial and clinically used formulation of vitamin K (Konakion® MM) destabilizes at gastric pH resulting in low bioavailability of this vitamin in neonates with cholestasis. Mixed micelles composed of EPC, DSPE-PEG 2000 and glycocholic acid, with and without vitamin K, were prepared by a film hydration method. The influence of pH on the stability of the micelles was analyzed by dynamic light scattering (DLS). The critical micelle concentration (CMC) was determined by fluorescence spectroscopy using pyrene and the morphology was evaluated by transmission electron microscopy . Caco-2 cells were used to study the cytocompatibilty. Mixed micelles with mean diameters from 7.1 to 11.0 nm and a narrow size distribution (PDI < 0.2) were obtained after 3 membrane extrusion cycles. Konakion® MM formed aggregated particles at gastric pH, which was avoided through steric stabilization by introducing PEG. TEM showed that mixed micelles had a spherical size (diameter of around 10 nm) with a narrow size distribution in agreement with the DLS results. The loading capacities for vitamin K of mixed micelles with varying molar fractions of DSPE-PEG and EPC (from 0/100 to 50/50 (mol/mol)) were 10.8-5.0 w%, respectively. The mixed micelles showed good cytocompatibility at concentrations of glycocholic acid between 0.12 and 1.20 mM. Mixed micelles with superior stability to Konakion® MM at low pH were obtained by introducing DSPE-PEG 2000. These are therefore attractive oral formulations for vitamin K.

  9. Magnetic Heating of Iron Oxide Nanoparticles and Magnetic Micelles for Cancer Therapy.

    PubMed

    Glover, Amanda L; Bennett, James B; Pritchett, Jeremy S; Nikles, Sarah M; Nikles, David E; Nikles, Jacqueline A; Brazel, Christopher S

    2013-01-01

    The inclusion of magnetic nanoparticles into block copolymer micelles was studied towards the development of a targeted, magnetically triggered drug delivery system for cancer therapy. Herein, we report the synthesis of magnetic nanoparticles and poly(ethylene glycol-b-caprolactone) block copolymers, and experimental verification of magnetic heating of the nanoparticles, self-assembly of the block copolymers to form magnetic micelles, and thermally-enhanced drug release. The semicrystalline core of the micelles melted at temperatures just above physiological conditions, indicating that they could be used to release a chemotherapy agent from a thermo-responsive polymer system. The magnetic nanoparticles were shown to heat effectively in high frequency magnetic fields ranging from 30-70 kA/m. Magnetic micelles also showed heating properties, that when combined with a chemotherapeutic agent and a targeting ligand could be developed for localized, triggered drug delivery. During the magnetic heating experiments, a time lag was observed in the temperature profile for magnetic micelles, likely due to the heat of fusion of melting of polycaprolactone micelle cores before bulk solution temperatures increased. Doxorubicin, incorporated into the micelles, released faster when the micelles were heated above the core melting point.

  10. Worm-like micelles of CTAB and sodium salicylate under turbulent flow.

    PubMed

    Rodrigues, Roberta K; da Silva, Marcelo A; Sabadini, Edvaldo

    2008-12-16

    Polymers with high molecular weight and worm-like micelles are drag-reducing agents under turbulent flow. However, in contrast to the polymeric systems, the worm-like micelles do not undergo mechanical degradation due to the turbulence, because their macromolecular structure can be spontaneously restored. This very favorable property, together with their drag-reduction capability, offer the possibility to use such worm-like micelles in heating and cooling systems to recirculate water while expending less energy. The formation, growth, and stability of worm-like micelles formed by cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal) were investigated using the self-fluorescence of salicylate ions and the ability of the giant micelles to promote hydrodynamic drag reduction under turbulent flow. The turbulence in solutions of CTAB-Sal was produced within the double-gap cell of a rotational rheometer. Detailed diagrams were obtained for different ratios of Sal and CTAB, which revealed transitions associated with the thermal stability of giant micelles under turbulent flow.

  11. Cryo-transmission electron tomography of native casein micelles from bovine milk

    PubMed Central

    Trejo, R.; Dokland, T.; Jurat-Fuentes, J.; Harte, F.

    2013-01-01

    Caseins are the principal protein components in milk and an important ingredient in the food industry. In liquid milk, caseins are found as micelles of casein proteins and colloidal calcium nanoclusters. Casein micelles were isolated from raw skim milk by size exclusion chromatography and suspended in milk protein-free serum produced by ultrafiltration (molecular weight cut-off of 3 kDa) of raw skim milk. The micelles were imaged by cryo-electron microscopy and subjected to tomographic reconstruction methods to visualize the 3-dimensional and internal organization of native casein micelles. This provided new insights into the internal architecture of the casein micelle that had not been apparent from prior cryo-transmission electron microscopy studies. This analysis demonstrated the presence of water-filled cavities (~20 to 30 nm in diameter), channels (diameter greater than ~5 nm), and several hundred high-density nanoclusters (6 to 12 nm in diameter) within the interior of the micelles. No spherical protein submicellar structures were observed. PMID:22118067

  12. Defining Chlorophyll-a Reference Conditions in European Lakes

    PubMed Central

    Alves, Maria Helena; Argillier, Christine; van den Berg, Marcel; Buzzi, Fabio; Hoehn, Eberhard; de Hoyos, Caridad; Karottki, Ivan; Laplace-Treyture, Christophe; Solheim, Anne Lyche; Ortiz-Casas, José; Ott, Ingmar; Phillips, Geoff; Pilke, Ansa; Pádua, João; Remec-Rekar, Spela; Riedmüller, Ursula; Schaumburg, Jochen; Serrano, Maria Luisa; Soszka, Hanna; Tierney, Deirdre; Urbanič, Gorazd; Wolfram, Georg

    2010-01-01

    The concept of “reference conditions” describes the benchmark against which current conditions are compared when assessing the status of water bodies. In this paper we focus on the establishment of reference conditions for European lakes according to a phytoplankton biomass indicator—the concentration of chlorophyll-a. A mostly spatial approach (selection of existing lakes with no or minor human impact) was used to set the reference conditions for chlorophyll-a values, supplemented by historical data, paleolimnological investigations and modelling. The work resulted in definition of reference conditions and the boundary between “high” and “good” status for 15 main lake types and five ecoregions of Europe: Alpine, Atlantic, Central/Baltic, Mediterranean, and Northern. Additionally, empirical models were developed for estimating site-specific reference chlorophyll-a concentrations from a set of potential predictor variables. The results were recently formulated into the EU legislation, marking the first attempt in international water policy to move from chemical quality standards to ecological quality targets. PMID:20401659

  13. Growth Behavior, Geometrical Shape, and Second CMC of Micelles Formed by Cationic Gemini Esterquat Surfactants.

    PubMed

    Bergström, L Magnus; Tehrani-Bagha, Alireza; Nagy, Gergely

    2015-04-28

    Micelles formed by novel gemini esterquat surfactants have been investigated with small-angle neutron scattering (SANS). The growth behavior of the micelles is found to differ conspicuously depending on the length of the gemini surfactant spacer group. The gemini surfactant with a long spacer form rather small triaxial ellipsoidal tablet-shaped micelles that grow weakly with surfactant concentration in the entire range of measured concentrations. Geminis with a short spacer, on the other hand, form weakly growing oblates or tablets at low concentrations that start to grow much more strongly into polydisperse rodlike or wormlike micelles at higher concentrations. The latter behavior is consistent with the presence of a second CMC that marks the transition from the weakly to the strongly growing regime. It is found that the growth behavior in terms of aggregation number as a function of surfactant concentration always appear concave in weakly growing regimes, while switching to convex behavior in strongly growing regimes. As a result, we are able to determine the second CMC of the geminis with short spacer by means of suggesting a rather precise definition of it, located at the point of inflection of the growth curve that corresponds to the transition from concave to convex growth behavior. Our SANS results are rationalized by comparison with the recently developed general micelle model. In particular, this theory is able to explain and reproduce the characteristic appearances of the experimental growth curves, including the presence of a second CMC and the convex strongly growing regime beyond. By means of optimizing the agreement between predictions from the general micelle model and results from SANS experiments, we are able to determine the three bending elasticity constants spontaneous curvature, bending rigidity, and saddle-splay constant for each surfactant.

  14. Reduction-responsive PEtOz-SS-PCL micelle with tailored size to overcome blood-brain barrier and enhance doxorubicin antiglioma effect.

    PubMed

    Li, Yuling; Baiyang, Li; Leran, Bu; Zhen, Wang; Yandong, Xie; Baixiang, Du; Dandan, Zhu; Yufu, Zhu; Jun, Liang; Rutong, Yu; Hongmei, Liu

    2017-11-01

    A series of novel reduction-responsive micelles with tailored size were designed and prepared to release doxorubicin (DOX) for treating glioma, which were developed based on amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-b-poly (ε-caprolactone) (PEtOz-SS-PCL) and the micelle size could be regulated by designing the polymer structure. The DOX-loaded PEtOz-SS-PCL micelles had small size and rapid drug release in reductive intracellular environments. Biodistribution and in vivo imaging studies in C6 glioma mice tumor model showed that DOX loaded PEtOz-SS-PCL43 micelles with the smallest size had superior accumulation and fast drug release in tumor sites. In vivo antitumor activity demonstrated that DOX-loaded PEtOz-SS-PCL43 micelles improved antitumor efficacy in contrast to PEtOz-SS-PCL micelles with larger size toward the orthotopic C6-Luci cells-bearing mice. This study shows great potential in tailoring the micelle size and introducing the responsive bonds or compartment for intracellular drug delivery and release in glioma treatment by designing the architecture of the polymer.

  15. Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation

    PubMed Central

    Hofman, Jan-Willem; Carstens, Myrra G.; van Zeeland, Femke; Helwig, Conny; Flesch, Frits M.; Hennink, Wim E.

    2008-01-01

    Purpose To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation. Methods Micelles of mPEG750-b-oligo(ɛ-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg®). Results Micelles composed of mPEG750-b-OCL5 with benzoyl and naphtoyl end groups had the highest loading capacity up to 30% (w/w), likely due to π–π interactions between the aromatic end group and the photosensitizer. MTHPC-loaded benzoylated micelles (0.5 mg/mL polymer) did not display photocytotoxicity or any mTHPC-uptake by the cells, in contrast to free and liposomal mTHPC. After dilution of the micelles below the critical aggregation concentration (CAC), or after micelle degradation by lipase, photocytotoxicity and cellular uptake of mTHPC were restored. Conclusion The high loading capacity of the micelles, the high stability of mTHPC-loaded micelles above the CAC, and the lipase-induced release of the photosensitizer makes these micelles very promising carriers for photodynamic therapy in vivo. PMID:18597164

  16. Self-consistent-field calculations of proteinlike incorporations in polyelectrolyte complex micelles

    NASA Astrophysics Data System (ADS)

    Lindhoud, Saskia; Stuart, Martien A. Cohen; Norde, Willem; Leermakers, Frans A. M.

    2009-11-01

    Self-consistent field theory is applied to model the structure and stability of polyelectrolyte complex micelles with incorporated protein (molten globule) molecules in the core. The electrostatic interactions that drive the micelle formation are mimicked by nearest-neighbor interactions using Flory-Huggins χ parameters. The strong qualitative comparison with experimental data proves that the Flory-Huggins approach is reasonable. The free energy of insertion of a proteinlike molecule into the micelle is nonmonotonic: there is (i) a small repulsion when the protein is inside the corona; the height of the insertion barrier is determined by the local osmotic pressure and the elastic deformation of the core, (ii) a local minimum occurs when the protein molecule is at the core-corona interface; the depth (a few kBT ’s) is related to the interfacial tension at the core-corona interface and (iii) a steep repulsion (several kBT ) when part of the protein molecule is dragged into the core. Hence, the protein molecules reside preferentially at the core-corona interface and the absorption as well as the release of the protein molecules has annealed rather than quenched characteristics. Upon an increase of the ionic strength it is possible to reach a critical micellization ionic (CMI) strength. With increasing ionic strength the aggregation numbers decrease strongly and only few proteins remain associated with the micelles near the CMI.

  17. Targeted polymeric micelles for siRNA treatment of experimental cancer by intravenous injection.

    PubMed

    Christie, R James; Matsumoto, Yu; Miyata, Kanjiro; Nomoto, Takahiro; Fukushima, Shigeto; Osada, Kensuke; Halnaut, Julien; Pittella, Frederico; Kim, Hyun Jin; Nishiyama, Nobuhiro; Kataoka, Kazunori

    2012-06-26

    Small interfering ribonucleic acid (siRNA) cancer therapies administered by intravenous injection require a delivery system for transport from the bloodstream into the cytoplasm of diseased cells to perform the function of gene silencing. Here we describe nanosized polymeric micelles that deliver siRNA to solid tumors and elicit a therapeutic effect. Stable multifunctional micelle structures on the order of 45 nm in size formed by spontaneous self-assembly of block copolymers with siRNA. Block copolymers used for micelle formation were designed and synthesized to contain three main features: a siRNA binding segment containing thiols, a hydrophilic nonbinding segment, and a cell-surface binding peptide. Specifically, poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLL) comprising lysine amines modified with 2-iminothiolane (2IT) and the cyclo-Arg-Gly-Asp (cRGD) peptide on the PEG terminus was used. Modification of PEG-b-PLL with 2IT led to improved control of micelle formation and also increased stability in the blood compartment, while installation of the cRGD peptide improved biological activity. Incorporation of siRNA into stable micelle structures containing the cRGD peptide resulted in increased gene silencing ability, improved cell uptake, and broader subcellular distribution in vitro and also improved accumulation in both the tumor mass and tumor-associated blood vessels following intravenous injection into mice. Furthermore, stable and targeted micelles inhibited the growth of subcutaneous HeLa tumor models and demonstrated gene silencing in the tumor mass following treatment with antiangiogenic siRNAs. This new micellar nanomedicine could potentially expand the utility of siRNA-based therapies for cancer treatments that require intravenous injection.

  18. Ocean Chlorophyll Studies from a U-2 Aircraft Platform

    NASA Technical Reports Server (NTRS)

    Kim, H. H.; Mcclain, C. R.; Blaine, L. R.; Hart, W. D.; Atkinson, L. P.; Yoder, J. A.

    1979-01-01

    Chlorophyll gradient maps of large ocean areas were generated from U-2 ocean color scanner data obtained over test sites in the Pacific and Atlantic Oceans. The delineation of oceanic features using the upward radiant intensity relies on an analysis method which presupposes that radiation backscattered from the atmosphere and ocean surface can be properly modeled using a measurement made at 778 nm. An estimation of the chlorophyll concentration was performed by properly ratioing radiances measured at 472 nm and 548 nm after removing the atmospheric effects. The correlation between the remotely sensed data and in-situ surface chlorophyll measurements was validated in two sets of data. The results show that the correlation between the in-situ measured chlorophyll and the derived quantity is a negative exponential function and the correlation coefficient was calculated to be -0.965.

  19. Sphere-to-rod transition of non-surface-active amphiphilic diblock copolymer micelles: a small-angle neutron scattering study.

    PubMed

    Kaewsaiha, Ploysai; Matsumoto, Kozo; Matsuoka, Hideki

    2007-08-28

    Micellization behavior of amphiphilic diblock copolymers with strong acid groups, poly(hydrogenated isoprene)-block-poly(styrenesulfonate), was investigated by small-angle neutron scattering (SANS). We have reported previously (Kaewsaiha, P.; Matsumoto, K.; Matsuoka, H. Langmuir 2005, 21, 9938) that this strongly ionic amphiphilic diblock copolymer shows almost no surface activity but forms micelles in water. In this study, the size, shape, and internal structures of the micelles formed by these unique copolymers in aqueous solution were duly investigated. The SANS data were well described by the theoretical form factor of a core-shell model and the Pedersen core-corona model. The micellar shape strongly depends on the hydrophobic chain length of the block copolymer. The polymer with the shortest hydrophobic chain was suggested to form spherical micelles, whereas the scattering curves of the longer hydrophobic chain polymers showed a q-1 dependence, reflecting the formation of rodlike micelles. Furthermore, the addition of salt at high concentration also induced the sphere-to-rod transition in micellar shape as a result of the shielding effect of electrostatic repulsion. The corona thickness was almost constant up to the critical salt concentration (around 0.2 M) and then decreased with further increases in salt concentration, which is in qualitatively agreement with existing theories. The spherical/rodlike micelle ratio was also constant up to the critical salt concentration and then decreased. The micelle size and shape of this unique polymer could be described by the common concept of the packing parameter, but the anomalously stable nature of the micelle (up to 1 M NaCl) is a special characteristic.

  20. κ-Casein terminates casein micelle build-up by its "soft" secondary structure.

    PubMed

    Nagy, Krisztina; Váró, György; Szalontai, Balázs

    2012-11-01

    In our previous paper (Nagy et al. in J Biol Chem 285:38811-38817, 2010) by using a multilayered model system, we showed that, from α-casein, aggregates (similar to natural casein micelles) can be built up step by step if Ca-phosphate nanocluster incorporation is ensured between the protein adsorption steps. It remained, however, an open question whether the growth of the aggregates can be terminated, similarly to in nature with casein micelles. Here, we show that, in the presence of Ca-phosphate nanoclusters, upon adsorbing onto earlier α-casein surfaces, the secondary structure of α-casein remains practically unaffected, but κ-casein exhibits considerable changes in its secondary structure as manifested by a shift toward having more β-structures. In the absence of Ca-phosphate, only κ-casein can still adsorb onto the underlying casein surface; this κ-casein also expresses considerable shift toward β-structures. In addition, this κ-casein cover terminates casein aggregation; no further adsorption of either α- or κ-casein can be achieved. These results, while obtained on a model system, may show that the Ca-insensitive κ-casein can, indeed, be the outer layer of the casein micelles, not only because of its "hairy" extrusion into the water phase, but because of its "softer" secondary structure, which can "occlude" the interacting motifs serving casein aggregation. We think that the revealed nature of the molecular interactions, and the growth mechanism found here, might be useful to understand the aggregation process of casein micelles also in vivo.

  1. Multifunctional Micelles Dually Responsive to Hypoxia and Singlet Oxygen: Enhanced Photodynamic Therapy via Interactively Triggered Photosensitizer Delivery.

    PubMed

    Li, Juanjuan; Meng, Xuan; Deng, Jian; Lu, Di; Zhang, Xin; Chen, Yanrui; Zhu, Jundong; Fan, Aiping; Ding, Dan; Kong, Deling; Wang, Zheng; Zhao, Yanjun

    2018-05-23

    Nanoparticulate antitumor photodynamic therapy (PDT) has been suffering from the limited dose accumulation in tumor. Herein, we report dually hypoxia- and singlet oxygen-responsive polymeric micelles to efficiently utilize the photosensitizer deposited in the disease site and hence facilely improve PDT's antitumor efficacy. Tailored methoxy poly(ethylene glycol)-azobenzene-poly(aspartic acid) copolymer conjugate with imidazole as the side chains was synthesized. The conjugate micelles (189 ± 19 nm) obtained by self-assembly could efficiently load a model photosensitizer, chlorin e6 (Ce6) with a loading of 4.1 ± 0.5% (w/w). The facilitated cellular uptake of micelles was achieved by the triggered azobenzene collapse that provoked poly(ethylene glycol) shedding; rapid Ce6 release was enabled by imidazole oxidation that induced micelle disassembly. In addition, the singlet oxygen-mediated cargo release not only addressed the limited diffusion range and short half-life of singlet oxygen but also decreased the oxygen level, which could in turn enhance internalization and increase the intracellular Ce6 concentration. The hypoxia-induced dePEGylation and singlet oxygen-triggered Ce6 release was demonstrated both in aqueous buffer and in Lewis lung carcinoma (LLC) cells. The cellular uptake study demonstrated that the dually responsive micelles could deliver significantly more Ce6 to the cells, which resulted in a substantially improved cytotoxicity. This concurred well with the superior in vivo antitumor ability of micelles in a LLC tumor-bearing mouse model. This study presented an intriguing nanoplatform to realize interactively triggered photosensitizer delivery and improved antitumor PDT efficacy.

  2. Preclinical safety evaluation of intravenously administered mixed micelles.

    PubMed

    Teelmann, K; Schläppi, B; Schüpbach, M; Kistler, A

    1984-01-01

    Mixed micelles, with their main constituents lecithin and glycocholic acid, form a new principle for the parenteral administration of compounds which are poorly water-soluble. Their composition of mainly physiological substances as well as their comparatively good stability substantiate their attractivity in comparison to existing solvents. A decomposition due to physical influences such as heat or storage for several years will almost exclusively affect the lecithin component in the form of hydrolysis into free fatty acids and lysolecithin. Their toxicity was examined experimentally in various studies using both undecomposed and artificially decomposed mixed micelles. In these studies the mixed micelles were locally and systemically well tolerated and proved to be neither embryotoxic, teratogenic nor mutagenic. Only when comparatively high doses of the undecomposed mixed micelles were administered, corresponding to approximately 30 to 50 times the anticipated clinical injection volume (of e.g. diazepam mixed micelles), did some vomitus (dogs), slight liver enzyme elevation (rats and dogs), and slightly increased liver weights (dogs) occur. After repeated injections of the artificially decomposed formulation (approximately 25% of lecithin hydrolyzed to free fatty acids and lysolecithin) effects such as intravascular haemolysis, liver enzyme elevations and intrahepatic cholestasis (dogs only) were observed but only when doses exceeding a threshold of approximately 40 to 60 mg lysolecithin/kg body weight were administered. All alterations were reversible after cessation of treatment.

  3. Multifunctional polymeric micelles for delivery of drugs and siRNA

    PubMed Central

    Jhaveri, Aditi M.; Torchilin, Vladimir P.

    2014-01-01

    Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend toward designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to “smart,” multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA). The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs. PMID:24795633

  4. The role of non-covalent interactions in anticancer drug loading and kinetic stability of polymeric micelles.

    PubMed

    Yang, Chuan; Attia, Amalina B Ebrahim; Tan, Jeremy P K; Ke, Xiyu; Gao, Shujun; Hedrick, James L; Yang, Yi-Yan

    2012-04-01

    A new series of acid- and urea-functionalized polycarbonate block copolymers were synthesized via organocatalytic living ring-opening polymerization using methoxy poly(ethylene glycol) (PEG) as a macroinitiator to form micelles as drug delivery carriers. The micelles were characterized for critical micelle concentration, particle size and size distribution, kinetic stability and loading capacity for a model anticancer drug, doxorubicin (DOX) having an amine group. The acid/urea groups were placed in block forms (i.e. acid as the middle block or the end block) or randomly distributed in the polycarbonate block to investigate molecular structure effect. The micelles formed from the polymers in both random and block forms provided high drug loading capacity due to strong ionic interaction between the acid in the polymer and the amine in DOX. However, the polymers with acid and urea groups placed in the block forms formed micelles with wider size distribution (two size populations), and their DOX-loaded micelles were less stable. The number of acid/urea groups in the random form was further varied from 5 to 8, 13 and 19 to study its effects on self-assembly behaviors and DOX loading. An increased number of acid/urea groups yielded DOX-loaded micelles with smaller size and enhanced kinetic stability because of improved inter-molecular polycarbonate-polycarbonate (urea-urea and urea-acid) hydrogen-bonding and polycarbonate-DOX (acid-amine) ionic interactions. However, when the number of acid/urea groups was 13 or higher, micelles aggregated in a serum-containing medium, and freeze-dried DOX-loaded micelles were unable to re-disperse in an aqueous solution. Among all the polymers synthesized in this study, 1b with 8 acid/urea groups in the random form had the optimum properties. In vitro release studies showed that DOX release from 1b micelles was sustained over 7 h without significant initial burst release. MTT assays demonstrated that the polymer was not toxic towards

  5. A 1H-n.m.r. study of casein micelles.

    PubMed Central

    Griffin, M C; Roberts, G C

    1985-01-01

    The 1H-n.m.r. spectrum of casein micelles consists of a small number of moderately sharp (linewidth approx. 60 Hz) resonances superimposed on the envelope of very broad lines expected for particles of this size. These sharp lines resemble, in chemical shift and relative intensity, the spectrum of the isolated 'macropeptide' released from the micelles by treatment with chymosin. The sharp lines in the casein micelle spectrum are further sharpened by addition of chymosin and broadened markedly by addition of ethanol. These observations are consistent with the proposal that the 'macropeptide' (the C-terminal 64 residues of K-casein) forms flexible 'hairs' on the surface of the micelles. PMID:3924034

  6. Process of forming compounds using reverse micelle or reverse microemulsion systems

    DOEpatents

    Linehan, John C.; Fulton, John L.; Bean, Roger M.

    1998-01-01

    The present invention is directed to a process for producing a nanometer-sized metal compound. The process comprises forming a reverse micelle or reverse microemulsion system comprising a polar fluid in a non-polar or low-polarity fluid. A first reactant comprising a multi-component, water-soluble metal compound is introduced into the polar fluid in a non-polar or low-polarity fluid. This first reactant can be introduced into the reverse micelle or reverse microemulsion system during formation thereof or subsequent to the formation of the reverse micelle or microemulsion system. The water-soluble metal compound is then reacted in the reverse micelle or reverse microemulsion system to form the nanometer-sized metal compound. The nanometer-sized metal compound is then precipitated from the reverse micelle or reverse microemulsion system.

  7. Core-Crosslinked Polymeric Micelles: Principles, Preparation, Biomedical Applications and Clinical Translation

    PubMed Central

    Rijcken, Cristianne J.; Kiessling, Fabian; Hennink, Wim E.; Lammers, Twan

    2015-01-01

    Polymeric micelles (PM) are extensively used to improve the delivery of hydrophobic drugs. Many different PM have been designed and evaluated over the years, and some of them have steadily progressed through clinical trials. Increasing evidence suggests, however, that for prolonged circulation times and for efficient EPR-mediated drug targeting to tumors and to sites of inflammation, PM need to be stabilized, to prevent premature disintegration. Core-crosslinking is among the most popular methods to improve the in vivo stability of PM, and a number of core-crosslinked polymeric micelles (CCPM) have demonstrated promising efficacy in animal models. The latter is particularly true for CCPM in which (pro−) drugs are covalently entrapped. This ensures proper drug retention in the micelles during systemic circulation, efficient drug delivery to pathological sites via EPR, and tailorable drug release kinetics at the target site. We here summarize recent advances in the CCPM field, addressing the chemistry involved in preparing them, their in vitro and in vivo performance, potential biomedical applications, and guidelines for efficient clinical translation. PMID:25893004

  8. PEG-b-PCL polymeric nano-micelle inhibits vascular angiogenesis by activating p53-dependent apoptosis in zebrafish

    PubMed Central

    Zhou, Tian; Dong, Qinglei; Shen, Yang; Wu, Wei; Wu, Haide; Luo, Xianglin; Liao, Xiaoling; Wang, Guixue

    2016-01-01

    Micro/nanoparticles could cause adverse effects on cardiovascular system and increase the risk for cardiovascular disease-related events. Nanoparticles prepared from poly(ethylene glycol) (PEG)-b-poly(ε-caprolactone) (PCL), namely PEG-b-PCL, a widely studied biodegradable copolymer, are promising carriers for the drug delivery systems. However, it is unknown whether polymeric PEG-b-PCL nano-micelles give rise to potential complications of the cardiovascular system. Zebrafish were used as an in vivo model to evaluate the effects of PEG-b-PCL nano-micelle on cardiovascular development. The results showed that PEG-b-PCL nano-micelle caused embryo mortality as well as embryonic and larval malformations in a dose-dependent manner. To determine PEG-b-PCL nano-micelle effects on embryonic angiogenesis, a critical process in zebrafish cardiovascular development, growth of intersegmental vessels (ISVs) and caudal vessels (CVs) in flk1-GFP transgenic zebrafish embryos using fluorescent stereomicroscopy were examined. The expression of fetal liver kinase 1 (flk1), an angiogenic factor, by real-time quantitative polymerase chain reaction (qPCR) and in situ whole-mount hybridization were also analyzed. PEG-b-PCL nano-micelle decreased growth of ISVs and CVs, as well as reduced flk1 expression in a concentration-dependent manner. Parallel to the inhibitory effects on angiogenesis, PEG-b-PCL nano-micelle exposure upregulated p53 pro-apoptotic pathway and induced cellular apoptosis in angiogenic regions by qPCR and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay. This study further showed that inhibiting p53 activity, either by pharmacological inhibitor or RNA interference, could abrogate the apoptosis and angiogenic defects caused by PEG-b-PCL nano-micelles, indicating that PEG-b-PCL nano-micelle inhibits angiogenesis by activating p53-mediated apoptosis. This study indicates that polymeric PEG-b-PCL nano-micelle could pose potential hazards

  9. PEG-b-PCL polymeric nano-micelle inhibits vascular angiogenesis by activating p53-dependent apoptosis in zebrafish.

    PubMed

    Zhou, Tian; Dong, Qinglei; Shen, Yang; Wu, Wei; Wu, Haide; Luo, Xianglin; Liao, Xiaoling; Wang, Guixue

    Micro/nanoparticles could cause adverse effects on cardiovascular system and increase the risk for cardiovascular disease-related events. Nanoparticles prepared from poly(ethylene glycol) (PEG)- b -poly( ε -caprolactone) (PCL), namely PEG- b -PCL, a widely studied biodegradable copolymer, are promising carriers for the drug delivery systems. However, it is unknown whether polymeric PEG- b -PCL nano-micelles give rise to potential complications of the cardiovascular system. Zebrafish were used as an in vivo model to evaluate the effects of PEG- b -PCL nano-micelle on cardiovascular development. The results showed that PEG- b -PCL nano-micelle caused embryo mortality as well as embryonic and larval malformations in a dose-dependent manner. To determine PEG- b -PCL nano-micelle effects on embryonic angiogenesis, a critical process in zebrafish cardiovascular development, growth of intersegmental vessels (ISVs) and caudal vessels (CVs) in flk1-GFP transgenic zebrafish embryos using fluorescent stereomicroscopy were examined. The expression of fetal liver kinase 1 (flk1), an angiogenic factor, by real-time quantitative polymerase chain reaction (qPCR) and in situ whole-mount hybridization were also analyzed. PEG- b -PCL nano-micelle decreased growth of ISVs and CVs, as well as reduced flk1 expression in a concentration-dependent manner. Parallel to the inhibitory effects on angiogenesis, PEG- b -PCL nano-micelle exposure upregulated p53 pro-apoptotic pathway and induced cellular apoptosis in angiogenic regions by qPCR and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay. This study further showed that inhibiting p53 activity, either by pharmacological inhibitor or RNA interference, could abrogate the apoptosis and angiogenic defects caused by PEG- b -PCL nano-micelles, indicating that PEG- b -PCL nano-micelle inhibits angiogenesis by activating p53-mediated apoptosis. This study indicates that polymeric PEG- b -PCL nano-micelle could

  10. Estimating chlorophyll content of spartina alterniflora at leaf level using hyper-spectral data

    NASA Astrophysics Data System (ADS)

    Wang, Jiapeng; Shi, Runhe; Liu, Pudong; Zhang, Chao; Chen, Maosi

    2017-09-01

    Spartina alterniflora, one of most successful invasive species in the world, was firstly introduced to China in 1979 to accelerate sedimentation and land formation via so-called "ecological engineering", and it is now widely distributed in coastal saltmarshes in China. A key question is how to retrieve chlorophyll content to reflect growth status, which has important implication of potential invasiveness. In this work, an estimation model of chlorophyll content of S. alterniflora was developed based on hyper-spectral data in the Dongtan Wetland, Yangtze Estuary, China. The spectral reflectance of S. alterniflora leaves and their corresponding chlorophyll contents were measured, and then the correlation analysis and regression (i.e., linear, logarithmic, quadratic, power and exponential regression) method were established. The spectral reflectance was transformed and the feature parameters (i.e., "san bian", "lv feng" and "hong gu") were extracted to retrieve the chlorophyll content of S. alterniflora . The results showed that these parameters had a large correlation coefficient with chlorophyll content. On the basis of the correlation coefficient, mathematical models were established, and the models of power and exponential based on SDb had the least RMSE and larger R2 , which had a good performance regarding the inversion of chlorophyll content of S. alterniflora.

  11. Structure of block copolymer micelles in the presence of co-solvents

    NASA Astrophysics Data System (ADS)

    Robertson, Megan; Wang, Shu; Le, Kim Mai; Piemonte, Rachele; Madsen, Louis

    2015-03-01

    Amphiphilic block copolymer micelles in water are under broad exploration for drug delivery applications due to their high loading capacity and targeted drug delivery. We aim to understand the kinetic and thermodynamic processes that underlie the self-assembly of diblock copolymer micelle systems. The present work focuses on diblock copolymers containing poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic polymer), which spontaneously self-assemble into spherical micelles in water. Addition of a common good solvent (a co-solvent) for both of the constituting blocks, such as tetrahydrofuran (THF), reduces the interfacial tension at the core-corona interface. We are currently investigating the effect of this phenomenon on the micelle structural properties, using scattering experiments and nuclear magnetic resonance. We have characterized the hydrodynamic radius, core radius, corona thickness, aggregation number, degree of swelling of the micelle core with the co-solvent, and unimer (free chain) concentration, as a function of the co-solvent concentration. Fundamental knowledge from these studies will inform design of drug delivery systems by allowing us to tailor micelle properties for optimal cargo loading.

  12. Physical characterization and antioxidant activity of thymol solubilized Tween 80 micelles

    PubMed Central

    Deng, Ling-Li; Taxipalati, Maierhaba; Que, Fei; Zhang, Hui

    2016-01-01

    Attempts were made to solubilize thymol in Tween 80 micelle to study the solubilization mechanism of thymol and the effect of solubilization on its antioxidant activity. The maximum solubilized concentration of thymol in a 2.0% (w/v) Tween 80 micelle solution is 0.2 wt%. There was no significant difference in Z-average diameter between the empty micelles and thymol solubilized micelles. 1H NMR spectra indicated that 3-H and 4-H on the benzene ring of thymol interacted with the ester group between the hydrophilic head group and the hydrophobic tail group of Tween 80 by Van der Waals’ force. Ferric reducing antioxidant potential (FRAP) and cupric ion reducing antioxidant capacity (CUPRAC) assays showed that the reducing antioxidant activity of free thymol did not change after solubilized in Tween 80 micelles. Compared to free thymol, the solubilized thymol showed higher activities to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. The present study suggested a possible preparation of thymol-carrying micelles with enhanced antioxidant activities that could be applied in food beverages. PMID:27905567

  13. Physical characterization and antioxidant activity of thymol solubilized Tween 80 micelles.

    PubMed

    Deng, Ling-Li; Taxipalati, Maierhaba; Que, Fei; Zhang, Hui

    2016-12-01

    Attempts were made to solubilize thymol in Tween 80 micelle to study the solubilization mechanism of thymol and the effect of solubilization on its antioxidant activity. The maximum solubilized concentration of thymol in a 2.0% (w/v) Tween 80 micelle solution is 0.2 wt%. There was no significant difference in Z-average diameter between the empty micelles and thymol solubilized micelles. 1 H NMR spectra indicated that 3-H and 4-H on the benzene ring of thymol interacted with the ester group between the hydrophilic head group and the hydrophobic tail group of Tween 80 by Van der Waals' force. Ferric reducing antioxidant potential (FRAP) and cupric ion reducing antioxidant capacity (CUPRAC) assays showed that the reducing antioxidant activity of free thymol did not change after solubilized in Tween 80 micelles. Compared to free thymol, the solubilized thymol showed higher activities to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. The present study suggested a possible preparation of thymol-carrying micelles with enhanced antioxidant activities that could be applied in food beverages.

  14. Physical characterization and antioxidant activity of thymol solubilized Tween 80 micelles

    NASA Astrophysics Data System (ADS)

    Deng, Ling-Li; Taxipalati, Maierhaba; Que, Fei; Zhang, Hui

    2016-12-01

    Attempts were made to solubilize thymol in Tween 80 micelle to study the solubilization mechanism of thymol and the effect of solubilization on its antioxidant activity. The maximum solubilized concentration of thymol in a 2.0% (w/v) Tween 80 micelle solution is 0.2 wt%. There was no significant difference in Z-average diameter between the empty micelles and thymol solubilized micelles. 1H NMR spectra indicated that 3-H and 4-H on the benzene ring of thymol interacted with the ester group between the hydrophilic head group and the hydrophobic tail group of Tween 80 by Van der Waals’ force. Ferric reducing antioxidant potential (FRAP) and cupric ion reducing antioxidant capacity (CUPRAC) assays showed that the reducing antioxidant activity of free thymol did not change after solubilized in Tween 80 micelles. Compared to free thymol, the solubilized thymol showed higher activities to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. The present study suggested a possible preparation of thymol-carrying micelles with enhanced antioxidant activities that could be applied in food beverages.

  15. Cryo-transmission electron tomography of native casein micelles from bovine milk.

    PubMed

    Trejo, R; Dokland, T; Jurat-Fuentes, J; Harte, F

    2011-12-01

    Caseins are the principal protein components in milk and an important ingredient in the food industry. In liquid milk, caseins are found as micelles of casein proteins and colloidal calcium nanoclusters. Casein micelles were isolated from raw skim milk by size exclusion chromatography and suspended in milk protein-free serum produced by ultrafiltration (molecular weight cut-off of 3 kDa) of raw skim milk. The micelles were imaged by cryo-electron microscopy and subjected to tomographic reconstruction methods to visualize the 3-dimensional and internal organization of native casein micelles. This provided new insights into the internal architecture of the casein micelle that had not been apparent from prior cryo-transmission electron microscopy studies. This analysis demonstrated the presence of water-filled cavities (∼20 to 30 nm in diameter), channels (diameter greater than ∼5 nm), and several hundred high-density nanoclusters (6 to 12 nm in diameter) within the interior of the micelles. No spherical protein submicellar structures were observed. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Influencing the structure of block copolymer micelles with small molecule additives

    NASA Astrophysics Data System (ADS)

    Robertson, Megan; Singh, Avantika; Cooksey, Tyler; Kidd, Bryce; Piemonte, Rachele; Wang, Shu; Mai Le, Kim; Madsen, Louis

    Amphiphilic block copolymer micelles in water are under broad exploration for drug delivery applications due to their high loading capacity and targeted drug delivery. We aim to understand the kinetic and thermodynamic processes that underlie the self-assembly of diblock copolymer micelle systems. The present work focuses on diblock copolymers containing poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic polymer), which spontaneously self-assemble into spherical micelles in water. Addition of a common good solvent (a co-solvent) for both of the constituting blocks, such as tetrahydrofuran (THF), reduces the interfacial tension at the core-corona interface. We are currently investigating the effect of this phenomenon on the micelle structural properties, using small-angle scattering and nuclear magnetic resonance. We have characterized the hydrodynamic radius, core radius, corona thickness, aggregation number, degree of swelling of the micelle core with the co-solvent, and unimer (free chain) concentration, as a function of the co-solvent concentration. Fundamental knowledge from these studies will inform design of drug delivery systems by allowing us to tailor micelle properties for optimal cargo loading.

  17. Development of FT-NIR Models for the Simultaneous Estimation of Chlorophyll and Nitrogen Content in Fresh Apple (Malus Domestica) Leaves

    PubMed Central

    Tamburini, Elena; Ferrari, Giuseppe; Marchetti, Maria Gabriella; Pedrini, Paola; Ferro, Sergio

    2015-01-01

    Agricultural practices determine the level of food production and, to great extent, the state of the global environment. During the last decades, the indiscriminate recourse to fertilizers as well as the nitrogen losses from land application have been recognized as serious issues of modern agriculture, globally contributing to nitrate pollution. The development of a reliable Near-Infra-Red Spectroscopy (NIRS)-based method, for the simultaneous monitoring of nitrogen and chlorophyll in fresh apple (Malus domestica) leaves, was investigated on a set of 133 samples, with the aim of estimating the nutritional and physiological status of trees, in real time, cheaply and non-destructively. By means of a FT (Fourier Transform)-NIR instrument, Partial Least Squares (PLS) regression models were developed, spanning a concentration range of 0.577%–0.817% for the total Kjeldahl nitrogen (TKN) content (R2 = 0.983; SEC = 0.012; SEP = 0.028), and of 1.534–2.372 mg/g for the total chlorophyll content (R2 = 0.941; SEC = 0.132; SEP = 0.162). Chlorophyll-a and chlorophyll-b contents were also evaluated (R2 = 0.913; SEC = 0.076; SEP = 0.101 and R2 = 0.899; SEC = 0.059; SEP = 0.101, respectively). All calibration models were validated by means of 47 independent samples. The NIR approach allows a rapid evaluation of the nitrogen and chlorophyll contents, and may represent a useful tool for determining nutritional and physiological status of plants, in order to allow a correction of nutrition programs during the season. PMID:25629703

  18. Improving Global Models of Remotely Sensed Ocean Chlorophyll Content Using Partial Least Squares and Geographically Weighted Regression

    NASA Astrophysics Data System (ADS)

    Gholizadeh, H.; Robeson, S. M.

    2015-12-01

    Empirical models have been widely used to estimate global chlorophyll content from remotely sensed data. Here, we focus on the standard NASA empirical models that use blue-green band ratios. These band ratio ocean color (OC) algorithms are in the form of fourth-order polynomials and the parameters of these polynomials (i.e. coefficients) are estimated from the NASA bio-Optical Marine Algorithm Data set (NOMAD). Most of the points in this data set have been sampled from tropical and temperate regions. However, polynomial coefficients obtained from this data set are used to estimate chlorophyll content in all ocean regions with different properties such as sea-surface temperature, salinity, and downwelling/upwelling patterns. Further, the polynomial terms in these models are highly correlated. In sum, the limitations of these empirical models are as follows: 1) the independent variables within the empirical models, in their current form, are correlated (multicollinear), and 2) current algorithms are global approaches and are based on the spatial stationarity assumption, so they are independent of location. Multicollinearity problem is resolved by using partial least squares (PLS). PLS, which transforms the data into a set of independent components, can be considered as a combined form of principal component regression (PCR) and multiple regression. Geographically weighted regression (GWR) is also used to investigate the validity of spatial stationarity assumption. GWR solves a regression model over each sample point by using the observations within its neighbourhood. PLS results show that the empirical method underestimates chlorophyll content in high latitudes, including the Southern Ocean region, when compared to PLS (see Figure 1). Cluster analysis of GWR coefficients also shows that the spatial stationarity assumption in empirical models is not likely a valid assumption.

  19. Designing Mixed Detergent Micelles for Uniform Neutron Contrast

    DOE PAGES

    Oliver, Ryan C.; Pingali, Sai Venkatesh; Urban, Volker S.

    2017-09-29

    Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) performed at the neutron contrast match point of detergent molecules allows observing the scattering signal from membrane proteins unobstructed by contributions from the detergent. However, we show here that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal at the average detergent contrast match point interferes with interpreting structural datamore » of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. Here, we present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell, and allows the micelle scattering to be fully contrast matched to unambiguously resolve membrane protein structure using solution SANS.« less

  20. Designing Mixed Detergent Micelles for Uniform Neutron Contrast

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oliver, Ryan C.; Pingali, Sai Venkatesh; Urban, Volker S.

    Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) performed at the neutron contrast match point of detergent molecules allows observing the scattering signal from membrane proteins unobstructed by contributions from the detergent. However, we show here that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal at the average detergent contrast match point interferes with interpreting structural datamore » of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. Here, we present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell, and allows the micelle scattering to be fully contrast matched to unambiguously resolve membrane protein structure using solution SANS.« less

  1. Preparation and in vivo/in vitro evaluation of formononetin phospholipid/vitamin E TPGS micelles.

    PubMed

    Cheng, Xudong; Yan, Hongmei; Jia, Xiaobin; Zhang, Zhenhai

    2016-01-01

    To enhance the formononetin (FN) antitumor effect, we developed a passive targeting FN-contained formulation. FN-contained Vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS)/phospholipid micelles were prepared by the solvent injection method. Particle size, polydispersity, zeta potential, encapsulation efficiency, drug release profile, and micelles morphology were evaluated and characterized by various methods including high-performance liquid chromatography, dynamic light scattering, and transmission electron microscopy. Cellular uptake of micelles was evaluated with fluorescence imaging coupled with HPLC method. Cytotoxicity of FN micelles and free FN was compared using MTT method. In vivo imaging was employed to assess the accumulation of DiR micelles and free DiR at tumor site. The antitumor effect of FN micelles was examined in tumor-bearing mice. The results showed that prepared FN micelles had an average particle diameter of 111.91 ± 5.82 nm with good stability. FN micelles enhanced the cellular uptake and improved cell cytotoxicity than free FN. Furthermore, DiR micelles quickly accumulated at the tumor site than free DiR. FN micelles significantly improved tumor inhibition rate compared to that observed with free FN in tumor-bearing mice with great biosafety. Thus, FN micelles demonstrated a clear treatment advantage and provided an ideal drug administration system to improve the antitumor effect of FN.

  2. Acyl chain unsaturation modulates distribution of lecithin molecular species between mixed micelles and vesicles in model bile. Implications for particle structure and metastable cholesterol solubilities.

    PubMed

    Cohen, D E; Carey, M C

    1991-08-01

    We determined the distribution of lecithin molecular species between vesicles and mixed micelles in cholesterol super-saturated model biles (molar taurocholate-lecithin-cholesterol ratio 67:23:10, 3 g/dl, 0.15 M NaCl, pH approximately 6-7) that contained equimolar synthetic lecithin mixtures or egg yolk or soybean lecithins. After apparent equilibration (48 h), biles were fractionated by Superose 6 gel filtration chromatography at 20 degrees C, and lecithin molecular species in the vesicle and mixed micellar fractions were quantified as benzoyl diacylglycerides by high performance liquid chromatography. With binary lecithin mixtures, vesicles were enriched with lecithins containing the most saturated sn-1 or sn-2 chains by as much as 2.4-fold whereas mixed micelles were enriched in the more unsaturated lecithins. Vesicles isolated from model biles composed of egg yolk (primarily sn-1 16:0 and 18:0 acyl chains) or soy bean (mixed saturated and unsaturated sn-1 acyl chains) lecithins were selectively enriched (6.5-76%) in lecithins with saturated sn-1 acyl chains whereas mixed micelles were enriched with lecithins composed of either sn-1 18:1, 18:2, and 18:3 unsaturated or sn-2 20:4, 22:4, and 22:6 polyunsaturated chains. Gel filtration, lipid analysis, and quasielastic light scattering revealed that apparent micellar cholesterol solubilities and metastable vesicle cholesterol/lecithin molar ratios were as much as 60% and 100% higher, respectively, in biles composed of unsaturated lecithins. Acyl chain packing constraints imposed by distinctly different particle geometries most likely explain the asymmetric distribution of lecithin molecular species between vesicles and mixed micelles in model bile as well as the variations in apparent micellar cholesterol solubilities and vesicle cholesterol/lecithin molar ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Fisetin and polymeric micelles encapsulating fisetin exhibit potent cytotoxic effects towards ovarian cancer cells.

    PubMed

    Xiao, Xue; Zou, Juan; Fang, Yin; Meng, Yibo; Xiao, Chao; Fu, Jiaxin; Liu, Shiyu; Bai, Peng; Yao, Yuan

    2018-03-15

    The anti-tumor activities of Natural compounds and their derivatives are of great interest to pharmaceutical industries. Fisetin is one of prospective natural compounds in this regard but unfortunately with poor hydrophilicity. The effects of unmodified and modified fisetin in cultured ovarian cancer cells were compared by transmission electronmicroscopy to determine apoptotic bodies, MTT assay to quantitate cell numbers, and fluorescence activated cell sorting analyse of various markers to determine the apoptotic state. In addition, the efficacy of fisetin and fisetin-micelles in vivo was determined by using immunocompromised mice. Apoptosis was measured by established markers using both western blot analysis and immunochemistry. Angiogenesis in a xenograft mouse model carring SKOV3 cells was evaluated by color Doppler ultrasound and immunohistochemistry. Multiple lines of evidence indicated that fisetin and fisetin micelles induce apoptosis in ovarian cancer cells in a dose-dependent manner. Histological analysis, terminal deoxynucleotidyltransferase-mediated nick-end labeling assay, western blot, immunohistochemical detection and microvessel density detection demonstrated that fisetin and fisetin micelles induced increased tumor apoptosis, proliferation suppression and antiangiogenesis activities. As far as we know, the present study is the first time to demonstrate the potency of both fisetin and fisetin micelles inducing apoptosis in ovarian cancer cells. Further studies will be needed to validate the therapeutic potential of fisetin and fisetin micelles in ovarian cancer treatment.

  4. High-frequency ultrasound-responsive block copolymer micelle.

    PubMed

    Wang, Jie; Pelletier, Maxime; Zhang, Hongji; Xia, Hesheng; Zhao, Yue

    2009-11-17

    Micelles of a diblock copolymer composed of poly(ethylene oxide) and poly(2-tetrahydropyranyl methacrylate) (PEO-b-PTHPMA) in aqueous solution could be disrupted by high-frequency ultrasound (1.1 MHz). It was found that, upon exposure to a high-intensity focused ultrasound (HIFU) beam at room temperature, the pH value of the micellar solution decreased over irradiation time. The infrared spectroscopic analysis of solid block copolymer samples collected from the ultrasound irradiated micellar solution revealed the formation of carboxylic acid dimers and hydroxyl groups. These characterization results suggest that the high-frequency HIFU beam could induce the hydrolysis reaction of THPMA at room temperature resulting in the cleavage of THP groups. The disruption of PEO-b-PTHPMA micelles by ultrasound was investigated by using dynamic light scattering, atomic force microscopy, and fluorescence spectroscopy. On the basis of the pH change, it was found that the disruption process was determined by a number of factors such as the ultrasound power, the micellar solution volume and the location of the focal spot of the ultrasound beam. This study shows the potential to develop ultrasound-sensitive block copolymer micelles by having labile chemical bonds in the polymer structure, and to use the high-frequency HIFU to trigger a chemical reaction for the disruption of micelles.

  5. Chlorophyll f and chlorophyll d are produced in the cyanobacterium Chlorogloeopsis fritschii when cultured under natural light and near-infrared radiation.

    PubMed

    Airs, R L; Temperton, B; Sambles, C; Farnham, G; Skill, S C; Llewellyn, C A

    2014-10-16

    We report production of chlorophyll f and chlorophyll d in the cyanobacterium Chlorogloeopsis fritschii cultured under near-infrared and natural light conditions. C. fritschii produced chlorophyll f and chlorophyll d when cultured under natural light to a high culture density in a 20 L bubble column photobioreactor. In the laboratory, the ratio of chlorophyll f to chlorophyll a changed from 1:15 under near-infrared, to an undetectable level of chlorophyll f under artificial white light. The results provide support that chlorophylls f and d are both red-light inducible chlorophylls in C. fritschii. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  6. Hydrotropic polymer micelles containing acrylic acid moieties for oral delivery of paclitaxel

    PubMed Central

    Kim, Sungwon; Kim, Ji Young; Huh, Kang Moo; Acharya, Ghanshyam; Park, Kinam

    2008-01-01

    Hydrotropic polymers (HPs) and their micelles have been recently developed as vehicles for delivery of poorly water-soluble drugs, such as paclitaxel (PTX), by oral administration. The release of PTX from HP micelles, however, was slow and it took more than a day for complete release of the loaded PTX. Since the gastrointestinal (GI) transit time is known to be only several hours, pH-sensitive HP micelles were prepared for fast release of the loaded PTX responding to pH changes along the GI tract. Acrylic acid (AA) was introduced, as a release modulator, into HPs by copolymerization with 4-(2-vinylbenzyloxy)-N,N-(diethylnicotinamide) (VBODENA). The AA content was varied from 0% to 50 % (in the molar ratio to VBODENA). HPs spontaneously produced micelles in water, and their critical micelle concentrations (CMCs) ranged from 31 μg/mL to 86 μg/mL. Fluorescence probe study using pyrene showed that blank HP micelles possessed a good pH-sensitivity, which was clearly observed at relatively high AA contents and pH > 6. The pH sensitivity also affected the PTX loading property. Above pH 5, the PTX loading content and loading efficiency in HP micelles were significantly reduced. Although this may be primarily due to the AA moieties, other factors may include PTX degradation and polymer aggregation. The PTX release from HP micelles with more than 20% (mol) AA contents was completed within 12 h in a simulated intestinal fluid (SIF, pH=6.5). The HP micelles without any AA moiety showed very slow release profiles. In the simulated gastric fluid (SGF, pH=1.6), severe degradation of the released PTX was observed. The pH-dependent release of PTX from HP micelles can be used to increase the bioavailability of PTX upon oral delivery. PMID:18672013

  7. Polymeric micelles and nanoemulsions as tumor-targeted drug carriers: Insight through intravital imaging.

    PubMed

    Rapoport, Natalya; Gupta, Roohi; Kim, Yoo-Shin; O'Neill, Brian E

    2015-05-28

    Intravital imaging of nanoparticle extravasation and tumor accumulation has revealed, for the first time, detailed features of carrier and drug behavior in circulation and tissue that suggest new directions for optimization of drug nanocarriers. Using intravital fluorescent microscopy, the extent of the extravasation, diffusion in the tissue, internalization by tissue cells, and uptake by the RES system were studied for polymeric micelles, nanoemulsions, and nanoemulsion-encapsulated drug. Discrimination of vascular and tissue compartments in the processes of micelle and nanodroplet extravasation and tissue accumulation was possible. A simple 1-D continuum model was suggested that allowed discriminating between various kinetic regimes of nanocarrier (or released drug) internalization in tumors of various sizes and cell density. The extravasation and tumor cell internalization occurred much faster for polymeric micelles than for nanoemulsion droplets. Fast micelle internalization resulted in the formation of a perivascular fluorescent coating around blood vessels. A new mechanism of micelle extravasation and internalization was suggested, based on the fast extravasation and internalization rates of copolymer unimers while maintaining micelle/unimer equilibrium in the circulation. The data suggested that to be therapeutically effective, nanoparticles with high internalization rate should manifest fast diffusion in the tumor tissue in order to avoid generation of concentration gradients that induce drug resistance. However an extra-fast diffusion should be avoided as it may result in the flow of extravasated nanoparticles from the tumor to normal organs, which would compromise targeting efficiency. The extravasation kinetics were different for nanodroplets and nanodroplet-encapsulated drug F-PTX suggesting a premature release of some fraction of the drug from the carrier. In conclusion, the development of an "ideal" drug carrier should involve the optimization of both

  8. Lysosome-oriented, dual-stage pH-responsive polymeric micelles for β-Lapachone delivery.

    PubMed

    Zhou, Yinjian; Dong, Ying; Huang, Gang; Wang, Yiguang; Huang, Xiaonan; Zhang, Fayun; Boothman, David A; Gao, Jinming; Liang, Wei

    2016-12-14

    β-Lapachone (β-lap), a novel anticancer agent, is bioactivated by NADP(H):quinone oxidoreductase 1 (NQO1), an enzyme over-expressed in numerous tumors, including lung, pancreas, breast, and prostate cancers. Fast renal clearance and methemaglobinemia / hemolytic side-effects from the clinical formulation (β-lap-hydroxyl propyl-β-cyclodextrin complex) hindered its clinical translation. Here, we investigated a dual model pH responsive polymers for β-lap delivery. Three pH-sensitive linkages, including acylhydrazone, ketal and imine bonds for β-lap prodrug syntheses result in an aryl imine linkage the most optimal linkage. The conversion to β-lap was 2.8%, 4.5% and 100% at pH 7.4, 6.5 and 5.0 in 8 h, respectively. β-lap aryl imine prodrug conjugated ultra pH-sensitive (UPS) polymer reached high β-lap loading density (8.3%) and exhibited dual-stages responsiveness to pH variation. In pHs under pH t , at stage I, micelle immediately dissociation and subsequently entering stage II, micelles start quickly release β-lap. In vitro release study showed that the micelles constantly release β-lap (14.9 ± 0.1%) at pHs above pH t in 72 h, whereas boosted release of β-lap (79.4 ± 1.2%) at pH 5.0. Micelle intracellular distribution predominantly in the lysosome organelle guaranteed their pH responsive dissociation and subsequently β-lap controlled release. The M-P micelles retained NQO1-dependent cytotoxicity in A549 lung cancer cells, similar to free drug in both efficacy and mechanism of cell death. The lysosome-oriented dual-stage ultra pH responsive β-lap prodrug micelles potentially offer an alternative nanotherapeutic strategy for lung, as well as other NQO1+ cancer therapies.

  9. Molecular dynamics simulation of interactions between a sodium dodecyl sulfate micelle and a poly(ethylene oxide) polymer.

    PubMed

    Shang, Barry Z; Wang, Zuowei; Larson, Ronald G

    2008-03-13

    We have performed atomistic molecular dynamics simulations of an anionic sodium dodecyl sulfate (SDS) micelle and a nonionic poly(ethylene oxide) (PEO) polymer in aqueous solution. The micelle consisted of 60 surfactant molecules, and the polymer chain lengths varied from 20 to 40 monomers. The force field parameters for PEO were adjusted by using 1,2-dimethoxymethane (DME) as a model compound and matching its hydration enthalpy and conformational behavior to experiment. Excellent agreement with previous experimental and simulation work was obtained through these modifications. The simulated scaling behavior of the PEO radius of gyration was also in close agreement with experimental results. The SDS-PEO simulations show that the polymer resides on the micelle surface and at the hydrocarbon-water interface, leading to a selective reduction in the hydrophobic contribution to the solvent-accessible surface area of the micelle. The association is mainly driven by hydrophobic interactions between the polymer and surfactant tails, while the interaction between the polymer and sulfate headgroups on the micelle surface is weak. The 40-monomer chain is mostly wrapped around the micelle, and nearly 90% of the monomers are adsorbed at low PEO concentration. Simulations were also performed with multiple 20-monomer chains, and gradual addition of polymer indicates that about 120 monomers are required to saturate the micelle surface. The stoichiometry of the resulting complex is in close agreement with experimental results, and the commonly accepted "beaded necklace" structure of the SDS-PEO complex is recovered by our simulations.

  10. Measuring the Acoustic Release of a Chemotherapeutic Agent from Folate-Targeted Polymeric Micelles.

    PubMed

    Abusara, Ayah; Abdel-Hafez, Mamoun; Husseini, Ghaleb

    2018-08-01

    In this paper, we compare the use of Bayesian filters for the estimation of release and re-encapsulation rates of a chemotherapeutic agent (namely Doxorubicin) from nanocarriers in an acoustically activated drug release system. The study is implemented using an advanced kinetic model that takes into account cavitation events causing the antineoplastic agent's release from polymeric micelles upon exposure to ultrasound. This model is an improvement over the previous representations of acoustic release that used simple zero-, first- and second-order release and re-encapsulation kinetics to study acoustically triggered drug release from polymeric micelles. The new model incorporates drug release and micellar reassembly events caused by cavitation allowing for the controlled release of chemotherapeutics specially and temporally. Different Bayesian estimators are tested for this purpose including Kalman filters (KF), Extended Kalman filters (EKF), Particle filters (PF), and multi-model KF and EKF. Simulated and experimental results are used to verify the performance of the above-mentioned estimators. The proposed methods demonstrate the utility and high-accuracy of using estimation methods in modeling this drug delivery technique. The results show that, in both cases (linear and non-linear dynamics), the modeling errors are expensive but can be minimized using a multi-model approach. In addition, particle filters are more flexible filters that perform reasonably well compared to the other two filters. The study improved the accuracy of the kinetic models used to capture acoustically activated drug release from polymeric micelles, which may in turn help in designing hardware and software capable of precisely controlling the delivered amount of chemotherapeutics to cancerous tissue.

  11. Branching, Chain Scission, and Solution Stability of Worm-Like Micelles

    NASA Astrophysics Data System (ADS)

    Beaucage, Greg; Vogtt, Karsten; Jiang, Hanqui

    As salt is added to a simple micelle solution such as SDS or SLES, the zero shear rate specific viscosity rises rapidly followed by a maximum and decay. The rapid rise in viscosity is associated with formation of elliptical and extended chain worm-like micelles, WLMs. Entanglement of these long chain micelles leads to the viscoelastic behavior we associate with shampoo and body wash. The plateau and drop in viscosity at high salt concentrations is caused by a special type of topological branching where the branch points have no energy penalty to motion along the chain according to Cates theory. These have some similarity to catenane crosslinks. Predictive dynamic theories for WLMs rely on structural details; the diameter, persistence length, contour length, branch length, segment length between branch points, and mesh size. Further, since the contour length and other large scale features are in kinetic equilibrium, with frequent chain breakage and formation, the thermodynamics of these long chain structures are of interest both in terms of chain scission as well as in terms of the stability of the colloidal solution as a whole. Recent structural studies of WLMs using static neutron scattering based on new scattering models will be presented demonstrating that these input parameters for dynamic models of complex topological systems are quantitatively and directly available. In this context it is important to consider a comparison between dynamic features, for instance entanglement, and their static analogs, chain overlap.

  12. Evaluation of Bio-optical Algorithms for Chlorophyll Mapping in the Southwestern Atlantic

    NASA Astrophysics Data System (ADS)

    Garcia, V. M.; Garcia, C. A.; Signorini, S.; McClain, C. R.

    2005-05-01

    Efforts have been made over the past decade to study bio-optical properties of seawater in the Southwestern Atlantic for mapping chlorophyll concentration from space. Coastal regions deserve a greater attention due to the optical complexity from continental influence. Here we present an attempt to derive reliable bio-optical chlorophyll algorithms in the shelf region 25-40o S and 60-45o W. This area is subject to large optical interference by continental runoffs from La Plata River and Patos Lagoon. Spectral upwelling radiance and surface chlorophyll concentration data have been collected in the past years and have been used to generate a regional version of the NASA's OC2v4 model. The regional 2-band algorithm (termed OC2-LP), reduces chlorophyll positive bias to 11% as compared to the global SeaWiFS OC4v4 algorithm (bias = 27%). However, OC2-LP remains with an overall inaccuracy of over 40% in chlorophyll concentration, as calculated by the absolute percentage difference between in-situ and model-derived values. In-situ chlorophyll data from two cruises to the study region (La Plata I - winter of 2003 and La Plata II - summer of 2004) have been used to test the accuracy of the derived algorithm as well as the global version. A marked seasonal difference was found, where both OC4v4 and OC2-LP overestimate chlorophyll in summer at a higher magnitude than in the winter. These results indicate the need for other approaches rather than use of empirical band-ratio models in coastal waters of this region.

  13. PEG-poly(amino acid) block copolymer micelles for tunable drug release.

    PubMed

    Ponta, Andrei; Bae, Younsoo

    2010-11-01

    To achieve tunable pH-dependent drug release in tumor tissues. Poly(ethylene glycol)-poly(aspartic acid) [PEG-p(Asp)] containing 12 kDa PEG and pAsp (5, 15, and 35 repeating units) were prepared. Hydrazide linkers with spacers [glycine (Gly) and 4-aminobenzoate (Abz)] were introduced to PEG-p(Asp), followed by drug conjugation [doxorubicin (DOX)]. The block copolymer-drug conjugates were either reconstituted or dialyzed in aqueous solutions to prepare micelles. Drug release patterns were observed under sink conditions at pH 5.0 and 7.4, 37°C, for 48 h. A collection of six block copolymers with different chain lengths and spacers was synthesized. Drug binding yields were 13-43.6%. The polymer-drug conjugates formed <50 nm polymer micelles irrespective of polymer compositions. Gly-introduced polymer micelles showed marginal change in particle size (40 ± 10 nm), while the size of Abz-micelles increased gradually from 10 to 40 nm as the polymer chain lengths increased. Drug release patterns of both Gly and Abz micelles were pH-dependent and tunable. The spacers appear to play a crucial role in controlling drug release and stability of polymer micelles in combination with block copolymer chain lengths. A drug delivery platform for tunable drug release was successfully developed with polymer micelles possessing spacer-modified hydrazone drug-binding linkers.

  14. Complete Regression of Xenograft Tumors upon Targeted Delivery of Paclitaxel via Π-Π Stacking Stabilized Polymeric Micelles

    PubMed Central

    Shi, Yang; van der Meel, Roy; Theek, Benjamin; Blenke, Erik Oude; Pieters, Ebel H.E.; Fens, Marcel H.A.M.; Ehling, Josef; Schiffelers, Raymond M.; Storm, Gert; van Nostrum, Cornelus F.; Lammers, Twan; Hennink, Wim E.

    2015-01-01

    Treatment of cancer patients with taxane-based chemotherapeutics, such as paclitaxel (PTX), is complicated by their narrow therapeutic index. Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of PTX, as they can be tailored to encapsulate large amounts of hydrophobic drugs and achieve prolonged circulation kinetics. As a result, PTX deposition in tumors is increased while drug exposure to healthy tissues is reduced. However, many PTX-loaded micelle formulations suffer from low stability and fast drug release in the circulation, limiting their suitability for systemic drug targeting. To overcome these limitations, we have developed paclitaxel (PTX)-loaded micelles which are stable without chemical crosslinking and covalent drug attachment. These micelles are characterized by excellent loading capacity and strong drug retention, attributed to π-π stacking interaction between PTX and the aromatic groups of the polymer chains in the micellar core. The micelles are based on methoxy poly(ethylene glycol)-b-(N-(2-benzoyloxypropyl) methacrylamide) (mPEG-b-p(HPMAm-Bz)) block copolymers, which improved the pharmacokinetics and the biodistribution of PTX, and substantially increased PTX tumor accumulation (by more than 2000%; as compared to Taxol® or control micellar formulations). Improved biodistribution and tumor accumulation were confirmed by hybrid μCT-FMT imaging using near-infrared labeled micelles and payload. The PTX-loaded micelles were well tolerated at different doses while they induced complete tumor regression in two different xenograft models (i.e. A431 and MDA-MB-468). Our findings consequently indicate that π-π stacking-stabilized polymeric micelles are promising carriers to improve the delivery of highly hydrophobic drugs to tumors and to increase their therapeutic index. PMID:25831471

  15. Biosynthesis of Chlorophyll a in a Purple Bacterial Phototroph and Assembly into a Plant Chlorophyll-Protein Complex.

    PubMed

    Hitchcock, Andrew; Jackson, Philip J; Chidgey, Jack W; Dickman, Mark J; Hunter, C Neil; Canniffe, Daniel P

    2016-09-16

    Improvements to photosynthetic efficiency could be achieved by manipulating pigment biosynthetic pathways of photosynthetic organisms in order to increase the spectral coverage for light absorption. The development of organisms that can produce both bacteriochlorophylls and chlorophylls is one way to achieve this aim, and accordingly we have engineered the bacteriochlorophyll-utilizing anoxygenic phototroph Rhodobacter sphaeroides to make chlorophyll a. Bacteriochlorophyll and chlorophyll share a common biosynthetic pathway up to the precursor chlorophyllide. Deletion of genes responsible for the bacteriochlorophyll-specific modifications of chlorophyllide and replacement of the native bacteriochlorophyll synthase with a cyanobacterial chlorophyll synthase resulted in the production of chlorophyll a. This pigment could be assembled in vivo into the plant water-soluble chlorophyll protein, heterologously produced in Rhodobacter sphaeroides, which represents a proof-of-principle for the engineering of novel antenna complexes that enhance the spectral range of photosynthesis.

  16. Curcumin-Loading-Dependent Stability of PEGMEMA-Based Micelles Affects Endocytosis and Exocytosis in Colon Carcinoma Cells.

    PubMed

    Chang, Teddy; Trench, David; Putnam, Joshua; Stenzel, Martina H; Lord, Megan S

    2016-03-07

    Polymeric micelles were formed from poly(poly(ethylene glycol) methyl ether methacrylate)-block-poly(styrene) (P(PEGMEMA)-b-PS) block copolymer of two different chain lengths. The micelles formed were approximately 16 and 46 nm in diameter and used to encapsulate curcumin. Upon loading of the curcumin into the micelles, their size increased to approximately 34 and 80 nm in diameter, respectively, with a loading efficiency of 58%. The unloaded micelles were not cytotoxic to human colon carcinoma cells, whereas only the smaller loaded micelles were cytotoxic after 72 h of exposure. The micelles were rapidly internalized by the cells within minutes of exposure, with the loaded micelles internalized to a greater extent owing to their enhanced stability compared to that of the unloaded micelles. The larger micelles were more rapidly internalized and exocytosed than the smaller micelles, demonstrating the effect of micelle size and drug loading on drug delivery and cytotoxicity.

  17. Polymeric micelles in mucosal drug delivery: Challenges towards clinical translation.

    PubMed

    Sosnik, Alejandro; Menaker Raskin, Maya

    2015-11-01

    Polymeric micelles are nanostructures formed by the self-aggregation of copolymeric amphiphiles above the critical micellar concentration. Due to the flexibility to tailor different molecular features, they have been exploited to encapsulate motley poorly-water soluble therapeutic agents. Moreover, the possibility to combine different amphiphiles in one single aggregate and produce mixed micelles that capitalize on the features of the different components substantially expands the therapeutic potential of these nanocarriers. Despite their proven versatility, polymeric micelles remain elusive to the market and only a few products are currently undergoing advanced clinical trials or reached clinical application, all of them for the therapy of different types of cancer and administration by the intravenous route. At the same time, they emerge as a nanotechnology platform with great potential for non-parenteral mucosal administration. However, for this, the interaction of polymeric micelles with mucus needs to be strengthened. The present review describes the different attempts to develop mucoadhesive polymeric micelles and discusses the challenges faced in the near future for a successful bench-to-bedside translation. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Structural changes of deposited casein micelles induced by membrane filtration.

    PubMed

    Gebhardt, R; Steinhauer, T; Meyer, P; Sterr, J; Perlich, J; Kulozik, U

    2012-01-01

    Casein micelles undergo shape changes when subjected to frontal filtration forces. Grazing incidence small angle X-ray scattering (GISAXS) and atomic force microscopy (AFM) allow a quantification of such structural changes on filtration cakes deposited on smooth silicon micro-sieves. A trans-membrane pressure of deltap = 400 mbar across the micro-sieve leads to an immediate film formation after deposition of casein solution. We observe significant changes in the GISAXS pattern depending on how many layers are stacked on top of each other. Compared to a deposit formed by one layer, GISAXS on a deposit formed by three layers of casein micelles leads to less scattering in the vertical and more scattering in the horizontal direction. Simulations show that the experimental results can be interpreted by a structural transformation from an originally spherical micelle shape to an ellipsoidal-deformed shape. The results are supported by AFM measurements showing a reduced lateral size of casein micelles deposited on top of a membrane pore. The observed shape changes could be due to filtration forces acting on densely packed deposits confining the micelles into ellipsoidal shapes.

  19. Effect of microfluidization on casein micelle size of bovine milk

    NASA Astrophysics Data System (ADS)

    Sinaga, H.; Deeth, H.; Bhandari, B.

    2018-02-01

    The properties of milk are likely to be dependent on the casein micelle size, and various processing technologies produce particular change in the average size of casein micelles. The main objective of this study was to manipulate casein micelle size by subjecting milk to microfluidizer. The experiment was performed as a complete block randomised design with three replications. The sample was passed through the microfluidizer at the set pressure of 83, 97, 112 and 126 MPa for one, two, three, four, five and six cycles, except for the 112 MPa. The results showed that microfluidized milk has smaller size by 3% with pressure up to 126 MPa. However, at each pressure, no further reduction was observed after increasing the passed up to 6 cycles. Although the average casein micelle size was similar, elevating pressure resulted in narrower size distribution. In contrast, increasing the number of cycles had little effect on casein micelle distribution. The finding from this study can be applied for future work to characterize the fundamental and functional properties of the treated milk.

  20. Preparation and evaluation of icariside II-loaded binary mixed micelles using Solutol HS15 and Pluronic F127 as carriers.

    PubMed

    Hou, Jian; Wang, Jing; Sun, E; Yang, Lei; Yan, Hong-Mei; Jia, Xiao-Bin; Zhang, Zhen-Hai

    2016-11-01

    An effective anti-cancer drug, icariside II (IS), has been used to treat a variety of cancers in vitro. However, its poor aqueous solubility and permeability lead to low oral bioavailability. The aim of this work was to use Solutol®HS15 and Pluronic F127 as surfactants to develop novel mixed micelles to enhance the oral bioavailability of IS by improving permeability and inhibiting efflux. The IS-loaded mixed micelles were prepared using the method of ethanol thin-film hydration. The physicochemical properties, dissolution property, oral bioavailability of the male SD rats, permeability and efflux of Caco-2 transport models, and gastrointestinal safety of the mixed micelles were evaluated. The optimized IS-loaded mixed micelles showed that at 4:1 ratio of Solutol®HS15 and Pluronic F127, the particle size was 12.88 nm with an acceptable polydispersity index of 0.172. Entrapment efficiency (94.6%) and drug loading (9.7%) contributed to the high solubility (11.7 mg/mL in water) of IS, which increased about 900-fold. The SF-IS mixed micelle release profile showed a better sustained release property than that of IS. In Caco-2 cell monolayer models, the efflux ratio dramatically decreased by 83.5%, and the relative bioavailability of the mixed micelles (AUC 0-∞ ) compared with that of IS (AUC 0-∞ ) was 317%, indicating potential for clinical application. In addition, a gastrointestinal safety assay also provided reliable clinical evidence for the safe use of this micelle.

  1. Solubilization of docetaxel in poly(ethylene oxide)-block-poly(butylene/styrene oxide) micelles.

    PubMed

    Elsabahy, Mahmoud; Perron, Marie-Eve; Bertrand, Nicolas; Yu, Ga-Er; Leroux, Jean-Christophe

    2007-07-01

    Poly(ethylene oxide)-block-poly(styrene oxide) (PEO-b-PSO) and PEO-b-poly(butylene oxide) (PEO-b-PBO) of different chain lengths were synthesized and characterized for their self-assembling properties in water by dynamic/static light scattering, spectrofluorimetry, and transmission electron microscopy. The resulting polymeric micelles were evaluated for their ability to solubilize and protect the anticancer drug docetaxel (DCTX) from degradation. The drug release kinetics as well as the cytotoxicity of the loaded micelles were assessed in vitro. All polymers formed micelles with a highly viscous core at low critical association concentrations (<10 mg/L). Micelle morphology depended on the nature of the hydrophobic block, with PBO- and PSO-based micelles yielding monodisperse spherical and cylindrical nanosized aggregates, respectively. The maximum solubilization capacity for DCTX ranged from 0.7 to 4.2% and was the highest for PSO micelles exhibiting the longest hydrophobic segment. Despite their high affinity for DCTX, PEO-b-PSO micelles were not able to efficiently protect DCTX against hydrolysis under accelerated stability testing conditions. Only PEO-b-PBO bearing 24 BO units afforded significant protection against degradation. In vitro, DCTX was released slower from the latter micelles, but all formulations possessed a similar cytotoxic effect against PC-3 prostate cancer cells. These data suggest that PEO-b-P(SO/BO) micelles could be used as alternatives to conventional surfactants for the solubilization of taxanes.

  2. Synthesis and characterization of Fe colloid catalysts in inverse micelle solutions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martino, A.; Stoker, M.; Hicks, M.

    1995-12-31

    Surfactant molecules, possessing a hydrophilic head group and a hydrophobic tail group, aggregate in various solvents to form structured solutions. In two component mixtures of surfactant and organic solvents (e.g., toluene and alkanes), surfactants aggregate to form inverse micelles. Here, the hydrophilic head groups shield themselves by forming a polar core, and the hydrophobic tails groups are free to move about in the surrounding oleic phase. The formation of Fe clusters in inverse miscelles was studied.Iron salts are solubilized within the polar interior of inverse micelles, and the addition of the reducing agent LiBH{sub 4} initiates a chemical reduction tomore » produce monodisperse, nanometer sized Fe based particles. The reaction sequence is sustained by material exchange between inverse micelles. The surfactant interface provides a spatial constraint on the reaction volume, and reactions carried out in these micro-heterogeneous solutions produce colloidal sized particles (10-100{Angstrom}) stabilized in solution against flocculation of surfactant. The clusters were stabilized with respect to size with transmission electron microscopy (TEM) and with respect to chemical composition with Mossbauer spectroscopy, electron diffraction, and x-ray photoelectron spectroscopy (XPS). In addition, these iron based clusters were tested for catalytic activity in a model hydrogenolysis reaction. The hydrogenolysis of naphthyl bibenzyl methane was used as a model for coal pyrolysis.« less

  3. [Study of building quantitative analysis model for chlorophyll in winter wheat with reflective spectrum using MSC-ANN algorithm].

    PubMed

    Liang, Xue; Ji, Hai-yan; Wang, Peng-xin; Rao, Zhen-hong; Shen, Bing-hui

    2010-01-01

    Preprocess method of multiplicative scatter correction (MSC) was used to reject noises in the original spectra produced by the environmental physical factor effectively, then the principal components of near-infrared spectroscopy were calculated by nonlinear iterative partial least squares (NIPALS) before building the back propagation artificial neural networks method (BP-ANN), and the numbers of principal components were calculated by the method of cross validation. The calculated principal components were used as the inputs of the artificial neural networks model, and the artificial neural networks model was used to find the relation between chlorophyll in winter wheat and reflective spectrum, which can predict the content of chlorophyll in winter wheat. The correlation coefficient (r) of calibration set was 0.9604, while the standard deviation (SD) and relative standard deviation (RSD) was 0.187 and 5.18% respectively. The correlation coefficient (r) of predicted set was 0.9600, and the standard deviation (SD) and relative standard deviation (RSD) was 0.145 and 4.21% respectively. It means that the MSC-ANN algorithm can reject noises in the original spectra produced by the environmental physical factor effectively and set up an exact model to predict the contents of chlorophyll in living leaves veraciously to replace the classical method and meet the needs of fast analysis of agricultural products.

  4. Development of lycopene micelle and lycopene chylomicron and a comparison of bioavailability

    NASA Astrophysics Data System (ADS)

    Jyun Chen, Yi; Inbaraj, Baskaran Stephen; Shiau Pu, Yeong; Chen, Bing Huei

    2014-04-01

    The objectives of this study were to develop lycopene micelles and lycopene chylomicrons from tomato extracts for the enhancement and comparison of bioavailability. Lycopene micelles and chylomicrons were prepared by a microemulsion technique involving tomato extract, soybean oil, water, vitamin E and surfactant Tween 80 or lecithin in different proportions. The encapsulation efficiency of lycopene was 78% in micelles and 80% in chylomicrons, with shape being roughly spherical and mean particle size being 7.5 and 131.5 nm. A bioavailability study was conducted in rats by both gavage and i.v. administration, with oral bioavailability of lycopene, phytoene and phytofluene being 6.8, 4.3 and 3.1% in micelles and 9.5, 9.4 and 7.1% in chylomicrons, respectively. This outcome reveals higher lycopene bioavailability through incorporation into micelle or chylomicron systems. Both size and shape should be considered for oral bioavailability determination. For i.v. injection, lycopene micelles should be more important than lycopene chylomicrons for future clinical applications.

  5. Effect of calcium concentration on the structure of casein micelles in thin films.

    PubMed

    Müller-Buschbaum, P; Gebhardt, R; Roth, S V; Metwalli, E; Doster, W

    2007-08-01

    The structure of thin casein films prepared with spin-coating is investigated as a function of the calcium concentration. Grazing incidence small-angle x-ray scattering and atomic force microscopy are used to probe the micelle structure. For comparison, the corresponding casein solutions are investigated with dynamic light-scattering experiments. In the thin films with added calcium three types of casein structures, aggregates, micelles, and mini-micelles, are observed in coexistence with atomic force microscopy and grazing incidence small-angle x-ray scattering. With increasing calcium concentration, the size of the aggregates strongly increases, while the size of micelles slightly decreases and the size of the mini-micelles increases. This effect is explained in the framework of the particle-stabilizing properties of the hairy layer of kappa-casein surrounding the casein micelles.

  6. Effect of Calcium Concentration on the Structure of Casein Micelles in Thin Films

    PubMed Central

    Müller-Buschbaum, P.; Gebhardt, R.; Roth, S. V.; Metwalli, E.; Doster, W.

    2007-01-01

    The structure of thin casein films prepared with spin-coating is investigated as a function of the calcium concentration. Grazing incidence small-angle x-ray scattering and atomic force microscopy are used to probe the micelle structure. For comparison, the corresponding casein solutions are investigated with dynamic light-scattering experiments. In the thin films with added calcium three types of casein structures, aggregates, micelles, and mini-micelles, are observed in coexistence with atomic force microscopy and grazing incidence small-angle x-ray scattering. With increasing calcium concentration, the size of the aggregates strongly increases, while the size of micelles slightly decreases and the size of the mini-micelles increases. This effect is explained in the framework of the particle-stabilizing properties of the hairy layer of κ-casein surrounding the casein micelles. PMID:17496032

  7. Ionic micelles and aromatic additives: a closer look at the molecular packing parameter.

    PubMed

    Lutz-Bueno, Viviane; Isabettini, Stéphane; Walker, Franziska; Kuster, Simon; Liebi, Marianne; Fischer, Peter

    2017-08-16

    Wormlike micellar aggregates formed from the mixture of ionic surfactants with aromatic additives result in solutions with impressive viscoelastic properties. These properties are of high interest for numerous industrial applications and are often used as model systems for soft matter physics. However, robust and simple models for tailoring the viscoelastic response of the solution based on the molecular structure of the employed additive are required to fully exploit the potential of these systems. We address this shortcoming with a modified packing parameter based model, considering the additive-surfactant pair. The role of charge neutralization on anisotropic micellar growth was investigated with derivatives of sodium salicylate. The impact of the additives on the morphology of the micellar aggregates is explained from the molecular level to the macroscopic viscoelasticity. Changes in the micelle's volume, headgroup area and additive structure are explored to redefine the packing parameter. Uncharged additives penetrated deeper into the hydrophobic region of the micelle, whilst charged additives remained trapped in the polar region, as revealed by a combination of 1 H-NMR, SAXS and rheological measurements. A deeper penetration of the additives densified the hydrophobic core of the micelle and induced anisotropic growth by increasing the effective volume of the additive-surfactant pair. This phenomenon largely influenced the viscosity of the solutions. Partially penetrating additives reduced the electrostatic repulsions between surfactant headgroups and neighboring micelles. The resulting increased network density governed the elasticity of the solutions. Considering a packing parameter composed of the additive-surfactant pair proved to be a facile means of engineering the viscoelastic response of surfactant solutions. The self-assembly of the wormlike micellar aggregates could be tailored to desired morphologies resulting in a specific and predictable

  8. Structure and Dynamics of Highly PEG-ylated Sterically Stabilized Micelles in Aqueous Media

    PubMed Central

    Vuković, Lela; Khatib, Fatima A.; Drake, Stephanie P.; Madriaga, Antonett; Brandenburg, Kenneth S.; Král, Petr; Onyuksel, Hayat

    2011-01-01

    Molecular assemblies of highly PEG-ylated phospholipids are important in many biomedical applications. We study sterically stabilized micelles (SSM) of self-assembled DSPE-PEG2000 in pure water and isotonic HEPES buffered saline solution. The observed SSM sizes of 2 – 15 nm largely depend on the solvent and the lipid concentration used. The critical micelle concentration (CMC) of DSPE-PEG2000 is ≈ 10 times higher in water than in buffer and the viscosity of the dispersion dramatically increases with the lipid concentration. To explain the experimentally observed results, we perform atomistic molecular dynamics simulations of the solvated SSM. Our modeling reveal that the observed assemblies have very different aggregation numbers of Nagg ≈ 90 (saline solution) and Nagg < 8 (water), due to very different screening of their charged −PO4− groups. We also demonstrate that the micelle cores can inflate and their corona highly fluctuate, allowing thus storage and delivery of molecules with different chemistry. PMID:21780810

  9. Structure and dynamics of highly PEG-ylated sterically stabilized micelles in aqueous media.

    PubMed

    Vuković, Lela; Khatib, Fatima A; Drake, Stephanie P; Madriaga, Antonett; Brandenburg, Kenneth S; Král, Petr; Onyuksel, Hayat

    2011-08-31

    Molecular assemblies of highly PEG-ylated phospholipids are important in many biomedical applications. We have studied sterically stabilized micelles (SSMs) of self-assembled DSPE–PEG2000 in pure water and isotonic HEPES-buffered saline solution. The observed SSM sizes of 2–15 nm largely depend on the solvent and the lipid concentration used. The critical micelle concentration of DSPE–PEG2000 is 10 times higher in water than in buffer, and the viscosity of the dispersion dramatically increases with the lipid concentration. To explain the experimentally observed results, we performed atomistic molecular dynamics simulations of solvated SSMs. Our modeling revealed that the observed assemblies have very different aggregation numbers (N(agg) ≈ 90 in saline solution and N(agg) < 8 in water) because of very different screening of their charged PO4(–) groups. We also demonstrate that the micelle cores can inflate and their coronas can fluctuate strongly, thus allowing storage and delivery of molecules with different chemistries.

  10. Design of polymer conjugated 3-helix micelles as nanocarriers with tunable shapes.

    PubMed

    Ma, Dan; DeBenedictis, Elizabeth P; Lund, Reidar; Keten, Sinan

    2016-11-24

    Amphiphilic peptide-polymer conjugates have the ability to form stable nanoscale micelles, which show great promise for drug delivery and other applications. A recent design has utilized the end-conjugation of alkyl chains to 3-helix coiled coils to achieve amphiphilicity, combined with the side-chain conjugation of polyethylene glycol (PEG) to tune micelle size through entropic confinement forces. Here we investigate this phenomenon in depth, using coarse-grained dissipative particle dynamics (DPD) simulations in an explicit solvent and micelle theory. We analyze the conformations of PEG chains conjugated to three different positions on 3-helix bundle peptides to ascertain the degree of confinement upon assembly, as well as the ordering of the subunits making up the micelle. We discover that the micelle size and stability is dictated by a competition between the entropy of PEG chain conformations in the assembled state, as well as intermolecular cross-interactions among PEG chains that promote cohesion between neighboring conjugates. Our analyses build on the role of PEG molecular weight and conjugation site and lead to computational phase diagrams that can be used to design 3-helix micelles. This work opens pathways for the design of multifunctional micelles with tunable size, shape and stability.

  11. Tuning Structural Properties of Biocompatible Block Copolymer Micelles by Varying Solvent Composition

    NASA Astrophysics Data System (ADS)

    Cooksey, Tyler; Singh, Avantika; Mai Le, Kim; Wang, Shu; Kelley, Elizabeth; He, Lilin; Vajjala Kesava, Sameer; Gomez, Enrique; Kidd, Bryce; Madsen, Louis; Robertson, Megan

    The self-assembly of block copolymers into micelles when introduced to selective solvents enables a wide array of applications, ranging from drug delivery to personal care products to nanoreactors. In order to probe the assembly and dynamics of micellar systems, the structural properties and solvent uptake of biocompatible poly(ethylene oxide-b- ɛ-caprolactone) (PEO-PCL) diblock copolymers in deuterated water (D2O) / tetrahydrofuran (THFd8) mixtures were investigated using small-angle neutron scattering in combination with nuclear magnetic resonance. PEO-PCL block copolymers, of varying molecular weight yet constant block ratio, formed spherical micelles through a wide range of solvent compositions. Varying the composition from 10 to 60 % by volume THFd8\\ in D2O / THFd8 mixtures was a means of varying the core-corona interfacial tension in the micelle system. An increase in THFd8 content in the bulk solvent increased the solvent uptake within the micelle core, which was comparable for the two series, irrespective of the polymer molecular weight. Differences in the behaviors of the micelle size parameters as the solvent composition varied originated from the differing trends in aggregation number for the two micelle series. Incorporation of the known unimer content determined from NMR allowed refinement of extracted micelle parameters.

  12. Applicability of linear regression equation for prediction of chlorophyll content in rice leaves

    NASA Astrophysics Data System (ADS)

    Li, Yunmei

    2005-09-01

    A modeling approach is used to assess the applicability of the derived equations which are capable to predict chlorophyll content of rice leaves at a given view direction. Two radiative transfer models, including PROSPECT model operated at leaf level and FCR model operated at canopy level, are used in the study. The study is consisted of three steps: (1) Simulation of bidirectional reflectance from canopy with different leaf chlorophyll contents, leaf-area-index (LAI) and under storey configurations; (2) Establishment of prediction relations of chlorophyll content by stepwise regression; and (3) Assessment of the applicability of these relations. The result shows that the accuracy of prediction is affected by different under storey configurations and, however, the accuracy tends to be greatly improved with increase of LAI.

  13. Spectral Feature Analysis for Quantitative Estimation of Cyanobacteria Chlorophyll-A

    NASA Astrophysics Data System (ADS)

    Lin, Yi; Ye, Zhanglin; Zhang, Yugan; Yu, Jie

    2016-06-01

    In recent years, lake eutrophication caused a large of Cyanobacteria bloom which not only brought serious ecological disaster but also restricted the sustainable development of regional economy in our country. Chlorophyll-a is a very important environmental factor to monitor water quality, especially for lake eutrophication. Remote sensed technique has been widely utilized in estimating the concentration of chlorophyll-a by different kind of vegetation indices and monitoring its distribution in lakes, rivers or along coastline. For each vegetation index, its quantitative estimation accuracy for different satellite data might change since there might be a discrepancy of spectral resolution and channel center between different satellites. The purpose this paper is to analyze the spectral feature of chlorophyll-a with hyperspectral data (totally 651 bands) and use the result to choose the optimal band combination for different satellites. The analysis method developed here in this study could be useful to recognize and monitor cyanobacteria bloom automatically and accrately. In our experiment, the reflectance (from 350nm to 1000nm) of wild cyanobacteria in different consistency (from 0 to 1362.11ug/L) and the corresponding chlorophyll-a concentration were measured simultaneously. Two kinds of hyperspectral vegetation indices were applied in this study: simple ratio (SR) and narrow band normalized difference vegetation index (NDVI), both of which consists of any two bands in the entire 651 narrow bands. Then multivariate statistical analysis was used to construct the linear, power and exponential models. After analyzing the correlation between chlorophyll-a and single band reflectance, SR, NDVI respetively, the optimal spectral index for quantitative estimation of cyanobacteria chlorophyll-a, as well corresponding central wavelength and band width were extracted. Results show that: Under the condition of water disturbance, SR and NDVI are both suitable for quantitative

  14. Incomplete Loading of Sodium Lauryl Sulfate and Fasted State Simulated Intestinal Fluid Micelles Within the Diffusion Layers of Dispersed Drug Particles During Dissolution.

    PubMed

    Galipeau, Kendra; Socki, Michael; Socia, Adam; Harmon, Paul A

    2018-01-01

    Poorly water soluble drug candidates have been common in developmental pipelines over the last several decades. This has fueled considerable research around understanding how bile salt and model micelles can improve drug particle dissolution rates and human drug exposure levels. However, in the pharmaceutical context only a single mechanism of how micelles load solute has been assumed, that being the direct loading mechanism put forth by Cussler and coworkers (Am Inst Chem Eng J. 1976;22(6):1006-1012) 40 years ago. In this model, micelles load at the particle surface and will be loaded to their equilibrium loading values. More recently, Kumar and Gandhi and coworkers (Langmuir. 2003;19:4014-4026) developed a comprehensive theory of micelle solubilization which also features an indirect loading mechanism which they argue should operate in ionic surfactant systems. In this mechanism, micelles cannot directly load at the solute particle surface and thus may not reach equilibrium loading values within the particle diffusion layer. In this work, we endeavor to understand if the indirect micelle loading mechanism represents a plausible description in the pharmaceutical context. The overall data in SLS and FaSSIF systems obtained here, as well as several other previously published datasets, can be described by the indirect micelle loading mechanism. Implications for pharmaceutical development of poorly soluble compounds are discussed. Copyright © 2018. Published by Elsevier Inc.

  15. Ocean Primary Production Estimates from Terra MODIS and Their Dependency on Satellite Chlorophyll Alpha Algorithms

    NASA Technical Reports Server (NTRS)

    Essias, Wayne E.; Abbott, Mark; Carder, Kendall; Campbell, Janet; Clark, Dennis; Evans, Robert; Brown, Otis; Kearns, Ed; Kilpatrick, Kay; Balch, W.

    2003-01-01

    Simplistic models relating global satellite ocean color, temperature, and light to ocean net primary production (ONPP) are sensitive to the accuracy and limitations of the satellite estimate of chlorophyll and other input fields, as well as the primary productivity model. The standard MODIS ONPP product uses the new semi-analytic chlorophyll algorithm as its input for two ONPP indexes. The three primary MODIS chlorophyll Q estimates from MODIS, as well as the SeaWiFS 4 chlorophyll product, were used to assess global and regional performance in estimating ONPP for the full mission, but concentrating on 2001. The two standard ONPP algorithms were examined with 8-day and 39 kilometer resolution to quantify chlorophyll algorithm dependency of ONPP. Ancillary data (MLD from FNMOC, MODIS SSTD1, and PAR from the GSFC DAO) were identical. The standard MODIS ONPP estimates for annual production in 2001 was 59 and 58 GT C for the two ONPP algorithms. Differences in ONPP using alternate chlorophylls were on the order of 10% for global annual ONPP, but ranged to 100% regionally. On all scales the differences in ONPP were smaller between MODIS and SeaWiFS than between ONPP models, or among chlorophyll algorithms within MODIS. Largest regional ONPP differences were found in the Southern Ocean (SO). In the SO, application of the semi-analytic chlorophyll resulted in not only a magnitude difference in ONPP (2x), but also a temporal shift in the time of maximum production compared to empirical algorithms when summed over standard oceanic areas. The resulting increase in global ONPP (6-7 GT) is supported by better performance of the semi-analytic chlorophyll in the SO and other high chlorophyll regions. The differences are significant in terms of understanding regional differences and dynamics of ocean carbon transformations.

  16. Near-Infrared Squaraine Dye Encapsulated Micelles for in Vivo Fluorescence and Photoacoustic Bimodal Imaging.

    PubMed

    Sreejith, Sivaramapanicker; Joseph, James; Lin, Manjing; Menon, Nishanth Venugopal; Borah, Parijat; Ng, Hao Jun; Loong, Yun Xian; Kang, Yuejun; Yu, Sidney Wing-Kwong; Zhao, Yanli

    2015-06-23

    Combined near-infrared (NIR) fluorescence and photoacoustic imaging techniques present promising capabilities for noninvasive visualization of biological structures. Development of bimodal noninvasive optical imaging approaches by combining NIR fluorescence and photoacoustic tomography demands suitable NIR-active exogenous contrast agents. If the aggregation and photobleaching are prevented, squaraine dyes are ideal candidates for fluorescence and photoacoustic imaging. Herein, we report rational selection, preparation, and micelle encapsulation of an NIR-absorbing squaraine dye (D1) for in vivo fluorescence and photoacoustic bimodal imaging. D1 was encapsulated inside micelles constructed from a biocompatible nonionic surfactant (Pluoronic F-127) to obtain D1-encapsulated micelles (D1(micelle)) in aqueous conditions. The micelle encapsulation retains both the photophysical features and chemical stability of D1. D1(micelle) exhibits high photostability and low cytotoxicity in biological conditions. Unique properties of D1(micelle) in the NIR window of 800-900 nm enable the development of a squaraine-based exogenous contrast agent for fluorescence and photoacoustic bimodal imaging above 820 nm. In vivo imaging using D1(micelle), as demonstrated by fluorescence and photoacoustic tomography experiments in live mice, shows contrast-enhanced deep tissue imaging capability. The usage of D1(micelle) proven by preclinical experiments in rodents reveals its excellent applicability for NIR fluorescence and photoacoustic bimodal imaging.

  17. Polymer Micelles with Cross-Linked Polyanion Core for Delivery of a Cationic Drug Doxorubicin

    PubMed Central

    Kim, Jong Oh; Kabanov, Alexander V.; Bronich, Tatiana K.

    2009-01-01

    Polymer micelles with cross-linked ionic cores were prepared by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) copolymer and divalent metal cations as templates. Doxorubicin (DOX), an anthracycline anticancer drug, was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. A substantial drug loading level (up to 50 w/w %) was achieved and it was strongly dependent on the structure of the cross-linked micelles and pH. The drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. The DOX-loaded polymer micelles exhibited noticeable pH-sensitive behavior with accelerated release of DOX in acidic environment due to the protonation of carboxylic groups in the cores of the micelles. The attempt to protect the DOX-loaded core with the polycationic substances resulted in the decrease of loading efficacy and had a slight effect on the release characteristics of the micelles. The DOX-loaded polymer micelles exhibited a potent cytotoxicity against human A2780 ovarian carcinoma cells. These results point to a potential of novel polymer micelles with cross-linked ionic cores to be attractive carriers for the delivery of DOX. PMID:19386272

  18. Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic honokiol delivery: I. Preparation and characterization

    NASA Astrophysics Data System (ADS)

    Gong, ChangYang; Wei, XiaWei; Wang, XiuHong; Wang, YuJun; Guo, Gang; Mao, YongQiu; Luo, Feng; Qian, ZhiYong

    2010-05-01

    This study aims to develop self-assembled poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles to encapsulate hydrophobic honokiol (HK) in order to overcome its poor water solubility and to meet the requirement of intravenous administration. Honokiol loaded micelles (HK-micelles) were prepared by self-assembly of PECE copolymer in aqueous solution, triggered by its amphiphilic characteristic assisted by ultrasonication without any organic solvents, surfactants and vigorous stirring. The particle size of the prepared HK-micelles measured by Malvern laser particle size analyzer were 58 nm, which is small enough to be a candidate for an intravenous drug delivery system. Furthermore, the HK-micelles could be lyophilized into powder without any adjuvant, and the re-dissolved HK-micelles are stable and homogeneous with particle size about 61 nm. Furthermore, the in vitro release profile showed a significant difference between the rapid release of free HK and the much slower and sustained release of HK-micelles. Moreover, the cytotoxicity results of blank micelles and HK-micelles showed that the PECE micelle was a safe carrier and the encapsulated HK retained its potent antitumor effect. In short, the HK-micelles were successfully prepared by an improved method and might be promising carriers for intravenous delivery of HK in cancer chemotherapy, being effective, stable, safe (organic solvent and surfactant free), and easy to produce and scale up.

  19. Polymeric Micelles: Recent Advancements in the Delivery of Anticancer Drugs.

    PubMed

    Gothwal, Avinash; Khan, Iliyas; Gupta, Umesh

    2016-01-01

    Nanotechnology, in health and medicine, extensively improves the safety and efficacy of different therapeutic agents, particularly the aspects related to drug delivery and targeting. Among various nano-carriers, polymer based macromolecular approaches have resulted in improved drug delivery for the diseases like cancers, diabetes, autoimmune disorders and many more. Polymeric micelles consisting of hydrophilic exterior and hydrophobic core have established a record of anticancer drug delivery from the laboratory to commercial reality. The nanometric size, tailor made functionality, multiple choices of polymeric micelle synthesis and stability are the unique properties, which have attracted scientists and researchers around the world to work upon in this opportunistic drug carrier. The capability of polymeric micelles as nano-carriers are nowhere less significant than nanoparticles, liposomes and other nanocarriers, as per as the commercial feasibility and presence is concerned. In fact polymeric micelles are among the most extensively studied delivery platforms for the effective treatment of different cancers as well as non-cancerous disorders. The present review highlights the sequential and recent developments in the design, synthesis, characterization and evaluation of polymeric micelles to achieve the effective anticancer drug delivery. The future possibilities and clinical outcome have also been discussed, briefly.

  20. Light-responsive micelles of spiropyran initiated hyperbranched polyglycerol for smart drug delivery.

    PubMed

    Son, Suhyun; Shin, Eeseul; Kim, Byeong-Su

    2014-02-10

    Light-responsive polymeric micelles have emerged as site-specific and time-controlled systems for advanced drug delivery. Spiropyran (SP), a well-known photochromic molecule, was used to initiate the ring-opening multibranching polymerization of glycidol to afford a series of hyperbranched polyglycerols (SP-hb-PG). The micelle assembly and disassembly were induced by an external light source owing to the reversible photoisomerization of hydrophobic SP to hydrophilic merocyanine (MC). Transmission electron microscopy, atomic force microscopy, UV/vis spectroscopy, and dynamic light scattering demonstrated the successful assembly and disassembly of SP-hb-PG micelles. In addition, the critical micelle concentration (CMC) was determined through the fluorescence analysis of pyrene to confirm the amphiphilicity of respective SP-hb-PGn (n = 15, 29, and 36) micelles, with CMC values ranging from 13 to 20 mg/L, which is correlated to the length of the polar polyglycerol backbone. Moreover, the superior biocompatibility of the prepared SP-hb-PG was evaluated using WI-38 cells and HeLa cells, suggesting the prospective applicability of the micelles in smart drug delivery systems.

  1. Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

    PubMed Central

    Liu, Yuling; Xu, Yingqi; Wu, Minghui; Fan, Lijiao; He, Chengwei; Wan, Jian-Bo; Li, Peng; Chen, Meiwan; Li, Hui

    2016-01-01

    Mitoxantrone (MIT) is a chemotherapeutic agent with promising anticancer efficacy. In this study, Pluronic F68-vitamine E succinate (F68-VES) amphiphilic polymer micelles were developed for delivering MIT and enhancing its anticancer activity. MIT-loaded F68–VES (F68–VES/MIT) micelles were prepared via the solvent evaporation method with self-assembly under aqueous conditions. F68–VES/MIT micelles were found to be of optimal particle size with the narrow size distribution. Transmission electron microscopy images of F68–VES/MIT micelles showed homogeneous spherical shapes and smooth surfaces. F68–VES micelles had a low critical micelle concentration value of 3.311 mg/L, as well as high encapsulation efficiency and drug loading. Moreover, F68–VES/MIT micelles were stable in the presence of fetal bovine serum for 24 hours and maintained sustained drug release in vitro. Remarkably, the half maximal inhibitory concentration (IC50) value of F68–VES/MIT micelles was lower than that of free MIT in both MDA-MB-231 and MCF-7 cells (two human breast cancer cell lines). In addition, compared with free MIT, there was an increased trend of apoptosis and cellular uptake of F68–VES/MIT micelles in MDA-MB-231 cells. Taken together, these results indicated that F68–VES polymer micelles were able to effectively deliver MIT and largely improve its potency in cancer therapy. PMID:27471384

  2. Spherical harmonics analysis of surface density fluctuations of spherical ionic SDS and nonionic C12E8 micelles: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Yoshii, Noriyuki; Nimura, Yuki; Fujimoto, Kazushi; Okazaki, Susumu

    2017-07-01

    The surface structure and its fluctuation of spherical micelles were investigated using a series of density correlation functions newly defined by spherical harmonics and Legendre polynomials based on the molecular dynamics calculations. To investigate the influence of head-group charges on the micelle surface structure, ionic sodium dodecyl sulfate and nonionic octaethyleneglycol monododecylether (C12E8) micelles were investigated as model systems. Large-scale density fluctuations were observed for both micelles in the calculated surface static structure factor. The area compressibility of the micelle surface evaluated by the surface static structure factor was tens-of-times larger than a typical value of a lipid membrane surface. The structural relaxation time, which was evaluated from the surface intermediate scattering function, indicates that the relaxation mechanism of the long-range surface structure can be well described by the hydrostatic approximation. The density fluctuation on the two-dimensional micelle surface has similar characteristics to that of three-dimensional fluids near the critical point.

  3. Spherical harmonics analysis of surface density fluctuations of spherical ionic SDS and nonionic C12E8 micelles: A molecular dynamics study.

    PubMed

    Yoshii, Noriyuki; Nimura, Yuki; Fujimoto, Kazushi; Okazaki, Susumu

    2017-07-21

    The surface structure and its fluctuation of spherical micelles were investigated using a series of density correlation functions newly defined by spherical harmonics and Legendre polynomials based on the molecular dynamics calculations. To investigate the influence of head-group charges on the micelle surface structure, ionic sodium dodecyl sulfate and nonionic octaethyleneglycol monododecylether (C 12 E 8 ) micelles were investigated as model systems. Large-scale density fluctuations were observed for both micelles in the calculated surface static structure factor. The area compressibility of the micelle surface evaluated by the surface static structure factor was tens-of-times larger than a typical value of a lipid membrane surface. The structural relaxation time, which was evaluated from the surface intermediate scattering function, indicates that the relaxation mechanism of the long-range surface structure can be well described by the hydrostatic approximation. The density fluctuation on the two-dimensional micelle surface has similar characteristics to that of three-dimensional fluids near the critical point.

  4. Enzyme-assisted extraction of stabilized chlorophyll from spinach.

    PubMed

    Özkan, Gülay; Ersus Bilek, Seda

    2015-06-01

    Zinc complex formation with chlorophyll derivatives in spinach pulp was studied by adding 300ppm Zn(2+) for production of stable food colorant, followed by the heating at 110°C for 15min. Zinc complex formation increased at pH values of 7.0 or greater. Pectinex Ultra SP-L was selected for enzyme-assisted release of zinc-chlorophyll derivatives from spinach pulp. Effect of enzyme concentration (1-9%), treatment temperature (30-60°C), and time (30-210min) on total chlorophyll content (TCC) were optimized using response surface methodology. A quadratic regression model (R(2)=0.9486) was obtained from the experimental design. Optimum treatment conditions were 8% enzyme concentration, 45°C, and 30min, which yielded a 50.747mgTCC/100g spinach pulp. Enzymatic treatment was followed by solvent extraction with ethanol at a solvent-to-sample ratio of 2.5:1 at 60°C for 45min for the highest TCC recovery. Pretreatment with enzyme and extraction in ethanol resulted in 39% increase in Zn-chlorophyll derivative yield. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Controlling the Size and Shape of the Elastin-Like Polypeptide based Micelles

    NASA Astrophysics Data System (ADS)

    Streletzky, Kiril; Shuman, Hannah; Maraschky, Adam; Holland, Nolan

    Elastin-like polypeptide (ELP) trimer constructs make reliable environmentally responsive micellar systems because they exhibit a controllable transition from being water-soluble at low temperatures to aggregating at high temperatures. It has been shown that depending on the specific details of the ELP design (length of the ELP chain, pH and salt concentration) micelles can vary in size and shape between spherical micelles with diameter 30-100 nm to elongated particles with an aspect ratio of about 10. This makes ELP trimers a convenient platform for developing potential drug delivery and bio-sensing applications as well as for understanding micelle formation in ELP systems. Since at a given salt concentration, the headgroup area for each foldon should be constant, the size of the micelles is expected to be proportional to the volume of the linear ELP available per foldon headgroup. Therefore, adding linear ELPs to a system of ELP-foldon should result in changes of the micelle volume allowing to control micelle size and possibly shape. The effects of addition of linear ELPs on size, shape, and molecular weight of micelles at different salt concentrations were studied by a combination of Dynamic Light Scattering and Static Light Scattering. The initial results on 50 µM ELP-foldon samples (at low salt) show that Rh of mixed micelles increases more than 5-fold as the amount of linear ELP raised from 0 to 50 µM. It was also found that a given mixture of linear and trimer constructs has two temperature-based transitions and therefore displays three predominant size regimes.

  6. Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles.

    PubMed

    Kheiri Manjili, Hamidreza; Ghasemi, Parisa; Malvandi, Hojjat; Mousavi, Mir Sajjad; Attari, Elahe; Danafar, Hossein

    2017-07-01

    Curcumin (CUR) has been associated with anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability. To progress the bioavailability and water solubility of CUR, we synthesized five series of mono methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by H NMR, FTIR, DSC and GPC techniques. In this study, CUR was encapsulated within micelles through a single-step nano-precipitation method, leading to formation of CUR-loaded mPEG-PCL (CUR/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The cytotoxicity of void CUR, mPEG-PCL and CUR/mPEG-PCL micelles was compared to each other by performing MTT assay of the treated MCF-7 and 4T1 cell line. Study of the in vivo pharmacokinetics of the CUR-loaded micelles was also carried out on selected copolymers in comparison with CUR solution formulations. The results showed that the zeta potential of CUR-loaded micelles was about -11.5mV and the average size was 81.0nm. CUR was encapsulated into mPEG-PCL micelles with loading capacity of 20.65±0.015% and entrapment efficiency of 89.32±0.34%. The plasma AUC (0-t), t 1/2 and C max of CUR micelles were increased by 52.8, 4.63 and 7.51-fold compared to the CUR solution, respectively. In vivo results showed that multiple injections of CUR-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of CUR. These results suggested that mPEG-PCL micelles would be a potential carrier for CUR. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Calculations of critical micelle concentration by dissipative particle dynamics simulations: the role of chain rigidity.

    PubMed

    Lee, Ming-Tsung; Vishnyakov, Aleksey; Neimark, Alexander V

    2013-09-05

    Micelle formation in surfactant solutions is a self-assembly process governed by complex interplay of solvent-mediated interactions between hydrophilic and hydrophobic groups, which are commonly called heads and tails. However, the head-tail repulsion is not the only factor affecting the micelle formation. For the first time, we present a systematic study of the effect of chain rigidity on critical micelle concentration and micelle size, which is performed with the dissipative particle dynamics simulation method. Rigidity of the coarse-grained surfactant molecule was controlled by the harmonic bonds set between the second-neighbor beads. Compared to flexible molecules with the nearest-neighbor bonds being the only type of bonded interactions, rigid molecules exhibited a lower critical micelle concentration and formed larger and better-defined micelles. By varying the strength of head-tail repulsion and the chain rigidity, we constructed two-dimensional diagrams presenting how the critical micelle concentration and aggregation number depend on these parameters. We found that the solutions of flexible and rigid molecules that exhibited approximately the same critical micelle concentration could differ substantially in the micelle size and shape depending on the chain rigidity. With the increase of surfactant concentration, primary micelles of more rigid molecules were found less keen to agglomeration and formation of nonspherical aggregates characteristic of flexible molecules.

  8. Dependence of the form factor of ganglioside micelles on a conformational change with temperature

    NASA Astrophysics Data System (ADS)

    Corti, Mario; Boretta, Marco; Cantù, Laura; Del Favero, Elena; Lesieur, Pierre

    1996-09-01

    The gangliosides GM2, GM1 and GD1b, biological amphiphiles with a double tail hydrophobic part and an oligosaccharide chain headgroup, form micelles in solution. Light scattering experiments have shown that ganglioside micelles which have gone through a temperature cycle have a smaller molecular mass and hydrodynamic radius than those which have been kept at room temperature. This fact has been interpreted with the hypothesis that, with temperature, the ganglioside molecules undergo a conformational change which affects their micellar properties appreciably. Careful small angle X-ray experiments, aimed to confirm the light scattering data and to evidence differences in the micellar internal structure are presented. Ganglioside micelles are quite inhomogeneous particles with respect to X-ray scattering, since there is a large contrast variation between the inner lipid part and the external hydrated sugar layer. Experimental form factors are fitted with a double-shell oblate-ellipsoid model.

  9. Solution structure of detergent micelles at conditions relevant to membrane protein crystallization.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Littrell, K.; Thiyagarajan, P.; Tiede, D.

    1999-07-02

    In this study small angle neutron scattering was used to characterize the formation of micelles in aqueous solutions of the detergents DMG and SPC as a function of detergent concentration and ionic strength of the solvent. The effects on the micelle structure of the additives glycerol and PEG, alone as well as in combination typical for actual membrane protein crystallization, were also explored. This research suggests that the micelles are cigar-like in form at the concentrations studied. The size of the micelles was observed to increase with increasing ionic strength but decrease with the addition of glycerol or PEG.

  10. Multifunctional polymeric micelles loaded with doxorubicin and poly(dithienyl-diketopyrrolopyrrole) for near-infrared light-controlled chemo-phototherapy of cancer cells.

    PubMed

    Liu, Hui; Wang, Kai; Yang, Cangjie; Huang, Shuo; Wang, Mingfeng

    2017-09-01

    Polymeric micelles loaded with multiple therapeutic modalities are important to overcome challenges such as drug resistance and improve the therapeutic efficacy. Here we report a new polymer micellar drug carrier that integrates chemotherapy and photothermal therapy in a single platform. Specifically, a narrow bandgap poly(dithienyl-diketopyrrolopyrrole) (PDPP) polymer was encapsulated together with a model anticancer drug doxorubicin (DOX) in the hydrophobic cores of polymeric micelles formed by Pluronic F127, an amphiphilic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer. The PDPP polymer served as an organic photothermal agent that absorbs near-infrared light (700-1000nm) and transforms into heat efficiently. The dual functional micelles co-loaded with PDPP and DOX in the hydrophobic compartment showed good colloidal stability after being stored at 4°C at least over two months, and remained visibly stable after 808-nm laser irradiation. The loaded DOX had negligible effect on the size and photothermal property of the micelles. The release of DOX from the micelles could be enhanced by the "breathing" effect of shrinking/swelling of the micelles induced by the temperature change, owing to the thermosensitive nature of the F127 polymers. Importantly, the ternary F127/PDPP/DOX micelles under 808-nm laser irradiation showed enhanced cytotoxicity against cancer cells such as HeLa cells, compared to F127 micelles containing single modality of either PDPP or DOX only. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Protein composition of different sized casein micelles in milk after the binding of lactoferrin or lysozyme.

    PubMed

    Anema, Skelte G; de Kruif, C G Kees

    2013-07-24

    Casein micelles with bound lactoferrin or lysozyme were fractionated into sizes ranging in radius from ∼50 to 100 nm. The κ-casein content decreased markedly and the αS-casein/β-casein content increased slightly as micelle size increased. For lactoferrin, higher levels were bound to smaller micelles. The lactoferrin/κ-casein ratio was constant for all micelle sizes, whereas the lactoferrin/αS-casein and lactoferrin/β-casein ratio decreased with increasing micelle size. This indicates that the lactoferrin was binding to the surface of the casein micelles. For lysozyme, higher levels bound to larger casein micelles. The lysozyme/αS-casein and lysozyme/β-casein ratios were nearly constant, whereas the lysozyme/κ-casein ratio increased with increasing micelle size, indicating that lysozyme bound to αS-casein and β-casein in the micelle core. Lactoferrin is a large protein that cannot enter the casein protein mesh; therefore, it binds to the micelle surface. The smaller lysozyme can enter the protein mesh and therefore binds to the more charged αS-casein and β-casein.

  12. Evaporative concentration of skimmed milk: effect on casein micelle hydration, composition, and size.

    PubMed

    Liu, Dylan Z; Dunstan, David E; Martin, Gregory J O

    2012-10-01

    Understanding the effect of evaporative concentration on casein micelle composition is of high importance for milk processing. Alterations to the hydration, composition and size of casein micelles were investigated in skimmed milk evaporated to concentrations of 12-45% total solids content. The size of casein micelles was determined by dynamic light scattering, and the water content and composition determined by analysis of supernatants and pellets obtained by ultracentrifugation. The mass balance and hydration results showed that during the evaporation process, while micelles were dehydrated, water was removed preferentially from the serum. The amount of soluble casein and calcium in the serum decreased as a function of increasing solids content, indicating a shift of these components to the micelles. The formation of a small proportion of micelle aggregates at high concentrations appeared dependent on the time kept at these concentrations. Upon redilution with water, casein micelles were immediately rehydrated and aggregates were broken up in a matter of minutes. Soluble calcium and pH returned to their original state over a number of hours; however, only a small percentage of original soluble casein returned to the serum over the 5h period investigated. These results showed that casein micelles are significantly affected by evaporative concentration and that the alterations are not completely and rapidly reversible. Copyright © 2012. Published by Elsevier Ltd.

  13. Comprehensive chlorophyll composition in the main edible seaweeds.

    PubMed

    Chen, Kewei; Ríos, José Julián; Pérez-Gálvez, Antonio; Roca, María

    2017-08-01

    Natural chlorophylls present in seaweeds have been studied regarding their biological activities and health benefit effects. However, detailed studies regarding characterization of the complete chlorophyll profile either qualitatively and quantitatively are scarce. This work deals with the comprehensive spectrometric study of the chlorophyll derivatives present in the five main coloured edible seaweeds. The novel complete MS 2 characterization of five chlorophyll derivatives: chlorophyll c 2 , chlorophyll c 1 , purpurin-18 a, pheophytin d and phytyl-purpurin-18 a has allowed to obtain fragmentation patterns associated with their different structural features. New chlorophyll derivatives have been identified and quantified by first time in red, green and brown seaweeds, including some oxidative structures. Quantitative data of the chlorophyll content comes to achieve significant information for food composition databases in bioactive compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Stability of casein micelles in milk

    NASA Astrophysics Data System (ADS)

    Tuinier, R.; de Kruif, C. G.

    2002-07-01

    Casein micelles in milk are proteinaceous colloidal particles and are essential for the production of flocculated and gelled products such as yogurt, cheese, and ice-cream. The colloidal stability of casein micelles is described here by a calculation of the pair potential, containing the essential contributions of brush repulsion, electrostatic repulsion, and van der Waals attraction. The parameters required are taken from the literature. The results are expressed by the second osmotic virial coefficient and are quite consistent with experimental findings. It appears that the stability is mainly attributable to a steric layer of κ-casein, which can be described as a salted polyelectrolyte brush.

  15. Statistical crystallography of surface micelle spacing

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1992-01-01

    The aggregation of the recently reported surface micelles of block polyelectrolytes is analyzed using techniques of statistical crystallography. A polygonal lattice (Voronoi mosaic) connects center-to-center points, yielding statistical agreement with crystallographic predictions; Aboav-Weaire's law and Lewis's law are verified. This protocol supplements the standard analysis of surface micelles leading to aggregation number determination and, when compared to numerical simulations, allows further insight into the random partitioning of surface films. In particular, agreement with Lewis's law has been linked to the geometric packing requirements of filling two-dimensional space which compete with (or balance) physical forces such as interfacial tension, electrostatic repulsion, and van der Waals attraction.

  16. Octreotide-functionalized and resveratrol-loaded unimolecular micelles for targeted neuroendocrine cancer therapy

    NASA Astrophysics Data System (ADS)

    Xu, Wenjin; Burke, Jocelyn F.; Pilla, Srikanth; Chen, Herbert; Jaskula-Sztul, Renata; Gong, Shaoqin

    2013-09-01

    Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) that is often resistant to standard therapies. Resveratrol suppresses MTC growth in vitro, but it has low bioavailability in vivo due to its poor water solubility and rapid metabolic breakdown, as well as lack of tumor-targeting ability. A novel unimolecular micelle based on a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for NET-targeted delivery. The hyperbranched amphiphilic block copolymer consisted of a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell, and a hydrophilic poly(ethylene glycol) (PEG) outer shell. Octreotide (OCT), a peptide that shows strong binding affinity to somatostatin receptors, which are overexpressed on NET cells, was used as the targeting ligand. Resveratrol was physically encapsulated by the micelle with a drug loading content of 12.1%. The unimolecular micelles exhibited a uniform size distribution and spherical morphology, which were determined by both transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular uptake, cellular proliferation, and Western blot analyses demonstrated that the resveratrol-loaded OCT-targeted micelles suppressed growth more effectively than non-targeted micelles. Moreover, resveratrol-loaded NET-targeted micelles affected MTC cells similarly to free resveratrol in vitro, with equal growth suppression and reduction in NET marker production. These results suggest that the H40-based unimolecular micelle may offer a promising approach for targeted NET therapy.

  17. Spatial variability of chlorophyll and nitrogen content of rice from hyperspectral imagery

    NASA Astrophysics Data System (ADS)

    Moharana, Shreedevi; Dutta, Subashisa

    2016-12-01

    Chlorophyll and nitrogen are the most essential parameters for paddy crop growth. Spectroradiometric measurements were collected at canopy level during critical growth period of rice. Chemical analysis was performed to quantify the total leaf content. By exploiting the ground based measurements, regression models were established for chlorophyll and nitrogen aimed indices with their corresponding crop growth variables. Vegetation index models were developed for mapping these parameters from Hyperion imagery in an agriculture system. It was inferred that the present Simple Ratio (SR) and Leaf Nitrogen Concentration (LNC) indices, which followed a linear and nonlinear relationship respectively, were completely different from published Tian et al. (2011). The nitrogen content varied widely from 1 to 4% and only 2 to 3% for paddy crop using present modified index models and Tian et al. (2011) respectively. The modified LNC index model performed better than the established Tian et al. (2011) model as far as estimated nitrogen content from Hyperion imagery was concerned. Furthermore, within the observed chlorophyll range obtained from the studied rice varieties grown in the rice agriculture system, the index models (LNC, OASVI, Gitelson, mSR and MTCI) performed well in the spatial distribution of rice chlorophyll content from Hyperion imagery. Spatial distribution of total chlorophyll content varied widely from 1.77 to 5.81 mg/g (LNC), 3.0 to 13 mg/g (OASVI), 0.5 to 10.43 mg/g (Gitelson), 2.18 to 10.61 mg/g (mSR) and 2.90 to 5.40 mg/g (MTCI). The spatial information of these parameters will help in proper nutrient management, yield forecasting, and will serve as inputs for crop growth and forecasting models for a precision rice agriculture system.

  18. Decadal Changes in Global Ocean Chlorophyll

    NASA Technical Reports Server (NTRS)

    Gregg, Watson W.; Conkright, Margarita E.; Koblinsky, Chester J. (Technical Monitor)

    2001-01-01

    The global ocean chlorophyll archive produced by the Coastal Zone Color Scanner (CZCS) was revised using compatible algorithms with the Sea-viewing Wide Field-of-view Sensor (SeaWIFS), and both were blended with in situ data. This methodology permitted a quantitative comparison of decadal changes in global ocean chlorophyll from the CZCS (1979-1986) and SeaWiFS (Sep. 1997-Dec. 2000) records. Global seasonal means of ocean chlorophyll decreased over the two observational segments, by 8% in winter to 16% in autumn. Chlorophyll in the high latitudes was responsible for most of the decadal change. Conversely, chlorophyll concentrations in the low latitudes increased. The differences and similarities of the two data records provide evidence of how the Earth's climate may be changing and how ocean biota respond. Furthermore, the results have implications for the ocean carbon cycle.

  19. Surface disturbance of cryptobiotic soil crusts: nitrogenase activity, chlorophyll content, and chlorophyll degradation

    USGS Publications Warehouse

    Belnap, Jayne; Harper, Kimball T.; Warren, Steven D.

    1994-01-01

    Cryptobiotic soil crusts are an important component of semiarid and arid ecosystems. An important role of these crusts is the contribution of fixed nitrogen to cold‐desert ecosystems. This study examines the residual effects of various intensities and combinations of different surface disturbances (raking, scalping, and tracked vehicles) on nitrogenase activity, chlorophyll content, and chlorophyll degradation in these soil crusts. Nine months after disturbance chlorophyll content of disturbed soils was not statistically different from undisturbed controls, except in the scalped treatments, indicating recovery of this characteristic is fairly quick unless surface material is removed. Differences in chlorophyll degradation among treatments were not statistically significant. However, nitrogenase activity in all treatments showed tremendous reductions, ranging from 77–97%, when compared to the control, indicating this characteristic is slow to recover. Consequently, assessment of crustal recovery from disturbance must include not only visual and biomass characteristics but other physiological measurements as well. Areas dominated by these crusts should be managed conservatively until the implications of crustal disturbance is better understood.

  20. Low-cost chlorophyll meter (LCCM): portable measuring device for leaf chlorophyll

    NASA Astrophysics Data System (ADS)

    Hutomo E. P., Evan; Adibawa, Marcelinus Alfasisurya S.; Prilianti, Kestrilia R.; Heriyanto, Heriyanto; Brotosudarmo, Tatas H. P.

    2016-11-01

    Portable leaf chlorophyll meter, named low-cost chlorophyll meter (LCCM), has been created. This device was created to help farmer determining the health condition of plant based on the greenness level of leaf surface. According to previous studies, leaf greenness with a certain amount of chlorophyll level has a direct correlation with the amount of nitrogen in the leaf that indicates health of the plant and this fact needed to provide an estimate of further measures to keep the plants healthy. Device that enables to measure the leaf color change is soil plant analysis development (SPAD) meter 502 from Konica Minolta but it is relatively expensive. To answer the need of low-cost chlorophyll scanner device, this research conducted experiment using light reflectance as the base mechanism. Reflectance system from LCCM consists of near-infrared light emitting diode (LED) and red LED as light resources and photodiode. The output from both of light resources calculated using normalized difference vegetation index (NDVI) formula as the results fetched and displayed on the smartphone application using Bluetooth communication protocol. Finally, the scanner has been made as well as the Android application named NDVI Reader. The LCCM system which has been tested on 20 sample of cassava leaf with SPAD meter as a variable control showed coefficient of determination 0.9681 and root-mean-square error (RMSE) 0.014.

  1. Chlorophyllase in Piper betle L. has a role in chlorophyll homeostasis and senescence dependent chlorophyll breakdown.

    PubMed

    Gupta, Supriya; Gupta, Sanjay Mohan; Sane, Aniruddha P; Kumar, Nikhil

    2012-06-01

    Total chlorophyll content and chlorophyllase (chlorophyll-chlorophyllido hydrolase EC 3.1.1.14) activity in fresh leaves of Piper betle L. landrace KS was, respectively, twofold higher and eight fold lower than KV, showing negative correlation between chlorophyll and chlorophyllase activity. Specific chlorophyllase activity was nearly eightfold more in KV than KS. ORF of 918 nt was found in cloned putative chlorophyllase cDNAs from KV and KS. The gene was present as single copy in both the landraces. The encoded polypeptide of 306 amino acids differed only at two positions between the KV and KS; 203 (cysteine to tyrosine) and 301 (glutamine to glycine). Difference in chlorophyllase gene expression between KV and KS was evident in fresh and excised leaves. Up regulation of chlorophyllase gene by ABA and down regulation by BAP was observed in both the landraces; however, there was quantitative difference between KV and KS. Data suggests that chlorophyllase in P. betle is involved in chlorophyll homeostasis and chlorophyll loss during post harvest senescence.

  2. Facile fabrication of core cross-linked micelles by RAFT polymerization and enzyme-mediated reaction.

    PubMed

    Wu, Yukun; Lai, Quanyong; Lai, Shuqi; Wu, Jing; Wang, Wei; Yuan, Zhi

    2014-06-01

    Polymeric micelles formed in aqueous solution by assembly of amphiphilic block copolymers have been extensively investigated due to their great potential as drug carriers. However, the stability of polymeric assembly is still one of the major challenges in delivering drugs to tissues and cells. Here, we report a facile route to fabricate core cross-linked (CCL) micelles using an enzymatic polymerization as the cross-linking method. We present synthesis of poly(ethylene glycol)-block-poly(N-isopropyl acrylamide-co-N-(4-hydroxyphenethyl) acrylamide) diblock copolymer PEG-b-P(NIPAAm-co-NHPAAm) via reversible addition-fragmentation chain transfer (RAFT) polymerization. The diblock copolymer was then self-assembled into non-cross-linked (NCL) micelles upon heating above the lower critical solution temperature (LCST), and subsequently cross-linked using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) as enzyme and oxidant. The characterization of the diblock copolymer and micelles were studied by NMR, DLS, UV-vis, and fluorescence spectroscopy. The fluorescence study reveals that the cross-linking process endows the micelles with much lower critical micelle concentration (CMC). In addition, the drug release study shows that the CCL micelles have lower release amount of doxorubicin (DOX) than the NCL micelles due to the enhanced stability of the CCL micelles by core cross-linking process. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy.

    PubMed

    Zhang, Wenli; Li, Caibin; Jin, Ya; Liu, Xinyue; Wang, Zhiyu; Shaw, John P; Baguley, Bruce C; Wu, Zimei; Liu, Jianping

    2018-11-01

    To improve drug retention in carriers for amphiphilic asulacrine (ASL), a novel active loading method using micelle gradient was developed to fabricate the ASL-loaded multiseed liposomes (ASL-ML). The empty ML were prepared by hydrating a thin film with empty micelles. Then the micelles in liposomal compartment acting as 'micelle pool' drove the drug to be loaded after the outer micelles were removed. Some reasoning studies including critical micelle concentration (CMC) determination, influencing factors tests on entrapment efficiency (EE), structure visualization, and drug release were carried out to explore the mechanism of active loading, ASL location, and the structure of ASL-ML. Comparisons were made between pre-loading and active loading method. Finally, the extended drug retention capacity of ML was evaluated through pharmacokinetic, drug tissue irritancy, and in vivo anti-tumor activity studies. Comprehensive results from fluorescent and transmission electron microscope (TEM) observation, encapsulation efficiency (EE) comparison, and release studies demonstrated the formation of ML-shell structure for ASL-ML without inter-carrier fusion. The location of drug mainly in inner micelles as well as the superiority of post-loading to the pre-loading method , in which drug in micelles shifted onto the bilayer membrane was an additional positive of this delivery system. It was observed that the drug amphiphilicity and interaction of micelles with drug were the two prerequisites for this active loading method. The extended retention capacity of ML has been verified through the prolonged half-life, reduced paw-lick responses in rats, and enhanced tumor inhibition in model mice. In conclusion, ASL-ML prepared by active loading method can effectively load drug into micelles with expected structure and improve drug retention.

  4. The Use of a Chlorophyll Meter (SPAD-502) for Field Determinations of Red Mangrove (Rhizophora Mangle L.) Leaf Chlorophyll Amount

    NASA Technical Reports Server (NTRS)

    Connelly, Xana M.

    1997-01-01

    The red mangrove Rhizophora mangle L., is a halophytic woody spermatophyte common to the land-sea interface of tropical and subtropical intertidal zones. It has been reported that 60 to 75% of the coastline of the earth's tropical regions are lined with mangroves. Mangroves help prevent shoreline erosion, provide breeding, nesting and feeding areas for many marine animals and birds. Mangroves are important contributors of primary production in the coastal environment, and this is largely proportional to the standing crop of leaf chlorophylls. Higher intensities of ultraviolet radiation, resulting from stratospheric ozone depletion, can lead to a reduction of chlorophyll in terrestrial plants. Since the most common method for determining chlorophyll concentration is by extraction and this is labor intensive and time consuming, few studies on photosynthetic pigments of mangroves have been reported. Chlorophyll meter readings have been related to leaf chlorophyll content in apples and maples. It has also been correlated to nitrogen status in corn and cotton. Peterson et al., (1993) used a chlorophyll meter to detect nitrogen deficiency in crops and in determining the need for additional nitrogen fertilizer. Efforts to correlate chlorophyll meter measurements to chlorophyll content of mangroves have not been reported. This paper describes the use of a hand-held chlorophyll meter (Minolta SPAD-502) to determine the amount of red mangrove foliar chlorophyll present in the field.

  5. Influence of succinylation on physicochemical property of yak casein micelles.

    PubMed

    Yang, Min; Yang, Jitao; Zhang, Yuan; Zhang, Weibing

    2016-01-01

    Succinylation is a chemical-modification method that affects the physicochemical characteristics and functional properties of proteins. This study assessed the influence of succinylation on the physicochemical properties of yak casein micelles. The results revealed that surface hydrophobicity indices decreased with succinylation. Additionally, denaturation temperature and denaturation enthalpy decreased with increasing succinylation level, except at 82%. The buffering properties of yak casein micelles were affected by succinylation. It was found that chemical modification contributed to a slight shift of the buffering peak towards a lower pH value and a markedly increase of the maximum buffering values of yak casein micelles at pH 4.5-6.0 and pH < 3. Succinylation increased yak casein micellar hydration and whiteness values. The findings obtained from this study will provide the basic information on the physicochemical properties of native and succinylated yak casein micelles. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Interactions between tea catechins and casein micelles and their impact on renneting functionality.

    PubMed

    Haratifar, Sanaz; Corredig, Milena

    2014-01-15

    Many studies have shown that tea catechins bind to milk proteins. This research focused on the association of tea polyphenols with casein micelles, and the consequences of the interactions on the renneting behaviour of skim milk. It was hypothesized that epigallocatechin-gallate (EGCG), the main catechin present in green tea, forms complexes with the casein micelles and that the association modifies the processing functionality of casein micelles. The binding of EGCG to casein micelles was quantified using HPLC. The formation of catechin-casein micelles complexes affected the rennet induced gelation of milk, and the effect was concentration dependent. Both the primary as well as the secondary stage of gelation were affected. These experiments clearly identify the need for a better understanding of the effect of tea polyphenols on the processing functionality of casein micelles, before milk products can be used as an appropriate platform for delivery of bioactive compounds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Evaluating the relationship between leaf chlorophyll concentration and SPAD-502 chlorophyll meter readings.

    PubMed

    Uddling, J; Gelang-Alfredsson, J; Piikki, K; Pleijel, H

    2007-01-01

    Relationships between chlorophyll concentration ([chl]) and SPAD values were determined for birch, wheat, and potato. For all three species, the relationships were non-linear with an increasing slope with increasing SPAD. The relationships for birch and wheat were strong (r (2) approximately 0.9), while the potato relationship was comparatively weak (r (2) approximately 0.5). Birch and wheat had very similar relationships when the chlorophyll concentration was expressed per unit leaf area, but diverged when it was expressed per unit fresh weight. Furthermore, wheat showed similar SPAD-[chl] relationships for two different cultivars and during two different growing seasons. The curvilinear shape of the SPAD-[chl] relationships agreed well with the simulated effects of non-uniform chlorophyll distribution across the leaf surface and multiple scattering, causing deviations from linearity in the high and low SPAD range, respectively. The effect of non-uniformly distributed chlorophyll is likely to be more important in explaining the non-linearity in the empirical relationships, since the effect of scattering was predicted to be comparatively weak. The simulations were based on the algorithm for the calculation of SPAD-502 output values. We suggest that SPAD calibration curves should generally be parameterised as non-linear equations, and we hope that the relationships between [chl] and SPAD and the simulations of the present study can facilitate the interpretation of chlorophyll meter calibrations in relation to optical properties of leaves in future studies.

  8. Temperature Effect on Micelle Formation: Molecular Thermodynamic Model Revisited.

    PubMed

    Khoshnood, Atefeh; Lukanov, Boris; Firoozabadi, Abbas

    2016-03-08

    Temperature affects the aggregation of macromolecules such as surfactants, polymers, and proteins in aqueous solutions. The effect on the critical micelle concentration (CMC) is often nonmonotonic. In this work, the effect of temperature on the micellization of ionic and nonionic surfactants in aqueous solutions is studied using a molecular thermodynamic model. Previous studies based on this technique have predicted monotonic behavior for ionic surfactants. Our investigation shows that the choice of tail transfer energy to describe the hydrophobic effect between the surfactant tails and the polar solvent molecules plays a key role in the predicted CMC. We modify the tail transfer energy by taking into account the effect of the surfactant head on the neighboring methylene group. The modification improves the description of the CMC and the predicted micellar size for aqueous solutions of sodium n-alkyl sulfate, dodecyl trimethylammonium bromide (DTAB), and n-alkyl polyoxyethylene. The new tail transfer energy describes the nonmonotonic behavior of CMC versus temperature. In the DTAB-water system, we redefine the head size by including the methylene group, next to the nitrogen, in the head. The change in the head size along with our modified tail transfer energy improves the CMC and aggregation size prediction significantly. Tail transfer is a dominant energy contribution in micellar and microemulsion systems. It also promotes the adsorption of surfactants at fluid-fluid interfaces and affects the formation of adsorbed layer at fluid-solid interfaces. Our proposed modifications have direct applications in the thermodynamic modeling of the effect of temperature on molecular aggregation, both in the bulk and at the interfaces.

  9. Dextran based Polymeric Micelles as Carriers for Delivery of Hydrophobic Drugs.

    PubMed

    Mocanu, Georgeta; Nichifor, Marieta; Sacarescu, Liviu

    2017-01-01

    The improvement of drugs bioavailability, especially of the hydrophobic ones, by using various nanoparticles is a very exciting field of the modern research. The applicability of nano-sized shell crosslinked micelles based on dextran as supports for controlled release of several hydrophobic drugs (nystatin, rifampicin, resveratrol, and curcumin) was investigated by in vitro drug loading/release experiments. The synthesized crosslinked micelles were loaded with drugs of various hydrophobicities and their retention/release behavior was followed by dialysis procedure. Crosslinked micelles obtained from dextran with octadecyl end groups, with or without N-(2- hydroxypropyl)-N,N-dimethyl-N-benzylammonium chloride groups attached to the main dextran chains, could retain the drugs in amounts which increased with increasing drug hydrophobicity (water insolubility), as follows: 30-60 mg rifampicin/g, 70-100 mg nystatin/g, 120-144 mg resveratrol/g and 146-260 mg curcumin/g. The rate of drug release from the loaded micelles was also dependent on the drug hydrophobicity and was always slower than the free drug recovery. Antioxidant activity of curcumin and resveratrol released from the loaded micelles was preserved. The results highlighted the potential of the new nano-sized micelles as carriers for prolonged and controlled delivery of various hydrophobic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Cellular mechanism of oral absorption of solidified polymer micelles.

    PubMed

    Abramov, Eva; Cassiola, Flavia; Schwob, Ouri; Karsh-Bluman, Adi; Shapero, Mara; Ellis, James; Luyindula, Dema; Adini, Irit; D'Amato, Robert J; Benny, Ofra

    2015-11-01

    Oral delivery of poorly soluble and permeable drugs represents a significant challenge in drug development. The oral delivery of drugs remains to be the ultimate route of any drugs. However, in many cases, drugs are not absorbed well in the gastrointestinal tract, or they lose their activity. Polymer micelles were recognized as an effective carrier system for drug encapsulation, and are now studied as a vehicle for oral delivery of insoluble compounds. We characterized the properties of monomethoxy polyethylene glycol-poly lactic acid (mPEG-PLA) micelles, and visualized their internalization in mouse small intestine. Using Caco-2 cells as a cellular model, we studied the kinetics of particle uptake, their transport, and the molecular mechanism of their intestinal absorption. Moreover, by inhibiting specific endocytosis pathways, pharmacologically and genetically, we found that mPEG-PLA nanoparticle endocytosis is mediated by clathrin in an energy-dependent manner, and that the low-density lipoprotein receptor is involved. Many current drugs used are non-water soluble and indeed, the ability to deliver these drugs via the gastrointestinal tract remains the holy grail for many researchers. The authors in this paper developed monomethoxy polyethylene glycol-poly lactic acid (mPEG-PLA) micelles as a drug nanocarrier, and studied the mechanism of uptake across intestinal cells. The findings should improve our current understanding and point to the development of more nanocarriers. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Tomato seeds maturity detection system based on chlorophyll fluorescence

    NASA Astrophysics Data System (ADS)

    Li, Cuiling; Wang, Xiu; Meng, Zhijun

    2016-10-01

    Chlorophyll fluorescence intensity can be used as seed maturity and quality evaluation indicator. Chlorophyll fluorescence intensity of seed coats is tested to judge the level of chlorophyll content in seeds, and further to judge the maturity and quality of seeds. This research developed a detection system of tomato seeds maturity based on chlorophyll fluorescence spectrum technology, the system included an excitation light source unit, a fluorescent signal acquisition unit and a data processing unit. The excitation light source unit consisted of two high power LEDs, two radiators and two constant current power supplies, and it was designed to excite chlorophyll fluorescence of tomato seeds. The fluorescent signal acquisition unit was made up of a fluorescence spectrometer, an optical fiber, an optical fiber scaffolds and a narrowband filter. The data processing unit mainly included a computer. Tomato fruits of green ripe stage, discoloration stage, firm ripe stage and full ripe stage were harvested, and their seeds were collected directly. In this research, the developed tomato seeds maturity testing system was used to collect fluorescence spectrums of tomato seeds of different maturities. Principal component analysis (PCA) method was utilized to reduce the dimension of spectral data and extract principal components, and PCA was combined with linear discriminant analysis (LDA) to establish discriminant model of tomato seeds maturity, the discriminant accuracy was greater than 90%. Research results show that using chlorophyll fluorescence spectrum technology is feasible for seeds maturity detection, and the developed tomato seeds maturity testing system has high detection accuracy.

  12. Protein unfolding in detergents: effect of micelle structure, ionic strength, pH, and temperature.

    PubMed Central

    Otzen, Daniel E

    2002-01-01

    The 101-residue monomeric protein S6 unfolds in the anionic detergent sodium dodecyl sulfate (SDS) above the critical micelle concentration, with unfolding rates varying according to two different modes. Our group has proposed that spherical micelles lead to saturation kinetics in unfolding (mode 1), while cylindrical micelles prevalent at higher SDS concentrations induce a power-law dependent increase in the unfolding rate (mode 2). Here I investigate in more detail how micellar properties affect protein unfolding. High NaCl concentrations, which induce cylindrical micelles, favor mode 2. This is consistent with our model, though other effects such as electrostatic screening cannot be discounted. Furthermore, unfolding does not occur in mode 2 in the cationic detergent LTAB, which is unable to form cylindrical micelles. A strong retardation of unfolding occurs at higher LTAB concentrations, possibly due to the formation of dead-end protein-detergent complexes. A similar, albeit much weaker, effect is seen in SDS in the absence of salt. Chymotrypsin inhibitor 2 exhibits the same modes of unfolding in SDS as S6, indicating that this type of protein unfolding is not specific for S6. The unfolding process in mode 1 has an activation barrier similar in magnitude to that in water, while the activation barrier in mode 2 is strongly concentration-dependent. The strong pH-dependence of unfolding in SDS and LTAB suggests that the rate of unfolding in anionic detergent is modulated by repulsion between detergent headgroups and anionic side chains, while cationic side chains modulate unfolding rates in cationic detergents. PMID:12324439

  13. The role of chlorophyll b in photosynthesis: Hypothesis

    PubMed Central

    Eggink, Laura L; Park, Hyoungshin; Hoober, J Kenneth

    2001-01-01

    Background The physico-chemical properties of chlorophylls b and c have been known for decades. Yet the mechanisms by which these secondary chlorophylls support assembly and accumulation of light-harvesting complexes in vivo have not been resolved. Presentation Biosynthetic modifications that introduce electronegative groups on the periphery of the chlorophyll molecule withdraw electrons from the pyrrole nitrogens and thus reduce their basicity. Consequently, the tendency of the central Mg to form coordination bonds with electron pairs in exogenous ligands, a reflection of its Lewis acid properties, is increased. Our hypothesis states that the stronger coordination bonds between the Mg atom in chlorophyll b and chlorophyll c and amino acid sidechain ligands in chlorophyll a/b- and a/c-binding apoproteins, respectively, enhance their import into the chloroplast and assembly of light-harvesting complexes. Testing Several apoproteins of light-harvesting complexes, in particular, the major protein Lhcb1, are not detectable in leaves of chlorophyll b-less plants. A direct test of the hypothesis – with positive selection – is expression, in mutant plants that synthesize only chlorophyll a, of forms of Lhcb1 in which weak ligands are replaced with stronger Lewis bases. Implications The mechanistic explanation for the effects of deficiencies in chlorophyll b or c points to the need for further research on manipulation of coordination bonds between these chlorophylls and chlorophyll-binding proteins. Understanding these interactions will possibly lead to engineering plants to expand their light-harvesting antenna and ultimately their productivity. PMID:11710960

  14. Reduction-responsive interlayer-crosslinked micelles prepared from star-shaped copolymer via click chemistry for drug controlled release

    NASA Astrophysics Data System (ADS)

    Dai, Yu; Wang, Hongquan; Zhang, Xiaojin

    2017-12-01

    To improve the stability of polymeric micelles, here we describe interlayer-crosslinked micelles prepared from star-shaped copolymer via click chemistry. The formation of interlayer-crosslinked micelles was investigated and confirmed by proton nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and fluorescence spectroscopy. The morphology of un-crosslinked micelles and crosslinked micelles observed by transmission electron microscope is both uniform nano-sized spheres (approximately 20 nm). The crosslinking enhances the stability of polymeric micelles and improves the drug loading capacity of polymeric micelles. The interlayer-crosslinked micelles prepared from star-shaped copolymer and a crosslinker containing a disulfide bond are reduction-responsive and can release the drug quickly in the presence of the reducing agents such as glutathione (GSH).

  15. Polymeric microcapsules assembled from a cationic/zwitterionic pair of responsive block copolymer micelles.

    PubMed

    Addison, Timothy; Cayre, Olivier J; Biggs, Simon; Armes, Steven P; York, David

    2010-05-04

    Using a layer-by-layer (LbL) approach, this work presents the preparation of hollow microcapsules with a membrane constructed entirely from a cationic/zwitterionic pair of pH-responsive block copolymer micelles. Our previous work with such systems highlighted that, in order to retain the responsive nature of the individual micelles contained within the multilayer membranes, it is important to optimize the conditions required for the selective dissolution of the sacrificial particulate templates. Consequently, here, calcium carbonate particles have been employed as colloidal templates as they can be easily dissolved in aqueous environments with the addition of chelating agents such as ethylenediaminetetraacetic acid (EDTA). Furthermore, the dissolution can be carried out in solutions buffered to a desirable pH so not to adversely affect the pH sensitive micelles forming the capsule membranes. First, we have deposited alternating layers of anionic poly[2-(dimethylamino)ethyl methacrylate-block-poly(2-(diethylamino)ethyl methacrylate)] (PDMA-PDEA) and cationic poly(2-(diethylamino)ethyl)methacrylate-block-poly(methacrylic acid) (PDEA-PMAA) copolymer micelles onto calcium carbonate colloidal templates. After deposition of five micelle bilayers, addition of dilute EDTA solution resulted in dissolution of the calcium carbonate and formation of hollow polymer capsules. The capsules were imaged using atomic force microscopy (AFM) and scanning electron microscopy (SEM), which shows that the micelle/micelle membrane is sufficiently robust to withstand dissolution of the supporting template. Quartz crystal microbalance studies were conducted and provide good evidence that the micelle multilayer structure is retained after EDTA treatment. In addition, a hydrophobic dye was incorporated into the micelle cores prior to adsorption. After dissolution of the particle template, the resulting hollow capsules retained a high concentration of dye, suggesting that the core

  16. Collective degrees of freedom involved in absorption and desorption of surfactant molecules in spherical non-ionic micelles

    NASA Astrophysics Data System (ADS)

    Ahn, Yong Nam; Mohan, Gunjan; Kopelevich, Dmitry I.

    2012-10-01

    Dynamics of absorption and desorption of a surfactant monomer into and out of a spherical non-ionic micelle is investigated by coarse-grained molecular dynamics (MD) simulations. It is shown that these processes involve a complex interplay between the micellar structure and the monomer configuration. A quantitative model for collective dynamics of these degrees of freedom is developed. This is accomplished by reconstructing a multi-dimensional free energy landscape of the surfactant-micelle system using constrained MD simulations in which the distance between the micellar and monomer centers of mass is held constant. Results of this analysis are verified by direct (unconstrained) MD simulations of surfactant absorption in the micelle. It is demonstrated that the system dynamics is likely to deviate from the minimum energy path on the energy landscape. These deviations create an energy barrier for the monomer absorption and increase an existing barrier for the monomer desorption. A reduced Fokker-Planck equation is proposed to model these effects.

  17. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol

    NASA Astrophysics Data System (ADS)

    Li, Xinru; Zhang, Yanhui; Fan, Yating; Zhou, Yanxia; Wang, Xiaoning; Fan, Chao; Liu, Yan; Zhang, Qiang

    2011-12-01

    Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15), were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12). Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

  18. Water dynamics in large and small reverse micelles: From two ensembles to collective behavior

    PubMed Central

    Moilanen, David E.; Fenn, Emily E.; Wong, Daryl; Fayer, Michael D.

    2009-01-01

    The dynamics of water in Aerosol-OT reverse micelles are investigated with ultrafast infrared spectroscopy of the hydroxyl stretch. In large reverse micelles, the dynamics of water are separable into two ensembles: slow interfacial water and bulklike core water. As the reverse micelle size decreases, the slowing effect of the interface and the collective nature of water reorientation begin to slow the dynamics of the core water molecules. In the smallest reverse micelles, these effects dominate and all water molecules have the same long time reorientational dynamics. To understand and characterize the transition in the water dynamics from two ensembles to collective reorientation, polarization and frequency selective infrared pump-probe experiments are conducted on the complete range of reverse micelle sizes from a diameter of 1.6–20 nm. The crossover between two ensemble and collective reorientation occurs near a reverse micelle diameter of 4 nm. Below this size, the small number of confined water molecules and structural changes in the reverse micelle interface leads to homogeneous long time reorientation. PMID:19586114

  19. Fluorescent polymeric micelles with aggregation-induced emission properties for monitoring the encapsulation of doxorubicin.

    PubMed

    Chen, Jen-Ing; Wu, Wen-Chung

    2013-05-01

    A new type of fluorescent polymeric micelles is developed by self-assembly from a series of amphiphilic block copolymers, poly(ethylene glycol)-b-poly[styrene-co-(2-(1,2,3,4,5-pentaphenyl-1H-silol-1-yloxy)ethyl methacrylate)] [PEG-b-P(S-co-PPSEMA)]. Their capability of loading doxorubicin (DOX) is investigated by monitoring the loading content, encapsulation efficiency, and photophysical properties of micelles. Förster resonance energy transfer from PPSEMA to DOX is observed in DOX-loaded micelles, which can serve as an indication of successful encapsulation of DOX in these micelles. The application of this new type of fluorescent polymeric micelles as a fluorescent probe and an anticancer drug carrier simultaneously is explored by studying the intracellular uptake of DOX-loaded micelles. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Structural ordering of casein micelles on silicon nitride micro-sieves during filtration.

    PubMed

    Gebhardt, Ronald; Holzmüller, Wolfgang; Zhong, Qi; Müller-Buschbaum, Peter; Kulozik, Ulrich

    2011-11-01

    The paper reports on the structure and formation of casein micelle deposits on silicon nitride micro-sieves during the frontal filtration. The most frequent radius of the fractionated casein micelles we use is R=60 nm as detected by static light scattering (SLS) and atomic force microscopy (AFM). We estimate the size and size distribution of the casein micelles which pass through the micro-sieve during the filtration process. A sharpening of the size distribution at the beginning of the filtration process (t=40s) is followed by a broadening and a shift of the most frequent radii towards smaller sizes at later times (t=840 s). The size distribution of the micelles deposited on the micro-sieve during filtration is bimodal and consists of the largest and smallest micelles. At larger filtration times, we observe a shift of both deposited size classes towards smaller sizes. The atomic force micrographs of the reference sample reveal a tendency of the casein micelles to order in a hexagonal lattice when deposited on the micro-sieves by solution casting. The deposition of two size classes can be explained by a formation of a mixed hexagonal lattice with large micelles building up the basis lattice and smaller sizes filling octahedral and tetrahedral holes of the lattice. The accompanied compression with increasing thickness of the casein layer could result from preferential deposition of smaller sizes in the course of the filtration. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity.

    PubMed

    Yuba, Eiji; Sakaguchi, Naoki; Kanda, Yuhei; Miyazaki, Maiko; Koiwai, Kazunori

    2017-11-04

    (1) Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC) and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability. (2) Methods: Interaction of micelles with fluorescence dye-loaded liposomes, intracellular distribution of micelles, and antigenic proteins were observed. Finally, antigen-specific cellular immune response was evaluated in vivo using ELIspot assay. (3) Results: Micelles induced leakage of contents from liposomes via lipid mixing at low pH. Micelles were taken up by dendritic cells mainly via macropinocytosis and delivered ovalbumin (OVA) into the cytosol. After intradermal injection of micelles and OVA, OVA-specific cellular immunity was induced in the spleen. (4) Conclusions: pH-responsive micelles composed of DLPC and deoxycholic acid are promising as enhancers of cytosol delivery of antigens and the induction capability of cellular immunity for the treatment of cancer immunotherapy and infectious diseases.

  2. Effects of surfactant micelles on viscosity and conductivity of poly(ethylene glycol) solutions

    NASA Astrophysics Data System (ADS)

    Wang, Shun-Cheng; Wei, Tzu-Chien; Chen, Wun-Bin; Tsao, Heng-Kwong

    2004-03-01

    The neutral polymer-micelle interaction is investigated for various surfactants by viscometry and electrical conductometry. In order to exclude the well-known necklace scenario, we consider aqueous solutions of low molecular weight poly(ethylene glycol) (2-20)×103, whose radial size is comparable to or smaller than micelles. The single-tail surfactants consist of anionic, cationic, and nonionic head groups. It is found that the viscosity of the polymer solution may be increased several times by micelles if weak attraction between a polymer segment and a surfactant exists, ɛmicelles. Even though ɛ is small, the interaction energy between a macromolecule and a micelle can be a few kBT due to many contacts, and thus leads to polymer adsorption on micelles' surfaces. The rapid growth of the viscosity with surfactant concentration is therefore attributed to the considerable cross links among micelles and polymers (transient network). In addition to substantial alteration of the transport properties, this weak interaction also influences the onset point of thermodynamic instability associated with polymer-surfactant solutions. The examples include the decrease of critical aggregation concentration for ionic surfactant and clouding point for nonionic surfactant due to PEG addition.

  3. Topography of the casein micelle surface by surface plasmon resonance (SPR) using a selection of specific monoclonal antibodies.

    PubMed

    Dupont, Didier; Johansson, Annette; Marchin, Stephane; Rolet-Repecaud, Odile; Marchesseau, Sylvie; Leonil, Joelle

    2011-08-10

    Several theoretical models of the casein micelle structure have been proposed in the past, but the exact organization of the four individual caseins (α(s1), α(s2), β, and κ) within this supramolecular structure remains unknown. The present study aims at determining the topography of the casein micelle surface by following the interaction between 44 monoclonal antibodies specific for different epitopes of α(s1)-, α(s2)-, β-, and κ-casein and the casein micelle in real time and no labeling using a surface plasmon resonance (SPR)-based biosensor. Although the four individual caseins were found to be accessible for antibody binding, data confirmed that the C-terminal extremity of κ-casein was highly accessible and located at the periphery of the structure. When casein micelles were submitted to proteolysis, the C-terminal extremity of κ-casein was rapidly hydrolyzed. Disintegration of the micellar structure resulted in an increased access for antibodies to hydrophobic areas of α(s1)- and α(s2)-casein.

  4. Glucose-installed, SPIO-loaded PEG- b-PCL micelles as MR contrast agents to target prostate cancer cells

    NASA Astrophysics Data System (ADS)

    Theerasilp, Man; Sunintaboon, Panya; Sungkarat, Witaya; Nasongkla, Norased

    2017-11-01

    Polymeric micelles of poly(ethylene glycol)- block-poly(ɛ-caprolactone) bearing glucose analog encapsulated with superparamagnetic iron oxide nanoparticles (Glu-SPIO micelles) were synthesized as an MRI contrast agent to target cancer cells based on high-glucose metabolism. Compared to SPIO micelles (non-targeting SPIO micelles), Glu-SPIO micelles demonstrated higher toxicity to human prostate cancer cell lines (PC-3) at high concentration. Atomic absorption spectroscopy was used to determine the amount of iron in cells. It was found that the iron in cancer cells treated by Glu-SPIO micelles were 27-fold higher than cancer cells treated by SPIO micelles at the iron concentration of 25 ppm and fivefold at the iron concentration of 100 ppm. To implement Glu-SPIO micelles as a MR contrast agent, the 3-T clinical MRI was applied to determine transverse relaxivities ( r 2*) and relaxation rate (1/ T 2*) values. In vitro MRI showed different MRI signal from cancer cells after cellular uptake of SPIO micelles and Glu-SPIO micelles. Glu-SPIO micelles was highly sensitive with the r 2* in agarose gel at 155 mM-1 s-1. Moreover, the higher 1/ T 2* value was found for cancer cells treated with Glu-SPIO micelles. These results supported that glucose ligand increased the cellular uptake of micelles by PC-3 cells with over-expressing glucose transporter on the cell membrane. Thus, glucose can be used as a small molecule ligand for targeting prostate cancer cells overexpressing glucose transporter.

  5. Hyperspectral imaging detection of decayed honey peaches based on their chlorophyll content.

    PubMed

    Sun, Ye; Wang, Yihang; Xiao, Hui; Gu, Xinzhe; Pan, Leiqing; Tu, Kang

    2017-11-15

    Honey peach is a very common but highly perishable market fruit. When pathogens infect fruit, chlorophyll as one of the important components related to fruit quality, decreased significantly. Here, the feasibility of hyperspectral imaging to determine the chlorophyll content thus distinguishing diseased peaches was investigated. Three optimal wavelengths (617nm, 675nm, and 818nm) were selected according to chlorophyll content via successive projections algorithm. Partial least square regression models were established to determine chlorophyll content. Three band ratios were obtained using these optimal wavelengths, which improved spatial details, but also integrates the information of chemical composition from spectral characteristics. The band ratio values were suitable to classify the diseased peaches with 98.75% accuracy and clearly show the spatial distribution of diseased parts. This study provides a new perspective for the selection of optimal wavelengths of hyperspectral imaging via chlorophyll content, thus enabling the detection of fungal diseases in peaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Synthesis of cadmium sulfide in situ in reverse micelles and in hydrocarbon gels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Petit, C.; Pileni, M.P.

    1988-04-21

    The synthesis in situ of cadmium sulfide semiconductors in AOT reverse micelles produces smaller and more monodispersed particles than are obtained in Triton reverse micelles or in aqueous solution. When gelatine is added to the previous solution, the semiconductor is entrapped in a hydrocarbon gel and it size remains the same as that obtained in reverse micelles. The size of the sulfite cadmium aggregate formed in AOT hydrocarbon gels is similar to that obtained under similar conditions in AOT reverse micelles. AOT surfactant can play the role of stabilizing agent. However, a more efficient stabilization is obtained by adding tomore » AOT reverse micelles another stabilizing agent such as sodium hexametaphosphate. The crystallite size is strongly dependent on the ratio of the cadmium and sulfur ions, defined by x = (Cd/sup 2 +/)/(S/sup 2 -//. The yield of reduced viologen obtained by CdS irradiation in AOT reverse micelles is 15 times more efficient than that formed in aqueous solutions whereas it is only three times more in hydrocarbon gels.« less

  7. AFM imaging of milk casein micelles: evidence for structural rearrangement upon acidification.

    PubMed

    Ouanezar, Mustapha; Guyomarc'h, Fanny; Bouchoux, Antoine

    2012-03-20

    Milk casein micelles are natural association colloids that we all encounter in everyday life, yet we still lack an accurate description of their internal structure and the interactions that stabilize it. In this letter, we provide for the first time detailed images of intact casein micelles as obtained through atomic force microscopy under liquid conditions close to physiological. The micelles appear as heterogeneous raspberry-like particles, which is consistent with a hierarchical/spongelike structure made of connected 10-40 nm dense casein regions. Upon in situ acidification to pH 5, the micelles decrease in size and lose their surface heterogeneities, indicating that this structure is highly sensitive to variations in mineral content and caseins net charge.

  8. Investigating Block-Copolymer Micelle Dynamics for Tunable Cargo Delivery

    NASA Astrophysics Data System (ADS)

    Li, Xiuli; Kidd, Bryce; Cooksey, Tyler; Robertson, Megan; Madsen, Louis

    Block-copolymer micelles (BCPMs) can carry molecular cargo in a nanoscopic package that is tunable using polymer structure in combination with cargo properties, as well as with external stimuli such as temperature or pH. For example, BCPMs can be used in targeted anticancer drug delivery due to their biocompatibility, in vivo degradability and prolonged circulation time. We are using NMR spectroscopy and diffusometry as well as SANS to investigate BCPMs. Here we study a diblock poly(ethylene oxide)-b-(caprolactone) (PEO-PCL) that forms spherical micelles at 1% (w/v) in the mixed solvent D2O/THF-d8. We quantify the populations and diffusion coefficients of coexisting micelles and free unimers over a range of temperatures and solvent compositions. We use temperature as a stimulus to enhance unimer exchange and hence trigger cargo release, in some cases at a few degrees above body temperature. We present evidence for dominance of the insertion-expulsion mechanism of unimer exchange in these systems, and we map phase diagrams versus temperature and solvent composition. This study sheds light on how intermolecular interactions fundamentally affect cargo release, unimer exchange, and overall micelle tunability.

  9. Blood-Stable, Tumor-Adaptable Disulfide Bonded mPEG-(Cys)4-PDLLA Micelles for Chemotherapy

    PubMed Central

    Lee, Seung-Young; Kim, Sungwon; Tyler, Jacqueline; Park, Kinam; Cheng, Ji-Xin

    2012-01-01

    Although targeted delivery mediated by ligand modified or tumor microenvironment sensitive nanocarriers has been extensively pursued for cancer chemotherapy, the efficiency is still limited by premature drug release after systemic administration. Herein we report a highly blood-stable, tumor-adaptable drug carrier made of disulfide (DS) bonded mPEG-(Cys)4-PDLLA micelles. Intravenously injected disulfide bonded micelles stably retained doxorubicin in the bloodstream and efficiently delivered the drug to a tumor, with a 7-fold increase of the drug in the tumor and 1.9-fold decrease in the heart, as compared with self-assembled (SA), non-crosslinked mPEG-PDLLA micelles. In vivo administration of disulfide bonded micelles led to doxorubicin accumulation in cancer cell nuclei, which was not observed after administration of self-assembled micelles. With a doxorubicin dose as low as 2 mg/kg, disulfide bonded micelles almost completely suppressed tumor growth in mice. PMID:23079665

  10. Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin.

    PubMed

    Talelli, Marina; Iman, Maryam; Varkouhi, Amir K; Rijcken, Cristianne J F; Schiffelers, Raymond M; Etrych, Tomas; Ulbrich, Karel; van Nostrum, Cornelus F; Lammers, Twan; Storm, Gert; Hennink, Wim E

    2010-10-01

    Doxorubicin (DOX) is clinically applied in cancer therapy, but its use is associated with dose limiting severe side effects. Core-crosslinked biodegradable polymeric micelles composed of poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate] (mPEG-b-p(HPMAm-Lac(n))) diblock copolymers have shown prolonged circulation in the blood stream upon intravenous administration and enhanced tumor accumulation through the enhanced permeation and retention (EPR) effect. However a (physically) entrapped anticancer drug (paclitaxel) was previously shown to be rapidly eliminated from the circulation, likely because the drug was insufficiently retained in the micelles. To fully exploit the EPR effect for drug targeting, a DOX methacrylamide derivative (DOX-MA) was covalently incorporated into the micellar core by free radical polymerization. The structure of the doxorubicin derivative is susceptible to pH-sensitive hydrolysis, enabling controlled release of the drug in acidic conditions (in either the intratumoral environment and/or the endosomal vesicles). 30-40% w/w of the added drug was covalently entrapped, and the micelles with covalently entrapped DOX had an average diameter of 80 nm. The entire drug payload was released within 24 h incubation at pH 5 and 37 degrees C, whereas only around 5% release was observed at pH 7.4. DOX micelles showed higher cytotoxicity in B16F10 and OVCAR-3 cells compared to DOX-MA, likely due to cellular uptake of the micelles via endocytosis and intracellular drug release in the acidic organelles. The micelles showed better anti-tumor activity than free DOX in mice bearing B16F10 melanoma carcinoma. The results presented in this paper show that mPEG-b-p(HPMAm-Lac(n)) polymeric micelles with covalently entrapped doxorubicin is a system highly promising for the targeted delivery of cytostatic agents. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Identification of Genes Associated with Chlorophyll Accumulation in Flower Petals

    PubMed Central

    Ohmiya, Akemi; Hirashima, Masumi; Yagi, Masafumi; Tanase, Koji; Yamamizo, Chihiro

    2014-01-01

    Plants have an ability to prevent chlorophyll accumulation, which would mask the bright flower color, in their petals. In contrast, leaves contain substantial amounts of chlorophyll, as it is essential for photosynthesis. The mechanisms of organ-specific chlorophyll accumulation are unknown. To identify factors that determine the chlorophyll content in petals, we compared the expression of genes related to chlorophyll metabolism in different stages of non-green (red and white) petals (very low chlorophyll content), pale-green petals (low chlorophyll content), and leaves (high chlorophyll content) of carnation (Dianthus caryophyllus L.). The expression of many genes encoding chlorophyll biosynthesis enzymes, in particular Mg-chelatase, was lower in non-green petals than in leaves. Non-green petals also showed higher expression of genes involved in chlorophyll degradation, including STAY-GREEN gene and pheophytinase. These data suggest that the absence of chlorophylls in carnation petals may be caused by the low rate of chlorophyll biosynthesis and high rate of degradation. Similar results were obtained by the analysis of Arabidopsis microarray data. In carnation, most genes related to chlorophyll biosynthesis were expressed at similar levels in pale-green petals and leaves, whereas the expression of chlorophyll catabolic genes was higher in pale-green petals than in leaves. Therefore, we hypothesize that the difference in chlorophyll content between non-green and pale-green petals is due to different levels of chlorophyll biosynthesis. Our study provides a basis for future molecular and genetic studies on organ-specific chlorophyll accumulation. PMID:25470367

  12. Structure and oil responsiveness of viscoelastic fluids based on mixed anionic/cationic wormlike surfactant micelles

    NASA Astrophysics Data System (ADS)

    Shibaev, A. V.; Makarov, A. V.; Aleshina, A. L.; Rogachev, A. V.; Kuklin, A. I.; Philippova, O. E.

    2017-05-01

    In this work, a combination of small-angle neutron scattering, dynamic light scattering and rheometry was applied in order to investigate the structure and oil responsiveness of anionic/cationic wormlike surfactant micelles formed in a mixture of potassium oleate and n-octyltrimethylammonium bromide (C8TAB). A new facile method of calculating the structure factor of charged interacting wormlike micelles was proposed. It was shown that the mean distance between the micelles decreases upon the increase of the amount of cationic co-surfactant and lowering of the net micellar charge. It was demonstrated that highly viscous fluids containing mixed anionic/cationic wormlike micelles are highly responsive to oil due to its solubilization inside the micellar cores, which leads to the disruption of micelles and formation of microemulsion droplets. Experimental data suggest that solubilization of oil proceeds differently in the case of mixed anionic/cationic micelles in the absence of salt, and anionic micelles of the same surfactant in the presence of KCl.

  13. Removal of Cr(VI) from Aqueous Environments Using Micelle-Clay Adsorption

    PubMed Central

    Qurie, Mohannad; Khamis, Mustafa; Manassra, Adnan; Ayyad, Ibrahim; Nir, Shlomo; Scrano, Laura; Bufo, Sabino A.; Karaman, Rafik

    2013-01-01

    Removal of Cr(VI) from aqueous solutions under different conditions was investigated using either clay (montmorillonite) or micelle-clay complex, the last obtained by adsorbing critical micelle concentration of octadecyltrimethylammonium ions onto montmorillonite. Batch experiments showed the effects of contact time, adsorbent dosage, and pH on the removal efficiency of Cr(VI) from aqueous solutions. Langmuir adsorption isotherm fitted the experimental data giving significant results. Filtration experiments using columns filled with micelle-clay complex mixed with sand were performed to assess Cr(VI) removal efficiency under continuous flow at different pH values. The micelle-clay complex used in this study was capable of removing Cr(VI) from aqueous solutions without any prior acidification of the sample. Results demonstrated that the removal effectiveness reached nearly 100% when using optimal conditions for both batch and continuous flow techniques. PMID:24222757

  14. Modelling ocean-colour-derived chlorophyll a

    NASA Astrophysics Data System (ADS)

    Dutkiewicz, Stephanie; Hickman, Anna E.; Jahn, Oliver

    2018-01-01

    This article provides a proof of concept for using a biogeochemical/ecosystem/optical model with a radiative transfer component as a laboratory to explore aspects of ocean colour. We focus here on the satellite ocean colour chlorophyll a (Chl a) product provided by the often-used blue/green reflectance ratio algorithm. The model produces output that can be compared directly to the real-world ocean colour remotely sensed reflectance. This model output can then be used to produce an ocean colour satellite-like Chl a product using an algorithm linking the blue versus green reflectance similar to that used for the real world. Given that the model includes complete knowledge of the (model) water constituents, optics and reflectance, we can explore uncertainties and their causes in this proxy for Chl a (called derived Chl a in this paper). We compare the derived Chl a to the actual model Chl a field. In the model we find that the mean absolute bias due to the algorithm is 22 % between derived and actual Chl a. The real-world algorithm is found using concurrent in situ measurement of Chl a and radiometry. We ask whether increased in situ measurements to train the algorithm would improve the algorithm, and find a mixed result. There is a global overall improvement, but at the expense of some regions, especially in lower latitudes where the biases increase. Not surprisingly, we find that region-specific algorithms provide a significant improvement, at least in the annual mean. However, in the model, we find that no matter how the algorithm coefficients are found there can be a temporal mismatch between the derived Chl a and the actual Chl a. These mismatches stem from temporal decoupling between Chl a and other optically important water constituents (such as coloured dissolved organic matter and detrital matter). The degree of decoupling differs regionally and over time. For example, in many highly seasonal regions, the timing of initiation and peak of the

  15. Light Absorption in Arctic Sea Ice - Black Carbon vs Chlorophyll

    NASA Astrophysics Data System (ADS)

    Ogunro, O. O.; Wingenter, O. W.; Elliott, S.; Hunke, E. C.; Flanner, M.; Wang, H.; Dubey, M. K.; Jeffery, N.

    2015-12-01

    The fingerprint of climate change is more obvious in the Arctic than any other place on Earth. This is not only because the surface temperature there has increased at twice the rate of global mean temperature but also because Arctic sea ice extent has reached a record low of 49% reduction relative to the 1979-2000 climatology. Radiation absorption through black carbon (BC) deposited on Arctic snow and sea ice surface is one of the major hypothesized contributors to the decline. However, we note that chlorophyll-a absorption owing to increasing biology activity in this region could be a major competitor during boreal spring. Modeling of sea-ice physical and biological processes together with experiments and field observations promise rapid progress in the quality of Arctic ice predictions. Here we develop a dynamic ice system module to investigate discrete absorption of both BC and chlorophyll in the Arctic, using BC deposition fields from version 5 of Community Atmosphere Model (CAM5) and vertically distributed layers of chlorophyll concentrations from Sea Ice Model (CICE). To this point, our black carbon mixing ratios compare well with available in situ data. Both results are in the same order of magnitude. Estimates from our calculations show that sea ice and snow around the Canadian Arctic Archipelago and Baffin Bay has the least black carbon absorption while values at the ice-ocean perimeter in the region of the Barents Sea peak significantly. With regard to pigment concentrations, high amounts of chlorophyll are produced in Arctic sea ice by the bottom microbial community, and also within the columnar pack wherever substantial biological activity takes place in the presence of moderate light. We show that the percentage of photons absorbed by chlorophyll in the spring is comparable to the amount attributed to BC, especially in areas where the total deposition rates are decreasing with time on interannual timescale. We expect a continuous increase in

  16. Controlled Fab installation onto polymeric micelle nanoparticles for tuned bioactivity

    NASA Astrophysics Data System (ADS)

    Chen, Shaoyi; Florinas, Stelios; Teitgen, Abigail; Xu, Ze-Qi; Gao, Changshou; Wu, Herren; Kataoka, Kazunori; Cabral, Horacio; Christie, R. James

    2017-12-01

    Antibodies and antigen-binding fragments (Fabs) can be used to modify the surface of nanoparticles for enhanced target binding. In our previous work, site-specific conjugation of Fabs to polymeric micelles using conventional methods was limited to approximately 30% efficiency, possibly due to steric hindrance related to macromolecular reactants. Here, we report a new method that enables conjugation of Fabs onto a micelle surface in a controlled manner with up to quantitative conversion of nanoparticle reactive groups. Variation of (i) PEG spacer length in a heterofunctionalized cross-linker and (ii) Fab/polymer feed ratios resulted in production of nanoparticles with a range of Fab densities on the surface up to the theoretical maximum value. The biological impact of variable Fab density was evaluated in vitro with respect to cell uptake and cytotoxicity of a drug-loaded (SN38) targeted polymeric micelle bearing anti-EphA2 Fabs. Fab conjugation increased cell uptake and potency compared with non-targeted micelles, although a Fab density of 60% resulted in decreased uptake and potency of the targeted micelles. Altogether, our findings demonstrate that conjugation strategies can be optimized to allow control of Fab density on the surface of nanoparticles and also that Fab density may need to be optimized for a given cell-surface target to achieve the highest bioactivity.

  17. Polymeric Micelles as Novel Carriers for Poorly Soluble Drugs--A Review.

    PubMed

    Reddy, B Pavan Kumar; Yadav, Hemant K S; Nagesha, Dattatri K; Raizaday, Abhay; Karim, Abdul

    2015-06-01

    Polymeric micelles are used as 'smart drug carriers' for targeting certain areas of the body by making them stimuli-sensitive or by attachment of a specific ligand molecule onto their surface. The main aim of using polymeric micelles is to deliver the poorly water soluble drugs. Now-a-days they are used especially in the areas of cancer therapy also. In this article we have reviewed several aspects of polymeric micelles concerning their mechanism of formation, chemical nature, preparation and characterization techniques, and their applications in the areas of drug delivery.

  18. Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance

    PubMed Central

    Dong, Kai; Yan, Yan; Wang, Pengchong; Shi, Xianpeng; Zhang, Lu; Wang, Ke; Xing, Jianfeng; Dong, Yalin

    2016-01-01

    In this study, a type of multifunctional mixed micelles were prepared by a novel biodegradable amphiphilic polymer (MPEG-SS-2SA) and a multidrug resistance (MDR) reversal agent (d-α-tocopheryl polyethylene glycol succinate, TPGS). The mixed micelles could achieve rapid intracellular drug release and reversal of MDR. First, the amphiphilic polymer, MPEG-SS-2SA, was synthesized through disulfide bonds between poly (ethylene glycol) monomethyl ether (MPEG) and stearic acid (SA). The structure of the obtained polymer was similar to poly (ethylene glycol)-phosphatidylethanolamine (PEG-PE). Then the mixed micelles, MPEG-SS-2SA/TPGS, were prepared by MPEG-SS-2SA and TPGS through the thin film hydration method and loaded paclitaxel (PTX) as the model drug. The in vitro release study revealed that the mixed micelles could rapidly release PTX within 24 h under a reductive environment because of the breaking of disulfide bonds. In cell experiments, the mixed micelles significantly inhibited the activity of mitochondrial respiratory complex II, also reduced the mitochondrial membrane potential, and the content of adenosine triphosphate, thus effectively inhibiting the efflux of PTX from cells. Moreover, in the confocal laser scanning microscopy, cellular uptake and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assays, the MPEG-SS-2SA/TPGS micelles achieved faster release and more uptake of PTX in Michigan Cancer Foundation-7/PTX cells and showed better antitumor effects as compared with the insensitive control. In conclusion, the biodegradable mixed micelles, MPEG-SS-2SA/TPGS, could be potential vehicles for delivering hydrophobic chemotherapeutic drugs in MDR cancer therapy. PMID:27785018

  19. Reverse micelle synthesis of oxide nanopowders: mechanisms of precipitate formation and agglomeration effects.

    PubMed

    Graeve, Olivia A; Fathi, Hoorshad; Kelly, James P; Saterlie, Michael S; Sinha, Kaustav; Rojas-George, Gabriel; Kanakala, Raghunath; Brown, David R; Lopez, Enrique A

    2013-10-01

    We present an analysis of reverse micelle stability in four model systems. The first two systems, composed of unstable microemulsions of isooctane, water, and Na-AOT with additions of either iron sulfate or yttrium nitrate, were used for the synthesis of iron oxide or yttrium oxide powders. These oxide powders were of nanocrystalline character, but with some level of agglomeration that was dependent on calcination temperature and cleaning procedures. Results show that even though the reverse micellar solutions were unstable, nanocrystalline powders with very low levels of agglomeration could be obtained. This effect can be attributed to the protective action of the surfactant on the surfaces of the powders that prevents neck formation until after all the surfactant has volatilized. A striking feature of the IR spectra collected on the iron oxide powders is the absence of peaks in the ~1715 cm(-1) to 1750 cm(-1) region, where absorption due to the symmetric C=O (carbonyl) stretching occurs. The lack of such peaks strongly suggests the carbonyl group is no longer free, but is actively participating in the surfactant-precipitate interaction. The final two microemulsion systems, containing CTAB as the surfactant, showed that loss of control of the reverse micelle synthesis process can easily occur when the amount of salt in the water domains exceeds a critical concentration. Both model systems eventually resulted in agglomerated powders of broad size distributions or particles that were large compared to the sizes of the reverse micelles, consistent with the notion that the microemulsions were not stable and the powders were precipitated in an uncontrolled fashion. This has implications for the synthesis of nanopowders by reverse micelle synthesis and provides a benchmark for process control if powders of the highest quality are desired. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Loading and release mechanisms of a biocide in polystyrene-block-poly(acrylic acid) block copolymer micelles.

    PubMed

    Vyhnalkova, Renata; Eisenberg, Adi; van de Ven, Theo G M

    2008-07-24

    The kinetics of loading of polystyrene197-block-poly(acrylic acid)47 (PS197-b-PAA47) micelles, suspended in water, with thiocyanomethylthiobenzothiazole biocide and its subsequent release were investigated. Loading of the micelles was found to be a two-step process. First, the surface of the PS core of the micelles is saturated with biocide, with a rate determined by the transfer of solid biocide to micelles during transient micelle-biocide contacts. Next, the biocide penetrates as a front into the micelles, lowering the Tg in the process (non-Fickian case II diffusion). The slow rate of release is governed by the height of the energy barrier that a biocide molecule must overcome to pass from PS into water, resulting in a uniform biocide concentration within the micelle, until Tg is increased to the point that diffusion inside the micelles becomes very slow. Maximum loading of biocide into micelles is approximately 30% (w/w) and is achieved in 1 h. From partition experiments, it can be concluded that the biocide has a similar preference for polystyrene as for ethylbenzene over water, implying that the maximum loading is governed by thermodynamics.

  1. Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement

    NASA Astrophysics Data System (ADS)

    Zhou, Weisai; Li, Caibin; Wang, Zhiyu; Zhang, Wenli; Liu, Jianping

    2016-09-01

    Polymeric micelles (PMs) self-assembled by amphiphilic block copolymers have been used as promising nanocarriers for tumor-targeted delivery due to their favorable properties, such as excellent biocompatibility, prolonged circulation time, favorable particle sizes (10-100 nm) to utilize enhanced permeability and retention effect and the possibility for functionalization. However, PMs can be easily destroyed due to dilution of body fluid and the absorption of proteins in system circulation, which may induce drug leakage from these micelles before reaching the target sites and compromise the therapeutic effect. This paper reviewed the factors that influence stability of micelles in terms of thermodynamics and kinetics consist of the critical micelle concentration of block copolymers, glass transition temperature of hydrophobic segments and polymer-polymer and polymer-cargo interaction. In addition, some effective strategies to improve the stability of micelles were also summarized.

  2. Nanoparticle packing within block copolymer micelles prepared by the interfacial instability method.

    PubMed

    Nabar, Gauri M; Winter, Jessica O; Wyslouzil, Barbara E

    2018-05-02

    The interfacial instability method has emerged as a viable approach for encapsulating high concentrations of nanoparticles (NPs) within morphologically diverse micelles. In this method, transient interfacial instabilities at the surface of an emulsion droplet guide self-assembly of block co-polymers and NP encapsulants. Although used by many groups, there are no systematic investigations exploring the relationship between NP properties and micelle morphology. Here, the effect of quantum dot (QD) and superparamagnetic iron oxide NP (SPION) concentration on the shape, size, and surface deformation of initially spherical poly(styrene-b-ethylene oxide) (PS-b-PEO) micelles was examined. Multi-NP encapsulation and uniform dispersion within micelles was obtained even at low NP concentrations. Increasing NP concentration initially resulted in larger numbers of elongated micelles and cylinders with tightly-controlled diameters smaller than those of spherical micelles. Beyond a critical NP concentration, micelle formation was suppressed; the dominant morphology became densely-loaded NP structures that were coated with polymer and exhibited increased polydispersity. Transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS) revealed that NPs in densely-loaded structures can be well-ordered, with packing volume fractions of up to 24%. These effects were enhanced in magnetic composites, possibly by dipole interactions. Mechanisms governing phase transitions triggered by NP loading in the interfacial instability process were proposed. The current study helps establish and elucidate the active role played by NPs in directing block copolymer assembly in the interfacial instability process, and provides important guiding principles for the use of this approach in generating NP-loaded block copolymer composites.

  3. EPR spin probe and spin label studies of some low molecular and polymer micelles

    NASA Astrophysics Data System (ADS)

    Wasserman, A. M.; Kasaikin, V. A.; Timofeev, V. P.

    1998-12-01

    The rotational mobility of spin probes of different shape and size in low molecular and polymer micelles has been studied. Several probes having nitroxide fragment localized either in the vicinity of micelle interface or in the hydrocarbon core have been used. Upon increasing the number of carbon atoms in hydrocarbon chain of detergent from 7 to 13 (sodium alkyl sulfate micelles) or from 12 to 16 (alkyltrimethylammonium bromide micelles) the rotational mobility of spin probes is decreased by the factor 1.5-2.0. The spin probe rotational mobility in polymer micelles (the complexes of alkyltrimethylammonium bromides and polymethacrylic or polyacrylic acids) is less than mobility in free micelles of the same surfactants. The study of EPR-spectra of spin labeled polymethacrylic acid (PMA) indicated that formation of water soluble complexes of polymer and alkyltrimethylammonium bromides in alkaline solutions (pH 9) does not affect the polymer segmental mobility. On the other hand, the polymer complexes formation in slightly acidic water solution (pH 6) breaks down the compact PMA conformation, thus increasing the polymer segmental mobility. Possible structures of polymer micelles are discussed.

  4. Structure formation in binary mixtures of surfactants: vesicle opening-up to bicelles and octopus-like micelles

    NASA Astrophysics Data System (ADS)

    Noguchi, Hiroshi

    Micelle formation in binary mixtures of surfactants is studied using a coarse-grained molecular simulation. When a vesicle composed of lipid and detergent types of molecules is ruptured, a disk-shaped micelle, the bicelle, is typically formed. It is found that cup-shaped vesicles and bicelles connected with worm-like micelles are also formed depending on the surfactant ratio and critical micelle concentration. The obtained octopus shape of micelles agree with those observed in the cryo-TEM images reported in [S. Jain and F. S. Bates, Macromol. 37, 1511 (2004).]. Two types of connection structures between the worm-like micelles and the bicelles are revealed.

  5. Effect of nucleoside analogue antimetabolites on the structure of PEO–PPO–PEO micelles investigated by SANS

    DOE PAGES

    Han, Youngkyu; Zhang, Zhe; Smith, Gregory S.; ...

    2017-04-19

    In this work, the effect of three nucleoside analogue antimetabolites (5-fluorouracil, floxuridine, and gemcitabine) on the structure of Pluronic L62 copolymer micelles was investigated using small-angle neutron scattering. These antimetabolites used for cancer chemotherapy have analogous molecular structures but different molecular sizes and aqueous solubilities. It was found that the addition of the three antimetabolites slightly reduced the micellar size and aggregation number, and the micellar anisotropy. The added antimetabolites also changed the internal molecular distribution of the micelles as measured by the scattering length densities, resulting in enhanced hydration of the hydrophobic core region of the micelle. The strengthmore » of the effect was found to correlate with the molecular properties of the model drugs, i.e. a larger molecular size and a higher aqueous solubility lead to enhanced hydration of the micellar core.« less

  6. Effect of nucleoside analogue antimetabolites on the structure of PEO–PPO–PEO micelles investigated by SANS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Han, Youngkyu; Zhang, Zhe; Smith, Gregory S.

    2017-01-01

    The effect of three nucleoside analogue antimetabolites (5-fluorouracil, floxuridine, and gemcitabine) on the structure of Pluronic L62 copolymer micelles was investigated using small-angle neutron scattering. These antimetabolites used for cancer chemotherapy have analogous molecular structures but different molecular sizes and aqueous solubilities. It was found that the addition of the three antimetabolites slightly reduced the micellar size and aggregation number, and the micellar anisotropy. The added antimetabolites also changed the internal molecular distribution of the micelles as measured by the scattering length densities, resulting in enhanced hydration of the hydrophobic core region of the micelle. The strength of the effectmore » was found to correlate with the molecular properties of the model drugs, i.e. a larger molecular size and a higher aqueous solubility lead to enhanced hydration of the micellar core.« less

  7. How to squeeze a sponge: casein micelles under osmotic stress, a SAXS study.

    PubMed

    Bouchoux, Antoine; Gésan-Guiziou, Geneviève; Pérez, Javier; Cabane, Bernard

    2010-12-01

    By combining the osmotic stress technique with small-angle x-ray scattering measurements, we followed the structural response of the casein micelle to an overall increase in concentration. When the aqueous phase that separates the micelles is extracted, they behave as polydisperse repelling spheres and their internal structure is not affected. When they are compressed, the micelles lose water and shrink to a smaller volume. Our results indicate that this compression is nonaffine, i.e., some parts of the micelle collapse, whereas other parts resist deformation. We suggest that this behavior is consistent with a spongelike casein micelle having a triple hierarchical structure. The lowest level of the structure consists of the CaP nanoclusters that serve as anchors for the casein molecules. The intermediate level consists of 10- to 40-nm hard regions that resist compression and contain the nanoclusters. Those regions are connected and/or partially merged with each other, thus forming a continuous and porous material. The third level of structure is the casein micelle itself, with an average size of 100 nm. In our view, such a structure is consistent with the observation of 10- to 20-nm casein particles in the Golgi vesicles of lactating cells: upon aggregation, those particles would rearrange, fuse, and/or swell to form the spongelike micelle. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. How to Squeeze a Sponge: Casein Micelles under Osmotic Stress, a SAXS Study

    PubMed Central

    Bouchoux, Antoine; Gésan-Guiziou, Geneviève; Pérez, Javier; Cabane, Bernard

    2010-01-01

    By combining the osmotic stress technique with small-angle x-ray scattering measurements, we followed the structural response of the casein micelle to an overall increase in concentration. When the aqueous phase that separates the micelles is extracted, they behave as polydisperse repelling spheres and their internal structure is not affected. When they are compressed, the micelles lose water and shrink to a smaller volume. Our results indicate that this compression is nonaffine, i.e., some parts of the micelle collapse, whereas other parts resist deformation. We suggest that this behavior is consistent with a spongelike casein micelle having a triple hierarchical structure. The lowest level of the structure consists of the CaP nanoclusters that serve as anchors for the casein molecules. The intermediate level consists of 10- to 40-nm hard regions that resist compression and contain the nanoclusters. Those regions are connected and/or partially merged with each other, thus forming a continuous and porous material. The third level of structure is the casein micelle itself, with an average size of 100 nm. In our view, such a structure is consistent with the observation of 10- to 20-nm casein particles in the Golgi vesicles of lactating cells: upon aggregation, those particles would rearrange, fuse, and/or swell to form the spongelike micelle. PMID:21112300

  9. Microfibres and macroscopic films from the coordination-driven hierarchical self-assembly of cylindrical micelles

    PubMed Central

    Lunn, David J.; Gould, Oliver E. C.; Whittell, George R.; Armstrong, Daniel P.; Mineart, Kenneth P.; Winnik, Mitchell A.; Spontak, Richard J.; Pringle, Paul G.; Manners, Ian

    2016-01-01

    Anisotropic nanoparticles prepared from block copolymers are of growing importance as building blocks for the creation of synthetic hierarchical materials. However, the assembly of these structural units is generally limited to the use of amphiphilic interactions. Here we report a simple, reversible coordination-driven hierarchical self-assembly strategy for the preparation of micron-scale fibres and macroscopic films based on monodisperse cylindrical block copolymer micelles. Coordination of Pd(0) metal centres to phosphine ligands immobilized within the soluble coronas of block copolymer micelles is found to induce intermicelle crosslinking, affording stable linear fibres comprised of micelle subunits in a staggered arrangement. The mean length of the fibres can be varied by altering the micelle concentration, reaction stoichiometry or aspect ratio of the micelle building blocks. Furthermore, the fibres aggregate on drying to form robust, self-supporting macroscopic micelle-based thin films with useful mechanical properties that are analogous to crosslinked polymer networks, but on a longer length scale. PMID:27538877

  10. Relationships between leaf chlorophyll content and spectral reflectance and algorithms for non-destructive chlorophyll assessment in higher plant leaves.

    PubMed

    Gitelson, Anatoly A; Gritz, Yuri; Merzlyak, Mark N

    2003-03-01

    Leaf chlorophyll content provides valuable information about physiological status of plants. Reflectance measurement makes it possible to quickly and non-destructively assess, in situ, the chlorophyll content in leaves. Our objective was to investigate the spectral behavior of the relationship between reflectance and chlorophyll content and to develop a technique for non-destructive chlorophyll estimation in leaves with a wide range of pigment content and composition using reflectance in a few broad spectral bands. Spectral reflectance of maple, chestnut, wild vine and beech leaves in a wide range of pigment content and composition was investigated. It was shown that reciprocal reflectance (R lambda)-1 in the spectral range lambda from 520 to 550 nm and 695 to 705 nm related closely to the total chlorophyll content in leaves of all species. Subtraction of near infra-red reciprocal reflectance, (RNIR)-1, from (R lambda)-1 made index [(R lambda)(-1)-(RNIR)-1] linearly proportional to the total chlorophyll content in spectral ranges lambda from 525 to 555 nm and from 695 to 725 nm with coefficient of determination r2 > 0.94. To adjust for differences in leaf structure, the product of the latter index and NIR reflectance [(R lambda)(-1)-(RNIR)-1]*(RNIR) was used; this further increased the accuracy of the chlorophyll estimation in the range lambda from 520 to 585 nm and from 695 to 740 nm. Two independent data sets were used to validate the developed algorithms. The root mean square error of the chlorophyll prediction did not exceed 50 mumol/m2 in leaves with total chlorophyll ranged from 1 to 830 mumol/m2.

  11. Charged triblock copolymer self-assembly into charged micelles

    NASA Astrophysics Data System (ADS)

    Chen, Yingchao; Zhang, Ke; Zhu, Jiahua; Wooley, Karen; Pochan, Darrin; Department of Material Science; Engineering University of Delaware Team; Department of Chemistry Texas A&M University Collaboration

    2011-03-01

    Micelles were formed through the self-assembly of amphiphlic block copolymer poly(acrylic acid)-block-poly(methyl acrylate)-block-polystyrene (PAA-PMA-PS). ~Importantly, the polymer is complexed with diamine molecules in pure THF solution prior to water titration solvent processing-a critical aspect in the control of final micelle geometry. The addition of diamine triggers acid-base complexation ~between the carboxylic acid PAA side chains and amines. ~Remarkably uniform spheres were found to form close-packed patterns when forced into dried films and thin, solvated films when an excess of amine was used in the polymer assembly process. Surface properties and structural features of these hexagonal-packed spherical micelles with charged corona have been explored by various characterization methods including Transmission Electron Microscopy (TEM), cryogenic TEM, z-potential analysis and Dynamic Light Scattering. The forming mechanism for this pattern and morphology changes against external stimulate such as salt will be discussed.

  12. Development and evaluation of N-naphthyl-N,O-succinyl chitosan micelles containing clotrimazole for oral candidiasis treatment.

    PubMed

    Tonglairoum, Prasopchai; Woraphatphadung, Thisirak; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Akkaramongkolporn, Prasert; Sajomsang, Warayuth; Opanasopit, Praneet

    2017-03-01

    Clotrimazole (CZ)-loaded N-naphthyl-N,O-succinyl chitosan (NSCS) micelles have been developed as an alternative for oral candidiasis treatment. NSCS was synthesized by reductive N-amination and N,O-succinylation. CZ was incorporated into the micelles using various methods, including the dropping method, the dialysis method, and the O/W emulsion method. The size and morphology of the CZ-loaded micelles were characterized using dynamic light scattering measurements (DLS) and a transmission electron microscope (TEM), respectively. The drug entrapment efficiency, loading capacity, release characteristics, and antifungal activity against Candida albicans were also evaluated. The CZ-loaded micelles prepared using different methods differed in the size of micelles. The micelles ranged in size from 120 nm to 173 nm. The micelles prepared via the O/W emulsion method offered the highest percentage entrapment efficiency and loading capacity. The CZ released from the CZ-loaded micelles at much faster rate compared to CZ powder. The CZ-loaded NSCS micelles can significantly hinder the growth of Candida cells after contact. These CZ-loaded NSCS micelles offer great antifungal activity and might be further developed to be a promising candidate for oral candidiasis treatment.

  13. Conjugation of arginine-glycine-aspartic acid peptides to poly(ethylene oxide)-b-poly(epsilon-caprolactone) micelles for enhanced intracellular drug delivery to metastatic tumor cells.

    PubMed

    Xiong, Xiao-Bing; Mahmud, Abdullah; Uludağ, Hasan; Lavasanifar, Afsaneh

    2007-03-01

    An arginine-glycine-aspartic acid (RGD) containing model peptide was conjugated to the surface of poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) micelles as a ligand that can recognize adhesion molecules overexpressed on the surface of metastatic cancer cells, that is, integrins, and that can enhance the micellar delivery of encapsulated hydrophobic drug into a tumor cell. Toward this goal, PEO-b-PCL copolymers bearing acetal groups on the PEO end were synthesized, characterized, and assembled to polymeric micelles. The acetal group on the surface of the PEO-b-PCL micelles was converted to reactive aldehyde under acidic condition at room temperature. An RGD-containing linear peptide, GRGDS, was conjugated on the surface of the aldehyde-decorated PEO-b-PCL micelles by incubation at room temperature. A hydrophobic fluorescent probe, that is, DiI, was physically loaded in prepared polymeric micelles to imitate hydrophobic drugs loaded in micellar carrier. The cellular uptake of DiI loaded GRGDS-modified micelles by melanoma B16-F10 cells was investigated at 4 and 37 degrees C by fluorescent spectroscopy and confocal microscopy techniques and was compared to the uptake of DiI loaded valine-PEO-b-PCL micelles (as the irrelevant ligand decorated micelles) and free DiI. GRGDS conjugation to polymeric micelles significantly facilitated the cellular uptake of encapsulated hydrophobic DiI most probably by intergrin-mediated cell attachment and endocytosis. The results indicate that acetal-terminated PEO-b-PCL micelles are amenable for introducing targeting moieties on the surface of polymeric micelles and that RGD-peptide conjugated PEO-b-PCL micelles are promising ligand-targeted carriers for enhanced drug delivery to metastatic tumor cells.

  14. FluorWPS: A Monte Carlo ray-tracing model to compute sun-induced chlorophyll fluorescence of three-dimensional canopy

    USDA-ARS?s Scientific Manuscript database

    A model to simulate radiative transfer (RT) of sun-induced chlorophyll fluorescence (SIF) of three-dimensional (3-D) canopy, FluorWPS, was proposed and evaluated. The inclusion of fluorescence excitation was implemented with the ‘weight reduction’ and ‘photon spread’ concepts based on Monte Carlo ra...

  15. Protons in non-ionic aqueous reverse micelles.

    PubMed

    Rodriguez, Javier; Martí, Jordi; Guàrdia, Elvira; Laria, Daniel

    2007-05-03

    Using molecular dynamics techniques, we investigate the solvation of an excess proton within an aqueous reverse micelle in vacuo, with the neutral surfactant diethylene glycol monodecyl ether [CH3(CH2)11(OC2H4)2OH]. The simulation experiments were performed using a multistate empirical valence bond Hamiltonian model. Our results show that the stable solvation environments for the excess proton are located in the water-surfactant interface and that its first solvation shell is composed exclusively by water molecules. The relative prevalence of Eigen- versus Zundel-like solvation structures is investigated; compared to bulk results, Zundel-like structures in micelles become somewhat more stable. Characteristic times for the proton translocation jumps have been computed using population relaxation time correlation functions. The micellar rate for proton transfer is approximately 40x smaller than that found in bulk water at ambient conditions. Differences in the computed rates are examined in terms of the hydrogen-bond connectivity involving the first solvation shell of the excess charge with the rest of the micellar environment. Simulation results would indicate that proton transfers are correlated with rare episodes during which the HB connectivity between the first and second solvation shells suffers profound modifications.

  16. Disulfide cross-linked polyurethane micelles as a reduction-triggered drug delivery system for cancer therapy.

    PubMed

    Yu, Shuangjiang; Ding, Jianxun; He, Chaoliang; Cao, Yue; Xu, Weiguo; Chen, Xuesi

    2014-05-01

    Nanoscale carriers that stably load drugs in blood circulation and release the payloads in desirable sites in response to a specific trigger are of great interest for smart drug delivery systems. For this purpose, a novel type of disulfide core cross-linked micelles, which are facilely fabricated by cross-linking of poly(ethylene glycol)/polyurethane block copolymers containing cyclic disulfide moieties via a thiol-disulfide exchange reaction, are developed. A broad-spectrum anti-cancer drug, doxorubicin (DOX), is loaded into the micelles as a model drug. The drug release from the core cross-linked polyurethane micelles (CCL-PUMs) loaded with DOX is suppressed in normal phosphate buffer saline (PBS), whereas it is markedly accelerated with addition of an intracellular reducing agent, glutathione (GSH). Notably, although DOX-loaded CCL-PUMs display lower cytotoxicity in vitro compared to either free DOX or DOX-loaded uncross-linked polyurethane micelles, the drug-loaded CCL-PUMs show the highest anti-tumor efficacy with reduced toxicity in vivo. Since enhanced anti-tumor efficacy and reduced toxic side effects are key aspects of efficient cancer therapy, the novel reduction-responsive CCL-PUMs may hold great potential as a bio-triggered drug delivery system for cancer therapy. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Chlorophyll loss associated with heat-induced senescence in bentgrass.

    PubMed

    Jespersen, David; Zhang, Jing; Huang, Bingru

    2016-08-01

    Heat stress-induced leaf senescence is characterized by the loss of chlorophyll from leaf tissues. The objectives of this study were to examine genetic variations in the level of heat-induced leaf senescence in hybrids of colonial (Agrostis capillaris)×creeping bentgrass (Agrostis stolonifera) contrasting in heat tolerance, and determine whether loss of leaf chlorophyll during heat-induced leaf senescence was due to suppressed chlorophyll synthesis and/or accelerated chlorophyll degradation in the cool-season perennial grass species. Plants of two hybrid backcross genotypes ('ColxCB169' and 'ColxCB190') were exposed to heat stress (38/33°C, day/night) for 28 d in growth chambers. The analysis of turf quality, membrane stability, photochemical efficiency, and chlorophyll content demonstrated significant variations in the level of leaf senescence induced by heat stress between the two genotypes, with ColXCB169 exhibiting a lesser degree of decline in chlorophyll content, photochemical efficiency and membrane stability than ColXCB190. The assays of enzymatic activity or gene expression of several major chlorophyll-synthesizing (porphobilinogen deaminase, Mg-chelatase, protochlorophyllide-reductase) and chlorophyll-degrading enzymes (chlorophyllase, pheophytinase, and chlorophyll-degrading peroxidase) indicated heat-induced decline in leaf chlorophyll content was mainly due to accelerated chlorophyll degradation, as manifested by increased gene expression levels of chlorophyllase and pheophytinase, and the activity of pheophytinase (PPH), while chlorophyll-synthesizing genes and enzymatic activities were not differentially altered by heat stress in the two genotypes. The analysis of heat-induced leaf senescence of pph mutants of Arabidopsis further confirmed that PPH could be one enzymes that plays key roles in regulating heat-accelerated chlorophyll degradation. Further research on enzymes responsible in part for the loss of chlorophyll during heat

  18. Effect of Urea on the Thermodynamics of Hexadecyltrimethylammonium Bromide Micelle Formation in Aqueous Solutions

    NASA Astrophysics Data System (ADS)

    Velikov, A. A.

    2018-02-01

    The effect of urea on the thermodynamics of hexadecyltrimethylammonium bromide (CTAB) micelle formation in aqueous urea solutions was studied by isothermal titration microcalorimetry. The thermodynamic functions of Δ H, Δ G, and Δ S of CTAB micelle formation were calculated. The critical micelle concentrations (CMC) were determined. The addition of urea to the solution decreased the micelle formation entropy. This was attributed to the "lowering" of the structural temperature of the solution, which led to an increased number of hydrogen bonds and structure formation of water.

  19. Coincident patterns of waste water suspended solids reduction, water transparency increase and chlorophyll decline in Narragansett Bay.

    PubMed

    Borkman, David G; Smayda, Theodore J

    2016-06-15

    Dramatic changes occurred in Narragansett Bay during the 1980s: water clarity increased, while phytoplankton abundance and chlorophyll concentration decreased. We examine how changes in total suspended solids (TSS) loading from wastewater treatment plants may have influenced this decline in phytoplankton chlorophyll. TSS loading, light and phytoplankton observations were compiled and a light- and temperature-dependent Skeletonema-based phytoplankton growth model was applied to evaluate chlorophyll supported by TSS nitrogen during 1983-1995. TSS loading declined 75% from ~0.60×10(6)kgmonth(-1) to ~0.15×10(6)kgmonth(-1) during 1983-1995. Model results indicate that nitrogen reduction related to TSS reduction was minor and explained a small fraction (~15%) of the long-term chlorophyll decline. The decline in NBay TSS loading appears to have increased water clarity and in situ irradiance and contributed to the long-term chlorophyll decline by inducing a physiological response of a ~20% reduction in chlorophyll per cell. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. A folate-integrated magnetic polymer micelle for MRI and dual targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Ao, Lijiao; Wang, Bi; Liu, Peng; Huang, Liang; Yue, Caixia; Gao, Duyang; Wu, Chunlei; Su, Wu

    2014-08-01

    This paper devotes a novel micellar structure for cancer theranostics by incorporating magnetic and therapeutic functionalities into a natural sourced targeting polymer vehicle. Heparin-folic acid micelles taking advantage of both excellent loading capability and cancer targeting ability have been employed to simultaneously incorporate superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin through an ultrasonication-assisted microemulsion method. In this system, folic acids not only take the responsibility of micelle construction, but also facilitate cellular uptake due to their specific reorganization by MCF-7 cells over-expressing folate receptors. The obtained micelles exhibit good colloidal stability, a high magnetic content, considerable drug loading and sustained in vitro drug release. These clustered SPIONs exhibited high r2 relaxivity (243.65 mM-1 s-1) and further served as efficient probes for MR imaging. Notably, the transport efficiency of these micelles could be significantly improved under an external magnetic field, owing to their quick magnetic response. As a result, the as-proposed micelle shows great potential in multimodal theranostics, including active targeting, MRI diagnosis and drug delivery.This paper devotes a novel micellar structure for cancer theranostics by incorporating magnetic and therapeutic functionalities into a natural sourced targeting polymer vehicle. Heparin-folic acid micelles taking advantage of both excellent loading capability and cancer targeting ability have been employed to simultaneously incorporate superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin through an ultrasonication-assisted microemulsion method. In this system, folic acids not only take the responsibility of micelle construction, but also facilitate cellular uptake due to their specific reorganization by MCF-7 cells over-expressing folate receptors. The obtained micelles exhibit good colloidal stability, a high magnetic content

  1. Cell membrane-inspired polymeric micelles as carriers for drug delivery.

    PubMed

    Liu, Gongyan; Luo, Quanqing; Gao, Haiqi; Chen, Yuan; Wei, Xing; Dai, Hong; Zhang, Zongcai; Ji, Jian

    2015-03-01

    In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.

  2. Bile Salt Mediated Growth of Reverse Wormlike Micelles in Nonpolar Liquids

    NASA Astrophysics Data System (ADS)

    Tung, Shih-Huang; Huang, Yi-En; Raghavan, Srinivasa

    2006-03-01

    We report the growth of reverse wormlike micelles induced by the addition of a bile salt in trace amounts to solutions of the phospholipid, lecithin in nonpolar organic solvents. Previous recipes for reverse wormlike micelles have usually required the addition of water to induce reverse micellar growth; here, we show that bile salts, due to their unique ``facially amphiphilic'' structure, can play a role analogous to water and promote the longitudinal aggregation of lecithin molecules into reverse micellar chains. The formation of transient entangled networks of these reverse micelles transforms low-viscosity lecithin organosols into strongly viscoelastic fluids. The zero-shear viscosity increases by more than five orders of magnitude, and it is the molar ratio of bile salt to lecithin that controls this viscosity enhancement. The growth of reverse wormlike micelles is also confirmed by small-angle neutron scattering (SANS) experiments on these fluids.

  3. High pressure-assisted encapsulation of vitamin D2 in reassembled casein micelles

    NASA Astrophysics Data System (ADS)

    Menéndez-Aguirre, O.; Stuetz, W.; Grune, T.; Kessler, A.; Weiss, J.; Hinrichs, J.

    2011-03-01

    For the encapsulation of vitamin D2, native casein micelles and vitamin D2 with or without additional Ca2+-Pi were treated at 600 MPa and 37 °C for 60 min. The pressure release rate was set at 20 or 600 MPa/min. Vitamin D2 was quantified by reversed-phase high-performance liquid chromatography, and physical properties of the micelles were analysed by photon correlation spectroscopy. The results demonstrate that simultaneous application of Ca2+-Pi and high pressure treatment with a fast release rate significantly increased loading of vitamin D2 per casein by 6.9-fold. The addition of Ca2+-Pi enhanced micelle aggregation and the vitamin was entrapped within the formed aggregates. However, high pressure treatment without Ca2+-Pi with a slow pressure release rate revealed similar results, increasing vitamin D2 per casein by 6.7-fold. The vitamin D2 loading in reassembled casein micelles is supposed to be due to hydrophobic interactions between the hydrophobic domains of the micelles.

  4. Redox-Responsive Biomimetic Polymeric Micelle for Simultaneous Anticancer Drug Delivery and Aggregation-Induced Emission Active Imaging.

    PubMed

    Hu, Jun; Zhuang, Weihua; Ma, Boxuan; Su, Xin; Yu, Tao; Li, Gaocan; Hu, Yanfei; Wang, Yunbing

    2018-05-10

    Intelligent polymeric micelles have been developed as potential nanoplatforms for efficient drug delivery and diagnosis. Herein, we successfully prepared redox-sensitive polymeric micelles combined aggregation-induced emission (AIE) imaging as an outstanding anticancer drug carrier system for simultaneous chemotherapy and bioimaging. The amphiphilic copolymer TPE-SS-PLAsp- b-PMPC could self-assemble into spherical micelles, and these biomimetic micelles exhibited great biocompatibility and remarkable ability in antiprotein adsorption, showing great potential for biomedical application. Anticancer drug doxorubicin (DOX) could be encapsulated during the self-assembly process, and these drug-loaded micelles showed intelligent drug release and improved antitumor efficacy due to the quick disassembly in response to high levels of glutathione (GSH) in the environment. Moreover, the intracellular DOX release could be traced through the fluorescent imaging of these AIE micelles. As expected, the in vivo antitumor study exhibited that these DOX-carried micelles showed better antitumor efficacy and less adverse effects than that of free DOX. These results strongly indicated that this smart biomimetic micelle system would be a prominent candidate for chemotherapy and bioimaging.

  5. Complex and hierarchical micelle architectures from diblock copolymers using living, crystallization-driven polymerizations.

    PubMed

    Gädt, Torben; Ieong, Nga Sze; Cambridge, Graeme; Winnik, Mitchell A; Manners, Ian

    2009-02-01

    Block copolymers consist of two or more chemically distinct polymer segments, or blocks, connected by a covalent link. In a selective solvent for one of the blocks, core-corona micelle structures are formed. We demonstrate that living polymerizations driven by the epitaxial crystallization of a core-forming metalloblock represent a synthetic tool that can be used to generate complex and hierarchical micelle architectures from diblock copolymers. The use of platelet micelles as initiators enables the formation of scarf-like architectures in which cylindrical micelle tassels of controlled length are grown from specific crystal faces. A similar process enables the fabrication of brushes of cylindrical micelles on a crystalline homopolymer substrate. Living polymerizations driven by heteroepitaxial growth can also be accomplished and are illustrated by the formation of tri- and pentablock and scarf architectures with cylinder-cylinder and platelet-cylinder connections, respectively, that involve different core-forming metalloblocks.

  6. From micelle supramolecular assemblies in selective solvents to isoporous membranes.

    PubMed

    Nunes, Suzana P; Karunakaran, Madhavan; Pradeep, Neelakanda; Behzad, Ali Reza; Hooghan, Bobby; Sougrat, Rachid; He, Haoze; Peinemann, Klaus-Viktor

    2011-08-16

    The supramolecular assembly of PS-b-P4VP copolymer micelles induced by selective solvent mixtures was used to manufacture isoporous membranes. Micelle order in solution was confirmed by cryo-scanning electron microscopy in casting solutions, leading to ordered pore morphology. When dioxane, a solvent that interacts poorly with the micelle corona, was added to the solution, polymer-polymer segment contact was preferential, increasing the intermicelle contact. Immersion in water gave rise to asymmetric porous membranes with exceptional pore uniformity and high porosity. The introduction of a small number of carbon nanotubes to the casting solution improved the membrane stability and the reversibility of the gate response in the presence of different pH values.

  7. Complexation of lysozyme with adsorbed PtBS-b-SCPI block polyelectrolyte micelles on silver surface.

    PubMed

    Papagiannopoulos, Aristeidis; Christoulaki, Anastasia; Spiliopoulos, Nikolaos; Vradis, Alexandros; Toprakcioglu, Chris; Pispas, Stergios

    2015-01-20

    We present a study of the interaction of the positively charged model protein lysozyme with the negatively charged amphiphilic diblock polyelectrolyte micelles of poly(tert-butylstyrene-b-sodium (sulfamate/carboxylate)isoprene) (PtBS-b-SCPI) on the silver/water interface. The adsorption kinetics are monitored by surface plasmon resonance, and the surface morphology is probed by atomic force microscopy. The micellar adsorption is described by stretched-exponential kinetics, and the micellar layer morphology shows that the micelles do not lose their integrity upon adsorption. The complexation of lysozyme with the adsorbed micellar layers depends on the micelles arrangement and density in the underlying layer, and lysozyme follows the local morphology of the underlying roughness. When the micellar adsorbed amount is small, the layers show low capacity in protein complexation and low resistance in loading. When the micellar adsorbed amount is high, the situation is reversed. The adsorbed layers both with or without added protein are found to be irreversibly adsorbed on the Ag surface.

  8. The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles.

    PubMed

    van Hasselt, P M; Janssens, G E P J; Slot, T K; van der Ham, M; Minderhoud, T C; Talelli, M; Akkermans, L M; Rijcken, C J F; van Nostrum, C F

    2009-01-19

    The purpose of this study was to assess the ability of polymeric micelles to enable gastrointestinal absorption of the extremely hydrophobic compound vitamin K, by comparison of its absorption in bile duct ligated and sham operated rats. Hereto, vitamin K was encapsulated in micelles composed of mPEG(5000)-b-p(HPMAm-lac(2)), a thermosensitive block copolymer. Vitamin K plasma levels rose significantly upon gastric administration of 1 mg vitamin K encapsulated in polymeric micelles in sham operated rats, but not after bile duct ligation (AUC 4543 and 1.64 ng/mL/h respectively, p<0.01). Duodenal administration of polymeric micelles together with bile acids in bile duct ligated rats fully restored absorption. Dynamic light scattering time series showed a significant and dose dependent rise in micellar size in the presence of bile acids in vitro, indicating the gradual formation of mixed micelles during the first 3 h of incubation. The highest bile acid amounts (11 mM deoxycholic acid and 41 mM taurocholic acid) eventually caused aggregation of the loaded micelles after the formation of mixed micelles. These data suggest that the gastrointestinal absorption of encapsulated vitamin K from polymeric micelles is mediated by free bile and that uptake of intact micelles through pinocytosis is insignificant.

  9. Chirality plays critical roles in enhancing the aqueous solubility of nocathiacin I by block copolymer micelles.

    PubMed

    Feng, Kun; Wang, Shuzhen; Ma, Hairong; Chen, Yijun

    2013-01-01

    Although drug solubilization by block copolymer micelles has been extensively studied, the rationale behind the choice of appropriate block copolymer micelles for various poorly water-soluble drugs has been of relatively less concern. The objective of this study was to use methoxy-poly(ethylene glycol)-polylactate micelles (MPEG-PLA) to solubilize glycosylated antibiotic nocathiacin I and to compare the effects of chirality on the enhancement of aqueous solubility. Nocathiacin I-loaded MPEG-PLA micelles with opposite optical property in PLA were synthesized and characterized. The drug release profile, micelle stability and preliminary safety properties of MPEG-PLA micelles were evaluated. Meanwhile, three other poorly water-soluble chiral compound-loaded micelles were also prepared and compared.  The aqueous solubility of nocathiacin I was greatly enhanced by both L- and D-copolymers, with the degree of enhancement appearing to depend on the chirality of the copolymers. Comparison of different chiral compounds confirmed the trend that aqueous solubility of chiral compounds can be more effectively enhanced by block copolymer micelles with specific stereochemical configuration. The present study introduced chiral concept on the selection and preparation of block copolymer micelles for the enhancement of aqueous solubility of poorly water-soluble drugs. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  10. Effect of high hydrostatic pressure and whey proteins on the disruption of casein micelle isolates.

    PubMed

    Harte, Federico M; Gurram, Subba Rao; Luedecke, Lloyd O; Swanson, Barry G; Barbosa-Cánovas, Gustavo V

    2007-11-01

    High hydrostatic pressure disruption of casein micelle isolates was studied by analytical ultracentrifugation and transmission electron microscopy. Casein micelles were isolated from skim milk and subjected to combinations of thermal treatment (85 degrees C, 20 min) and high hydrostatic pressure (up to 676 MPa) with and without whey protein added. High hydrostatic pressure promoted extensive disruption of the casein micelles in the 250 to 310 MPa pressure range. At pressures greater than 310 MPa no further disruption was observed. The addition of whey protein to casein micelle isolates protected the micelles from high hydrostatic pressure induced disruption only when the mix was thermally processed before pressure treatment. The more whey protein was added (up to 5 g/l) the more the protection against high hydrostatic pressure induced micelle disruption was observed in thermally treated samples subjected to 310 MPa.

  11. Retrieval of chlorophyll from remote-sensing reflectance in the china seas.

    PubMed

    He, M X; Liu, Z S; Du, K P; Li, L P; Chen, R; Carder, K L; Lee, Z P

    2000-05-20

    The East China Sea is a typical case 2 water environment, where concentrations of phytoplankton pigments, suspended matter, and chromophoric dissolved organic matter (CDOM) are all higher than those in the open oceans, because of the discharge from the Yangtze River and the Yellow River. By using a hyperspectral semianalytical model, we simulated a set of remote-sensing reflectance for a variety of chlorophyll, suspended matter, and CDOM concentrations. From this simulated data set, a new algorithm for the retrieval of chlorophyll concentration from remote-sensing reflectance is proposed. For this method, we took into account the 682-nm spectral channel in addition to the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) channels. When this algorithm was applied to a field data set, the chlorophyll concentrations retrieved through the new algorithm were consistent with field measurements to within a small error of 18%, in contrast with that of 147% between the SeaWiFS ocean chlorophyll 2 algorithm and the in situ observation.

  12. Y-shaped Folic Acid-Conjugated PEG-PCL Copolymeric Micelles for Delivery of Curcumin.

    PubMed

    Feng, Runliang; Zhu, Wenxia; Chu, Wei; Teng, Fangfang; Meng, Ning; Deng, Peizong; Song, Zhimei

    2017-01-01

    Curcumin is a natural hydrophobic product showing anticancer activity. Many studies show its potential use in the field of cancer treatment due to its safety and efficiency. However, its application is limited due to its low water-solubility and poor selective delivery to cancer. A Y-shaped folic acid-modified poly (ethylene glycol)-b-poly (ε-caprolactone)2 copolymer was prepared to improve curcumin solubility and realize its selective delivery to cancer. The copolymer was synthesized through selective acylation reaction of folic acid with α- monoamino poly(ethylene glycol)-b-poly(ε-caprolactone)2. Curcumin was encapsulated into the copolymeric micelles with 93.71% of encapsulation efficiency and 11.94 % of loading capacity. The results from confocal microscopy and cellular uptake tests showed that folic acid-modified copolymeric micelles could improve cellular uptake of curcumin in Hela and HepG2 cells compared with folic acid-unmodified micelles. In vitro cytotoxicity assay showed that folic acid-modified micelles improved anticancer activity against Hela and HepG2 cells in comparison to folic acidunmodified micelles. Meanwhile, both drug-loaded micelles demonstrated higher activity against Hela cell lines than HepG2. The research results suggested that the folic acid-modified Y-shaped copolymeric micelles should be used to enhance hydrophobic anticancer drugs' solubility and their specific delivery to folic acid receptors-overexpressed cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. HPMA-based polymeric micelles for curcumin solubilization and inhibition of cancer cell growth.

    PubMed

    Naksuriya, Ornchuma; Shi, Yang; van Nostrum, Cornelus F; Anuchapreeda, Songyot; Hennink, Wim E; Okonogi, Siriporn

    2015-08-01

    Curcumin (CM) has been reported as a potential anticancer agent. However, its pharmaceutical applications as therapeutic agent are hampered because of its poor aqueous solubility. The present study explores the advantages of polymeric micelles composed of block copolymers of methoxypoly(ethylene glycol) (mPEG) and N-(2-hydroxypropyl) methacrylamide (HPMA) modified with monolactate, dilactate and benzoyl side groups to enhance CM solubility and inhibitory activity against cancer cells. Amphiphilic block copolymers, ω-methoxypoly(ethylene glycol)-b-(N-(2-benzoyloxypropyl) methacrylamide) (PEG-HPMA-Bz) were synthesized and characterized by (1)H NMR and GPC. One polymer with a molecular weight of 28,000Da was used to formulate CM and compared with other aromatic substituted polymers. CM was loaded by a fast heating method (PEG-HPMA-DL and PEG-HPMA-Bz-L) and a nanoprecipitation method (PEG-HPMA-Bz). Physicochemical characteristics and cytotoxicity/cytocompatibility of the CM loaded polymeric micelles were evaluated. It was found that HPMA-based polymeric micelles significantly enhanced the solubility of CM. The PEG-HPMA-Bz micelles showed the best solubilization properties. CM loaded polymeric micelles showed sustained release of the loading CM for more than 20days. All of CM loaded polymeric micelles formulations showed a significantly potent cytotoxic effect against three cancer cell lines. HPMA-based polymeric micelles are therefore promising nanodelivery systems of CM for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Parenterally administrable nano-micelles of 3,4-difluorobenzylidene curcumin for treating pancreatic cancer.

    PubMed

    Kesharwani, Prashant; Banerjee, Sanjeev; Padhye, Subhash; Sarkar, Fazlul H; Iyer, Arun K

    2015-08-01

    Pancreatic cancer remains one of the most devastating diseases in terms of patient mortality rates for which current treatment options are very limited. 3,4-Difluorobenzylidene curcumin (CDF) is a nontoxic analog of curcumin (CMN) developed in our laboratory, which exhibits extended circulation half-life, while maintaining high anticancer activity and improved pancreas specific accumulation in vivo, compared with CMN. CDF however has poor aqueous solubility and its dose escalation for systemic administration remains challenging. We have engineered self-assembling nano-micelles of amphiphilic styrene-maleic acid copolymer (SMA) with CDF by non-covalent hydrophobic interactions. The SMA-CDF nano-micelles were characterized for size, charge, drug loading, release, serum stability, and in vitro anticancer activity. The SMA-CDF nano-micelles exhibited tunable CDF loading from 5 to 15% with excellent aqueous solubility, stability, favorable hemocompatibility and sustained drug release characteristics. The outcome of cytotoxicity testing of SMA-CDF nano-micelles on MiaPaCa-2 and AsPC-1 pancreatic cancer cell lines revealed pronounced antitumor response due to efficient intracellular trafficking of the drug loaded nano-micelles. Additionally, the nano-micelles are administrable via the systemic route for future in vivo studies and clinical translation. The currently developed SMA based nano-micelles thus portend to be a versatile carrier for dose escalation and targeted delivery of CDF, with enhanced therapeutic margin and safety. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Micelles as Delivery Vehicles for Oligofluorene for Bioimaging

    PubMed Central

    Su, Fengyu; Alam, Ruhaniyah; Mei, Qian; Tian, Yanqing; Meldrum, Deirdre R.

    2011-01-01

    With the successful development of organic/polymeric light emitting diodes, many organic and polymeric fluorophores with high quantum efficiencies and optical stability were synthesized. However, most of these materials which have excellent optical properties are insoluble in water, limiting their applications in biological fields. Herein, we used micelles formed from an amino-group-containing poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG-NH2) to incorporate a hydrophobic blue emitter oligofluorene (OF) to enable its application in biological conditions. Although OF is completely insoluble in water, it was successfully transferred into aqueous solutions with a good retention of its photophysical properties. OF exhibited a high quantum efficiency of 0.84 in a typical organic solvent of tetrahydrofuran (THF). In addition, OF also showed a good quantum efficiency of 0.46 after being encapsulated into micelles. Two cells lines, human glioblastoma (U87MG) and esophagus premalignant (CP-A), were used to study the cellular internalization of the OF incorporated micelles. Results showed that the hydrophobic OF was located in the cytoplasm, which was confirmed by co-staining the cells with nucleic acid specific SYTO 9, lysosome specific LysoTracker Red®, and mitochondria specific MitoTracker Red. MTT assay indicated non-toxicity of the OF-incorporated micelles. This study will broaden the application of hydrophobic functional organic compounds, oligomers, and polymers with good optical properties to enable their applications in biological research fields. PMID:21915324

  16. Micelles as delivery vehicles for oligofluorene for bioimaging.

    PubMed

    Su, Fengyu; Alam, Ruhaniyah; Mei, Qian; Tian, Yanqing; Meldrum, Deirdre R

    2011-01-01

    With the successful development of organic/polymeric light emitting diodes, many organic and polymeric fluorophores with high quantum efficiencies and optical stability were synthesized. However, most of these materials which have excellent optical properties are insoluble in water, limiting their applications in biological fields. Herein, we used micelles formed from an amino-group-containing poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG-NH(2)) to incorporate a hydrophobic blue emitter oligofluorene (OF) to enable its application in biological conditions. Although OF is completely insoluble in water, it was successfully transferred into aqueous solutions with a good retention of its photophysical properties. OF exhibited a high quantum efficiency of 0.84 in a typical organic solvent of tetrahydrofuran (THF). In addition, OF also showed a good quantum efficiency of 0.46 after being encapsulated into micelles. Two cells lines, human glioblastoma (U87MG) and esophagus premalignant (CP-A), were used to study the cellular internalization of the OF incorporated micelles. Results showed that the hydrophobic OF was located in the cytoplasm, which was confirmed by co-staining the cells with nucleic acid specific SYTO 9, lysosome specific LysoTracker Red®, and mitochondria specific MitoTracker Red. MTT assay indicated non-toxicity of the OF-incorporated micelles. This study will broaden the application of hydrophobic functional organic compounds, oligomers, and polymers with good optical properties to enable their applications in biological research fields.

  17. Curcumin Cocrystal Micelles-Multifunctional Nanocomposites for Management of Neurodegenerative Ailments.

    PubMed

    Desai, Preshita P; Patravale, Vandana B

    2018-04-01

    Curcumin, a potent antioxidant polyphenol with neuroprotective and antiamyloid activities, has significant potential in the treatment of neurodegenerative disorders such as Alzheimer's disease. However, its clinical translation is delayed due to poor bioavailability. For effective use of curcumin in Alzheimer's disease, it is imperative to increase its bioavailability with enhanced delivery at a therapeutic site that is, brain. With this objective, pharmaceutical cocrystals of curcumin were developed and incorporated in micellar nanocarriers for nose-to-brain delivery. For cocrystals, an antioxidant hydrophilic coformer was strategically selected using molecular modeling approach. The cocrystals were formulated using a planetary ball mill, and the process was optimized using 3 2 factorial design followed by characterization using differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectroscopy analysis. The cocrystal micelles exhibited globule size of 28.79 ± 0.86 nm. Further, curcumin cocrystal and co-crystal micelles exhibited a significantly low (p value <0.01) IC 50 concentration for antioxidant activity as compared to curcumin corroborating superior antioxidant performance. In vivo studies revealed about 1.7-fold absolute bioavailability of curcumin cocrystal micelles with C max of 1218.38 ± 58.11 ng/mL and showed significantly high brain distribution even beyond 6 hours of dosing. Thus, the studies confirmed enhanced bioavailability, higher brain uptake, retention, and delayed clearance with curcumin cocrystal micellar nanocarriers. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Structures of Chlorophyll Catabolites in Bananas (Musa acuminata) Reveal a Split Path of Chlorophyll Breakdown in a Ripening Fruit

    PubMed Central

    Moser, Simone; Müller, Thomas; Holzinger, Andreas; Lütz, Cornelius; Kräutler, Bernhard

    2012-01-01

    Abstract The disappearance of chlorophyll is a visual sign of fruit ripening. Yet, chlorophyll breakdown in fruit has hardly been explored; its non-green degradation products are largely unknown. Here we report the analysis and structure elucidation of colorless tetrapyrrolic chlorophyll breakdown products in commercially available, ripening bananas (Musa acuminata, Cavendish cultivar). In banana peels, chlorophyll catabolites were found in an unprecedented structural richness: a variety of new fluorescent chlorophyll catabolites (FCCs) and nonfluorescent chlorophyll catabolites (NCCs) were detected. As a rule, FCCs exist only "fleetingly" and are hard to observe. However, in bananas several of the FCCs (named Mc-FCCs) were persistent and carried an ester function at the propionate side-chain. NCCs were less abundant, and exhibited a free propionic acid group, but functional modifications elsewhere. The modifications of NCCs in banana peels were similar to those found in NCCs from senescent leaves. They are presumed to be introduced by enzymatic transformations at the stage of the mostly unobserved, direct FCC-precursors. The observed divergent functional group characteristics of the Mc-FCCs versus those of the Mc-NCCs indicated two major "late" processing lines of chlorophyll breakdown in ripening bananas. The "last common precursor" at the branching point to either the persistent FCCs, or towards the NCCs, was identified as a temporarily abundant "secondary" FCC. The existence of two "downstream" branches of chlorophyll breakdown in banana peels, and the striking accumulation of persistent Mc-FCCs call for attention as to the still-elusive biological roles of the resulting colorless linear tetrapyrroles. PMID:22807397

  19. Relaxation times and modes of disturbed aggregate distribution in micellar solutions with fusion and fission of micelles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zakharov, Anatoly I.; Adzhemyan, Loran Ts.; Shchekin, Alexander K., E-mail: akshch@list.ru

    2015-09-28

    We have performed direct numerical calculations of the kinetics of relaxation in the system of surfactant spherical micelles under joint action of the molecular mechanism with capture and emission of individual surfactant molecules by molecular aggregates and the mechanism of fusion and fission of the aggregates. As a basis, we have taken the difference equations of aggregation and fragmentation in the form of the generalized kinetic Smoluchowski equations for aggregate concentrations. The calculations have been made with using the droplet model of molecular surfactant aggregates and two modified Smoluchowski models for the coefficients of aggregate-monomer and aggregate-aggregate fusions which takemore » into account the effects of the aggregate size and presence of hydrophobic spots on the aggregate surface. A full set of relaxation times and corresponding relaxation modes for nonequilibrium aggregate distribution in the aggregation number has been found. The dependencies of these relaxation times and modes on the total concentration of surfactant in the solution and the special parameter controlling the probability of fusion in collisions of micelles with other micelles have been studied.« less

  20. Leaf Surface Effects on Retrieving Chlorophyll Content from Hyperspectral Remote Sensing

    NASA Astrophysics Data System (ADS)

    Qiu, Feng; Chen, JingMing; Ju, Weimin; Wang, Jun; Zhang, Qian

    2017-04-01

    Light reflected directly from the leaf surface without entering the surface layer is not influenced by leaf internal biochemical content. Leaf surface reflectance varies from leaf to leaf due to differences in the surface roughness features and is relatively more important in strong absorption spectral regions. Therefore it introduces dispersion of data points in the relationship between biochemical concentration and reflectance (especially in the visible region). Separation of surface from total leaf reflection is important to improve the link between leaf pigments content and remote sensing data. This study aims to estimate leaf surface reflectance from hyperspectral remote sensing data and retrieve chlorophyll content by inverting a modified PROSPECT model. Considering leaf surface reflectance is almost the same in the visible and near infrared spectral regions, a surface layer with a reflectance independent of wavelength but varying from leaf to leaf was added to the PROSPECT model. The specific absorption coefficients of pigments were recalibrated. Then the modified model was inverted on independent datasets to check the performance of the model in predicting the chlorophyll content. Results show that differences in estimated surface layer reflectance of various species are noticeable. Surface reflectance of leaves with epicuticular waxes and trichomes is usually higher than other samples. Reconstruction of leaf reflectance and transmittance in the 400-1000 nm wavelength region using the modified PROSPECT model is excellent with low root mean square error (RMSE) and bias. Improvements for samples with high surface reflectance (e.g. maize) are significant, especially for high pigment leaves. Moreover, chlorophyll retrieved from inversion of the modified model is consequently improved (RMSE from 5.9-13.3 ug/cm2 with mean value 8.1 ug/cm2, while mean correlation coefficient is 0.90) compared to results of PROSPECT-5 (RMSE from 9.6-20.2 ug/cm2 with mean value 13

  1. Novel Brassinosteroid-Modified Polyethylene Glycol Micelles for Controlled Release of Agrochemicals.

    PubMed

    Pérez Quiñones, Javier; Brüggemann, Oliver; Kjems, Jørgen; Shahavi, Mohammad Hassan; Peniche Covas, Carlos

    2018-02-21

    Two synthetic analogues of brassinosteroids (DI31 and S7) exhibit good plant growth enhancer activity. However, their hydrophobicity and quick metabolism in plants have limited their application and benefits in agriculture. Our objective was to prepare novel brassinosteroid-modified polyethylene glycol (PEG) micelles to achieve controlled release with extended stability while retaining agrochemical activity. Spectroscopic studies confirmed quantitative disubstitution of studied PEGs with the brassinosteroids, while elemental analysis assessed purity of the synthesized conjugates. Conjugates were also characterized by X-ray diffraction and thermal analysis. Dynamic and static light scattering showed stable and homogeneous approximately spherical micelles with average hydrodynamic diameters of 22-120 nm and almost neutral ζ potential. Spherical 30-140 nm micelles were observed by electron microscopy. Sustained in vitro releases at pH 5.5 were extended up to 96 h. Prepared PEG micelles showed good agrochemical activity in the radish seed bioassay and no cytotoxicity to the human microvascular endothelial cell line in the MTS test.

  2. Multimodality CT/SPECT Evaluation of Micelle Drug Carriers for Treatment of Breast Tumors

    DTIC Science & Technology

    2008-07-01

    Sherry, D.A. Boothman, J. Gao, Multifunctional polymeric micelles as cancer -targeted, MRI-ultrasensitive drug delivery systems , Nano Lett. 6 (11) (2006...1–4) (1999) 3–27. [40] D. Sutton, N. Nasongkla, E. Blanco, J. Gao, Functionalized micellar systems for cancer targeted drug delivery . Pharm. Res. (in...Polymer micelles are nanoscale drug delivery systems that have the potential to improve breast tumor treatment. Micelles can increase the half-life

  3. Plant leaf chlorophyll content retrieval based on a field imaging spectroscopy system.

    PubMed

    Liu, Bo; Yue, Yue-Min; Li, Ru; Shen, Wen-Jing; Wang, Ke-Lin

    2014-10-23

    A field imaging spectrometer system (FISS; 380-870 nm and 344 bands) was designed for agriculture applications. In this study, FISS was used to gather spectral information from soybean leaves. The chlorophyll content was retrieved using a multiple linear regression (MLR), partial least squares (PLS) regression and support vector machine (SVM) regression. Our objective was to verify the performance of FISS in a quantitative spectral analysis through the estimation of chlorophyll content and to determine a proper quantitative spectral analysis method for processing FISS data. The results revealed that the derivative reflectance was a more sensitive indicator of chlorophyll content and could extract content information more efficiently than the spectral reflectance, which is more significant for FISS data compared to ASD (analytical spectral devices) data, reducing the corresponding RMSE (root mean squared error) by 3.3%-35.6%. Compared with the spectral features, the regression methods had smaller effects on the retrieval accuracy. A multivariate linear model could be the ideal model to retrieve chlorophyll information with a small number of significant wavelengths used. The smallest RMSE of the chlorophyll content retrieved using FISS data was 0.201 mg/g, a relative reduction of more than 30% compared with the RMSE based on a non-imaging ASD spectrometer, which represents a high estimation accuracy compared with the mean chlorophyll content of the sampled leaves (4.05 mg/g). Our study indicates that FISS could obtain both spectral and spatial detailed information of high quality. Its image-spectrum-in-one merit promotes the good performance of FISS in quantitative spectral analyses, and it can potentially be widely used in the agricultural sector.

  4. Plant Leaf Chlorophyll Content Retrieval Based on a Field Imaging Spectroscopy System

    PubMed Central

    Liu, Bo; Yue, Yue-Min; Li, Ru; Shen, Wen-Jing; Wang, Ke-Lin

    2014-01-01

    A field imaging spectrometer system (FISS; 380–870 nm and 344 bands) was designed for agriculture applications. In this study, FISS was used to gather spectral information from soybean leaves. The chlorophyll content was retrieved using a multiple linear regression (MLR), partial least squares (PLS) regression and support vector machine (SVM) regression. Our objective was to verify the performance of FISS in a quantitative spectral analysis through the estimation of chlorophyll content and to determine a proper quantitative spectral analysis method for processing FISS data. The results revealed that the derivative reflectance was a more sensitive indicator of chlorophyll content and could extract content information more efficiently than the spectral reflectance, which is more significant for FISS data compared to ASD (analytical spectral devices) data, reducing the corresponding RMSE (root mean squared error) by 3.3%–35.6%. Compared with the spectral features, the regression methods had smaller effects on the retrieval accuracy. A multivariate linear model could be the ideal model to retrieve chlorophyll information with a small number of significant wavelengths used. The smallest RMSE of the chlorophyll content retrieved using FISS data was 0.201 mg/g, a relative reduction of more than 30% compared with the RMSE based on a non-imaging ASD spectrometer, which represents a high estimation accuracy compared with the mean chlorophyll content of the sampled leaves (4.05 mg/g). Our study indicates that FISS could obtain both spectral and spatial detailed information of high quality. Its image-spectrum-in-one merit promotes the good performance of FISS in quantitative spectral analyses, and it can potentially be widely used in the agricultural sector. PMID:25341439

  5. Importance of casein micelle size and milk composition for milk gelation.

    PubMed

    Glantz, M; Devold, T G; Vegarud, G E; Lindmark Månsson, H; Stålhammar, H; Paulsson, M

    2010-04-01

    The economic output of the dairy industry is to a great extent dependent on the processing of milk into other milk-based products such as cheese. The yield and quality of cheese are dependent on both the composition and technological properties of milk. The objective of this study was to evaluate the importance and effects of casein (CN) micelle size and milk composition on milk gelation characteristics in order to evaluate the possibilities for enhancing gelation properties through breeding. Milk was collected on 4 sampling occasions at the farm level in winter and summer from dairy cows with high genetic merit, classified as elite dairy cows, of the Swedish Red and Swedish Holstein breeds. Comparisons were made with milk from a Swedish Red herd, a Swedish Holstein herd, and a Swedish dairy processor. Properties of CN micelles, such as their native and rennet-induced CN micelle size and their zeta-potential, were analyzed by photon correlation spectroscopy, and rennet-induced gelation characteristics, including gel strength, gelation time, and frequency sweeps, were determined. Milk parameters of the protein, lipid, and carbohydrate profiles as well as minerals were used to obtain correlations with native CN micelle size and gelation characteristics. Milk pH and protein, CN, and lactose contents were found to affect milk gelation. Smaller native CN micelles were shown to form stronger gels when poorly coagulating milk was excluded from the correlation analysis. In addition, milk pH correlated positively, whereas Mg and K correlated negatively with native CN micellar size. The milk from the elite dairy cows was shown to have good gelation characteristics. Furthermore, genetic progress in relation to CN micelle size was found for these cows as a correlated response to selection for the Swedish breeding objective if optimizing for milk gelation characteristics. The results indicate that selection for smaller native CN micelles and lower milk pH through breeding would

  6. Design and evaluation of mPEG-PLA micelles functionalized with drug-interactive domains as improved drug carriers for docetaxel delivery.

    PubMed

    Qi, Dingqing; Gong, Feirong; Teng, Xin; Ma, Mingming; Wen, Huijing; Yuan, Weihao; Cheng, Yi; Lu, Chong

    2017-10-01

    Polymeric micelles are very attractive drug delivery systems for hydrophobic agents, owing to their readily tailorable chemical structure and ease for scale-up preparation. However, the intrinsic poor stability of drug-loaded micelles presents one of the major challenges for most micellar systems in the translation to clinical applications. In this study, a simple, well-defined, and easy-to-scale up 9-Fluorenylmethoxycarbonyl (Fmoc) and tert-butoxycarbonyl (Boc) containing lysine dendronized mPEG-PLA (mPEG-PLA-Lys(FB) 2 ) micellar formulation was designed and prepared for docetaxel (DTX) delivery, in an effort to improve the stability of the micelles, and its physicochemical properties, pharmacokinetics, and anti-tumor efficacy against SKOV-3 ovarian cancer were evaluated. MPEG-PLA-Lys(FB) 2 was synthesized via a three-step synthetic route, and it actively interacted with DTX in aqueous media to form stable micelles with small particle sizes (~17-19 nm) and narrow size distribution (PI < 0.1), which can be lyophilized and easily reconstituted in saline without significant change in particle size distribution. In vitro drug-release study demonstrated that mPEG-PLA-Lys(FB) 2 micelles achieved delayed and sustained release manner of DTX in comparison with mPEG-PLA micelles. Further in vivo xenograft tumor model in nude mice DTX/mPEG-PLA-Lys(FB) 2 micelles demonstrated significantly higher inhibitory effect on tumor growth than the marketed formulation Taxotere. Thus, our system may hold promise as a simple and effective delivery system for DTX with a potential for translation into clinical study.

  7. Therapeutic surfactant-stripped frozen micelles

    NASA Astrophysics Data System (ADS)

    Zhang, Yumiao; Song, Wentao; Geng, Jumin; Chitgupi, Upendra; Unsal, Hande; Federizon, Jasmin; Rzayev, Javid; Sukumaran, Dinesh K.; Alexandridis, Paschalis; Lovell, Jonathan F.

    2016-05-01

    Injectable hydrophobic drugs are typically dissolved in surfactants and non-aqueous solvents which can induce negative side-effects. Alternatives like `top-down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and `bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2-3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated.

  8. Phenformin-loaded polymeric micelles for targeting both cancer cells and cancer stem cells in vitro and in vivo.

    PubMed

    Krishnamurthy, Sangeetha; Ng, Victor W L; Gao, Shujun; Tan, Min-Han; Yang, Yi Yan

    2014-11-01

    Conventional cancer chemotherapy often fails as most anti-cancer drugs are not effective against drug-resistant cancer stem cells. These surviving cancer stem cells lead to relapse and metastasis. In this study, an anti-diabetic drug, phenformin, capable of eliminating cancer stem cells was loaded into micelles via self-assembly using a mixture of a diblock copolymer of poly(ethylene glycol) (PEG) and urea-functionalized polycarbonate and a diblock copolymer of PEG and acid-functionalized polycarbonate through hydrogen bonding. The phenformin-loaded micelles, having an average diameter of 102 nm with narrow size distribution, were stable in serum-containing solution over 48 h and non-cytotoxic towards non-cancerous cells. More than 90% of phenformin was released from the micelles over 96 h. Lung cancer stem cells (side population cells, i.e. SP cells) and non-SP cells were sorted from H460 human lung cancer cell line, and treated with free phenformin and phenformin-loaded micelles. The results showed that the drug-loaded micelles were more effective in inhibiting the growth of both SP and non-SP cells. In vivo studies conducted in an H460 human lung cancer mouse model demonstrated that the drug-loaded micelles had greater anti-tumor efficacy, and reduced the population of SP cells in the tumor tissues more effectively than free phenformin. Liver function analysis was performed following drug treatments, and the results indicated that the drug-loaded micelles did not cause liver damage, a harmful side-effect of phenformin when used clinically. These phenformin-loaded micelles may be used to target both cancer cells and cancer stem cells in chemotherapy for the prevention of relapse and metastasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Stealth properties of poly(ethylene oxide)-based triblock copolymer micelles: a prerequisite for a pH-triggered targeting system.

    PubMed

    Van Butsele, K; Morille, M; Passirani, C; Legras, P; Benoit, J P; Varshney, S K; Jérôme, R; Jérôme, C

    2011-10-01

    Evaluation of the biocompatibility of pH-triggered targeting micelles was performed with the goal of studying the effect of a poly(ethylene oxide) (PEO) coating on micelle stealth properties. Upon protonation under acidic conditions, pH-sensitive poly(2-vinylpyridine) (P2VP) blocks were stretched, exhibiting positive charges at the periphery of the micelles as well as being a model targeting unit. The polymer micelles were based on two different macromolecular architectures, an ABC miktoarm star terpolymer and an ABC linear triblock copolymer, which combined three different polymer blocks, i.e. hydrophobic poly(ε-caprolactone), PEO and P2VP. Neutral polymer micelles were formed at physiological pH. These systems were tested for their ability to avoid macrophage uptake, their complement activation and their pharmacological behavior after systemic injection in mice, as a function of their conformation (neutral or protonated). After protonation, complement activation and macrophage uptake were up to twofold higher than for neutral systems. By contrast, when P2VP blocks and the targeting unit were buried by the PEO shell at physiological pH, micelle stealth properties were improved, allowing their future systemic injection with an expected long circulation in blood. Smart systems responsive to pH were thus developed which therefore hold great promise for targeted drug delivery to an acidic tumoral environment. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. Chemotherapeutic Effect of CD147 Antibody-labeled Micelles Encapsulating Doxorubicin Conjugate Targeting CD147-Expressing Carcinoma Cells.

    PubMed

    Asakura, Tadashi; Yokoyama, Masayuki; Shiraishi, Koichi; Aoki, Katsuhiko; Ohkawa, Kiyoshi

    2018-03-01

    CD147 (basigin/emmprin) is expressed on the surface of carcinoma cells. For studying the efficacy of CD147-targeting medicine on CD147-expressing cells, we studied the effect of anti-CD147-labeled polymeric micelles (CD147ab micelles) that encapsulated a conjugate of doxorubicin with glutathione (GSH-DXR), with specific accumulation and cytotoxicity against CD147-expressing A431 human epidermoid carcinoma cells, Ishikawa human endometrial adenocarcinoma cells, and PC3 human prostate carcinoma cells. By treatment of each cell type with CD147ab micelles for 1 h, a specific accumulation of CD147ab micelles in CD147-expressing cells was observed. In addition, the cytotoxicity of GSH-DXR-encapsulated micelles against each cell type was measured by treatment of the micelles for 1 h. The cytotoxic effect of CD147ab micelles carrying GSH-DXR was 3- to 10-fold higher for these cells than that of micelles without GSH-DXR. These results suggest that GSH-DXR-encapsulated CD147ab micelles could serve as an effective drug delivery system to CD147-expressing carcinoma cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells

    PubMed Central

    Wang, Ke; Zhang, Tao; Liu, Lina; Wang, Xiaolei; Wu, Ping; Chen, Zhigang; Ni, Chao; Zhang, Junshu; Hu, Fuqiang; Huang, Jian

    2012-01-01

    Background and methods: Curcumin has extraordinary anticancer properties but has limited use due to its insolubility in water and instability, which leads to low systemic bioavailability. We have developed a novel nanoparticulate formulation of curcumin encapsulated in stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles to overcome these hurdles. Results: The synthesized CSO-SA copolymer was able to self-assemble to form nanoscale micelles in aqueous medium. The mean diameter of the curcumin-loaded CSO-SA micelles was 114.7 nm and their mean surface potential was 18.5 mV. Curcumin-loaded CSO-SA micelles showed excellent internalization ability that increased curcumin accumulation in cancer cells. Curcumin-loaded CSO-SA micelles also had potent antiproliferative effects on primary colorectal cancer cells in vitro, resulting in about 6-fold greater inhibition compared with cells treated with a solution containing an equivalent concentration of free curcumin. Intravenous administration of curcumin-loaded CSO-SA micelles marginally suppressed tumor growth but did not increase cytotoxicity to mice, as confirmed by no change in body weight. Most importantly, curcumin-loaded CSO-SA micelles were effective for inhibiting subpopulations of CD44+/CD24+ cells (putative colorectal cancer stem cell markers) both in vitro and in vivo. Conclusion: The present study identifies an effective and safe means of using curcumin-loaded CSO-SA micelles for cancer therapy. PMID:22927762

  12. Intraperitoneal Administration of a Tumor-Associated Antigen SART3, CD40L, and GM-CSF Gene-Loaded Polyplex Micelle Elicits a Vaccine Effect in Mouse Tumor Models

    PubMed Central

    Furugaki, Kouichi; Cui, Lin; Kunisawa, Yumi; Osada, Kensuke; Shinkai, Kentaro; Tanaka, Masao; Kataoka, Kazunori; Nakano, Kenji

    2014-01-01

    Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when re-challenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype. PMID:25013909

  13. Modular Design Features of a Peptide Amphiphile Micelle Vaccine Platform and Their Impact on an Immune Response

    NASA Astrophysics Data System (ADS)

    Barrett, John Christopher

    Inducing a strong and specific immune response is the hallmark of a successful vaccine. Nanoparticles have emerged as promising vaccine delivery devices to discover and elicit immune responses. Modular platforms are attractive for their engineerability and broad potential applications. Fine-tuning a nanoparticle vaccine to create an immune response with specific antibody and other cellular responses is influenced by many factors such as shape, size and composition. Peptide amphiphile micelles are a unique biomaterials platform that can function as a modular vaccine delivery system, enabling control over many of these important factors. Peptide amphiphiles (PAs) consist of a hydrophilic peptide antigen conjugated to a hydrophobic lipid tail. The PAs then self-assemble into micelles, with the micelle characteristics determined by the chemical composition of the PA and micelle preparation methods. PA micelles contain a large design space, so it is important to have a basic understanding of how each design feature can affect the platform's interaction with the immune system. In this dissertation, the structure, composition, and biodistribution properties of PA micelles are evaluated for their ability to impact an immune response against a Group A Streptococcus B cell antigen (J8). Through structural design and physical characterization, micelles are shown to self-assemble into either short rod-like or long cylindrical shapes. Analyzing these shape effects on the immune response showed that cylindrical micelles induced higher antibody titers than rod-like micelles, providing evidence that the cylindrical micelle shape is important to induce immune responses and a possible mechanism of action. Shape was also seen to impact the activation profile of dendritic cells, B cells and T cells. Assembly into cylindrical micelles also stabilizes the secondary structure of peptide antigens, which may impact the immune response raised. In composition, the hydrophobic

  14. Development of fisetin-loaded folate functionalized pluronic micelles for breast cancer targeting.

    PubMed

    Pawar, Atmaram; Singh, Srishti; Rajalakshmi, S; Shaikh, Karimunnisa; Bothiraja, C

    2018-01-15

    The natural flavonoid fisetin (FS) has shown anticancer properties but its in-vivo administration remains challenging due to its poor aqueous solubility. The aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA) conjugated micelles (FS-PF-FA) by the way of increasing solubility, bioavailability and active targetability of FS shall increase its therapeutic efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS-PF-FA micelles were prepared by thin-film hydration method and evaluated in comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 ± 6.1 nm), good encapsulation efficiency (82.50 ± 1.78%), zeta potential (-26.7 ± 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF micelles was increased by 6-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to free FS. Further, the FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed human breast cancer MCF-7 cells. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 14.3 ± 1.2 µg/ml for FS while it was greatly decreased to 9.8 ± 0.78 µg/ml, i.e. a 31.46% decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 ± 0.4 µg/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF. The results indicate that the FS-PF-FA micelles have the potential to be applied for targeting anticancer drug delivery.

  15. Development of casein microgels from cross-linking of casein micelles by genipin.

    PubMed

    Silva, Naaman F Nogueira; Saint-Jalmes, Arnaud; de Carvalho, Antônio F; Gaucheron, Frédéric

    2014-09-02

    Casein micelles are porous colloidal particles, constituted of casein molecules, water, and minerals. The vulnerability of the supramolecular structure of casein micelles face to changes in the environmental conditions restrains their applications in other domains besides food. Thus, redesigning casein micelles is a challenge to create new functionalities for these biosourced particles. The objective of this work was to create stable casein microgels from casein micelles using a natural cross-linker, named genipin. Suspensions of purified casein micelles (25 g L(-1)) were mixed with genipin solutions to have final concentrations of 5, 10, and 20 mM genipin. Covalently linked casein microgels were formed via cross-linking of lysyl and arginyl residues of casein molecules. The reacted products exhibited blue color. The cross-linking reaction induced gradual changes on the colloidal properties of the particles. The casein microgels were smaller and more negatively charged and presented smoother surfaces than casein micelles. These results were explained based on the cross-linking of free NH2 present in an external layer of κ-casein. Light scattering and rheological measurements showed that the reaction between genipin and casein molecules was intramicellar, as one single population of particles was observed and the values of viscosity (and, consequently, the volume fraction of the particles) were reduced. Contrary to the casein micelles, the casein microgels were resistant to the presence of dissociating agents, e.g., citrate (calcium chelating) and urea, but swelled as a consequence of internal electrostatic repulsion and the disruption of hydrophobic interactions between protein chains. The casein microgels did not dissociate at the air-solution interface and formed solid-like interfaces rather than a viscoelastic gel. The potential use of casein microgels as adaptable nanocarriers is proposed in the article.

  16. Physico-chemical strategies to enhance stability and drug retention of polymeric micelles for tumor-targeted drug delivery

    PubMed Central

    Shi, Yang; Lammers, Twan; Storm, Gert; Hennink, Wim E.

    2017-01-01

    Polymeric micelles (PM) have been extensively used for tumor-targeted delivery of hydrophobic anti-cancer drugs. The lipophilic core of PM is naturally suitable for loading hydrophobic drugs and the hydrophilic shell endows them with colloidal stability and stealth properties. Decades of research on PM have resulted in tremendous numbers of PM-forming amphiphilic polymers, and approximately a dozen micellar nanomedicines have entered the clinic. The first generation of PM can be considered solubilizers of hydrophobic drugs, with short circulation times resulting from poor micelle stability and unstable drug entrapment. To more optimally exploit the potential of PM for targeted drug delivery, several physical (e.g. π-π stacking, stereocomplexation, hydrogen bonding, host-guest complexation and coordination interaction) and chemical (e.g. free radical polymerization, click chemistry, disulfide and hydrazone bonding) strategies have been developed to improve micelle stability and drug retention. In this review, we describe the most promising physico-chemical approaches to enhance micelle stability and drug retention, and we summarize how these strategies have resulted in systems with promising therapeutic efficacy in animal models, paving the way for clinical translation. PMID:27413999

  17. Improving the Algae Bloom Prediction through the Assimilation of the Remotely Sensed Chlorophyll-A Data in a Generic Ecological Model in the North Sea

    NASA Astrophysics Data System (ADS)

    El Serafy, Ghada

    2010-05-01

    Harmful algae can cause damage to co-existing organisms, tourism and farmers. Accurate predictions of algal future composition and abundance as well as when and where algal blooms may occur could help early warning and mitigating. The Generic Ecological Model, GEM, [Blauw et al 2008] is an instrument that can be applied to any water system (fresh, transitional or coastal) to calculate the primary production, chlorophyll-a concentration and phytoplankton species composition. It consists of physical, chemical and ecological model components which are coupled together to build one generic and flexible modeling tool. For the North Sea, the model has been analyzed to assess sensitivity of the simulated chlorophyll-a concentration to a subset of ecologically significant set of factors. The research led to the definition of the most significant set of parameters to the algae blooming process in the North Sea [Salacinska et al 2009]. In order to improve the prediction of the model, the set of parameters and the chlorophyll-a concentration can be further estimated through the use of data assimilation. In this research, the Ensemble Kalman Filter (EnKF) data assimilation technique is used to assimilate the chlorophyll-a data of the North Sea, retrieved from MEdium Resolution Imaging Sensor (MERIS) spectrometer data [Peters et al 2005], in the GEM model. The chlorophyll-a data includes concentrations and error information that enable their use in data assimilation. For the same purpose, the uncertainty of the ecological generic model, GEM has been quantified by means of Monte Carlo approach. Through a study covering the year of 2003, the research demonstrates that both data and model are sufficiently robust for a successful assimilation. The results show that through the assimilation of the satellite data, a better description of the algae bloom has been achieved and an improvement of the capability of the model to predict the algae bloom for the North Sea has been confirmed

  18. Structures of chlorophyll catabolites in bananas (Musa acuminata) reveal a split path of chlorophyll breakdown in a ripening fruit.

    PubMed

    Moser, Simone; Müller, Thomas; Holzinger, Andreas; Lütz, Cornelius; Kräutler, Bernhard

    2012-08-27

    The disappearance of chlorophyll is a visual sign of fruit ripening. Yet, chlorophyll breakdown in fruit has hardly been explored; its non-green degradation products are largely unknown. Here we report the analysis and structure elucidation of colorless tetrapyrrolic chlorophyll breakdown products in commercially available, ripening bananas (Musa acuminata, Cavendish cultivar). In banana peels, chlorophyll catabolites were found in an unprecedented structural richness: a variety of new fluorescent chlorophyll catabolites (FCCs) and nonfluorescent chlorophyll catabolites (NCCs) were detected. As a rule, FCCs exist only "fleetingly" and are hard to observe. However, in bananas several of the FCCs (named Mc-FCCs) were persistent and carried an ester function at the propionate side-chain. NCCs were less abundant, and exhibited a free propionic acid group, but functional modifications elsewhere. The modifications of NCCs in banana peels were similar to those found in NCCs from senescent leaves. They are presumed to be introduced by enzymatic transformations at the stage of the mostly unobserved, direct FCC-precursors. The observed divergent functional group characteristics of the Mc-FCCs versus those of the Mc-NCCs indicated two major "late" processing lines of chlorophyll breakdown in ripening bananas. The "last common precursor" at the branching point to either the persistent FCCs, or towards the NCCs, was identified as a temporarily abundant "secondary" FCC. The existence of two "downstream" branches of chlorophyll breakdown in banana peels, and the striking accumulation of persistent Mc-FCCs call for attention as to the still-elusive biological roles of the resulting colorless linear tetrapyrroles. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Femtosecond Visible Transient Absorption Spectroscopy of Chlorophyll f-Containing Photosystem I.

    PubMed

    Kaucikas, Marius; Nürnberg, Dennis; Dorlhiac, Gabriel; Rutherford, A William; van Thor, Jasper J

    2017-01-24

    Photosystem I (PSI) from Chroococcidiopsis thermalis PCC 7203 grown under far-red light (FRL; >725 nm) contains both chlorophyll a and a small proportion of chlorophyll f. Here, we investigated excitation energy transfer and charge separation using this FRL-grown form of PSI (FRL-PSI). We compared femtosecond transient visible absorption changes of normal, white-light (WL)-grown PSI (WL-PSI) with those of FRL-PSI using excitation at 670 nm, 700 nm, and (in the case of FRL-PSI) 740 nm. The possibility that chlorophyll f participates in energy transfer or charge separation is discussed on the basis of spectral assignments. With selective pumping of chlorophyll f at 740 nm, we observe a final ∼150 ps decay assigned to trapping by charge separation, and the amplitude of the resulting P700 +• A 1 -• charge-separated state indicates that the yield is directly comparable to that of WL-PSI. The kinetics shows a rapid 2 ps time constant for almost complete transfer to chlorophyll f if chlorophyll a is pumped with a wavelength of 670 nm or 700 nm. Although the physical role of chlorophyll f is best supported as a low-energy radiative trap, the physical location should be close to or potentially within the charge-separating pigments to allow efficient transfer for charge separation on the 150 ps timescale. Target models can be developed that include a branching in the formation of the charge separation for either WL-PSI or FRL-PSI. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Mechano-responsive hydrogels crosslinked by reactive block copolymer micelles

    NASA Astrophysics Data System (ADS)

    Xiao, Longxi

    Hydrogels are crosslinked polymeric networks that can swell in water without dissolution. Owing to their structural similarity to the native extracelluar matrices, hydrogels have been widely used in biomedical applications. Synthetic hydrogels have been designed to respond to various stimuli, but mechanical signals have not incorporated into hydrogel matrices. Because most tissues in the body are subjected to various types of mechanical forces, and cells within these tissues have sophisticated mechano-transduction machinery, this thesis is focused on developing hydrogel materials with built-in mechano-sensing mechanisms for use as tissue engineering scaffolds or drug release devices. Self-assembled block copolymer micelles (BCMs) with reactive handles were employed as the nanoscopic crosslinkers for the construction of covalently crosslinked networks. BCMs were assembled from amphiphilic diblock copolymers of poly(n-butyl acrylate) and poly(acrylic acid) partially modified with acrylate. Radical polymerization of acrylamide in the presence of micellar crosslinkers gave rise to elastomeric hydrogels whose mechanical properties can be tuned by varying the BCM composition and concentration. TEM imaging revealed that the covalently integrated BCMs underwent strain-dependent reversible deformation. A model hydrophobic drug, pyrene, loaded into the core of BCMs prior to the hydrogel formation, was dynamically released in response to externally applied mechanical forces, through force-induced reversible micelle deformation and the penetration of water molecules into the micelle core. The mechano-responsive hydrogel has been studied for tissue repair and regeneration purposes. Glycidyl methacrylate (GMA)-modified hyaluronic acid (HA) was photochemically crosslinked in the presence of dexamethasone (DEX)-loaded crosslinkable BCMs. The resultant HA gels (HAxBCM) contain covalently integrated micellar compartments with DEX being sequestered in the hydrophobic core. Compared

  1. Penetration of blood-brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system.

    PubMed

    Zou, Dan; Wang, Wei; Lei, Daoxi; Yin, Ying; Ren, Peng; Chen, Jinju; Yin, Tieying; Wang, Bochu; Wang, Guixue; Wang, Yazhou

    2017-01-01

    For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.

  2. Brushed block copolymer micelles with pH-sensitive pendant groups for controlled drug delivery.

    PubMed

    Lee, Hyun Jin; Bae, Younsoo

    2013-08-01

    To investigate the effects of small aliphatic pendent groups conjugated through an acid-sensitive linker to the core of brushed block copolymer micelles on particle properties. The brushed block copolymers were synthesized by conjugating five types of 2-alkanone (2-butanone, 2-hexanone, 2-octanone, 2-decanone, and 2-dodecanone) through an acid-labile hydrazone linker to poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers. Only block copolymers with 2-hexanone and 2-octanone (PEG-HEX and PEG-OCT) formed micelles with a clinically relevant size (< 50 nm in diameter), low critical micelle concentration (CMC, < 20 μM), and drug entrapment yields (approximately 5 wt.%). Both micelles degraded in aqueous solutions in a pH-dependent manner, while the degradation was accelerated in an acidic condition (pH 5.0) in comparison to pH 7.4. Despite these similar properties, PEG-OCT micelles controlled the entrapment and pH-dependent release of a hydrophobic drug most efficiently, without altering particle size, shape, and stability. The molecular weight of PEG (12 kDa vs 5 kDa) induced no change in pH-controlled drug release rates of PEG-OCT micelles. Acid-labile small aliphatic pendant groups are useful to control the entrapment and release of a hydrophobic drug physically entrapped in the core of brushed block copolymer micelles.

  3. Modulation of partition and localization of perfume molecules in sodium dodecyl sulfate micelles.

    PubMed

    Fan, Yaxun; Tang, Haiqiu; Strand, Ross; Wang, Yilin

    2016-01-07

    The influence of perfume molecules on the self-assembly of the anionic surfactant sodium dodecyl sulfate (SDS) and their localization in SDS micelles have been investigated by ζ potential, small angle X-ray scattering (SAXS), one- and two-dimensional NMR and isothermal titration microcalorimetry (ITC). A broad range of perfume molecules varying in octanol/water partition coefficients P are employed. The results indicate that the surface charge, size and aggregation number of the SDS micelles strongly depend on the hydrophobicity/hydrophilicity degree of perfume molecules. Three distinct regions along the log P values are identified. Hydrophilic perfumes (log P < 2.0) partially incorporate into the SDS micelles and do not lead to micelle swelling, whereas hydrophobic perfumes (log P > 3.5) are solubilized close to the end of the hydrophobic chains in the SDS micelles and enlarge the micelles with higher ζ potential and a larger aggregation number. The incorporated fraction and micelle properties show increasing tendency for the perfumes in the intermediate log P region (2.0 < log P < 3.5). Besides, the molecular conformation of perfume molecules also affects these properties. The perfumes with a linear chain structure or an aromatic group can penetrate into the palisade layer and closely pack with the SDS molecules. Furthermore, the thermodynamic parameters obtained from ITC show that the binding of the perfumes in the intermediate log P region is more spontaneous than those in the other two log P regions, and the micellization of SDS with the perfumes is driven by entropy.

  4. Using Leaf Chlorophyll to Parameterize Light-Use-Efficiency Within a Thermal-Based Carbon, Water and Energy Exchange Model

    NASA Technical Reports Server (NTRS)

    Houlborg, Rasmus; Anderson, Martha C.; Daughtry, C. S. T.; Kustas, W. P.; Rodell, Matthew

    2010-01-01

    Chlorophylls absorb photosynthetically active radiation and thus function as vital pigments for photosynthesis, which makes leaf chlorophyll content (C(sub ab) useful for monitoring vegetation productivity and an important indicator of the overall plant physiological condition. This study investigates the utility of integrating remotely sensed estimates of C(sub ab) into a thermal-based Two-Source Energy Balance (TSEB) model that estimates land-surface CO2 and energy fluxes using an analytical, light-use-efficiency (LUE) based model of canopy resistance. The LUE model component computes canopy-scale carbon assimilation and transpiration fluxes and incorporates LUE modifications from a nominal (species-dependent) value (LUE(sub n)) in response to short term variations in environmental conditions, However LUE(sub n) may need adjustment on a daily timescale to accommodate changes in plant phenology, physiological condition and nutrient status. Day to day variations in LUE(sub n) were assessed for a heterogeneous corn crop field in Maryland, U,S.A. through model calibration with eddy covariance CO2 flux tower observations. The optimized daily LUE(sub n) values were then compared to estimates of C(sub ab) integrated from gridded maps of chlorophyll content weighted over the tower flux source area. The time continuous maps of daily C(sub ab) over the study field were generated by focusing in-situ measurements with retrievals generated with an integrated radiative transfer modeling tool (accurate to within +/-10%) using at-sensor radiances in green, red and near-infrared wavelengths acquired with an aircraft imaging system. The resultant daily changes in C(sub ab) within the tower flux source area generally correlated well with corresponding changes in daily calibrated LUE(sub n) derived from the tower flux data, and hourly water, energy and carbon flux estimation accuracies from TSEB were significantly improved when using C(sub ab) for delineating spatio

  5. GRP78 enabled micelle-based glioma targeted drug delivery.

    PubMed

    Ran, Danni; Mao, Jiani; Shen, Qing; Xie, Cao; Zhan, Changyou; Wang, Ruifeng; Lu, Weiyue

    2017-06-10

    GRP78, a specific cancer cell-surface marker, is implicated in cancer cells proliferation, apoptosis resistance, metastasis and drug resistance. l-VAP (SNTRVAP) is a tumor homing peptide exhibiting high binding affinity in vitro to GRP78 protein overexpressed on glioma, glioma stem cells, vasculogenic mimicry and neovasculature. Even though short peptides are often non-immunogenic and demonstrate high affinity to tumor cells, their targeting efficacy is always undermined by rapid blood clearance and enzymatic degradation. In the present study, two d peptides RI-VAP (retro inverso isomer of l-VAP) and d-VAP (retro isomer of l-VAP) were developed by structure-guided peptide design and retro-inverso isomerization technique for glioma targeting. RI-VAP and d-VAP were predicted to bind their receptor GRP78 protein with similar binding affinity, which was experimentally confirmed. The results of in vivo imaging demonstrated that RI-VAP and d-VAP had remarkably advantage over l-VAP for tumor accumulation. In addition, RI-VAP and d-VAP modified paclitaxel-loaded polymeric micelle had better anti-tumor efficacy in comparison to taxol, paclitaxel-loaded plain micelles and l-VAP modified micelles. Overall, the VAP modified micelles suggested in the present study could effectively achieve glioma-targeted drug delivery, validating the potential of the stable VAP peptides in improving the therapeutic efficacy of paclitaxel for glioma. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Biochemical characterization of GM1 micelles-Amphotericin B interaction.

    PubMed

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M

    2015-01-01

    In this work a thorough characterization of the GM1 micelle-Amphotericin B (AmB) interaction was performed. The micelle formation as well as the drug loading occurs spontaneously, although influenced by the physicochemical conditions, pH and temperature. The chromatographic profile of GM1-AmB complexes at different molar ratios shows the existence of two populations. The differential absorbance of GM1, monomeric and aggregate AmB, allowed us to discriminate the presence of all of them in both fractions. Thus, we noted that at higher proportion of AmB in the complex, increases the larger population which is composed mainly of aggregated AmB. The physical behavior of these micelles shows that both GM1- AmB complexes were stable in solution for at least 30 days. However upon freeze-thawing or lyophilization-solubilization cycles, only the smallest population, enriched in monomeric AmB, showed a complete solubilization. In vitro, GM1-AmB micelles were significantly less toxic on cultured cells than other commercial micellar formulations as Fungizone, but had a similar behavior to liposomal formulations as Ambisome. Regarding the antifungal activity of the new formulation, it was very similar to that of other formulations. The characterization of these GM1-AmB complexes is discussed as a potential new formulation able to improve the antifungal therapeutic efficiency of AmB.

  7. Engineering Folate-Targeting Diselenide-containing Triblock Copolymer as a Redox-Responsive Shell-sheddable Micelle for Antitumor Therapy In Vivo.

    PubMed

    Behroozi, Farnaz; Abdkhodaie, Mohammad-Jafar; Sadeghi Abandansari, Hamid; Satarian, Leila; Molazem, Mohammad; Al-Jamal, Khuloud T; Baharvand, Hossein

    2018-06-18

    -polymer, containing diselenide as a redox-sensitive linkage. The linkage was smartly located at the hydrophilic-hydrophilic bridge in the co-polymer offering complete collapse of the micelle when exposed to the right trigger. The system was able to delay tumor growth and reduce toxicity in a breast cancer tumor model following intraperitoneal injection in mice. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Sans study of reverse micelles formed upon extraction of inorganic acids by TBP in n-octane.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chiarizia, R.; Briand, A.; Jensen, M. P.

    2008-01-01

    Small-angle neutron scattering (SANS) data for n-octane solutions of TBP loaded with progressively larger amounts of HNO{sub 3}, HClO{sub 4}, H{sub 2}SO{sub 4}, and H{sub 3}PO{sub 4} up to and beyond the LOC (limiting organic concentration of acid) condition, were interpreted using the Baxter model for hard spheres with surface adhesion. The coherent picture of the behavior of the TBP solutions derived from the SANS investigation discussed in this paper confirmed our recently developed model for third phase formation. This model analyses the features of the scattering data in the low Q region as arising from van der Waals interactionsmore » between the polar cores of reverse micelles. Our SANS data indicated that the TBP micelles swell when acid and water are extracted into their polar core. The swollen micelles have critical diameters ranging from 15 to 22 {angstrom}, and polar core diameters between 10 and 15 {angstrom}, depending on the specific system. At the respective LOC conditions, the TBP weight-average aggregation numbers are -4 for HClO{sub 4}, -6 for H2SO{sub 4}, -7 for HCl, and -10 for H{sub 3}PO{sub 4}. The comparison between the behavior of HNO{sub 3}, a non-third phase forming acid, and the other acids provided an explanation of the effect of the water molecules present in the polar core of the micelles on third phase formation. The thickness of the lipophilic shell of the micelles indicated that the butyl groups of TBP lie at an angle of -25 degrees relative to a plane tangent to the micellar core. The critical energy of intermicellar attraction, U(r), was about -2 k{sub B}T for all the acids investigated. This value is the same as that reported in our previous publications on the extraction of metal nitrates by TBP, confirming that the same mechanism and energetics are operative in the formation of a third phase, independent of whether the chemical species extracted are metal nitrate salts or inorganic acids.« less

  9. Remote sensing of chlorophyll in an atmosphere-ocean environment: a theoretical study.

    PubMed

    Kattawar, G W; Humphreys, T J

    1976-01-01

    A Monte Carlo program was written to compute the effect of chlorophyll on the ratio of upwelling to down-welling radiance and irradiance as a function of wavelength, height above the ocean, and depth within the ocean. This program simulates the actual physical situation, since a real atmospheric model was used, i.e., one that contained both aerosol and Rayleigh scattering as well as ozone absorption. The complete interaction of the radiation field with the ocean was also taken into account. The chlorophyll was assumed to be uniformly mixed in the ocean and was also assumed to act only as an absorbing agent. For the ocean model both scattering and absorption by hydrosols was included. Results have been obtained for both a very clear ocean and a medium turbid ocean. Recommendations are made for optimum techniques for remotely sensing chlorophyll both in situ and in vitro.

  10. Enhanced effect of folated pluronic F87-PLA/TPGS mixed micelles on targeted delivery of paclitaxel.

    PubMed

    Xiong, Xiang Yuan; Pan, Xiaoqian; Tao, Long; Cheng, Feng; Li, Zi Ling; Gong, Yan Chun; Li, Yu Ping

    2017-10-01

    Targeted drug delivery systems have great potential to overcome the side effect and improve the bioavailability of conventional anticancer drugs. In order to further improve the antitumor efficacy of paclitaxel (PTX) loaded in folated Pluronic F87/poly(lactic acid) (FA-F87-PLA) micelles, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) were added into FA-F87-PLA to form FA-F87-PLA/TPGS mixed micelles. The LE of PTX-loaded mixed micelles (13.5%) was highest in the mass ratio 5 to 3 of FA-F87-PLA to TPGS. The in vitro cytotoxicity assays indicated that the IC50 values for free PTX injections, PTX-loaded FA-F87-PLA micelles and PTX-loaded FA-F87-PLA/TPGS mixed micelles after 72h of incubation were 1.52, 0.42 and 0.037mg/L, respectively. The quantitative cellular uptake of coumarin 6-loaded FA-F87-PLA/TPGS and FA-F87-PLA micelles showed that the cellular uptake efficiency of mixed micelles was higher for 2 and 4h incubation, respectively. In vivo pharmacokinetic studies found that the AUC of PTX-loaded FA-F87-PLA/TPGS mixed micelles is almost 1.4 times of that of PTX-loaded FA-F87-PLA micelles. The decreased particle size and inhibition of P-glycoprotein effect induced by the addition of TPGS could result in enhancing the cellular uptake and improving the antitumor efficiency of PTX-loaded FA-F87-PLA/TPGS mixed micelles. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Improved oral bioavailability and therapeutic efficacy of dabigatran etexilate via Soluplus-TPGS binary mixed micelles system.

    PubMed

    Hu, Mei; Zhang, Jinjie; Ding, Rui; Fu, Yao; Gong, Tao; Zhang, Zhirong

    2017-04-01

    The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of Soluplus ® and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral absorption and bioavailability of DBAE. DBAE was first encapsulated into Soluplus/TPGS mixed micelles by a simple thin film hydration method. The DBAE loaded micelles displayed an average size distribution of around 83.13 nm. The cellular uptake of DBAE loaded micelles in Caco-2 cell monolayer was significantly enhanced by 2-2.6 fold over time as compared with DBAE suspension. Both lipid raft/caveolae and macropinocytosis-mediated the cell uptake of DBAE loaded micelles through P-glycoprotein (P-gp)-independent pathway. Compared with the DBAE suspension, the intestinal absorption of DBAE from DBAE mixed micelles in rats was significantly improved by 8 and 5-fold in ileum at 2 h and 4 h, respectively. Moreover, DBAE mixed micelles were absorbed into systemic circulation via both portal vein and lymphatic pathway. The oral bioavailability of DBAE mixed micelles in rats was 3.37 fold higher than that of DBAE suspension. DBAE mixed micelles exhibited a comparable anti-thrombolytic activity with a thrombosis inhibition rate of 63.18% compared with DBAE suspension in vivo. Thus, our study provides a promising drug delivery system to enhance the oral bioavailability and therapeutic efficacy of DBAE.

  12. Temperature-dependent dynamics of bovine casein micelles in the range 10-40 °C.

    PubMed

    Liu, Dylan Z; Weeks, Michael G; Dunstan, David E; Martin, Gregory J O

    2013-12-15

    Milk is a complex colloidal system that responds to changes in temperature imposed during processing. Whilst much has been learned about the effects of temperature on milk, little is known about the dynamic response of casein micelles to changes in temperature. In this study, a comprehensive physico-chemical study of casein micelles in skim milk was performed between 10 and 40 °C. When fully equilibrated, the amount of soluble casein, soluble calcium and the pH of skim milk all decreased as a function of increasing temperature, whilst the hydration and volume fraction of the casein micelles decreased. The effect of temperature on casein micelle size, as determined by dynamic light scattering and differential centrifugation, was less straightforward. Real-time measurements of turbidity and pH were used to investigate the dynamics of the system during warming and cooling of milk in the range 10-40 °C. Changes in pH are indicative of changes to the mineral system and the turbidity is a measure of alterations to the casein micelles. The pH and turbidity showed that alterations to both the casein micelles and the mineral system occurred very rapidly on warming. However, whilst mineral re-equilibration occurred very rapidly on cooling, changes to the casein micelle structure continued after 40 min of measurement, returning to equilibrium after 16 h equilibration. Casein micelle structure and the mineral system of milk were both dependent on temperature in the range 10-40 °C. The dynamic response of the mineral system to changes in temperature appeared almost instantaneous whereas equilibration of casein was considerably slower, particularly upon cooling. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Amphiphilic polymeric micelles as the nanocarrier for peroral delivery of poorly soluble anticancer drugs.

    PubMed

    Tian, Ye; Mao, Shirui

    2012-06-01

    Many amphiphilic copolymers have recently been synthesized as novel promising micellar carriers for the delivery of poorly water-soluble anticancer drugs. Studies on the formulation and oral delivery of such micelles have demonstrated their efficacy in enhancing drug uptake and absorption, and exhibit prolonged circulation time in vitro and in vivo. In this review, literature on hydrophobic modifications of several hydrophilic polymers, including polyethylene glycol, chitosan, hyaluronic acid, pluronic and tocopheryl polyethylene glycol succinate, is summarized. Parameters influencing the properties of polymeric micelles for oral chemotherapy are discussed and strategies to overcome main barriers for polymeric micelles peroral absorption are proposed. During the design of polymeric micelles for peroral chemotherapy, selecting or synthesizing copolymers with good compatibility with the drug is an effective strategy to increase drug loading and encapsulation efficiency. Stability of the micelles can be improved in different ways. It is recommended to take permeability, mucoadhesion, sustained release, and P-glycoprotein inhibition into consideration during copolymer preparation or to consider adding some excipients in the formulation. Furthermore, both the copolymer structure and drug loading methods should be controlled in order to get micelles with appropriate particle size for better absorption.

  14. Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles.

    PubMed

    Shi, Chunli; Guo, Xing; Qu, Qianqian; Tang, Zhaomin; Wang, Yi; Zhou, Shaobing

    2014-10-01

    In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Versatile polyion complex micelles for peptide and siRNA vectorization to engineer tolerogenic dendritic cells.

    PubMed

    Mebarek, Naila; Vicente, Rita; Aubert-Pouëssel, Anne; Quentin, Julie; Mausset-Bonnefont, Anne-Laure; Devoisselle, Jean-Marie; Jorgensen, Christian; Bégu, Sylvie; Louis-Plence, Pascale

    2015-05-01

    Dendritic cells (DCs) are professional antigen-presenting cells that play a critical role in maintaining the balance between immunity and tolerance and, as such are a promising immunotherapy tool to induce immunity or to restore tolerance. The main challenge to harness the tolerogenic properties of DCs is to preserve their immature phenotype. We recently developed polyion complex micelles, formulated with double hydrophilic block copolymers of poly(methacrylic acid) and poly(ethylene oxide) blocks and able to entrap therapeutic molecules, which did not induce DC maturation. In the current study, the intrinsic destabilizing membrane properties of the polymers were used to optimize endosomal escape property of the micelles in order to propose various strategies to restore tolerance. On the first hand, we showed that high molecular weight (Mw) copolymer-based micelles were efficient to favor the release of the micelle-entrapped peptide into the endosomes, and thus to improve peptide presentation by immature (i) DCs. On the second hand, we put in evidence that low Mw copolymer-based micelles were able to favor the cytosolic release of micelle-entrapped small interfering RNAs, dampening the DCs immunogenicity. Therefore, we demonstrate the versatile use of polyionic complex micelles to preserve tolerogenic properties of DCs. Altogether, our results underscored the potential of such micelle-loaded iDCs as a therapeutic tool to restore tolerance in autoimmune diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Drug release patterns and cytotoxicity of PEG-poly(aspartate) block copolymer micelles in cancer cells.

    PubMed

    Eckman, Allison M; Tsakalozou, Eleftheria; Kang, Nayon Y; Ponta, Andrei; Bae, Younsoo

    2012-07-01

    To test physicochemical and biological properties of PEG-poly(aspartate) [PEG-p(Asp)] block copolymer micelles entrapping doxorubicin hydrochloride (DOX) through ionic interaction. PEG-p(Asp) was synthesized from 5 kDa PEG and 20 Asp units. Carboxyl groups of p(Asp) were present as benzyl ester [PEG-p(Asp/Bz)], sodium salt [PEG-p(Asp/Na)] or free acid [PEG-p(Asp/H)]. Block copolymers and DOX were mixed at various ratios to prepare polymer micelles, which were subsequently characterized to determine particle size, drug loading and release patterns, and cytotoxicity against prostate (PC3 and DU145) and lung (A549) cancer cell lines. PEG-p(Asp/Bz), Na- and H-micelles entrapped 1.1, 56.8 and 40.6 wt.% of DOX, respectively. Na- and H-micelles (<100 nm) showed time-dependent DOX release at pH 7.4, which was accelerated at pH 5.0. Na-micelles were most stable at pH 7.4, retaining 31.8% of initial DOX for 48 h. Cytotoxicity of Na-micelles was 23.2% (A549), 28.5% (PC3) and 45.9% (DU145) more effective than free DOX. Ionic interaction appeared to entrap DOX efficiently in polymer micelles from PEG-p(Asp) block copolymers. Polymer micelles possessing counter ions (Na) of DOX in the core were the most stable, releasing drugs for prolonged time in a pH-dependent manner, and suppressing cancer cells effectively.

  17. The association of low-molecular-weight hydrophobic compounds with native casein micelles in bovine milk

    PubMed Central

    Cheema, M.; Mohan, M. S.; Campagna, S. R.; Jurat-Fuentes, J. L.; Harte, F. M.

    2015-01-01

    The agreed biological function of the casein micelles in milk is to carry minerals (calcium, magnesium, and phosphorus) from mother to young along with amino acids for growth and development. Recently, native and modified casein micelles were used as encapsulating and delivery agents for various hydrophobic low-molecular-weight probes. The ability of modified casein micelles to bind certain probes may derive from the binding affinity of native casein micelles. Hence, a study with milk from single cows was conducted to further elucidate the association of hydrophobic molecules into native casein micelles and further understand their biological function. Hydrophobic and hydrophilic extraction followed by ultraperformance liquid chromatography-high resolution mass spectrometry analysis were performed over protein fractions obtained from size exclusion fractionation of raw skim milk. Hydrophobic compounds, including phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin, showed strong association exclusively to casein micelles as compared with whey proteins, whereas hydrophilic compounds did not display any preference for their association among milk proteins. Further analysis using liquid chromatography-tandem mass spectrometry detected 42 compounds associated solely with the casein-micelles fraction. Mass fragments in tandem mass spectrometry identified 4 of these compounds as phosphatidylcholine with fatty acid composition of 16:0/18:1, 14:0/16:0, 16:0/16:0, and 18:1/18:0. These results support that transporting low-molecular-weight hydrophobic molecules is also a biological function of the casein micelles in milk. PMID:26074238

  18. Chlorophyll-Based Organic-Inorganic Heterojunction Solar Cells.

    PubMed

    Li, Yue; Zhao, Wenjie; Li, Mengzhen; Chen, Gang; Wang, Xiao-Feng; Fu, Xueqi; Kitao, Osamu; Tamiaki, Hitoshi; Sakai, Kotowa; Ikeuchi, Toshitaka; Sasaki, Shin-Ichi

    2017-08-10

    Solid-state chlorophyll solar cells (CSCs) employing a carboxylated chlorophyll derivative, methyl trans-3 2 -carboxypyropheophorbide a, as a light-harvesting dye sensitizer chlorophyll (DSC) deposited on mesoporous TiO 2 , on which four zinc hydroxylated chlorophyll derivatives were spin-coated for hole transporter chlorophylls (HTCs), are described. Key parameters, including the effective carrier mobility of the HTC films, as determined by the space charge-limited current method, and the frontier molecular orbitals of these DSCs and HTCs, as estimated from cyclic voltammetry and electronic absorption spectra, suggest that both charge separation and carrier transport are favorable. The power conversion efficiencies (PCEs) of the present CSCs with fluorine-doped tin oxide (FTO)/TiO 2 /DSC/HTCs/Ag were determined to follow the order of HTC-1>HTC-2>HTC-3>HTC-4, which coincided perfectly with the order of their hole mobilities. The maximum PCE achieved was 0.86 % with HTC-1. The photovoltaic devices studied herein with two types of chlorophyll derivatives as dye sensitizers and hole transporters provide a unique solution for the utilization of solar energy with a view to truly realizing "green energy". © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Synthesis of Cross-Linked Polymeric Micelle pH Nanosensors: An Investigation of Design Flexibility.

    PubMed

    Kumar, E K Pramod; Jølck, Rasmus I; Andresen, Thomas L

    2015-09-01

    The design flexibility that polymeric micelles offer in the fabrication of optical nanosensors for ratiometric pH measurements is investigated. pH nanosensors based on polymeric micelles are synthesized either by a mixed-micellization approach or by a postmicelle modification strategy. In the mixed-micellization approach, self-assembly of functionalized unimers followed by shell cross-linking by copper-catalyzed azide-alkyne cycloaddition (CuAAC) results in stabilized cRGD-functionalized micelle pH nanosensors. In the postmicelle modification strategy, simultaneous cross-linking and fluorophore conjugation at the micelle shell using CuAAC results in a stabilized micelle pH nanosensor. Compared to the postmicelle modification strategy, the mixed-micellization approach increases the control of the overall composition of the nanosensors. Both approaches provide stable nanosensors with similar pKa profiles and thereby nanosensors with similar pH sensitivity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Predicting crappie recruitment in Ohio reservoirs with spawning stock size, larval density, and chlorophyll concentrations

    USGS Publications Warehouse

    Bunnell, David B.; Hale, R. Scott; Vanni, Michael J.; Stein, Roy A.

    2006-01-01

    Stock-recruit models typically use only spawning stock size as a predictor of recruitment to a fishery. In this paper, however, we used spawning stock size as well as larval density and key environmental variables to predict recruitment of white crappies Pomoxis annularis and black crappies P. nigromaculatus, a genus notorious for variable recruitment. We sampled adults and recruits from 11 Ohio reservoirs and larvae from 9 reservoirs during 1998-2001. We sampled chlorophyll as an index of reservoir productivity and obtained daily estimates of water elevation to determine the impact of hydrology on recruitment. Akaike's information criterion (AIC) revealed that Ricker and Beverton-Holt stock-recruit models that included chlorophyll best explained the variation in larval density and age-2 recruits. Specifically, spawning stock catch per effort (CPE) and chlorophyll explained 63-64% of the variation in larval density. In turn, larval density and chlorophyll explained 43-49% of the variation in age-2 recruit CPE. Finally, spawning stock CPE and chlorophyll were the best predictors of recruit CPE (i.e., 74-86%). Although larval density and recruitment increased with chlorophyll, neither was related to seasonal water elevation. Also, the AIC generally did not distinguish between Ricker and Beverton-Holt models. From these relationships, we concluded that crappie recruitment can be limited by spawning stock CPE and larval production when spawning stock sizes are low (i.e., CPE , 5 crappies/net-night). At higher levels of spawning stock sizes, spawning stock CPE and recruitment were less clearly related. To predict recruitment in Ohio reservoirs, managers should assess spawning stock CPE with trap nets and estimate chlorophyll concentrations. To increase crappie recruitment in reservoirs where recruitment is consistently poor, managers should use regulations to increase spawning stock size, which, in turn, should increase larval production and recruits to the fishery.

  1. Structural characterization of casein micelles: shape changes during film formation.

    PubMed

    Gebhardt, R; Vendrely, C; Kulozik, U

    2011-11-09

    The objective of this study was to determine the effect of size-fractionation by centrifugation on the film structure of casein micelles. Fractionated casein micelles in solution were asymmetrically distributed with a small distribution width as measured by dynamic light scattering. Films prepared from the size-fractionated samples showed a smooth surface in optical microscopy images and a homogeneous microstructure in atomic force micrographs. The nano- and microstructure of casein films was probed by micro-beam grazing incidence small angle x-ray scattering (μGISAXS). Compared to the solution measurements, the sizes determined in the film were larger and broadly distributed. The measured GISAXS patterns clearly deviate from those simulated for a sphere and suggest a deformation of the casein micelles in the film. © 2011 IOP Publishing Ltd

  2. Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

    PubMed Central

    2010-01-01

    Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd. PMID:21170410

  3. Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Jeong, Sang Young; Kim, Hyo Jeong; Kwak, Byung-Kook; Lee, Ha-Young; Seong, Hasoo; Shin, Byung Cheol; Yuk, Soon Hong; Hwang, Sung-Joo; Cho, Sun Hang

    2010-12-01

    Biocompatible poly-[ N-(2-hydroxyethyl)- d, l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

  4. Calibrations between chlorophyll meter values and chlorophyll contents vary as the result of differences in leaf structure

    USDA-ARS?s Scientific Manuscript database

    In order to relate leaf chlorophyll meter values with total leaf chlorophyll contents (µg cm-2), calibration equations are established with measured data on leaves. Many studies have documented differences in calibration equations using different species and using different growing conditions for th...

  5. Core-Shell-Corona Micelles with a Responsive Shell.

    PubMed

    Gohy, Jean-François; Willet, Nicolas; Varshney, Sunil; Zhang, Jian-Xin; Jérôme, Robert

    2001-09-03

    A reactor for the synthesis of gold nanoparticles is one of the uses of a poly(styrene)-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) triblock copolymer (PS-b-P2VP-b-PEO) which forms core-shell-corona micelles in water. Very low polydispersity spherical micelles are observed that consist of a PS core surrounded by a pH-sensitive P2VP shell and a corona of PEO chains end-capped by a hydroxyl group. The corona can act as a site for attaching responsive or sensing molecules. © 2001 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.

  6. Near-infrared diffuse reflection systems for chlorophyll content of tomato leaves measurement

    NASA Astrophysics Data System (ADS)

    Jiang, Huanyu; Ying, Yibin; Lu, Huishan

    2006-10-01

    In this study, two measuring systems for chlorophyll content of tomato leaves were developed based on near-infrared spectral techniques. The systems mainly consists of a FT-IR spectrum analyzer, optic fiber diffuses reflection accessories and data card. Diffuse reflectance of intact tomato leaves was measured by an optics fiber optic fiber diffuses reflection accessory and a smart diffuses reflection accessory. Calibration models were developed from spectral and constituent measurements. 90 samples served as the calibration sets and 30 samples served as the validation sets. Partial least squares (PLS) and principal component regression (PCR) technique were used to develop the prediction models by different data preprocessing. The best model for chlorophyll content had a high correlation efficient of 0.9348 and a low standard error of prediction RMSEP of 4.79 when we select full range (12500-4000 cm -1), MSC path length correction method by the log(1/R). The results of this study suggest that FT-NIR method can be feasible to detect chlorophyll content of tomato leaves rapidly and nondestructively.

  7. Mining a sea of data: deducing the environmental controls of ocean chlorophyll.

    PubMed

    Irwin, Andrew J; Finkel, Zoe V

    2008-01-01

    Chlorophyll biomass in the surface ocean is regulated by a complex interaction of physiological, oceanographic, and ecological factors and in turn regulates the rates of primary production and export of organic carbon to the deep ocean. Mechanistic models of phytoplankton responses to climate change require the parameterization of many processes of which we have limited knowledge. We develop a statistical approach to estimate the response of remote-sensed ocean chlorophyll to a variety of physical and chemical variables. Irradiance over the mixed layer depth, surface nitrate, sea-surface temperature, and latitude and longitude together can predict 83% of the variation in log chlorophyll in the North Atlantic. Light and nitrate regulate biomass through an empirically determined minimum function explaining nearly 50% of the variation in log chlorophyll by themselves and confirming that either light or macronutrients are often limiting and that much of the variation in chlorophyll concentration is determined by bottom-up mechanisms. Assuming the dynamics of the future ocean are governed by the same processes at work today, we should be able to apply these response functions to future climate change scenarios, with changes in temperature, nutrient distributions, irradiance, and ocean physics.

  8. Curcumin-encapsulated polymeric micelles suppress the development of colon cancer in vitro and in vivo.

    PubMed

    Yang, Xi; Li, Zhaojun; Wang, Ning; Li, Ling; Song, Linjiang; He, Tao; Sun, Lu; Wang, Zhihan; Wu, Qinjie; Luo, Na; Yi, Cheng; Gong, Changyang

    2015-05-18

    To develop injectable formulation and improve the stability of curcumin (Cur), Cur was encapsulated into monomethyl poly (ethylene glycol)-poly (ε-caprolactone)-poly (trimethylene carbonate) (MPEG-P(CL-co-TMC)) micelles through a single-step solid dispersion method. The obtained Cur micelles had a small particle size of 27.6 ± 0.7 nm with polydisperse index (PDI) of 0.11 ± 0.05, drug loading of 14.07 ± 0.94%, and encapsulation efficiency of 96.08 ± 3.23%. Both free Cur and Cur micelles efficiently suppressed growth of CT26 colon carcinoma cells in vitro. The results of in vitro anticancer studies confirmed that apoptosis induction and cellular uptake on CT26 cells had completely increased in Cur micelles compared with free Cur. Besides, Cur micelles were more effective in suppressing the tumor growth of subcutaneous CT26 colon in vivo, and the mechanisms included the inhibition of tumor proliferation and angiogenesis and increased apoptosis of tumor cells. Furthermore, few side effects were found in Cur micelles. Overall, our findings suggested that Cur micelles could be a stabilized aqueous formulation for intravenous application with improved antitumor activity, which may be a potential treatment strategy for colon cancer in the future.

  9. Structure and stabilizing interactions of casein micelles probed by high-pressure light scattering and FTIR.

    PubMed

    Gebhardt, Ronald; Takeda, Naohiro; Kulozik, Ulrich; Doster, Wolfgang

    2011-03-17

    Caseins form heterogeneous micelles composed of three types of disordered protein chains (α, β, κ), which include protein-bound calcium phosphate particles. We probe the stability limits of the micelle by applying hydrostatic pressure. The resulting changes of the size distribution and the average molecular weight are recorded in situ with static and dynamic light scattering. Pressure induces irreversible dissociation of the micelles into monomers above a critical value depending on their size. The critical pressure increases with temperature, pH, and calcium concentration due to the interplay of hydrophobic and electrostatic interactions. The pressure transition curves are biphasic, reflecting the equilibrium of two micelle states with different stability, average size, entropy, and calcium bound. The fast process of pressure dissociation is used to probe the slow equilibrium of the two micelle states under various conditions. Binding and release of β-casein from the micelle is suggested as the molecular mechanism of stabilization associated with the two states. In situ FTIR spectroscopy covering the P-O stretching region indicates that bound calcium phosphate particles are released from serine phosphate residues at pressures above 100 MPa. The resulting imbalance of charge triggers the complete decomposition of the micelle. © 2011 American Chemical Society

  10. Polymeric micelles as a new drug carrier system and their required considerations for clinical trials.

    PubMed

    Yokoyama, Masayuki

    2010-02-01

    A polymeric micelle is a macromolecular assembly composed of an inner core and an outer shell, and most typically is formed from block copolymers. In the last two decades, polymeric micelles have been actively studied as a new type of drug carrier system, in particular for drug targeting of anticancer drugs to solid tumors. In this review, polymeric micelle drug carrier systems are discussed with a focus on toxicities of the polymeric micelle carrier systems and on pharmacological activities of the block copolymers. In the first section, the importance of the above-mentioned evaluation of these properties is explained, as this importance does not seem to be well recognized compared with the importance of targeting and enhanced pharmacological activity of drugs, particularly in the basic studies. Then, designs, types and classifications of the polymeric micelle system are briefly summarized and explained, followed by a detailed discussion regarding several examples of polymeric micelle carrier systems. Readers will gain a strategy of drug delivery with polymeric carriers as well as recent progress of the polymeric micelle carrier systems in their basic studies and clinical trials. The purpose of this review is to achieve tight connections between the basic studies and clinical trials.

  11. Polymeric micelles based on poly(methacrylic acid) block-containing copolymers with different membrane destabilizing properties for cellular drug delivery.

    PubMed

    Mebarek, Naila; Aubert-Pouëssel, Anne; Gérardin, Corine; Vicente, Rita; Devoisselle, Jean-Marie; Bégu, Sylvie

    2013-10-01

    Poly(methacrylic acid)-b-poly(ethylene oxide) are double hydrophilic block copolymers, which are able to form micelles by complexation with a counter-polycation, such as poly-l-lysine. A study was carried out on the ability of the copolymers to interact with model membranes as a function of their molecular weights and as a function of pH. Different behaviors were observed: high molecular weight copolymers respect the membrane integrity, whereas low molecular weight copolymers with a well-chosen asymmetry degree can induce a membrane alteration. Hence by choosing the appropriate molecular weight, micelles with distinct membrane interaction behaviors can be obtained leading to different intracellular traffics with or without endosomal escape, making them interesting tools for cell engineering. Especially micelles constituted of low molecular weight copolymers could exhibit the endosomal escape property, which opens vast therapeutic applications. Moreover micelles possess a homogeneous nanometric size and show variable properties of disassembly at acidic pH, of stability in physiological conditions, and finally of cyto-tolerance. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. In Vivo Single-Cell Fluorescence and Size Scaling of Phytoplankton Chlorophyll Content.

    PubMed

    Álvarez, Eva; Nogueira, Enrique; López-Urrutia, Ángel

    2017-04-01

    In unicellular phytoplankton, the size scaling exponent of chlorophyll content per cell decreases with increasing light limitation. Empirical studies have explored this allometry by combining data from several species, using average values of pigment content and cell size for each species. The resulting allometry thus includes phylogenetic and size scaling effects. The possibility of measuring single-cell fluorescence with imaging-in-flow cytometry devices allows the study of the size scaling of chlorophyll content at both the inter- and intraspecific levels. In this work, the changing allometry of chlorophyll content was estimated for the first time for single phytoplankton populations by using data from a series of incubations with monocultures exposed to different light levels. Interspecifically, our experiments confirm previous modeling and experimental results of increasing size scaling exponents with increasing irradiance. A similar pattern was observed intraspecifically but with a larger variability in size scaling exponents. Our results show that size-based processes and geometrical approaches explain variations in chlorophyll content. We also show that the single-cell fluorescence measurements provided by imaging-in-flow devices can be applied to field samples to understand the changes in the size dependence of chlorophyll content in response to environmental variables affecting primary production. IMPORTANCE The chlorophyll concentrations in phytoplankton register physiological adjustments in cellular pigmentation arising mainly from changes in light conditions. The extent of these adjustments is constrained by the size of the phytoplankton cells, even within single populations. Hence, variations in community chlorophyll derived from photoacclimation are also dependent on the phytoplankton size distribution. Copyright © 2017 American Society for Microbiology.

  13. In Vivo Single-Cell Fluorescence and Size Scaling of Phytoplankton Chlorophyll Content

    PubMed Central

    Nogueira, Enrique; López-Urrutia, Ángel

    2017-01-01

    ABSTRACT In unicellular phytoplankton, the size scaling exponent of chlorophyll content per cell decreases with increasing light limitation. Empirical studies have explored this allometry by combining data from several species, using average values of pigment content and cell size for each species. The resulting allometry thus includes phylogenetic and size scaling effects. The possibility of measuring single-cell fluorescence with imaging-in-flow cytometry devices allows the study of the size scaling of chlorophyll content at both the inter- and intraspecific levels. In this work, the changing allometry of chlorophyll content was estimated for the first time for single phytoplankton populations by using data from a series of incubations with monocultures exposed to different light levels. Interspecifically, our experiments confirm previous modeling and experimental results of increasing size scaling exponents with increasing irradiance. A similar pattern was observed intraspecifically but with a larger variability in size scaling exponents. Our results show that size-based processes and geometrical approaches explain variations in chlorophyll content. We also show that the single-cell fluorescence measurements provided by imaging-in-flow devices can be applied to field samples to understand the changes in the size dependence of chlorophyll content in response to environmental variables affecting primary production. IMPORTANCE The chlorophyll concentrations in phytoplankton register physiological adjustments in cellular pigmentation arising mainly from changes in light conditions. The extent of these adjustments is constrained by the size of the phytoplankton cells, even within single populations. Hence, variations in community chlorophyll derived from photoacclimation are also dependent on the phytoplankton size distribution. PMID:28115378

  14. Photoenhanced gene transfection by a curcumin loaded CS-g-PZLL micelle.

    PubMed

    Lin, Jian-Tao; Pan, Wen-Jia; Zhang, Jun-Ai; Wang, Wei; Zhong, Jia; Su, Jia-Min; Li, Tong; Zou, Ying; Wang, Guan-Hai

    2017-09-01

    The codelivery of drug and gene is a promising method for cancer treatment. In our previous works, we prepared a cationic micelles based on chitosan and poly-(N-3-carbobenzyloxylysine) (CS-g-PZLL), but transfection ratio of CS-g-PZLL to Hela cell was low. Herein, to improve the transfection efficiency of CS-g-PZLL, curcumin was loaded in the CS-g-PZLL micelle. After irradiation, the obtained curcumin loaded micelle showed a better transfection, and the p53 protein expression in Hela cells was higher. The apoptosis assay showed that the complex could induce a more significant apoptosis to Hela cells than that of curcumin or p53 used alone, and the curcumin loaded micelle inducing apoptosis was best after irradiation. Therefore, CS-g-PZLL is a safe and effective carrier for the codelivery of drug/gene, and curcumin could be used as a photosensitizer to induce a photoenhanced gene transfection, which should be encouraged in improving transfection and tumor therapy. Copyright © 2017. Published by Elsevier B.V.

  15. STAY-GREEN and Chlorophyll Catabolic Enzymes Interact at Light-Harvesting Complex II for Chlorophyll Detoxification during Leaf Senescence in Arabidopsis[C][W

    PubMed Central

    Sakuraba, Yasuhito; Schelbert, Silvia; Park, So-Yon; Han, Su-Hyun; Lee, Byoung-Doo; Andrès, Céline Besagni; Kessler, Felix; Hörtensteiner, Stefan; Paek, Nam-Chon

    2012-01-01

    During leaf senescence, plants degrade chlorophyll to colorless linear tetrapyrroles that are stored in the vacuole of senescing cells. The early steps of chlorophyll breakdown occur in plastids. To date, five chlorophyll catabolic enzymes (CCEs), NONYELLOW COLORING1 (NYC1), NYC1-LIKE, pheophytinase, pheophorbide a oxygenase (PAO), and red chlorophyll catabolite reductase, have been identified; these enzymes catalyze the stepwise degradation of chlorophyll to a fluorescent intermediate, pFCC, which is then exported from the plastid. In addition, STAY-GREEN (SGR), Mendel’s green cotyledon gene encoding a chloroplast protein, is required for the initiation of chlorophyll breakdown in plastids. Senescence-induced SGR binds to light-harvesting complex II (LHCII), but its exact role remains elusive. Here, we show that all five CCEs also specifically interact with LHCII. In addition, SGR and CCEs interact directly or indirectly with each other at LHCII, and SGR is essential for recruiting CCEs in senescing chloroplasts. PAO, which had been attributed to the inner envelope, is found to localize in the thylakoid membrane. These data indicate a predominant role for the SGR-CCE-LHCII protein interaction in the breakdown of LHCII-located chlorophyll, likely to allow metabolic channeling of phototoxic chlorophyll breakdown intermediates upstream of nontoxic pFCC. PMID:22366162

  16. An improved ENSO simulation by representing chlorophyll-induced climate feedback in the NCAR Community Earth System Model.

    PubMed

    Kang, Xianbiao; Zhang, Rong-Hua; Gao, Chuan; Zhu, Jieshun

    2017-12-07

    The El Niño-Southern oscillation (ENSO) simulated in the Community Earth System Model of the National Center for Atmospheric Research (NCAR CESM) is much stronger than in reality. Here, satellite data are used to derive a statistical relationship between interannual variations in oceanic chlorophyll (CHL) and sea surface temperature (SST), which is then incorporated into the CESM to represent oceanic chlorophyll -induced climate feedback in the tropical Pacific. Numerical runs with and without the feedback (referred to as feedback and non-feedback runs) are performed and compared with each other. The ENSO amplitude simulated in the feedback run is more accurate than that in the non-feedback run; quantitatively, the Niño3 SST index is reduced by 35% when the feedback is included. The underlying processes are analyzed and the results show that interannual CHL anomalies exert a systematic modulating effect on the solar radiation penetrating into the subsurface layers, which induces differential heating in the upper ocean that affects vertical mixing and thus SST. The statistical modeling approach proposed in this work offers an effective and economical way for improving climate simulations.

  17. Casein micelles: size distribution in milks from individual cows.

    PubMed

    de Kruif, C G Kees; Huppertz, Thom

    2012-05-09

    The size distribution and protein composition of casein micelles in the milk of Holstein-Friesian cows was determined as a function of stage and number of lactations. Protein composition did not vary significantly between the milks of different cows or as a function of lactation stage. Differences in the size and polydispersity of the casein micelles were observed between the milks of different cows, but not as a function of stage of milking or stage of lactation and not even over successive lactations periods. Modal radii varied from 55 to 70 nm, whereas hydrodynamic radii at a scattering angle of 73° (Q² = 350 μm⁻²) varied from 77 to 115 nm and polydispersity varied from 0.27 to 0.41, in a log-normal distribution. Casein micelle size in the milks of individual cows was not correlated with age, milk production, or lactation stage of the cows or fat or protein content of the milk.

  18. Drug Combination Synergy in Worm-like Polymeric Micelles Improves Treatment Outcome for Small Cell and Non-Small Cell Lung Cancer.

    PubMed

    Wan, Xiaomeng; Min, Yuanzeng; Bludau, Herdis; Keith, Andrew; Sheiko, Sergei S; Jordan, Rainer; Wang, Andrew Z; Sokolsky-Papkov, Marina; Kabanov, Alexander V

    2018-03-27

    Nanoparticle-based systems for concurrent delivery of multiple drugs can improve outcomes of cancer treatments, but face challenges because of differential solubility and fairly low threshold for incorporation of many drugs. Here we demonstrate that this approach can be used to greatly improve the treatment outcomes of etoposide (ETO) and platinum drug combination ("EP/PE") therapy that is the backbone for treatment of prevalent and deadly small cell lung cancer (SCLC). A polymeric micelle system based on amphiphilic block copolymer poly(2-oxazoline)s (POx) poly(2-methyl-2-oxazoline- block-2-butyl-2-oxazoline- block-2-methyl-2-oxazoline) (P(MeOx- b-BuOx- b-MeOx) is used along with an alkylated cisplatin prodrug to enable co-formulation of EP/PE in a single high-capacity vehicle. A broad range of drug mixing ratios and exceptionally high two-drug loading of over 50% wt. drug in dispersed phase is demonstrated. The highly loaded POx micelles have worm-like morphology, unprecedented for drug loaded polymeric micelles reported so far, which usually form spheres upon drug loading. The drugs co-loading in the micelles result in a slowed-down release, improved pharmacokinetics, and increased tumor distribution of both drugs. A superior antitumor activity of co-loaded EP/PE drug micelles compared to single drug micelles or their combination as well as free drug combination was demonstrated using several animal models of SCLC and non-small cell lung cancer.

  19. Leaf Chlorophyll Content Estimation of Winter Wheat Based on Visible and Near-Infrared Sensors.

    PubMed

    Zhang, Jianfeng; Han, Wenting; Huang, Lvwen; Zhang, Zhiyong; Ma, Yimian; Hu, Yamin

    2016-03-25

    The leaf chlorophyll content is one of the most important factors for the growth of winter wheat. Visual and near-infrared sensors are a quick and non-destructive testing technology for the estimation of crop leaf chlorophyll content. In this paper, a new approach is developed for leaf chlorophyll content estimation of winter wheat based on visible and near-infrared sensors. First, the sliding window smoothing (SWS) was integrated with the multiplicative scatter correction (MSC) or the standard normal variable transformation (SNV) to preprocess the reflectance spectra images of wheat leaves. Then, a model for the relationship between the leaf relative chlorophyll content and the reflectance spectra was developed using the partial least squares (PLS) and the back propagation neural network. A total of 300 samples from areas surrounding Yangling, China, were used for the experimental studies. The samples of visible and near-infrared spectroscopy at the wavelength of 450,900 nm were preprocessed using SWS, MSC and SNV. The experimental results indicate that the preprocessing using SWS and SNV and then modeling using PLS can achieve the most accurate estimation, with the correlation coefficient at 0.8492 and the root mean square error at 1.7216. Thus, the proposed approach can be widely used for winter wheat chlorophyll content analysis.

  20. Gallium(III) complexes of methyl pyropheophorbide-a as synthetic models for investigation of diastereomerically controlled axial ligation towards chlorophylls.

    PubMed

    Sasaki, Shin-Ichi; Mizoguchi, Tadashi; Tamiaki, Hitoshi

    2006-03-01

    Gallium(III) chlorins possessing a series of axial ligands were synthesized as model compounds of natural chlorophylls. A pair of diastereomers arising from the fifth axial coordination onto the asymmetric chlorin pi-macrocycle could be discriminated in a solution by both (1)H- and (13)C NMR spectroscopies.

  1. Tailor-made dimensions of diblock copolymer truncated micelles on a solid by UV irradiation.

    PubMed

    Liou, Jiun-You; Sun, Ya-Sen

    2015-09-28

    We investigated the structural evolution of truncated micelles in ultrathin films of polystyrene-block-poly(2-vinylpyridine), PS-b-P2VP, of monolayer thickness on bare silicon substrates (SiOx/Si) upon UV irradiation in air- (UVIA) and nitrogen-rich (UVIN) environments. The structural evolution of micelles upon UV irradiation was monitored using GISAXS measurements in situ, while the surface morphology was probed using atomic force microscopy ex situ and the chemical composition using X-ray photoelectron spectroscopy (XPS). This work provides clear evidence for the interpretation of the relationship between the structural evolution and photochemical reactions in PS-b-P2VP truncated micelles upon UVIA and UVIN. Under UVIA treatment, photolysis and cross-linking reactions coexisted within the micelles; photolysis occurred mainly at the top of the micelles, whereas cross-linking occurred preferentially at the bottom. The shape and size of UVIA-treated truncated micelles were controlled predominantly by oxidative photolysis reactions, which depended on the concentration gradient of free radicals and oxygen along the micelle height. Because of an interplay between photolysis and photo-crosslinking, the scattering length densities (SLD) of PS and P2VP remained constant. In contrast, UVIN treatments enhanced the contrast in SLD between the PS shell and the P2VP core as cross-linking dominated over photolysis in the presence of nitrogen. The enhancement of the SLD contrast was due to the various degrees of cross-linking under UVIN for the PS and P2VP blocks.

  2. Trends in Ocean Colour and Chlorophyll Concentration from 1889 to 2000, Worldwide

    PubMed Central

    Wernand, Marcel R.; van der Woerd, Hendrik J.; Gieskes, Winfried W. C.

    2013-01-01

    Marine primary productivity is an important agent in the global cycling of carbon dioxide, a major ‘greenhouse gas’, and variations in the concentration of the ocean's phytoplankton biomass can therefore explain trends in the global carbon budget. Since the launch of satellite-mounted sensors globe-wide monitoring of chlorophyll, a phytoplankton biomass proxy, became feasible. Just as satellites, the Forel-Ule (FU) scale record (a hardly explored database of ocean colour) has covered all seas and oceans – but already since 1889. We provide evidence that changes of ocean surface chlorophyll can be reconstructed with confidence from this record. The EcoLight radiative transfer numerical model indicates that the FU index is closely related to chlorophyll concentrations in open ocean regions. The most complete FU record is that of the North Atlantic in terms of coverage over space and in time; this dataset has been used to test the validity of colour changes that can be translated to chlorophyll. The FU and FU-derived chlorophyll data were analysed for monotonously increasing or decreasing trends with the non-parametric Mann-Kendall test, a method to establish the presence of a consistent trend. Our analysis has not revealed a globe-wide trend of increase or decrease in chlorophyll concentration during the past century; ocean regions have apparently responded differentially to changes in meteorological, hydrological and biological conditions at the surface, including potential long-term trends related to global warming. Since 1889, chlorophyll concentrations have decreased in the Indian Ocean and in the Pacific; increased in the Atlantic Ocean, the Mediterranean, the Chinese Sea, and in the seas west and north-west of Japan. This suggests that explanations of chlorophyll changes over long periods should focus on hydrographical and biological characteristics typical of single ocean regions, not on those of ‘the’ ocean. PMID:23776435

  3. Trends in ocean colour and chlorophyll concentration from 1889 to 2000, worldwide.

    PubMed

    Wernand, Marcel R; van der Woerd, Hendrik J; Gieskes, Winfried W C

    2013-01-01

    Marine primary productivity is an important agent in the global cycling of carbon dioxide, a major 'greenhouse gas', and variations in the concentration of the ocean's phytoplankton biomass can therefore explain trends in the global carbon budget. Since the launch of satellite-mounted sensors globe-wide monitoring of chlorophyll, a phytoplankton biomass proxy, became feasible. Just as satellites, the Forel-Ule (FU) scale record (a hardly explored database of ocean colour) has covered all seas and oceans--but already since 1889. We provide evidence that changes of ocean surface chlorophyll can be reconstructed with confidence from this record. The EcoLight radiative transfer numerical model indicates that the FU index is closely related to chlorophyll concentrations in open ocean regions. The most complete FU record is that of the North Atlantic in terms of coverage over space and in time; this dataset has been used to test the validity of colour changes that can be translated to chlorophyll. The FU and FU-derived chlorophyll data were analysed for monotonously increasing or decreasing trends with the non-parametric Mann-Kendall test, a method to establish the presence of a consistent trend. Our analysis has not revealed a globe-wide trend of increase or decrease in chlorophyll concentration during the past century; ocean regions have apparently responded differentially to changes in meteorological, hydrological and biological conditions at the surface, including potential long-term trends related to global warming. Since 1889, chlorophyll concentrations have decreased in the Indian Ocean and in the Pacific; increased in the Atlantic Ocean, the Mediterranean, the Chinese Sea, and in the seas west and north-west of Japan. This suggests that explanations of chlorophyll changes over long periods should focus on hydrographical and biological characteristics typical of single ocean regions, not on those of 'the' ocean.

  4. Solubilization of poorly soluble photosensitizer hypericin by polymeric micelles and polyethylene glycol.

    PubMed

    Búzová, Diana; Kasák, Peter; Miškovský, Pavol; Jancura, Daniel

    2013-06-01

    Hypericin (Hyp) is a promising photosensitizer for photodiagnostic and photodynamic therapy of cancer. However, Hyp has a large conjugated system and in aqueous solutions forms insoluble aggregates which do not possess biological activity. This makes intravenous injection of Hyp problematic and restricts its medical applications. To overcome this problem, Hyp is incorporated into drug delivery systems which can increase its solubility and bioavailability. One of the possibilities is utilization of polymeric micelles. The most used hydrophilic block for preparation of polymeric micelles is polyethylen glycol (PEG). PEG is a polymer which for its lack of immunogenicity, antigenicity and toxicity obtained approval for use in human medicine. In this work we have studied the solubilization of Hyp aggregates in the presence of PEG-PE and PEG-cholesterol micelles. The concentration of polymeric micelles which allows total monomerization of Hyp corresponds to the critical micellar concentration of these micelles (~10(-6) M). We have also investigated the effect of the molecular weight and concentration of PEG on the transition of aggregated Hyp to its monomeric form. PEGs with low molecular weight (< 1000 g/mol) do not significantly contribute to the solubilization of Hyp. However, PEGs with molecular weight > 2000 g/mol efficiently transform Hyp aggregates to the monomeric state of this photosensitizer.

  5. In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs.

    PubMed

    Eliezar, Jeaniffer; Scarano, Wei; Boase, Nathan R B; Thurecht, Kristofer J; Stenzel, Martina H

    2015-02-09

    The biodistribution of micelles with and without folic acid targeting ligands were studied using a block copolymer consisting of acrylic acid (AA) and polyethylene glycol methyl ether acrylate (PEGMEA) blocks. The polymers were prepared using RAFT polymerization in the presence of a folic acid functionalized RAFT agent. Oxoplatin was conjugated onto the acrylic acid block to form amphiphilic polymers which, when diluted in water, formed stable micelles. In order to probe the in vivo stability, a selection of micelles were cross-linked using 1,8-diamino octane. The sizes of the micelles used in this study range between 75 and 200 nm, with both spherical and worm-like conformation. The effects of cross-linking, folate conjugation and different conformation on the biodistribution were studied in female nude mice (BALB/c) following intravenous injection into the tail vein. Using optical imaging to monitor the fluorophore-labeled polymer, the in vivo biodistribution of the micelles was monitored over a 48 h time-course after which the organs were removed and evaluated ex vivo. These experiments showed that both cross-linking and conjugation with folic acid led to increased fluorescence intensities in the organs, especially in the liver and kidneys, while micelles that are not conjugated with folate and not cross-linked are cleared rapidly from the body. Higher accumulation in the spleen, liver, and kidneys was also observed for micelles with worm-like shapes compared to the spherical micelles. While the various factors of cross-linking, micelle shape, and conjugation with folic acid all contribute separately to prolong the circulation time of the micelle, optimization of these parameters for drug delivery devices could potentially overcome adverse effects such as liver and kidney toxicity.

  6. Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.

    PubMed

    Lu, Lu; Zheng, Yan; Weng, Shuqiang; Zhu, Wenwei; Chen, Jinhong; Zhang, Xiaomin; Lee, Robert J; Yu, Bo; Jia, Huliang; Qin, Lunxiu

    2016-06-01

    7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA-SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors.

    PubMed

    Uthaman, Saji; Bom, Joon-suk; Kim, Hyeon Sik; John, Johnson V; Bom, Hee-Seung; Kim, Seon-Jong; Min, Jung-Joon; Kim, Il; Park, In-Kyu

    2016-05-01

    Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI. © 2016 Wiley Periodicals, Inc.

  8. Effect of headgroup size, charge, and solvent structure on polymer-micelle interactions, studied by molecular dynamics simulations.

    PubMed

    Shang, Barry Z; Wang, Zuowei; Larson, Ronald G

    2009-11-19

    We performed atomistic molecular dynamics simulations of anionic and cationic micelles in the presence of poly(ethylene oxide) (PEO) to understand why nonionic water-soluble polymers such as PEO interact strongly with anionic micelles but only weakly with cationic micelles. Our micelles include sodium n-dodecyl sulfate (SDS), n-dodecyl trimethylammonium chloride (DTAC), n-dodecyl ammonium chloride (DAC), and micelles in which we artificially reverse the sign of partial charges in SDS and DTAC. We observe that the polymer interacts hydrophobically with anionic SDS but only weakly with cationic DTAC and DAC, in agreement with experiment. However, the polymer also interacts with the artificial anionic DTAC but fails to interact hydrophobically with the artificial cationic SDS, illustrating that large headgroup size does not explain the weak polymer interaction with cationic micelles. In addition, we observe through simulation that this preference for interaction with anionic micelles still exists in a dipolar "dumbbell" solvent, indicating that water structure and hydrogen bonding alone cannot explain this preferential interaction. Our simulations suggest that direct electrostatic interactions between the micelle and polymer explain the preference for interaction with anionic micelles, even though the polymer overall carries no net charge. This is possible given the asymmetric distribution of negative charges on smaller atoms and positive charges on larger units in the polymer chain.

  9. Curcumin Delivery by Poly(Lactide)-Based Co-Polymeric Micelles: An In Vitro Anticancer Study.

    PubMed

    Kumari, Preeti; Swami, Muddineti Omkara; Nadipalli, Sravan Kumar; Myneni, Srividya; Ghosh, Balaram; Biswas, Swati

    2016-04-01

    This work describes the synthesis of block co-polymeric micelles, methoxy-poly(ethylene glycol)-poly(D,L-lactide) (mPEG-PLA) to encapsulate Curcumin (CUR), thereby improving the dispersibility and chemical stability of curcumin, prolonging its cellular uptake and enhancing its bioavailability. CUR-mPEG-PLA micelles, was prepared using the thin-film hydration method and evaluated in vitro. The preparation process was optimized with a central composite design (CCD). Micelles were characterized by size, transmission electron microscopy, loading capacity, and critical micelle concentration (CMC). The cytotoxicity of CUR-mPEG-PLA micelles was investigated against murine melanoma cells, B16F10 and human breast cancer cells, MDA-MB-231. The average size of the CUR-mPEG-PLA micelles was 110 ± 5 nm with polydispersity index in the range of 0.15-0.31, and the encapsulating efficiency for CUR was 91.89 ± 1.2, and 11.06 ± 0.8% for drug-loading. Sustained release of CUR from micelles was observed with 9.73% CUR release from micelles compared to 64.24% release of free curcumin in first 6 h under sink condition. The CUR-mPEG-PLA was efficiently taken up by the cancer cells, B16F10 and MDA-MB-231. Following 24 h incubation, CUR-mPEG-PLA induced higher cytotoxicity compared to free CUR in MDA-MB-231 cell lines indicating exposure of higher dose of free CUR to cells lead to up-regulation of drug efflux mechanisms leading to decreased cell death in case of free CUR administration. Our results indicate that the proposed micellar system has the potential to serve as an efficient carrier for CUR by effectively solubilizing, stabilizing and delivering the drug in a controlled manner to the cancer cells.

  10. Micelle Catalysis of an Aromatic Substitution Reaction

    ERIC Educational Resources Information Center

    Corsaro, Gerald; Smith J. K.

    1976-01-01

    Describes an experiment in which the iodonation of aniline reaction is shown to undergo catalysis in solution of sodium lauryl sulfate which forms micelles with negatively charged pseudo surfaces. (MLH)

  11. Lil3 dimerization and chlorophyll binding in Arabidopsis thaliana.

    PubMed

    Mork-Jansson, Astrid Elisabeth; Gargano, Daniela; Kmiec, Karol; Furnes, Clemens; Shevela, Dmitriy; Eichacker, Lutz Andreas

    2015-10-07

    The two-helix light harvesting like (Lil) protein Lil3 belongs to the family of chlorophyll binding light harvesting proteins of photosynthetic membranes. A function in tetrapyrrol synthesis and stabilization of geranylgeraniol reductase has been shown. Lil proteins contain the chlorophyll a/b-binding motif; however, binding of chlorophyll has not been demonstrated. We find that Lil3.2 from Arabidopsis thaliana forms heterodimers with Lil3.1 and binds chlorophyll. Lil3.2 heterodimerization (25±7.8 nM) is favored relative to homodimerization (431±59 nM). Interaction of Lil3.2 with chlorophyll a (231±49 nM) suggests that heterodimerization precedes binding of chlorophyll in Arabidopsis thaliana. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. Azo polymeric micelles designed for colon-targeted dimethyl fumarate delivery for colon cancer therapy.

    PubMed

    Ma, Zhen-Gang; Ma, Rui; Xiao, Xiao-Lin; Zhang, Yong-Hui; Zhang, Xin-Zi; Hu, Nan; Gao, Jin-Lai; Zheng, Yu-Feng; Dong, De-Li; Sun, Zhi-Jie

    2016-10-15

    Colon-targeted drug delivery and circumventing drug resistance are extremely important for colon cancer chemotherapy. Our previous work found that dimethyl fumarate (DMF), the approved drug by the FDA for the treatment of multiple sclerosis, exhibited anti-tumor activity on colon cancer cells. Based on the pharmacological properties of DMF and azo bond in olsalazine chemical structure, we designed azo polymeric micelles for colon-targeted dimethyl fumarate delivery for colon cancer therapy. We synthesized the star-shape amphiphilic polymer with azo bond and fabricated the DMF-loaded azo polymeric micelles. The four-arm polymer star-PCL-azo-mPEG (sPCEG-azo) (constituted by star-shape PCL (polycaprolactone) and mPEG (methoxypolyethylene glycols)-olsalazine) showed self-assembly ability. The average diameter and polydispersity index of the DMF-loaded sPCEG-azo polymeric micelles were 153.6nm and 0.195, respectively. In vitro drug release study showed that the cumulative release of DMF from the DMF-loaded sPCEG-azo polymeric micelles was no more than 20% in rat gastric fluid within 10h, whereas in the rat colonic fluids, the cumulative release of DMF reached 60% in the initial 2h and 100% within 10h, indicating that the DMF-loaded sPCEG-azo polymeric micelles had excellent colon-targeted property. The DMF-loaded sPCEG-azo polymeric micelles had no significant cytotoxicity on colon cancer cells in phosphate buffered solution (PBS) and rat gastric fluid. In rat colonic fluid, the micelles showed significant cytotoxic effect on colon cancer cells. The blank sPCEG-azo polymeric micelles (without DMF) showed no cytotoxic effect on colon cancer cells in rat colonic fluids. In conclusion, the DMF-loaded sPCEG-azo polymeric micelles show colon-targeted DMF release and anti-tumor activity, providing a novel approach potential for colon cancer therapy. Colon-targeted drug delivery and circumventing drug resistance are extremely important for colon cancer chemotherapy. Our

  13. The association of low-molecular-weight hydrophobic compounds with native casein micelles in bovine milk.

    PubMed

    Cheema, M; Mohan, M S; Campagna, S R; Jurat-Fuentes, J L; Harte, F M

    2015-08-01

    The agreed biological function of the casein micelles in milk is to carry minerals (calcium, magnesium, and phosphorus) from mother to young along with amino acids for growth and development. Recently, native and modified casein micelles were used as encapsulating and delivery agents for various hydrophobic low-molecular-weight probes. The ability of modified casein micelles to bind certain probes may derive from the binding affinity of native casein micelles. Hence, a study with milk from single cows was conducted to further elucidate the association of hydrophobic molecules into native casein micelles and further understand their biological function. Hydrophobic and hydrophilic extraction followed by ultraperformance liquid chromatography-high resolution mass spectrometry analysis were performed over protein fractions obtained from size exclusion fractionation of raw skim milk. Hydrophobic compounds, including phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin, showed strong association exclusively to casein micelles as compared with whey proteins, whereas hydrophilic compounds did not display any preference for their association among milk proteins. Further analysis using liquid chromatography-tandem mass spectrometry detected 42 compounds associated solely with the casein-micelles fraction. Mass fragments in tandem mass spectrometry identified 4 of these compounds as phosphatidylcholine with fatty acid composition of 16:0/18:1, 14:0/16:0, 16:0/16:0, and 18:1/18:0. These results support that transporting low-molecular-weight hydrophobic molecules is also a biological function of the casein micelles in milk. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Shape-designed single-polymer micelles: a proof-of-concept simulation

    NASA Astrophysics Data System (ADS)

    Moths, Brian; Witten, Thomas A.

    Much effort has been directed towards self-assembling nanostructures. Strong, local interactions between specific building blocks often determine these structures (e.g., globular proteins). We seek to produce designed structures that are instead determined by collective effects of weak interactions (e.g., surfactant self-assembly). Such structures may reversibly change conformation or disassemble in response to changing solvent conditions, and, being soft, have potential to adapt to fluctuating or unknown application-imposed shape requirements. Concretely, we aim to realize such a structure in the form of a single polymer micelle--an amphiphilic polymer exhibiting a condensed, phase-segregated conformation when immersed in solvent. Connecting all amphiphiles into a single chain provides geometric constraints controlling the surface curvature profile, thus dictating a non-trivial shape. We present 2D Monte Carlo simulation results demonstrating the feasibility of such soft, shape-designed micelles. Preliminary results demonstrate a stable concave ``dimple'' in a micelle composed of a single A-B multiblock linear copolymer. We discuss both current limitations on shape robustness and effects of block asymmetry, block molecular weights and overall chain length on micelle shape. This work was supported in part by the National Science Foundation's MRSEC Program under Award Number DMR-1420709.

  15. Investigating the Control of Chlorophyll Degradation by Genomic Correlation Mining.

    PubMed

    Ghandchi, Frederick P; Caetano-Anolles, Gustavo; Clough, Steven J; Ort, Donald R

    2016-01-01

    Chlorophyll degradation is an intricate process that is critical in a variety of plant tissues at different times during the plant life cycle. Many of the photoactive chlorophyll degradation intermediates are exceptionally cytotoxic necessitating that the pathway be carefully coordinated and regulated. The primary regulatory step in the chlorophyll degradation pathway involves the enzyme pheophorbide a oxygenase (PAO), which oxidizes the chlorophyll intermediate pheophorbide a, that is eventually converted to non-fluorescent chlorophyll catabolites. There is evidence that PAO is differentially regulated across different environmental and developmental conditions with both transcriptional and post-transcriptional components, but the involved regulatory elements are uncertain or unknown. We hypothesized that transcription factors modulate PAO expression across different environmental conditions, such as cold and drought, as well as during developmental transitions to leaf senescence and maturation of green seeds. To test these hypotheses, several sets of Arabidopsis genomic and bioinformatic experiments were investigated and re-analyzed using computational approaches. PAO expression was compared across varied environmental conditions in the three separate datasets using regression modeling and correlation mining to identify gene elements co-expressed with PAO. Their functions were investigated as candidate upstream transcription factors or other regulatory elements that may regulate PAO expression. PAO transcript expression was found to be significantly up-regulated in warm conditions, during leaf senescence, and in drought conditions, and in all three conditions significantly positively correlated with expression of transcription factor Arabidopsis thaliana activating factor 1 (ATAF1), suggesting that ATAF1 is triggered in the plant response to these processes or abiotic stresses and in result up-regulates PAO expression. The proposed regulatory network includes the

  16. Micelle-templated, poly(lactic-co-glycolic acid) nanoparticles for hydrophobic drug delivery.

    PubMed

    Nabar, Gauri M; Mahajan, Kalpesh D; Calhoun, Mark A; Duong, Anthony D; Souva, Matthew S; Xu, Jihong; Czeisler, Catherine; Puduvalli, Vinay K; Otero, José Javier; Wyslouzil, Barbara E; Winter, Jessica O

    2018-01-01

    Poly(lactic- co -glycolic acid) (PLGA) is widely used for drug delivery because of its biocompatibility, ability to solubilize a wide variety of drugs, and tunable degradation. However, achieving sub-100 nm nanoparticles (NPs), as might be desired for delivery via the enhanced permeability and retention effect, is extremely difficult via typical top-down emulsion approaches. Here, we present a bottom-up synthesis method yielding PLGA/block copolymer hybrids (ie, "PolyDots"), consisting of hydrophobic PLGA chains entrapped within self-assembling poly(styrene- b -ethylene oxide) (PS- b -PEO) micelles. PolyDots exhibit average diameters <50 nm and lower polydispersity than conventional PLGA NPs. Drug encapsulation efficiencies of PolyDots match conventional PLGA NPs (ie, ~30%) and are greater than those obtained from PS- b -PEO micelles (ie, ~7%). Increasing the PLGA:PS- b -PEO weight ratio alters the drug release mechanism from chain relaxation to erosion controlled. PolyDots are taken up by model glioma cells via endocytotic mechanisms within 24 hours, providing a potential means for delivery to cytoplasm. PolyDots can be lyophilized with minimal change in morphology and encapsulant functionality, and can be produced at scale using electrospray. Encapsulation of PLGA within micelles provides a bottom-up route for the synthesis of sub-100 nm PLGA-based nanocarriers with enhanced stability and drug-loading capacity, and tunable drug release, suitable for potential clinical applications.

  17. Premature drug release of polymeric micelles and its effects on tumor targeting.

    PubMed

    Miller, Tobias; Breyer, Sandra; van Colen, Gwenaelle; Mier, Walter; Haberkorn, Uwe; Geissler, Simon; Voss, Senta; Weigandt, Markus; Goepferich, Achim

    2013-03-10

    Based on the enhanced permeability and retention (EPR) effect, nanoparticles are believed to accumulate in tumors. In this conjunction, the stability of drug encapsulation is assumed to be sufficient. For clarification purposes, PEGylated poly-(D,L-lactic acid) (PEG-PDLLA) micelles which incorporated the hydrophobic model drug dechloro-4-iodo-fenofibrate (IFF) were investigated. H2N-PEG-PDLLA was synthesized, coupled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and labeled with 111-indium. From this polymeric species, mixed micelles with H3CO-PEG-PDLLA were prepared which encapsulated the 125-iodine or 131-iodine labeled drug IFF. Bioimaging and biodistribution experiments in healthy and AR42J-tumor bearing mice were carried out to quantify the uptake of the drug and its carrier in single organs. As a result, upon injection of this system, a rapid dissociation of the polymeric carrier and the incorporated drug (<10 min post inj.) was revealed. Regardless of the premature release, the drug showed an enhanced tumor accumulation compared to the polymeric carrier. In conclusion, the self-assembling system allowed for successful solubilization of the hydrophobic drug by physical incorporation into micelles whereas the tumor targeting properties of the drug delivery system could not be sufficiently shown. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Micelle-induced depletion interaction and resultant structure in charged colloidal nanoparticle system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ray, D.; Aswal, V. K., E-mail: vkaswal@barc.gov.in; Kohlbrecher, J.

    2015-04-28

    The evolution of the interaction and the resultant structure in the mixed system of anionic silica nanoparticles (Ludox LS30) and non-ionic surfactant decaethylene glycol monododecylether (C12E10), undergoing phase separation, have been studied using small-angle neutron scattering and dynamic light scattering. The measurements have been carried out for a fixed concentration of nanoparticle (1 wt. %) with varying concentration of surfactant (0 to 1 wt. %), in the absence and presence of an electrolyte. It is found that the micelles of non-ionic surfactant adsorb on the nanoparticle in the absence of electrolyte (form stable system), whereas these micelles become non-adsorbing in the presence of electrolytemore » (show phase separation). The phase separation arises because of C12E10 micelles, causing depletion interaction between nanoparticles and leading to their aggregation. The interaction is modeled by double Yukawa potential accounting for attractive depletion as well as repulsive electrostatic forces. Both the interactions (attraction and repulsion) are found to be of long-range. The nanoparticle aggregation (phase separation) is governed by the increase in the magnitude and the range of the depletion attraction with the increase in the surfactant concentration. The nanoparticle aggregates formed are quite large in size (order of micron) and are characterized by the surface fractal having simple cubic packing of nanoparticles within the aggregates.« less

  19. Dual drug release from hydrogels covalently containing polymeric micelles that possess different drug release properties.

    PubMed

    Murata, Mari; Uchida, Yusuke; Takami, Taku; Ito, Tomoki; Anzai, Ryosuke; Sonotaki, Seiichi; Murakami, Yoshihiko

    2017-05-01

    In the present study, we designed hydrogels for dual drug release: the hydrogels that covalently contained the polymeric micelles that possess different drug release properties. The hydrogels that were formed from polymeric micelles possessing a tightly packed (i.e., well-entangled) inner core exhibited a higher storage modulus than the hydrogels that were formed from the polymeric micelles possessing a loosely packed structure. Furthermore, we conducted release experiments and fluorescent observations to evaluate the profiles depicting the release of two compounds, rhodamine B and auramine O, from either polymeric micelles or hydrogels. According to our results, (1) hydrogels that covalently contains polymeric micelles that possess different drug release properties successfully exhibit the independent release behaviors of the two compounds and (2) fluorescence microscopy can greatly facilitate efforts to evaluate drug release properties of materials. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Poly(2-(diethylamino)ethyl methacrylate)-based, pH-responsive, copolymeric mixed micelles for targeting anticancer drug control release.

    PubMed

    Chen, Quan; Li, Siheng; Feng, Zixiong; Wang, Meng; Cai, Chengzhi; Wang, Jufang; Zhang, Lijuan

    2017-01-01

    We have demonstrated a novel drug delivery system to improve the selectivity of the current chemotherapy by pH-responsive, polymeric micelle carriers. The micelle carriers were prepared by the self-assembly of copolymers containing the polybasic poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) block. The mixed copolymers exhibited a comparatively low critical micelle concentration (CMC; 1.95-5.25 mg/L). The resultant mixed micelles were found to be <100 nm and were used to encapsulate the anticancer drug doxorubicin (DOX) with pretty good drug-loading content (24%) and entrapment efficiency (55%). Most importantly, the micelle carrier exhibited a pH-dependent conformational conversion and promoted the DOX release at the tumorous pH. Our in vitro studies demonstrated the comparable level of DOX-loaded mixed micelle delivery into tumor cells with the free DOX (80% of the tumor cells were killed after 48 h incubation). The DOX-loaded mixed micelles were effective to inhibit the proliferation of tumor cells after prolonged incubation. Overall, the pH-responsive mixed micelle system provided desirable potential in the controlled release of anticancer therapeutics.

  1. Pharmacometrics and delivery of novel nanoformulated PEG-b-poly(ε-caprolactone) micelles of rapamycin

    PubMed Central

    Yáñez, Jaime A.; Forrest, M. Laird; Ohgami, Yusuke

    2008-01-01

    Purpose To determine the pharmacokinetics, tissue, and blood distribution of rapamycin PEG-block-poly(ε-caprolactone) (PEG-b-PCL) micelle formulations with and without the addition of α-tocopherol compared to control rapamycin in Tween 80/PEG 400/N,N-dimethylacetamide (DMA) (7:64:29). Methods Rapamycin was incorporated at 10% w/w into PEG-b-PCL micelles (5:10 kDa) using a solvent extraction technique. The co-incorporation of 2:1 α-tocopherol:PEG-b-PCL was also studied. Rapamycin was quantified utilizing LC/MS in a Waters XTerra MS C18 column with 32-desmethoxyrapamycin as the internal standard. Male Sprague Dawley rats (N = 4 per group; ~200 g) were cannulated via the left jugular and dosed intravenously (IV) with the rapamycin control and micelle formulations (10 mg/kg, 1:9 ratio for rapamycin to PEG-b-PCL). For tissue distribution 24 h after IV dosing, whole blood, plasma, red blood cells, and all the representative tissues were collected. The tissues were rapidly frozen under liquid nitrogen and ground to a fine powder. The rapamycin concentrations in plasma and red blood cells were utilized to determine the blood distribution (partition coefficient between plasma and red blood cells). For the determination of the pharmacokinetic parameters, blood, plasma, and urine samples were collected over 48 h. The pharmacokinetic parameters were calculated using WinNonlin® (Version 5.1) software. Results Rapamycin concentrations were considerably less in brain after administration of both micelle formulations compared to a rapamycin in the Tween 80/PEG 400/DMA control group. There was a 2-fold and 1.6-fold increase in the plasma fraction for rapamycin micelles with and without α-tocopherol. There was a decrease in volume of distribution for both formulations, an increase in AUC, a decrease in clearance, and increase in half life respectively for rapamycin in PEG-b-PCL + α-tocopherol micelles and in PEG-b-PCL micelles. There was no mortality with the micelle

  2. Cationic micelles self-assembled from cholesterol-conjugated oligopeptides as an efficient gene delivery vector.

    PubMed

    Guo, Xin Dong; Tandiono, Fanny; Wiradharma, Nikken; Khor, Dingyue; Tan, Chuan Guan; Khan, Majad; Qian, Yu; Yang, Yi-Yan

    2008-12-01

    Cholesterol-conjugated H(5)R(10) and H(10)R(10) oligopeptides (HR15-Chol and HR20-Chol) were designed and synthesized. These amphiphilic oligopeptides were able to self-assemble into cationic micelles in aqueous solution at low concentrations, and their critical micelle concentrations in sodium acetate buffer (20mM, pH 5.0) were 17.8 and 28.2mg/L respectively. The micelle formation was further evidenced via SEM and dynamic light scattering analyses. The average hydrodynamic size of HR15-Chol and HR20-Chol micelles was about 425 and 435 nM in diameter with zeta potential of 64 and 66 mV respectively. The formation of micelles increased local concentration of cationic charge, leading to higher DNA binding efficiency as compared to the control peptides HR15 and HR20. The minimum size observed for HR15-Chol/DNA and HR20-Chol/DNA complexes was about 175-176 nM, and the maximum zeta potential was around 61-62 mV. In comparison, HR15 and HR20 formed DNA complexes with a similar size but significantly lower zeta potential (i.e. about 31-40 mV). In particular, after being challenged by DMEM medium, the size of peptide/DNA complexes was increased significantly and their surface charge was neutralized. Nevertheless, the size of the micelle/DNA complexes formed from HR15-Chol and HR20-Chol was still about 200 nM with positive charge of around 20 mV at high N/P ratios. The micelles induced much higher overall gene expression (i.e. luciferase expression) levels than the peptides in both HepG2 and HEK293 cell lines. Increasing the histidine residue from 0 to 5 to 10 further increased gene expression efficiency. In particular, HR20-Chol micelles yielded 95% GFP-positive HepG2 cells at N/P 50, much higher than that induced by PEI at its optimal N/P ratio (i.e. 10), which was 6.8%. In 4T1 cells, HR20-Chol induced 2 times higher luciferase expression level than PEI at their optimal N/P ratios. Moreover, HR20-Chol micelle/DNA complexes were less cytotoxic than PEI/DNA complexes. These

  3. Theranostic reduction-sensitive gemcitabine prodrug micelles for near-infrared imaging and pancreatic cancer therapy

    NASA Astrophysics Data System (ADS)

    Han, Haijie; Wang, Haibo; Chen, Yangjun; Li, Zuhong; Wang, Yin; Jin, Qiao; Ji, Jian

    2015-12-01

    A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy.A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which

  4. Mapping of chlorophyll a distributions in coastal zones

    NASA Technical Reports Server (NTRS)

    Johnson, R. W.

    1978-01-01

    It is pointed out that chlorophyll a is an important environmental parameter for monitoring water quality, nutrient loads, and pollution effects in coastal zones. High chlorophyll a concentrations occur in areas which have high nutrient inflows from sources such as sewage treatment plants and industrial wastes. Low chlorophyll a concentrations may be due to the addition of toxic substances from industrial wastes or other sources. Remote sensing provides an opportunity to assess distributions of water quality parameters, such as chlorophyll a. A description is presented of the chlorophyll a analysis and a quantitative mapping of the James River, Virginia. An approach considered by Johnson (1977) was used in the analysis. An application of the multiple regression analysis technique to a data set collected over the New York Bight, an environmentally different area of the coastal zone, is also discussed.

  5. Improved solubility and oral bioavailability of apigenin via Soluplus/Pluronic F127 binary mixed micelles system.

    PubMed

    Zhang, Zhenhai; Cui, Changchang; Wei, Fang; Lv, Huixia

    2017-08-01

    The aim of this study was to develop a novel mix micelles system composing of two biocompatible copolymers of Soluplus ® and Pluronic F127 to improve the solubility, oral bioavailability of insoluble drug apigenin (AP) as model drug. The AP-loaded mixed micelles (AP-M) were prepared by ethanol thin-film hydration method. The formed optimal formulation of AP-M were provided with small size (178.5 nm) and spherical shape at ratio of 4:1 (Soluplus ® :Pluronic F127), as well as increasing solubility of to 5.61 mg/mL in water which was about 3442-fold compared to that of free AP. The entrapment efficiency and drug loading of AP-M were 95.72 and 5.32%, respectively, and a sustained release of AP-M was obtained as in vitro release study indicated. Transcellular transport study showed that the cell uptake of AP was increased in Caco-2 cell transport models. The oral bioavailability of AP-M was 4.03-fold of free AP in SD rats, indicating the mixed micelles of Soluplus ® and Pluronic F127 is an industrially feasible drug delivery system to promote insoluble drug oral absorption in the gastrointestinal tract.

  6. Aripiprazole-Loaded Polymeric Micelles: Fabrication, Optimization and Evaluation using Response Surface Method.

    PubMed

    Patil, Payal Hasmukhlal; Wankhede, Pooja R; Mahajan, H S; Zawar, Laxmikant

    2018-01-04

    The fundamental objective of current study was to encapsulate Ari-piprazole (ARP) within Pluronic F127 micelles to improve its aqueous solubility. The recent patents on Ar-ipiprazole (JP2013136621) and micelles (WO2016004369A1) facilitated selection of drug and polymer. The drug-laden micelles were fabricated using thin-film hydration technique. Optimization of the micellar formulation was done by using response surface method (RSM). The Pluronic F127 concentration of 150 mg and 75 rpm rotational speed of rotary evaporator were found to be optimized conditions for formulating micelles. The prepared batches were further characterized for PDI (polydispersity index), zeta potential, % DLC (% Drug loading content), % EE (% Entrapment Efficiency) and % drug release study; results of these parameters were found to be 0.228, −4.04 mV and 76.50 % and 18.56 % respectively. It was observed from the In vitro release study that 97.37 ± 1.81 % drug had released from micelles after 20 hrs which were found about thrice as compared to that of pure drug. The optimized ARP micellar for-mulation was characterized using DSC (Differential Scanning Colorimetry), FT-IR (Fourier Trans-formed Infrared Spectroscopy), P-XRD (Powdered X-ray Diffraction Study) and TEM (Transmission Electronic Microscopy) studies. ARP-loaded micelles displayed a hydrodynamic diameter of 170.3 nm and a sphere-shaped morphology as determined by dynamic light scattering as well as TEM study. It is concluded that the prepared polymeric micellar system has an excellent potential to be used as a delivery carrier for Aripiprazole with increased solubility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Phase behavior of casein micelles/exocellular polysaccharide mixtures: Experiment and theory

    NASA Astrophysics Data System (ADS)

    Tuinier, R.; de Kruif, C. G.

    1999-05-01

    Dispersions of casein micelles and an exocellular polysaccharide (EPS), obtained from Lactococcus lactis subsp. cremoris NIZO B40 EPS, show a phase separation. The phase separation is of the colloidal gas-liquid type. We have determined a phase diagram that describes the separation of skim milk with EPS into a casein-micelle rich phase and an EPS rich phase. We compare the phase diagram with those calculated from theories developed by Vrij, and by Lekkerkerker and co-workers, showing that the experimental phase boundary can be predicted quite well. From dynamic light scattering measurements of the self-diffusion of the casein micelles in the presence of EPS the spinodal could be located and it corresponds with the experimental phase boundary.

  8. Drug-conjugated PLA-PEG-PLA copolymers: a novel approach for controlled delivery of hydrophilic drugs by micelle formation.

    PubMed

    Danafar, H; Rostamizadeh, K; Davaran, S; Hamidi, M

    2017-12-01

    A conjugate of the antihypertensive drug, lisinopril, with triblock poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) copolymer was synthesized by the reaction of PLA-PEG-PLA copolymer with lisinopril in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The conjugated copolymer was characterized in vitro by hydrogen nuclear magnetic resonance (HNMR), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) techniques. Then, the lisinopril conjugated PLA-PEG-PLA were self-assembled into micelles in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The results revealed that the micelles formed by the lisinopril-conjugated PLA-PEG-PLA have spherical structure with the average size of 162 nm. The release behavior of conjugated copolymer, micelles and micelles physically loaded by lisinopril were compared in different media. In vitro release study showed that in contrast to physically loaded micelles, the release rate of micelles consisted of the conjugated copolymer was dependent on pH of media where it was higher at lower pH compared to the neutral medium. Another feature of the conjugated micelles was their more sustained release profile compared to the lisinopril-conjugated copolymer and physically loaded micelles.

  9. Novel thermosensitive polymeric micelles for docetaxel delivery.

    PubMed

    Yang, Mi; Ding, Yitao; Zhang, Leyang; Qian, Xiaoping; Jiang, Xiqun; Liu, Baorui

    2007-06-15

    Targeted delivery of antitumor drugs triggered by hyperthermia has significant advantages in clinical applications, since it is easy to implement and side effects are reduced. To release drugs site-specifically upon local heating often requires the drugs to be loaded into a thermosensitive polymer matrix with a low critical solution temperature (LCST) between 37 and 42 degrees C. However, the LCSTs of most thermosensitive materials were below 37 degrees C, which limits their application in clinic because they would precipitate once injected into human body and lost thermal targeting function. Herein, we prepared a novel thermosensitive copolymer (poly(N-isopropylacrylamide-co-acrylamide)-b-poly (DL-lactide)) that exhibits no obvious physical change up to 41 degrees C when heated. Docetaxel loaded micelles made of such thermosensitive polymer were prepared by dialysis method and the maximum loading content was found to be up to 27%. The physical properties, such as structure, morphology, and size distribution of the micelles with and without docetaxel were investigated by NMR, X-ray diffraction, dynamic light scattering, atomic force microscopy, etc. The efficacy of this drug delivery system was also evaluated by examining the proliferation inhibiting activity against different cell lines in vitro. After hyperthermia, the cytotoxicity of docetaxel-loaded micelles increased prominently. Our results demonstrated that this copolymer could be an ideal candidate for thermal targeted antitumor drug delivery. (c) 2007 Wiley Periodicals, Inc.

  10. Optimization of Weight Ratio for DSPE-PEG/TPGS Hybrid Micelles to Improve Drug Retention and Tumor Penetration.

    PubMed

    Jin, Ya; Wu, Zimei; Li, Caibin; Zhou, Weisai; Shaw, John P; Baguley, Bruce C; Liu, Jianping; Zhang, Wenli

    2018-01-04

    To enhance therapeutic efficacy and prevent phlebitis caused by Asulacrine (ASL) precipitation post intravenous injection, ASL-loaded hybrid micelles with size below 40 nm were developed to improve drug retention and tumor penetration. ASL-micelles were prepared using different weight ratios of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol-2000 (DSPE-PEG 2000 ) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymers. Stability of micelles was optimized in terms of critical micelle concentration (CMC) and drug release properties. The encapsulation efficiency (EE) and drug loading were determined using an established dialysis-mathematic fitting method. Multicellular spheroids (MCTS) penetration and cytotoxicity were investigated on MCF-7 cell line. Pharmacokinetics of ASL-micelles was evaluated in rats with ASL-solution as control. The ASL-micelles prepared with DSPE-PEG 2000 and TPGS (1:1, w/w) exhibited small size (~18.5 nm), higher EE (~94.12%), better sustained in vitro drug release with lower CMC which may be ascribed to the interaction between drug and carriers. Compared to free ASL, ASL-micelles showed better MCTS penetration capacity and more potent cytotoxicity. Pharmacokinetic studies demonstrated that the half-life and AUC values of ASL-micelles were approximately 1.37-fold and 3.49-fold greater than that of free ASL. The optimized DSPE-PEG 2000 /TPGS micelles could serve as a promising vehicle to improve drug retention and penetration in tumor.

  11. Impacts of Organic Macromolecules, Chlorophyll and Soot on Arctic Sea Ice

    NASA Astrophysics Data System (ADS)

    Ogunro, O. O.; Wingenter, O. W.; Elliott, S.; Flanner, M.; Dubey, M. K.

    2014-12-01

    Recent intensification of Arctic amplification can be strongly connected to positive feedback relating black carbon deposition to sea ice surface albedo. In addition to soot deposition on the ice and snow pack, ice algal chlorophyll is likely to compete as an absorber and redistributor of energy. Hence, solar radiation absorption by chlorophyll and some components of organic macromolecules in/under the ice column is currently being examined to determine the level of influence on predicted rate of ice loss. High amounts of organic macromolecules and chlorophyll are produced in global sea ice by the bottom microbial community and also in vertically distributed layers where substantial biological activities take place. Brine channeling in columnar ice can allow for upward flow of nutrients which leads to greater primary production in the presence of moderate light. Modeling of the sea-ice processes in tandem with experiments and field observations promises rapid progress in enhancing Arctic ice predictions. We are designing and conducting global climate model experiments to determine the impact of organic macromolecules and chlorophyll on Arctic sea ice. Influences on brine network permeability and radiation/albedo will be considered in this exercise. Absorption by anthropogenic materials such as soot and black carbon will be compared with that of natural pigments. We will indicate areas of soot and biological absorption dominance in the sense of single scattering, then couple into a full radiation transfer scheme to attribute the various contributions to polar climate change amplification. The work prepares us to study more traditional issues such as chlorophyll warming of the pack periphery and chemical effects of the flow of organics from ice internal communities. The experiments started in the Arctic will broaden to include Antarctic sea ice and shelves. Results from the Arctic simulations will be presented.

  12. Toxicity Evaluation and Anti-Tumor Study of Docetaxel Loaded mPEG-Polyester Micelles for Breast Cancer Therapy.

    PubMed

    Tan, Li Wei; Ma, Bu Yun; Zhao, Qian; Zhang, Lan; Chen, Li Juan; Peng, Jin Rong; Qian, Zhi Yong

    2017-04-01

    In this work, docetaxel (DTX) was encapsulated in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) micelles and monomethoxy poly(ethylene glycol)-poly(D, L-lactic acid) (mPEG-PLA) micelles, respectively. For the further application, the acute/genetic toxicity evaluation and pharmacokinetic/pharmacodynamic study of the two kinds of micellar nanomedicines were performed. In the study of anticancer activity in vitro and in vivo, DTX micelles showed better tumorgrowth inhibition than free DTX. The pharmacokinetic and tissue distribution studies showed that the DTX incorporated in micelles (especially in DTX-mPEG-PCL) retained significantly higher concentration in plasma and tumor tissue compared with free DTX. The acute toxicity and genotoxicity studies indicated that DTX micelles were safer than the docetaxel injection in cancer therapy and DTX-mPEG-PCL had less damage to DNA than DTX-mPEG-PLA. So the micelles had a pronounced effect on reducing acute toxicity and genotoxicity of docetaxel. In conclusion, DTX micelles were efficient and safe on breast carcinoma chemotherapy.

  13. [Chlorophyll synthesis in cotyledons after gamma ray irradiation of black pine seeds].

    PubMed

    Bogdanović, M; Jelić, G

    1992-01-01

    The radiosensitivity of the greening system of Pinus nigra Arn. cotyledons has been studied in this paper. An exponential relation exists between the effect and dose for chlorophyll synthesis in the dark. Chlorophyll synthesis in the light roughly parallels that of chlorophyll synthesis in the dark. The restoration of chlorophyll was observed both in the light and in the dark. A stimulative effect of low doses of gamma radiation on chlorophyll synthesis was noticed. The radiosensitivity of chlorophyll a and chlorophyll b synthesis varied with the experimental conditions, suggesting that chlorophyll b synthesis might occur independently of chlorophyll a synthesis.

  14. Distinct CPT-induced deaths in lung cancer cells caused by clathrin-mediated internalization of CP micelles

    NASA Astrophysics Data System (ADS)

    Liu, Yu-Sheng; Cheng, Ru-You; Lo, Yu-Lun; Hsu, Chin; Chen, Su-Hwei; Chiu, Chien-Chih; Wang, Li-Fang

    2016-02-01

    We previously synthesized a chondroitin sulfate-graft-poly(ε-caprolactone) copolymer (H-CP) with a high content of poly(ε-caprolactone) (18.7 mol%), which self-assembled in water into a rod-like micelle to encapsulate hydrophobic camptothecin (CPT) in the core (micelle/CPT) for tumor-targeted drug delivery. As a result of the recognition of the micelle by CD44, the micelle/CPT entered CRL-5802 cells efficiently and released CPT efficaciously, resulting in higher tumor suppression than commercial CPT-11. In this study, H1299 cells were found to have a higher CD44 expression than CRL-5802 cells. However, the lower CD44-expressing CRL-5802 cells had a higher percentage of cell death and higher cellular uptake of the micelle/CPT than the higher CD44-expressing H1299 cells. Examination of the internalization pathway of the micelle/CPT in the presence of different endocytic chemical inhibitors showed that the CRL-5802 cells involved clathrin-mediated endocytosis, which was not found in the H1299 cells. Analysis of the cell cycle of the two cell lines exposed to the micelle/CPT revealed that the CRL-5802 cells arrested mainly in the S phase and the H1299 cells arrested mainly in the G2-M phase. A consistent result was also found in the evaluation of γ-H2AX expression, which was about three-fold higher in the CRL-5802 cells than in the H1299 cells. A near-infrared dye, IR780, was encapsulated into the micelle to observe the in vivo biodistribution of the micelle/IR780 in tumor-bearing mice. The CRL-5802 tumor showed a higher fluorescence intensity than the H1299 tumor at any tracing time after 1 h. Thus we tentatively concluded that CRL-5802 cells utilized the clathrin-mediated internalization pathway and arrested in the S phase on exposure to the micelle/CPT; all are possible reasons for the better therapeutic outcome in CRL-5802 cells than in H1299 cells.We previously synthesized a chondroitin sulfate-graft-poly(ε-caprolactone) copolymer (H-CP) with a high content of

  15. Patchy micelles based on coassembly of block copolymer chains and block copolymer brushes on silica particles.

    PubMed

    Zhu, Shuzhe; Li, Zhan-Wei; Zhao, Hanying

    2015-04-14

    Patchy particles are a type of colloidal particles with one or more well-defined patches on the surfaces. The patchy particles with multiple compositions and functionalities have found wide applications from the fundamental studies to practical uses. In this research patchy micelles with thiol groups in the patches were prepared based on coassembly of free block copolymer chains and block copolymer brushes on silica particles. Thiol-terminated and cyanoisopropyl-capped polystyrene-block-poly(N-isopropylacrylamide) block copolymers (PS-b-PNIPAM-SH and PS-b-PNIPAM-CIP) were synthesized by reversible addition-fragmentation chain transfer polymerization and chemical modifications. Pyridyl disulfide-functionalized silica particles (SiO2-SS-Py) were prepared by four-step surface chemical reactions. PS-b-PNIPAM brushes on silica particles were prepared by thiol-disulfide exchange reaction between PS-b-PNIPAM-SH and SiO2-SS-Py. Surface micelles on silica particles were prepared by coassembly of PS-b-PNIPAM-CIP and block copolymer brushes. Upon cleavage of the surface micelles from silica particles, patchy micelles with thiol groups in the patches were obtained. Dynamic light scattering, transmission electron microscopy, and zeta-potential measurements demonstrate the preparation of patchy micelles. Gold nanoparticles can be anchored onto the patchy micelles through S-Au bonds, and asymmetric hybrid structures are formed. The thiol groups can be oxidized to disulfides, which results in directional assembly of the patchy micelles. The self-assembly behavior of the patchy micelles was studied experimentally and by computer simulation.

  16. Non-radiative relaxation of photoexcited chlorophylls: Theoretical and experimental study

    DOE PAGES

    Bricker, William P.; Shenai, Prathamesh M.; Ghosh, Avishek; ...

    2015-09-08

    Nonradiative relaxation of high-energy excited states to the lowest excited state in chlorophylls marks the first step in the process of photosynthesis. We perform ultrafast transient absorption spectroscopy measurements, that reveal this internal conversion dynamics to be slightly slower in chlorophyll B than in chlorophyll A. With modeling this process, non-adiabatic excited state molecular dynamics simulations uncovers a critical role played by the different side groups in the two molecules in governing the intramolecular redistribution of excited state wavefunction, leading, in turn, to different time-scales. Even given smaller electron-vibrational couplings compared to common organic conjugated chromophores, these molecules are ablemore » to efficiently dissipate about 1 eV of electronic energy into heat on the timescale of around 200 fs. This is achieved via selective participation of specific atomic groups and complex global migration of the wavefunction from the outer to inner ring, which may have important implications for biological light-harvesting function.« less

  17. Quantification of plant chlorophyll content using Google Glass.

    PubMed

    Cortazar, Bingen; Koydemir, Hatice Ceylan; Tseng, Derek; Feng, Steve; Ozcan, Aydogan

    2015-04-07

    Measuring plant chlorophyll concentration is a well-known and commonly used method in agriculture and environmental applications for monitoring plant health, which also correlates with many other plant parameters including, e.g., carotenoids, nitrogen, maximum green fluorescence, etc. Direct chlorophyll measurement using chemical extraction is destructive, complex and time-consuming, which has led to the development of mobile optical readers, providing non-destructive but at the same time relatively expensive tools for evaluation of plant chlorophyll levels. Here we demonstrate accurate measurement of chlorophyll concentration in plant leaves using Google Glass and a custom-developed software application together with a cost-effective leaf holder and multi-spectral illuminator device. Two images, taken using Google Glass, of a leaf placed in our portable illuminator device under red and white (i.e., broadband) light-emitting-diode (LED) illumination are uploaded to our servers for remote digital processing and chlorophyll quantification, with results returned to the user in less than 10 seconds. Intensity measurements extracted from the uploaded images are mapped against gold-standard colorimetric measurements made through a commercially available reader to generate calibration curves for plant leaf chlorophyll concentration. Using five plant species to calibrate our system, we demonstrate that our approach can accurately and rapidly estimate chlorophyll concentration of fifteen different plant species under both indoor and outdoor lighting conditions. This Google Glass based chlorophyll measurement platform can display the results in spatiotemporal and tabular forms and would be highly useful for monitoring of plant health in environmental and agriculture related applications, including e.g., urban plant monitoring, indirect measurements of the effects of climate change, and as an early indicator for water, soil, and air quality degradation.

  18. Noncovalent fabrication and tunable fusion of block copolymer-giant polyoxometalate hybrid micelles.

    PubMed

    Zhang, Liying; Li, Haolong; Wu, Lixin

    2014-09-21

    The block copolymers (BCs), as structure-directing agents, co-assembling with nanoscale inorganic additives is an important route to fabricate nanostructured hybrid materials. In this work, we present a facile approach to fabricate hybrid micelles composed of BCs and polyoxometalates (POMs), in which the POM clusters are premodified with the groups that can specifically interact with a certain BC block. A representative POM (NH4)42[Mo(132)O(372)(CH(3)COO)(30)(H2O)72] (Mo(132)) is chosen as the example and encapsulated with cationic molecules containing carboxyphenyl groups through electrostatic interactions, and then the resulting hybrid complex can further co-assemble with poly(styrene-block-4-vinylpyridine) (PS-b-P4VP) through hydrogen bonding with the pyridine groups, which leads to the formation of hybrid micelles and the localization of Mo(132) in the micelle cores. The micelles exhibit a high stability despite time and dilution. Furthermore, the fusion of the micelles can be readily adjusted by varying the length of PS blocks, which is promising to be used in constructing polymer-POM hybrid materials with discrete or continuous hybrid domains. This work is based on the electrostatic premodification of POMs and thus its concept is generally suitable for the whole anionic POM system, which may create a large class of BC-POM nanocomposites with tunable structures.

  19. Investigation of a new thermosensitive block copolymer micelle: hydrolysis, disruption, and release.

    PubMed

    Pelletier, Maxime; Babin, Jérôme; Tremblay, Luc; Zhao, Yue

    2008-11-04

    Thermosensitive polymer micelles are generally obtained with block copolymers in which one block exhibits a lower critical solution temperature in aqueous solution. We investigate a different design that is based on the use of one block bearing a thermally labile side group, whose hydrolysis upon heating shifts the hydrophilic-hydrophobic balance toward the destabilization of block copolymer micelles. Atom transfer radical polymerization was utilized to synthesize a series of diblock copolymers composed of hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(2-tetrahydropyranyl methacrylate) (PTHPMA). We show that micelles of PEO-b-PTHPMA in aqueous solution can be destabilized as a result of the thermosensitive hydrolytic cleavage of tetrahydropyranyl (THP) groups that transforms PTHPMA into hydrophilic poly(methacrylic acid). The three related processes occurring in aqueous solution, namely, hydrolytic cleavage of THP, destabilization of micelles, and release of loaded Nile Red (NR), were investigated simultaneously using 1H NMR, dynamic light scattering, and fluorescence spectroscopy, respectively. At 80 degrees C, the results suggest that the three events proceed with a similar kinetics. Although slower than at elevated temperatures, the disruption of PEO-b-PTHPMA micelles can take place at the body temperature (approximately 37 degrees C), and the release kinetics of NR can be adjusted by changing the relative lengths of the two blocks or the pH of the solution.

  20. Simulating Carbon Flux Dynamics with the Product of PAR Absorbed by Chlorophyll (fAPARchl)

    NASA Astrophysics Data System (ADS)

    Yao, T.; Zhang, Q.

    2016-12-01

    A common way to estimate the gross primary production (GPP) is to use the fraction of photosynthetically radiation (PAR) absorbed by vegetation (FPAR). However, only the PAR absorbed by chlorophyll of the canopy, not the PAR absorbed by the foliage or by the entire canopy, is used for photosynthesis. MODIS fAPARchl product, which refers to the fraction of PAR absorbed by chlorophyll of the canopy, is derived from Moderate Resolution Imaging Spectroradiometer (MODIS) surface reflectance by using an advanced leaf-canopy-soil-water-snow coupled radiative transfer model PROSAIL4. PROSAIL4 can retrieve surface water cover fraction, snow cover fraction, and physiologically active canopy chemistry components (chlorophyll concentration and water content), fraction of photosynthetically active radiation (PAR) absorbed by a canopy (fAPARcanopy), fraction of PAR absorbed by photosynthetic vegetation (PV) component (mainly chlorophyll) throughout the canopy (fAPARPV, i.e., fAPARchl) and fraction of PAR absorbed by non-photosynthetic vegetation (NPV) component of the canopy (fAPARNPV). We have successfully retrieved these vegetation parameters for selected areas with PROSAIL4 and the MODIS images, or simulated spectrally MODIS-like images. In this study, the product of PAR absorbed by chlorophyll (fAPARchl) has been used to simulate carbon flux over different kinds of vegetation types. The results show that MODIS fAPARchl product has the ability to better characterize phenology than current phenology model in the Community Land Model and it also will likely be able to increase the accuracy of carbon fluxes simulations.