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Sample records for linear polymers dendrimers

  1. Amplified release through the stimulus triggered degradation of self-immolative oligomers, dendrimers, and linear polymers.

    Wong, Andrew D; DeWit, Matthew A; Gillies, Elizabeth R

    2012-08-01

    In recent years, numerous delivery systems based on polymers, dendrimers, and nano-scale assemblies have been developed to improve the properties of drug molecules. In general, for the drug molecules to be active, they must be released from these delivery systems, ideally in a selective manner at the therapeutic target. As the changes in physiological conditions are relatively subtle from one tissue to another and the concentrations of specific enzymes are often quite low, a release strategy involving the amplification of a biological signal is particularly attractive. This article describes the development of oligomers, dendrimers, and linear polymers based on self-immolative spacers. This new class of molecules is designed to undergo a cascade of intramolecular reactions in response to the cleavage of a trigger moiety, resulting in molecular fragmentation and the release of multiple reporter or drug molecules. Progress in the development of these materials as drug delivery vehicles and sensors will be highlighted. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. INVERSION SYMMETRY, ARCHITECTURE AND DISPERSITY, AND THEIR EFFECTS ON THERMODYNAMICS IN BULK AND CONFINED REGIONS: FROM RANDOMLY BRANCHED POLYMERS TO LINEAR CHAINS, STARS AND DENDRIMERS

    P.D.Gujrati

    2002-01-01

    Full Text Available Theoretical evidence is presented in this review that architectural aspects can play an important role, not only in the bulk but also in confined geometries by using our recursive lattice theory, which is equally applicable to fixed architectures (regularly branched polymers, stars, dendrimers, brushes, linear chains, etc. and variable architectures, i.e. randomly branched structures. Linear chains possess an inversion symmetry (IS of a magnetic system (see text, whose presence or absence determines the bulk phase diagram. Fixed architectures possess the IS and yield a standard bulk phase diagram in which there exists a theta point at which two critical lines C and C' meet and the second virial coefficient A2 vanishes. The critical line C appears only for infinitely large polymers, and an order parameter is identified for this criticality. The critical line C' exists for polymers of all sizes and represents phase separation criticality. Variable architectures, which do not possess the IS, give rise to a topologically different phase diagram with no theta point in general. In confined regions next to surfaces, it is not the IS but branching and monodispersity, which becomes important in the surface regions. We show that branching plays no important role for polydisperse systems, but become important for monodisperse systems. Stars and linear chains behave differently near a surface.

  3. Conformational and Structural Properties of High Functionality Dendrimer-like Star Polymers Synthesized from Living Polymerization Techniques; TOPICAL

    Pople, John A.

    2001-01-01

    The design, synthesis and solution properties of dendritic-linear hybrid macromolecules is described. The synthetic strategy employs living ring-opening polymerization in combination with selective and quantitative organic transformations for the preparation of new molecular architectures similar to classical star polymers and dendrimers. The polymers were constructed from high molecular weight poly(e-caprolactone) initiated from the surface hydroxyl groups of dendrimers derived from bis(hydroxymethyl) propionic acid (bis-MPA) in the presence of stannous 2-ethyl hexanoate (Sn(Oct)2). In this way, star and hyperstar poly(e-caprolactones) were elaborated depending on the generation of dendrimer employed. The ROP from these hydroxy groups was found to be a facile process leading to controlled molecular weight, low dispersity products (Mw/Mn) and lt; 1.15. In addition to the use of dendrimers as building blocks to star polymers, functional dendrons derived from bis-MPA were attached to chain ends of the star polymers, yielding structures that closely resemble that of the most advanced dendrimers. Measurements of the solution properties (hydrodynamic volume vs. molecular weight) on the dendritic-linear hybrids show a deviation from linearity, with a lower than expected hydrodynamic volume, analogous to the solution properties of dendrimers of high generation number. The onset of the deviation begins with the polymers initiated from the second generation dendrimer of bis-MPA and becomes more exaggerated with the higher generations. It was found that polymerization amplifies the nonlinear solution behavior of dendrimers. Small angle neutron scattering (SANS) measurements revealed that the radius of gyration scaled with arm functionality (f) as f 2/3, in accordance with the Daoud-Cotton model for many arm star polymer

  4. Second-Order Nonlinear Optical Dendrimers and Dendronized Hyperbranched Polymers.

    Tang, Runli; Li, Zhen

    2017-01-01

    Second-order nonlinear optical (NLO) dendrimers with a special topological structure were regarded as the most promising candidates for practical applications in the field of optoelectronic materials. Dendronized hyperbranched polymers (DHPs), a new type of polymers with dendritic structures, proposed and named by us recently, demonstrated interesting properties and some advantages over other polymers. Some of our work concerning these two types of polymers are presented herein, especially focusing on the design idea and structure-property relationship. To enhance their comprehensive NLO performance, dendrimers were designed and synthesized by adjusting their isolation mode, increasing the number of the dendritic generation, modifying their topological structure, introducing isolation chromophores, and utilizing the Ar-Ar F self-assembly effect. To make full use of the advantages of both the structural integrity of dendrimers and the convenient one-pot synthesis of hyperbranched polymers, DHPs were explored by utilizing low-generation dendrons as big monomers to construct hyperbranched polymers. These selected works could provide valuable information to deeply understand the relationship between the structure and properties of functional polymers with dendritic structures, but not only limited to the NLO ones, and might contribute much to the further development of functional polymers with rational design. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. The effect of dendrimer charge inversion in complexes with linear polyelectrolytes

    Lyulin, S.V.; Lyulin, A.V.; Darinskii, A.A.; Emri, I.

    2005-01-01

    The structure of complexes formed by charged dendrimers and oppositely charged linear chains with a charge of at least the same as that of dendrimers was studied by computer simulation using the Brownian dynamics method. The freely jointed, free-draining model of the dendrimer and the linear chain

  6. From dendrimers to fractal polymers and beyond

    Charles N. Moorefield

    2013-01-01

    Full Text Available The advent of dendritic chemistry has facilitated materials research by allowing precise control of functional component placement in macromolecular architecture. The iterative synthetic protocols used for dendrimer construction were developed based on the desire to craft highly branched, high molecular weight, molecules with exact mass and tailored functionality. Arborols, inspired by trees and precursors of the utilitarian macromolecules known as dendrimers today, were the first examples to employ predesigned, 1 → 3 C-branched, building blocks; physical characteristics of the arborols, including their globular shapes, excellent solubilities, and demonstrated aggregation, combined to reveal the inherent supramolecular potential (e.g., the unimolecular micelle of these unique species. The architecture that is a characteristic of dendritic materials also exhibits fractal qualities based on self-similar, repetitive, branched frameworks. Thus, the fractal design and supramolecular aspects of these constructs are suggestive of a larger field of fractal materials that incorporates repeating geometries and are derived by complementary building block recognition and assembly. Use of terpyridine-M2+-terpyridine (where, M = Ru, Zn, Fe, etc connectivity in concert with mathematical algorithms, such as forms the basis for the Seirpinski gasket, has allowed the beginning exploration of fractal materials construction. The propensity of the fractal molecules to self-assemble into higher order architectures adds another dimension to this new arena of materials and composite construction.

  7. Dendrimers: a class of polymers in the nanotechnology for the delivery of active pharmaceuticals.

    Samad, Abdus; Alam, Md Intakhab; Saxena, Kinshuk

    2009-01-01

    Dendrimers represent a class of novel polymers having unique molecular architectures characterized by their well-defined structure, with a high degree of molecular uniformity, low polydispersity and properties that make them attractive materials for the development of nanomedicines. The dendrimer drug delivery can be achieved by coupling a drug through one of two approaches. Hydrophobic drugs can be complexed within the hydrophobic dendrimer interior to make them water-soluble or drugs can be covalently coupled onto the surface of the dendrimer. In addition, dendrimers have been shown to be capable of bypassing efflux transporters. A new generation of dendrimer-based delivery systems will enable the efficient transport of drugs across cellular barriers. This review deals principally with the synthesis, characterization and recent applications of dendrimers. In future it will only ever be possible to designate a dendrimer as safe means of drug delivery related to a specific application. However, so far limited clinical experience using dendrimers makes it impossible to designate any particular system which is safe and non toxic. Although there is widespread concern as to the safety of nanosized particles, preclinical and clinical experience gained during the development of polymeric excipients, biomedical polymers and polymer therapeutics showed that judicious development of dendrimer chemistry for each specific application will ensure development of safe and important materials for biomedical and pharmaceutical use.

  8. Modeling the formation of ordered nano-assemblies comprised by dendrimers and linear polyelectrolytes: The role of Coulombic interactions

    Eleftheriou, E.; Karatasos, K.

    2012-10-01

    Models of mixtures of peripherally charged dendrimers with oppositely charged linear polyelectrolytes in the presence of explicit solvent are studied by means of molecular dynamics simulations. Under the influence of varying strength of electrostatic interactions, these systems appear to form dynamically arrested film-like interconnected structures in the polymer-rich phase. Acting like a pseudo-thermodynamic inverse temperature, the increase of the strength of the Coulombic interactions drive the polymeric constituents of the mixture to a gradual dynamic freezing-in. The timescale of the average density fluctuations of the formed complexes initially increases in the weak electrostatic regime reaching a finite limit as the strength of electrostatic interactions grow. Although the models are overall electrically neutral, during this process the dendrimer/linear complexes develop a polar character with an excess charge mainly close to the periphery of the dendrimers. The morphological characteristics of the resulted pattern are found to depend on the size of the polymer chains on account of the distinct conformational features assumed by the complexed linear polyelectrolytes of different length. In addition, the length of the polymer chain appears to affect the dynamics of the counterions, thus affecting the ionic transport properties of the system. It appears, therefore, that the strength of electrostatic interactions together with the length of the linear polyelectrolytes are parameters to which these systems are particularly responsive, offering thus the possibility for a better control of the resulted structure and the electric properties of these soft-colloidal systems.

  9. Dynamics of complexation of a charged dendrimer by linear polyelectrolyte: Computer modelling

    Lyulin, S.V.; Darinskii, A.A.; Lyulin, A.V.

    2007-01-01

    Brownian-dynamics simulations have been performed for complexes formed by a charged dendrimer and a long oppositely charged linear polyelectrolyte when overcharging phenomenon is always observed. After a complex formation the orientational mobility of the individual dendrimer bonds, the fluctuations

  10. Charge inversion of dendrimers in complexes with linear polyelectrolytes in the solutions with low pH

    Larin, S.V.; Lyulin, S.V.; Lyulin, A.V.; Darinskii, A.A.

    2009-01-01

    Complexes of fully ionized third-generation dendrimers with oppositely charged linear polyelectrolyte chains are studied by the Brownian dynamics method. A freely jointed model of a dendrimer and a linear chain is used. Electrostatic interactions are considered within the Debye-Hückel approximation

  11. Supramolecular coordination polymer formed from artificial light-harvesting dendrimer.

    Lee, Hosoowi; Jeong, Young-Hwan; Kim, Joo-Ho; Kim, Inhye; Lee, Eunji; Jang, Woo-Dong

    2015-09-30

    We report the formation of supramolecular coordination polymers formed from multiporphyrin dendrimers (PZnPM; M = FB or Cu), composed of the focal freebase porphyrin (PFB) or cupper porphyrin (PCu) with eight zinc porphyrin (PZn) wings, and multipyridyl porphyrins (PyPM; M = FB or Cu), PFB or PCu with eight pyridyl groups, through multiple axial coordination interactions of pyridyl groups to PZns. UV-vis absorption spectra were recorded upon titration of PyPFB to PZnPFB. Differential spectra, obtained by subtracting the absorption of PZnPFB without guest addition as well as the absorption of PyPFB, exhibited clear isosbestic points with saturation binding at 1 equiv addition of PyPFB to PZnPFB. Job's plot analysis also indicated 1:1 stoichiometry for the saturation binding. The apparent association constant between PZnPFB and PyPFB (2.91 × 10(6) M(-1)), estimated by isothermal titration calorimetry, was high enough for fibrous assemblies to form at micromolar concentrations. The formation of a fibrous assembly from PZnPFB and PyPFB was visualized by atomic force microscopy and transmission electron microscopy (TEM). When a 1:1 mixture solution of PZnPFB and PyPFB (20 μM) in toluene was cast onto mica, fibrous assemblies with regular height (ca. 2 nm) were observed. TEM images obtained from 1:1 mixture solution of PZnPFB and PyPFB (0.1 wt %) in toluene clearly showed the formation of nanofibers with a regular diameter of ca. 6 nm. Fluorescence emission measurement of PZnPM indicated efficient intramolecular energy transfer from PZn to the focal PFB or PCu. By the formation of supramolecular coordination polymers, the intramolecular energy transfer changed to intermolecular energy transfer from PZnPM to PyPM. When the nonfluorescent PyPCu was titrated to fluorescent PZnPFB, fluorescence emission from the focal PFB was gradually decreased. By the titration of fluorescent PyPFB to nonfluorescent PZnPCu, fluorescence emission from PFB in PyPFB was gradually increased

  12. Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures

    2015-02-09

    Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures. Research Area:7.4 The views, opinions and/or findings contained in this report...journals: Final Report: Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular

  13. Constitutional Isomers of Dendrimer-like Star Polymers: Design, Synthesis and Conformational and Structural Properties; TOPICAL

    Pople, John A.

    2001-01-01

    The design, synthesis and solution properties of six constitutional isomers of dendrimer-like star polymers is described. Each of the polymers have comparable molecular weights ((approx) 80,000 g/mol), narrow polydispersities ( and lt; 1.19) and an identical number of branching junctures (45) and surface hydroxyl functionalities (48). The only difference in the six isomers is the placement of the branching junctures. The polymers are constructed from high molecular weight poly(e-caprolactone) with branching junctures derived from 2,2'-bis(hydroxylmethyl) propionic acid (bis-MPA) emanating from a central core. The use of various generations of dendritic initiators and dendrons coupled with the ring opening polymerization of e-caprolactones allowed a modular approach to the dendrimer-like star polymer isomers. The most pronounced effects on the physical properties/morphology and hydrodynamic volume was for those polymers in which the branching was distributed throughout the sample in a dendrimer-like fashion. The versatility of this approach has provided the possibility of understanding the relationship between architecture and physical properties. Dynamic light scattering and small angle X-ray scattering techniques were used to determine the hydrodynamic radius Rh and radius of gyration Rg respectively. The relationship between Rg and molecular weight was indicative of a compact star-like structure, and did not show advanced bias towards either the dense core or dense shell models. The radial density distribution of the isomers was therefore modeled according to a many arm star polymer, and good agreement was found with experimental measures of Rh/Rg

  14. Mechanisms of Light Energy Harvesting in Dendrimers and Hyperbranched Polymers

    David L. Andrews

    2011-12-01

    Full Text Available Since their earliest synthesis, much interest has arisen in the use of dendritic and structurally allied forms of polymer for light energy harvesting, especially as organic adjuncts for solar energy devices. With the facility to accommodate a proliferation of antenna chromophores, such materials can capture and channel light energy with a high degree of efficiency, each polymer unit potentially delivering the energy of one photon—or more, when optical nonlinearity is involved. To ensure the highest efficiency of operation, it is essential to understand the processes responsible for photon capture and channelling of the resulting electronic excitation. Highlighting the latest theoretical advances, this paper reviews the principal mechanisms, which prove to involve a complex interplay of structural, spectroscopic and electrodynamic properties. Designing materials with the capacity to capture and control light energy facilitates applications that now extend from solar energy to medical photonics.

  15. Dendrimers for Drug Delivery

    Abhay Singh Chauhan

    2018-04-01

    Full Text Available Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine (PAMAM dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i formulation and (ii nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

  16. Designing Dendrimer and Miktoarm Polymer Based Multi-Tasking Nanocarriers for Efficient Medical Therapy.

    Sharma, Anjali; Kakkar, Ashok

    2015-09-17

    To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in meeting daunting challenges associated with synthetically articulating multiple functions into a single scaffold. Branched and hyper-branched macromolecular architectures have offered opportunities in enabling carriers with capabilities including location, delivery, imaging etc. Development of simple and versatile synthetic methodologies for these nanomaterials has been the key in diversifying macromolecule based medical therapy and treatment. This review highlights the advancement from conventional "only one function" to multifunctional nanomedicine. It is achieved by synthetic elaboration of multivalent platforms in miktoarm polymers and dendrimers by physical encapsulation, covalent linking and combinations thereof.

  17. Designing Dendrimer and Miktoarm Polymer Based Multi-Tasking Nanocarriers for Efficient Medical Therapy

    Anjali Sharma

    2015-09-01

    Full Text Available To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in meeting daunting challenges associated with synthetically articulating multiple functions into a single scaffold. Branched and hyper-branched macromolecular architectures have offered opportunities in enabling carriers with capabilities including location, delivery, imaging etc. Development of simple and versatile synthetic methodologies for these nanomaterials has been the key in diversifying macromolecule based medical therapy and treatment. This review highlights the advancement from conventional “only one function” to multifunctional nanomedicine. It is achieved by synthetic elaboration of multivalent platforms in miktoarm polymers and dendrimers by physical encapsulation, covalent linking and combinations thereof.

  18. Influence of trap location on the efficiency of trapping in dendrimers and regular hyperbranched polymers.

    Lin, Yuan; Zhang, Zhongzhi

    2013-03-07

    The trapping process in polymer systems constitutes a fundamental mechanism for various other dynamical processes taking place in these systems. In this paper, we study the trapping problem in two representative polymer networks, Cayley trees and Vicsek fractals, which separately model dendrimers and regular hyperbranched polymers. Our goal is to explore the impact of trap location on the efficiency of trapping in these two important polymer systems, with the efficiency being measured by the average trapping time (ATT) that is the average of source-to-trap mean first-passage time over every staring point in the whole networks. For Cayley trees, we derive an exact analytic formula for the ATT to an arbitrary trap node, based on which we further obtain the explicit expression of ATT for the case that the trap is uniformly distributed. For Vicsek fractals, we provide the closed-form solution for ATT to a peripheral node farthest from the central node, as well as the numerical solutions for the case when the trap is placed on other nodes. Moreover, we derive the exact formula for the ATT corresponding to the trapping problem when the trap has a uniform distribution over all nodes. Our results show that the influence of trap location on the trapping efficiency is completely different for the two polymer networks. In Cayley trees, the leading scaling of ATT increases with the shortest distance between the trap and the central node, implying that trap's position has an essential impact on the trapping efficiency; while in Vicsek fractals, the effect of location of the trap is negligible, since the dominant behavior of ATT is identical, respective of the location where the trap is placed. We also present that for all cases of trapping problems being studied, the trapping process is more efficient in Cayley trees than in Vicsek fractals. We demonstrate that all differences related to trapping in the two polymer systems are rooted in their underlying topological structures.

  19. On the dimerization of linear polymers

    Aragao Carvalho, C. de.

    1988-08-01

    We use the continuum limit of the Su-Schrieffer-Heeger model for linear polymers to construct its effective potential (Gibbs free energy) both at zero and finite temperature. We study both trans and cis-polymers. Our results show that, depending on a renormalization condition to be extracted from experiment, there are several possibilities for the minima of the dimerized ground state of cis-polymers. All calculations are done in the one-loop approximation. (author). 16 refs, 3 figs

  20. Linear polarizers based on oriented polymer blends

    Jagt, H.J.B.; Dirix, Y.J.L.; Hikmet, R.A.M.; Bastiaansen, C.W.M.

    1998-01-01

    Linear sheet polarizers based on the anisotropic scattering of light by drawn polymer blends are introduced here. The proper selection of materials and processing conditions for the production of large-area, flexible films of phase-segregated polymer blends suitable for polarization applications are

  1. Responsive gelation of hydrophobized linear polymer

    Madsen, Claus Greve; Toeth, Joachim; Jørgensen, Lene

    In this study we present the rheological properties of a physically linked polymer network, composed of linear hydrophilic chains, modified with hydrophobic moieties in each end. Solutions of the polymer in ethanol-water mixtures showed Newtonian behaviour up to about 99 % ethanol, with the highest...

  2. Optical absorption in dendrimers

    Supritz, C.; Engelmann, A.; Reineker, P.

    2004-01-01

    Dendrimers are highly branched molecules, which are expected to be useful, for example, as efficient artificial light harvesting systems in nano-technological applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers, where this distance increases from the system periphery to the center. We investigate the linear absorption spectra of these dendrimer types using the Frenkel exciton concept. The electron-phonon interaction is taken into account by introducing a heat bath that interacts with the exciton in a stochastic manner

  3. Research progress on synthesis and characteristic about dendrimers

    Tang, Zitao

    2017-12-01

    Dendrimers are hyper-branched polymers which have perfectly defined structures. Different from the common polymers, dendrimers are synthesized by a step-by-step iterative style, which starts from a central core and forms branching parts outward. The dendrimers also have different physical and chemical characteristics from common polymers. In this paper, contributions to dendrimer synthesis from different researchers with different scientific background, synthesis of different dendrimers, and applications of them will be reviewed.

  4. Energy transport in dendrimers

    Supritz, C.; Engelmann, A.; Reineker, P.

    2006-01-01

    Dendrimers are highly branched polymers which are expected to be useful, for example, as efficient artificial light harvesting systems in nano-technological applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers where this distance increases from the system periphery to the center. An open question is still whether energy transport (via Frenkel excitons) occurs in a coherent or incoherent manner. We model the hyperbranched dendrimer molecule as an arrangement of two-level systems and apply the Frenkel exciton concept. The two-level systems are interacting with each other via transfer integrals modeling the special spatial structure of dendrimers. To take into account the electron-phonon interaction we introduce a heat bath that interacts with the exciton in a stochastic manner. In this way we describe the coupled coherent and incoherent Frenkel exciton transport inside a dendrimer. In order to mimic the influence of an energy capturing reaction center (like in photosynthesis) on exciton transport, we attach a sink to the dendrimer core

  5. Energy transport in dendrimers

    Supritz, C. [Abteilung Theoretische Physik, Universitaet Ulm, Albert-Einstein-Allee 11, 89069 Ulm (Germany)]. E-mail: christoph.supritz@uni-ulm.de; Engelmann, A. [Abteilung Theoretische Physik, Universitaet Ulm, Albert-Einstein-Allee 11, 89069 Ulm (Germany); Reineker, P. [Abteilung Theoretische Physik, Universitaet Ulm, Albert-Einstein-Allee 11, 89069 Ulm (Germany)

    2006-07-15

    Dendrimers are highly branched polymers which are expected to be useful, for example, as efficient artificial light harvesting systems in nano-technological applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers where this distance increases from the system periphery to the center. An open question is still whether energy transport (via Frenkel excitons) occurs in a coherent or incoherent manner. We model the hyperbranched dendrimer molecule as an arrangement of two-level systems and apply the Frenkel exciton concept. The two-level systems are interacting with each other via transfer integrals modeling the special spatial structure of dendrimers. To take into account the electron-phonon interaction we introduce a heat bath that interacts with the exciton in a stochastic manner. In this way we describe the coupled coherent and incoherent Frenkel exciton transport inside a dendrimer. In order to mimic the influence of an energy capturing reaction center (like in photosynthesis) on exciton transport, we attach a sink to the dendrimer core.

  6. Synthesis of Dendrimer Containing Carbazole Unit as a Core Chromophore

    Han, Seung Choul; Lee, Jae Wook; Jin, Sungho

    2012-01-01

    Dendrimers, which are prepared by repetition of a given set of reactions using either divergent or convergent strategies, are highly branched and regular macromolecules with well-defined structures and have served as functional objects in nanotechnology and nano-materials science. Following conventional organic small molecules and polymers, dendrimers are now regarded as the third class of materials for use in organic light-emitting diodes (OLEDs) and have attracted much attention due to their distinguished properties. Dendrimers contain three distinct structural parts that are the core, end-groups, and branched units connecting core and periphery. For light-emitting dendrimers, the core is usually selected as the luminescent chromophore, and the dendrons and their periphery are charge transporting units and can also tune the solubility. In contrast to linear polymers, dendrimers are sphere-like with dimensions of the order of nanometers depending on the generation number. By careful structural design, dendrimers combine the potential advantages of both small molecules and polymers. Therefore, the innovative strategy different from conventional convergent and divergent routes has been required to simplify dendrimer synthesis. Recent solid chemistry is the click chemistry which is the copper-catalyzed 1,3-dipolar cycloaddition reaction between alkyne and azide developed by Sharpless and Tornφe. This reaction has many advantages: very high yields, mild and simple reaction conditions, oxygen and water tolerance, and easy isolation of product. This reaction is clearly a breakthrough in the synthesis of dendrimers and dendritic and polymer materials. We have developed the fusion and stitching methods for the synthesis of various dendrimers using click chemistry between an alkyne and an azide. Overall, this method was found to be a straightforward strategy for the synthesis of triazole-based dendrimers. Taking advantage of this fact, herein we report a feasible route

  7. Computer simulations of dendrimer-polyelectrolyte complexes.

    Pandav, Gunja; Ganesan, Venkat

    2014-08-28

    We carry out a systematic analysis of static properties of the clusters formed by complexation between charged dendrimers and linear polyelectrolyte (LPE) chains in a dilute solution under good solvent conditions. We use single chain in mean-field simulations and analyze the structure of the clusters through radial distribution functions of the dendrimer, cluster size, and charge distributions. The effects of LPE length, charge ratio between LPE and dendrimer, the influence of salt concentration, and the dendrimer generation number are examined. Systems with short LPEs showed a reduced propensity for aggregation with dendrimers, leading to formation of smaller clusters. In contrast, larger dendrimers and longer LPEs lead to larger clusters with significant bridging. Increasing salt concentration was seen to reduce aggregation between dendrimers as a result of screening of electrostatic interactions. Generally, maximum complexation was observed in systems with an equal amount of net dendrimer and LPE charges, whereas either excess LPE or dendrimer concentrations resulted in reduced clustering between dendrimers.

  8. Dendrimers: new hope for cancer

    Ghosh, S.S.

    2010-01-01

    A class of nanomaterials called dendrimers have been found particularly useful in cancer treatment. Dendrimers have often been referred to as the Polymers of the 21st century. The name Dendrimer comes from the Greek dendron, meaning tree. They are nearly perfect monodisperse (a consistent size and form) macromolecules with a regular and highly branched three-dimensional architecture having an average size of around 5x10 -9 m, which can be artificially synthesized

  9. [Dendrimers in biomedical sciences and nanotechnology].

    Sekowski, Szymon; Miłowska, Katarzyna; Gabryelak, Teresa

    2008-12-30

    Dendrimers are relatively new, hyper-branched polymers that have many interesting abilities. Dendrimers could be used, for example, as drug or gene carriers, contrast agents, sensors for different metal ions, and in developing innovation technology. These spherical polymers are also characterized by pharmacological activity against different bacterial and viral diseases. Dendrimers are currently being intensively investigated as anti-prion and anti-amyloid fibril agents. They can be used to build specific dendrimer films to be applied in modern technology. This review describes different uses of dendrimer particles in biomedical sciences and nanotechnology and shows advantages of their application.

  10. Structure-skin permeability relationship of dendrimers.

    Venuganti, Venkata Vamsi; Sahdev, Preety; Hildreth, Michael; Guan, Xiangming; Perumal, Omathanu

    2011-09-01

    To investigate skin penetration of poly (amidoamine) (PAMAM) dendrimers as a function of surface charge and molecular weight in presence and absence of iontophoresis. Dendrimers were labeled with fluoroisothiocynate (FITC); skin penetration of dendrimers was studied using excised porcine skin in-vitro. Skin penetration of FITC-labeled dendrimers was quantified using confocal laser scanning microscope (CLSM). G2-G6 NH(2), G3.5-COOH and G4-OH dendrimers were used. Cationic dendrimers showed higher skin penetration than neutral and anionic dendrimers. Skin penetration of cationic dendrimer increased linearly with increase in treatment time. Iontophoresis enhanced skin penetration of cationic and neutral dendrimers. Increase in current strength and current duration increased skin transport of dendrimers. Passive and iontophoretic skin penetration of cationic dendrimers was inversely related to their molecular weight. Dendrimer penetrated the skin through intercellular lipids and hair follicles. With iontophoresis, dendrimer was also found in localized skin regions. The study demonstrates that the physicochemical properties of dendrimers influence their skin transport. Findings can be used to design dendrimer-based nanocarriers for drug delivery to skin.

  11. Cyclopropanation reactions catalysed by dendrimers possessing one metalloporphyrin active site at the core: linear and sigmoidal kinetic behaviour for different dendrimer generations

    Vinš, P.; de Cózar, A.; Rivilla, I.; Nováková, Kateřina; Zangi, R.; Cvačka, Josef; Arrastia, I.; Arrieta, A.; Drašar, P.; Miranda, J. I.; Cossío, F. P.

    2016-01-01

    Roč. 72, č. 8 (2016), s. 1120-1131 ISSN 0040-4020 R&D Projects: GA ČR(CZ) GAP304/10/1951 Institutional support: RVO:61388963 Keywords : cyclopropanation * catalysis * kinetic analysis * dendrimers * molecular dynamics * DOSY Subject RIV: CC - Organic Chemistry Impact factor: 2.651, year: 2016

  12. Optical absorption in compact and extended dendrimers

    Supritz, C.; Engelmann, A.; Reineker, P.

    2005-01-01

    Dendrimers are highly branched molecules, which are expected to be useful, for example, as efficient artificial light harvesting systems, in nano-technological or in medical applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers, where this distance increases from the system periphery to the center. We investigate the linear optical absorption spectra of these dendrimer types using the Frenkel exciton concept. The electron-phonon interaction is taken into account by introducing a heat bath that interacts with the exciton in a stochastic manner. We discuss compact dendrimers with equal excitation energies at all molecules, dendrimers with a functionalized core as well as with a whole branch functionalized. Furthermore the line shape of a compact dendrimer is discussed when neighboring molecules at the periphery interact and when all molecules have randomly distributed excitation energies due to disorder. Finally, we discuss two models for extended dendrimers

  13. The Debye light scattering equation’s scaling relation reveals the purity of synthetic dendrimers

    Tseng, Hui-Yu; Chen, Hsiao-Ping [National Chung Cheng University, Department of Chemistry and Biochemistry (China); Tang, Yi-Hsuan [Kaohsiung Medical University, Department of Medicinal and Applied Chemistry (China); Chen, Hui-Ting [Kaohsiung Medical University, Department of Fragrance and Cosmetic Science (China); Kao, Chai-Lin, E-mail: clkao@kmu.edu.tw [Kaohsiung Medical University, Department of Medicinal and Applied Chemistry (China); Wang, Shau-Chun, E-mail: chescw@ccu.edu.tw [National Chung Cheng University, Department of Chemistry and Biochemistry (China)

    2016-03-15

    Spherical dendrimer structures cannot be structurally modeled using conventional polymer models of random coil or rod-like configurations during the calibration of the static light scattering (LS) detectors used to determine the molecular weight (M.W.) of a dendrimer or directly assess the purity of a synthetic compound. In this paper, we used the Debye equation-based scaling relation, which predicts that the static LS intensity per unit concentration is linearly proportional to the M.W. of a synthetic dendrimer in a dilute solution, as a tool to examine the purity of high-generational compounds and to monitor the progress of dendrimer preparations. Without using expensive equipment, such as nuclear magnetic resonance or mass spectrometry, this method only required an affordable flow injection set-up with an LS detector. Solutions of the purified dendrimers, including the poly(amidoamine) (PAMAM) dendrimer and its fourth to seventh generation pyridine derivatives with size range of 5–9 nm, were used to establish the scaling relation with high linearity. The use of artificially impure mixtures of six or seven generations revealed significant deviations from linearity. The raw synthesized products of the pyridine-modified PAMAM dendrimer, which included incompletely reacted dendrimers, were also examined to gauge the reaction progress. As a reaction toward a particular generational derivative of the PAMAM dendrimers proceeded over time, deviations from the linear scaling relation decreased. The difference between the polydispersity index of the incompletely converted products and that of the pure compounds was only about 0.01. The use of the Debye equation-based scaling relation, therefore, is much more useful than the polydispersity index for monitoring conversion processes toward an indicated functionality number in a given preparation.Graphical abstract.

  14. The Debye light scattering equation’s scaling relation reveals the purity of synthetic dendrimers

    Tseng, Hui-Yu; Chen, Hsiao-Ping; Tang, Yi-Hsuan; Chen, Hui-Ting; Kao, Chai-Lin; Wang, Shau-Chun

    2016-01-01

    Spherical dendrimer structures cannot be structurally modeled using conventional polymer models of random coil or rod-like configurations during the calibration of the static light scattering (LS) detectors used to determine the molecular weight (M.W.) of a dendrimer or directly assess the purity of a synthetic compound. In this paper, we used the Debye equation-based scaling relation, which predicts that the static LS intensity per unit concentration is linearly proportional to the M.W. of a synthetic dendrimer in a dilute solution, as a tool to examine the purity of high-generational compounds and to monitor the progress of dendrimer preparations. Without using expensive equipment, such as nuclear magnetic resonance or mass spectrometry, this method only required an affordable flow injection set-up with an LS detector. Solutions of the purified dendrimers, including the poly(amidoamine) (PAMAM) dendrimer and its fourth to seventh generation pyridine derivatives with size range of 5–9 nm, were used to establish the scaling relation with high linearity. The use of artificially impure mixtures of six or seven generations revealed significant deviations from linearity. The raw synthesized products of the pyridine-modified PAMAM dendrimer, which included incompletely reacted dendrimers, were also examined to gauge the reaction progress. As a reaction toward a particular generational derivative of the PAMAM dendrimers proceeded over time, deviations from the linear scaling relation decreased. The difference between the polydispersity index of the incompletely converted products and that of the pure compounds was only about 0.01. The use of the Debye equation-based scaling relation, therefore, is much more useful than the polydispersity index for monitoring conversion processes toward an indicated functionality number in a given preparation.Graphical abstract

  15. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

    Kalomiraki, Marina; Thermos, Kyriaki; Chaniotakis, Nikos A

    2016-01-01

    Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases. PMID:26730187

  16. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

    Kalomiraki M

    2015-12-01

    Full Text Available Marina Kalomiraki,1 Kyriaki Thermos,2 Nikos A Chaniotakis1 1Laboratory of Analytical Chemistry, Department of Chemistry, 2Department of Pharmacology, School of Medicine, University of Crete Voutes, Heraklion, Greece Abstract: Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases. Keywords: nanoparticles, ocular diseases, encapsulation, macromolecule, diagnostic agent

  17. Dendrimer-protein interactions versus dendrimer-based nanomedicine.

    Shcharbin, Dzmitry; Shcharbina, Natallia; Dzmitruk, Volha; Pedziwiatr-Werbicka, Elzbieta; Ionov, Maksim; Mignani, Serge; de la Mata, F Javier; Gómez, Rafael; Muñoz-Fernández, Maria Angeles; Majoral, Jean-Pierre; Bryszewska, Maria

    2017-04-01

    Dendrimers are hyperbranched polymers belonging to the huge class of nanomedical devices. Their wide application in biology and medicine requires understanding of the fundamental mechanisms of their interactions with biological systems. Summarizing, electrostatic force plays the predominant role in dendrimer-protein interactions, especially with charged dendrimers. Other kinds of interactions have been proven, such as H-bonding, van der Waals forces, and even hydrophobic interactions. These interactions depend on the characteristics of both participants: flexibility and surface charge of a dendrimer, rigidity of protein structure and the localization of charged amino acids at its surface. pH and ionic strength of solutions can significantly modulate interactions. Ligands and cofactors attached to a protein can also change dendrimer-protein interactions. Binding of dendrimers to a protein can change its secondary structure, conformation, intramolecular mobility and functional activity. However, this strongly depends on rigidity versus flexibility of a protein's structure. In addition, the potential applications of dendrimers to nanomedicine are reviwed related to dendrimer-protein interactions. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Dual functions of a new n-type conjugated dendrimer: light-emitting material and additive for polymer electroluminescent devices

    Park, Jong Hyeok; Kim, Chulhee; Kim, Young Chul

    2009-01-01

    We demonstrate a novel light-emitting diode (LED) of a graded bilayer structure that comprises poly(N-vinylcarbazole) (PVK) with good hole transport ability as the energy donor and a new distyrylanthracene-triazine-based dendrimer with enhanced electron transport ability as the light-emitting molecule. The device contains a graded bilayer structure of the PVK film covered with the dendrimer film prepared by sequential spin-casting of the dendrimer layer from a solvent that only swells the PVK layer. The bilayer device demonstrated a significantly enhanced electoluminescence quantum efficiency compared with the dendrimer single layer device or the PVK : dendrimer blend device with optimized composition. We also prepared composite LEDs with an MEH-PPV : emissive dendrimer blend. By doping the electron-deficient MEH-PPV layer with a small amount of the distyrylanthracene-triazine-based dendrimer, we could not only enhance the device performance but also depress the long-wavelength emission of MEH-PPV.

  19. Dual functions of a new n-type conjugated dendrimer: light-emitting material and additive for polymer electroluminescent devices

    Park, Jong Hyeok [Department of Chemical Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Kim, Chulhee [Hyperstructured Organic Materials Research Center, Department of Polymer Science and Engineering, Inha University, Incheon 402-751 (Korea, Republic of); Kim, Young Chul, E-mail: kimyc@khu.ac.k [Department of Chemical Engineering and RIC-CAMID, Kyung Hee University, Yongin-si, Kyunggi-do 499-701 (Korea, Republic of)

    2009-02-07

    We demonstrate a novel light-emitting diode (LED) of a graded bilayer structure that comprises poly(N-vinylcarbazole) (PVK) with good hole transport ability as the energy donor and a new distyrylanthracene-triazine-based dendrimer with enhanced electron transport ability as the light-emitting molecule. The device contains a graded bilayer structure of the PVK film covered with the dendrimer film prepared by sequential spin-casting of the dendrimer layer from a solvent that only swells the PVK layer. The bilayer device demonstrated a significantly enhanced electoluminescence quantum efficiency compared with the dendrimer single layer device or the PVK : dendrimer blend device with optimized composition. We also prepared composite LEDs with an MEH-PPV : emissive dendrimer blend. By doping the electron-deficient MEH-PPV layer with a small amount of the distyrylanthracene-triazine-based dendrimer, we could not only enhance the device performance but also depress the long-wavelength emission of MEH-PPV.

  20. Dual functions of a new n-type conjugated dendrimer: light-emitting material and additive for polymer electroluminescent devices

    Hyeok Park, Jong; Kim, Chulhee; Kim, Young Chul

    2009-02-01

    We demonstrate a novel light-emitting diode (LED) of a graded bilayer structure that comprises poly(N-vinylcarbazole) (PVK) with good hole transport ability as the energy donor and a new distyrylanthracene-triazine-based dendrimer with enhanced electron transport ability as the light-emitting molecule. The device contains a graded bilayer structure of the PVK film covered with the dendrimer film prepared by sequential spin-casting of the dendrimer layer from a solvent that only swells the PVK layer. The bilayer device demonstrated a significantly enhanced electoluminescence quantum efficiency compared with the dendrimer single layer device or the PVK : dendrimer blend device with optimized composition. We also prepared composite LEDs with an MEH-PPV : emissive dendrimer blend. By doping the electron-deficient MEH-PPV layer with a small amount of the distyrylanthracene-triazine-based dendrimer, we could not only enhance the device performance but also depress the long-wavelength emission of MEH-PPV.

  1. Branched-linear and agglomerate protein polymers as vaccine platforms.

    Wang, Leyi; Xia, Ming; Huang, Pengwei; Fang, Hao; Cao, Dianjun; Meng, Xiang-Jin; McNeal, Monica; Jiang, Xi; Tan, Ming

    2014-09-01

    Many viral structural proteins and their truncated domains share a common feature of homotypic interaction forming dimers, trimers, and/or oligomers with various valences. We reported previously a simple strategy for construction of linear and network polymers through the dimerization feature of viral proteins for vaccine development. In this study, technologies were developed to produce more sophisticated polyvalent complexes through both the dimerization and oligomerization natures of viral antigens. As proof of concept, branched-linear and agglomerate polymers were made via fusions of the dimeric glutathione-s-transferase (GST) with either a tetrameric hepatitis E virus (HEV) protruding protein or a 24-meric norovirus (NoV) protruding protein. Furthermore, a monomeric antigen, either the M2e epitope of influenza A virus or the VP8* antigen of rotavirus, was inserted and displayed by the polymer platform. All resulting polymers were easily produced in Escherichia coli at high yields. Immunization of mice showed that the polymer vaccines induced significantly higher specific humoral and T cell responses than those induced by the dimeric antigens. Additional evidence in supporting use of polymer vaccines included the significantly higher neutralization activity and protective immunity of the polymer vaccines against the corresponding viruses than those of the dimer vaccines. Thus, our technology for production of polymers containing different viral antigens offers a strategy for vaccine development against infectious pathogens and their associated diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Structural and Interfacial Properties of Hyperbranched-Linear Polymer Surfactant

    Qiang, Taotao; Bu, Qiaoqiao; Huang, Zhaofeng; Wang, Xuechuan

    2014-01-01

    With oleic acid grafting modification, a series of hyperbranched-linear polymer surfactants (HLPS) were prepared by hydroxyl-terminated hyperbranched polymer (HBP), which was gained through a step synthesis method using trimethylolpropane and AB2 monomer. The AB2 monomers were obtained through the Michael addition reaction of methyl acrylate and diethanol amine. The structures of HLPS were characterised by Fourier transform infrared spectrophotometer and nuclear magnetic resonance (NMR), whic...

  3. Polyphenylene dendrimers

    Marek, T.

    2002-01-01

    Complete text of publication follows. The most attractive property of polyphenylene dendrimers is their rigidity. They retain the molecular symmetry and monodispersity of the usual, commercially available alyphatic dendrimers, while the composition of the dendritic branches makes them self-supporting. In solution flexible dendrimers usually form a globular 3D-structure in which the dendritic branches are evenly distributed over the whole molecular volume, however, it has been shown that, depending on the generation of the particular dendrimer, their peripheral groups tend to fold back into the interior of the molecule. Moreover, when being adsorbed on a surface (or by the removal of the solvent), they often tend to flatten out. In contrast to this behaviour, it has been shown that rigid dendrimers based on polyphenylenes have stiff branches and the backfolding in solutions is impossible. Furthermore, when polyphenylene dendrimers are absorbed on a mica substrate their original shape is retained. These features and their size, lying in the low nanometer scale, make these molecules attractive candidates for several applications such as supports for functional groups and as hosts for smaller guest molecules. We have studied the free volume in a series of rigid polyphenylene dendrimers by positron lifetime spectroscopy (PLTS) and molecular dynamics calculations, in order to assess the expected relationship between the size (number of generations, molecular weight) of these molecules and the intramolecular free volume. We have found that the size of these inner free volumes is stable, and increases with the increasing number generations

  4. Dendrimer Prodrugs

    Soraya da Silva Santos

    2016-05-01

    Full Text Available The main objective of this review is to describe the importance of dendrimer prodrugs in the design of new drugs, presenting numerous applications of these nanocomposites in the pharmaceutical field. Therefore, the use of dendrimer prodrugs as carrier for drug delivery, to improve pharmacokinetic properties of prototype, to promote drug sustained-release, to increase selectivity and, consequently, to decrease toxicity, are just some examples of topics that have been extensively reported in the literature, especially in the last decade. The examples discussed here give a panel of the growing interest dendrimer prodrugs have been evoking in the scientific community.

  5. Novel linear polymers able to inhibit bacterial quorum sensing.

    Cavaleiro, Eliana; Duarte, Ana Sofia; Esteves, Ana Cristina; Correia, António; Whitcombe, Michael J; Piletska, Elena V; Piletsky, Sergey A; Chianella, Iva

    2015-05-01

    Bacterial phenotypes, such as biofilm formation, antibiotic resistance and virulence expression, are associated with quorum sensing. Quorum sensing is a density-dependent regulatory system of gene expression controlled by specific signal molecules, such as N-acyl homoserine lactones (AHLs), produced and released by bacteria. This study reports the development of linear polymers capable to attenuate quorum sensing by adsorption of AHLs. Linear polymers were synthesized using MMA as backbone monomer and methacrylic acid and itaconic acid as functional monomers. Two different quorum sensing-controlled phenotypes, Vibrio fischeri bioluminescence and Aeromonas hydrophila biofilm formation, were evaluated to test the polymers' efficiency. Results showed that both phenotypes were significantly affected by the polymers, with the itaconic acid-containing material being more effective than the methacrylic acid one. The polymer inhibitory effects were reverted by the addition of lactones, confirming attenuation of quorum sensing through sequestration of signal molecules. The polymers also showed no cytotoxicity when tested using a mammalian cell line. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Synthesis of PAMAM dendrimers and investigations of their interaction with POPC/POPG lipids

    Gneid, Hassan

    2014-01-01

    PAMAM dendrimers are three dimensional organic polymers synthesised by repetitive steps to achieve a controlled size and shape with a choice of surface functional groups. One of the potential applications of dendrimers is for drug/gene delivery which requires the dendrimer to interact with the cellular membranes. This study is designed to probe the interactions between PAMAM dendrimers and lipid bilayers. To investigate these interactions PAMAM dendrimers up to the third generation were synth...

  7. MECHANICAL PROPERTIES OF BLENDS OF PAMAM DENDRIMERS WITH POLY(VINYL CHLORIDE) AND POLY(VINYL ACETATE)

    Hybrid blends of poly(amidoamine) PAMAM dendrimers with two linear high polymers, poly(vinyl chloride), PVC, and poly(vinyl acetate), PVAc, are reported. The interaction between the blend components was studied using dynamic mechanical analysis, xenon nuclear magnetic resonacne ...

  8. High-efficiency synthesis of dendrimer-like poly(ethylene oxide) via “arm-first” approach

    Zhu, Saisai; Xia, Ru; Chen, Peng; Yang, Bin; Miao, Jibin; Zheng, Zhengzhi; Su, Lifeng; Qian, Jiasheng; Cao, Ming; Feng, Xiaoshuang

    2017-01-01

    In this study, a dendrimer-like polymer based on poly(ethylene oxide) (PEO) was synthesized through a combination of anionic ring-opening polymerization (AROP) and click reaction via arm-first method. Firstly, the polymeric arm, a linear PEO

  9. Tweaking Dendrimers and Dendritic Nanoparticles for Controlled Nano-bio Interactions: Potential Nanocarriers for Improved Cancer Targeting

    Bugno, Jason; Hsu, Hao-Jui; Hong, Seungpyo

    2016-01-01

    Nanoparticles have shown great promise in the treatment of cancer, with a demonstrated potential in targeted drug delivery. Among a myriad of nanocarriers that have been recently developed, dendrimers have attracted a great deal of scientific interests due to their unique chemical and structural properties that allow for precise engineering of their characteristics. Despite this, the clinical translation of dendrimers has been hindered due to their drawbacks, such as scale-up issues, rapid systemic elimination, inefficient tumor accumulation, and limited drug loading. In order to overcome these limitations, a series of reengineered dendrimers have been recently introduced using various approaches, including: i) modifications of structure and surfaces; ii) integration with linear polymers; and iii) hybridization with other types of nanocarriers. Chemical modifications and surface engineering have tailored dendrimers to improve their pharmacokinetics and tissue permeation. Copolymerization of dendritic polymers with linear polymers has resulted in various amphiphilic copolymers with self-assembly capabilities and improved drug loading efficiencies. Hybridization with other nanocarriers integrates advantageous characteristics of both systems, which includes prolonged plasma circulation times and enhanced tumor targeting. This review provides a comprehensive summary of the newly emerging drug delivery systems that involve reengineering of dendrimers in an effort to precisely control their nano-bio interactions, mitigating their inherent weaknesses. PMID:26453160

  10. Dendrimers for siRNA Delivery

    Swati Biswas

    2013-02-01

    Full Text Available Since the discovery of the “starburst polymer”, later renamed as dendrimer, this class of polymers has gained considerable attention for numerous biomedical applications, due mainly to the unique characteristics of this macromolecule, including its monodispersity, uniformity, and the presence of numerous functionalizable terminal groups. In recent years, dendrimers have been studied extensively for their potential application as carriers for nucleic acid therapeutics, which utilize the cationic charge of the dendrimers for effective dendrimer-nucleic acid condensation. siRNA is considered a promising, versatile tool among various RNAi-based therapeutics, which can effectively regulate gene expression if delivered successfully inside the cells. This review reports on the advancements in the development of dendrimers as siRNA carriers.

  11. Peptide dendrimers

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2005-01-01

    Roč. 11, - (2005), 757-788 ISSN 1075-2617 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : multiple antigen peptides * peptide dendrimers * synthetic vaccine * multipleantigenic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.803, year: 2005

  12. Electronic transport study in PAMAM dendrimers

    Vieira, Nirton C.S.; Soares, Demetrio A.W.; Fernandes, Edson G.R.; Queiroz, Alvaro A.A. de

    2005-01-01

    Dendrimers are nanomaterials that have many potential applications in medicine, including diagnosis and therapeutic procedures. Dendrimers are isomolecular polymers, with a very well controlled architecture and a thousand times smaller than cells. Dendrimers containing biocatalysts are of great interest for clinical applications in biosensors because of the way in which their chemical and electric conduction mechanism can be tailored. In this work, the polyamidoamine dendrimer (PAMAM) of generation 4 was synthesized by divergent route and characterized by NMR spectroscopy. The electronic transport properties of PAMAM in a metal-polymer type heterojunction were studied. The electrical conduction mechanism of PAMAM studied in the temperature range of 291-323 K indicates a conduction mechanism thermally activated. (author)

  13. High-efficiency synthesis of dendrimer-like poly(ethylene oxide) via “arm-first” approach

    Zhu, Saisai

    2017-04-14

    In this study, a dendrimer-like polymer based on poly(ethylene oxide) (PEO) was synthesized through a combination of anionic ring-opening polymerization (AROP) and click reaction via arm-first method. Firstly, the polymeric arm, a linear PEO with one alkynyl group and two bromo groups, was synthesized by AROP of ethylene oxide followed by functionalization with propargyl bromide and esterified with 2-bromopropionic bromide. Second, a star PEO carrying three azide groups was synthesized though AROP of ethylene oxide used 1,1,1-tris(hydrosymethyl) ethane as initiator followed esterificated with 2-bromopropionic acid and azidation. By azide–alkyne click reactions between the azide-terminated PEO star polymer and linear PEO with functionalization alkynyl group, a three generation dendrimer-like PEO, G3-PEO-24Br, was successfully synthesized. The resulting polymers were observed to have precisely controlled molecular weights and compositions with narrow molecular weight distributions.

  14. Effect of molecular topology on the transport properties of dendrimers in dilute solution at Θ temperature: A Brownian dynamics study

    Bosko, Jaroslaw T.; Ravi Prakash, J.

    2008-01-01

    Structure and transport properties of dendrimers in dilute solution are studied with the aid of Brownian dynamics simulations. To investigate the effect of molecular topology on the properties, linear chain, star, and dendrimer molecules of comparable molecular weights are studied. A bead-spring chain model with finitely extensible springs and fluctuating hydrodynamic interactions is used to represent polymer molecules under Θ conditions. Structural properties as well as the diffusivity and zero-shear-rate intrinsic viscosity of polymers with varied degrees of branching are analyzed. Results for the free-draining case are compared to and found in very good agreement with the Rouse model predictions. Translational diffusivity is evaluated and the difference between the short-time and long-time behavior due to dynamic correlations is observed. Incorporation of hydrodynamic interactions is found to be sufficient to reproduce the maximum in the intrinsic viscosity versus molecular weight observed experimentally for dendrimers. Results of the nonequilibrium Brownian dynamics simulations of dendrimers and linear chain polymers subjected to a planar shear flow in a wide range of strain rates are also reported. The flow-induced molecular deformation of molecules is found to decrease hydrodynamic interactions and lead to the appearance of shear thickening. Further, branching is found to suppress flow-induced molecular alignment and deformation.

  15. Structural and Interfacial Properties of Hyperbranched-Linear Polymer Surfactant.

    Qiang, Taotao; Bu, Qiaoqiao; Huang, Zhaofeng; Wang, Xuechuan

    2014-01-01

    With oleic acid grafting modification, a series of hyperbranched-linear polymer surfactants (HLPS) were prepared by hydroxyl-terminated hyperbranched polymer (HBP), which was gained through a step synthesis method using trimethylolpropane and AB 2 monomer. The AB 2 monomers were obtained through the Michael addition reaction of methyl acrylate and diethanol amine. The structures of HLPS were characterised by Fourier transform infrared spectrophotometer and nuclear magnetic resonance (NMR), which indicated that HBP was successfully modified by oleic acid. Furthermore, the properties of surface tension and critical micelle concentration of HLPS solution showed that HLPS can significantly reduce the surface tension of water. The morphology of the HLPS solution was characterised by dynamic light scattering, which revealed that HLPS exhibited a nonmonotonic appearance in particle size at different scattering angles owing to the different replaced linear portions. The relationships of the surface pressure to monolayer area and time were measured using the Langmuir-Blodgett instrument, which showed that the surface tension of monolayer molecules increased with the increasing of hydrophobic groups. In addition, the interface conditions of different replaced HLPS solutions were simulated.

  16. Understanding specific and nonspecific toxicities: a requirement for the development of dendrimer-based pharmaceuticals

    McNerny, Daniel Q.; Leroueil, Pascale R.; Baker, James R.

    2010-01-01

    Dendrimer conjugates for pharmaceutical development are capable of enhancing the local delivery of cytotoxic drugs. The ability to conjugate different targeting ligands to the dendrimer allows for the cytotoxic drug to be focused at the intended target cell while minimizing collateral damage in normal cells. Dendrimers offer several advantages over other polymer conjugates by creating a better defined, more monodisperse therapeutic scaffold. Toxicity from the dendrimer, targeted and nonspecif...

  17. The influence of polymer topology on pharmacokinetics: differences between cyclic and linear PEGylated poly(acrylic acid) comb polymers.

    Chen, Bo; Jerger, Katherine; Fréchet, Jean M J; Szoka, Francis C

    2009-12-16

    Water-soluble polymers for the delivery of chemotherapeutic drugs passively target solid tumors as a consequence of reduced renal clearance and the enhanced permeation and retention (EPR) effect. Elimination of the polymers in the kidney occurs due to filtration through biological nanopores with a hydrodynamic diameter comparable to the polymer. Therefore we have investigated chemical features that may broadly be grouped as "molecular architecture" such as: molecular weight, chain flexibility, number of chain ends and branching, to learn how they impact polymer elimination. In this report we describe the synthesis of four pairs of similar molecular weight cyclic and linear polyacrylic acid polymers grafted with polyethylene glycol (23, 32, 65, 114 kDa) with low polydispersities using ATRP and "click" chemistry. The polymers were radiolabeled with (125)I and their pharmacokinetics and tissue distribution after intravenous injection were determined in normal and C26 adenocarcinoma tumored BALB/c mice. Cyclic polymers above the renal threshold of 30 kDa had a significantly longer elimination time (between 10 and 33% longer) than did the comparable linear polymer (for the 66 kDa cyclic polymer, t(1/2,beta)=35+/-2 h) and a greater area under the serum concentration versus time curve. This resulted in a greater tumor accumulation of the cyclic polymer than the linear polymer counterpart. Thus water-soluble cyclic comb polymers join a growing list of polymer topologies that show greatly extended circulation times compared to their linear counterparts and provide alternative polymer architecture for use as drug carriers.

  18. Dendrimers bind antioxidant polyphenols and cisplatin drug.

    Amine Abderrezak

    Full Text Available Synthetic polymers of a specific shape and size play major role in drug delivery systems. Dendrimers are unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape with potential applications in gene and drug delivery. We examine the interaction of several dendrimers of different compositions mPEG-PAMAM (G3, mPEG-PAMAM (G4 and PAMAM (G4 with hydrophilic and hydrophobic drugs cisplatin, resveratrol, genistein and curcumin at physiological conditions. FTIR and UV-visible spectroscopic methods as well as molecular modeling were used to analyse drug binding mode, the binding constant and the effects of drug complexation on dendrimer stability and conformation. Structural analysis showed that cisplatin binds dendrimers in hydrophilic mode via Pt cation and polymer terminal NH(2 groups, while curcumin, genistein and resveratrol are located mainly in the cavities binding through both hydrophobic and hydrophilic contacts. The overall binding constants of durg-dendrimers are ranging from 10(2 M(-1 to 10(3 M(-1. The affinity of dendrimer binding was PAMAM-G4>mPEG-PAMAM-G4>mPEG-PAMAM-G3, while the order of drug-polymer stability was curcumin>cisplatin>genistein>resveratrol. Molecular modeling showed larger stability for genisten-PAMAM-G4 (ΔG = -4.75 kcal/mol than curcumin-PAMAM-G4 ((ΔG = -4.53 kcal/mol and resveratrol-PAMAM-G4 ((ΔG = -4.39 kcal/mol. Dendrimers might act as carriers to transport hydrophobic and hydrophilic drugs.

  19. Polymer architecture and drug delivery.

    Qiu, Li Yan; Bae, You Han

    2006-01-01

    Polymers occupy a major portion of materials used for controlled release formulations and drug-targeting systems because this class of materials presents seemingly endless diversity in topology and chemistry. This is a crucial advantage over other classes of materials to meet the ever-increasing requirements of new designs of drug delivery formulations. The polymer architecture (topology) describes the shape of a single polymer molecule. Every natural, seminatural, and synthetic polymer falls into one of categorized architectures: linear, graft, branched, cross-linked, block, star-shaped, and dendron/dendrimer topology. Although this topic spans a truly broad area in polymer science, this review introduces polymer architectures along with brief synthetic approaches for pharmaceutical scientists who are not familiar with polymer science, summarizes the characteristic properties of each architecture useful for drug delivery applications, and covers recent advances in drug delivery relevant to polymer architecture.

  20. A conducting polymer artificial muscle with 12% linear strain

    Bay, Lasse; West, Keld; Sommer-Larsen, P.

    2003-01-01

    in a freely suspended polymer foil in response to a potential change and it includes attention to the composition of the polymer, to the synthesis conditions, and involves microstructuring of the polymer. As such, an analysis of the influence of the alkyl chain length on the properties of PPy doped with ABSs...... has shown that the obtainable strain decreases with increasing chain length for alkyl chains longer than C$-8$/....

  1. DNA compaction by poly (amido amine) dendrimers of ammonia cored and ethylene diamine cored

    Qamhieh, K.; Al-Shawwa, J.

    2017-06-01

    The complexes build-up of DNA and soft particles poly amidoamine (PAMAM) dendrimers of ammonia cored of generations (G1-G6) and ethylenediamine cored of generations (G1-G10) have been studied, using a new theoretical model developed by Qamhieh and coworkers. The model describes the interaction between linear polyelectrolyte (LPE) chain and ion-penetrable spheres. Many factors affecting LPE/dendrimer complex have been investigated such as dendrimer generation, the Bjerrum length, salt concentration, and rigidity of the LPE chain represented by the persistence length. It is found that the wrapping chain length around dendrimer increases by increasing dendrimer`s generation, Bjerrum length, and salt concentration, while decreases by increasing the persistence length of the LPE chain. Also we can conclude that the wrapping length of LPE chain around ethylenediamine cored dendrimers is larger than its length around ammonia cored dendrimers.

  2. Adsorption of branched and dendritic polymers onto flat surfaces: A Monte Carlo study

    Sommer, J.-U.; Kłos, J. S.; Mironova, O. N.

    2013-01-01

    Using Monte Carlo simulations based on the bond fluctuation model we study the adsorption of starburst dendrimers with flexible spacers onto a flat surface. The calculations are performed for various generation number G and spacer length S in a wide range of the reduced temperature τ as the measure of the interaction strength between the monomers and the surface. Our simulations indicate a two-step adsorption scenario. Below the critical point of adsorption, τ c , a weakly adsorbed state of the dendrimer is found. Here, the dendrimer retains its shape but sticks to the surface by adsorbed spacers. By lowering the temperature below a spacer-length dependent value, τ*(S) c , a step-like transition into a strongly adsorbed state takes place. In the flatly adsorbed state the shape of the dendrimer is well described by a mean field model of a dendrimer in two dimensions. We also performed simulations of star-polymers which display a simple crossover-behavior in full analogy to linear chains. By analyzing the order parameter of the adsorption transition, we determine the critical point of adsorption of the dendrimers which is located close to the critical point of adsorption for star-polymers. While the order parameter for the adsorbed spacers displays a critical crossover scaling, the overall order parameter, which combines both critical and discontinuous transition effects, does not display simple scaling. The step-like transition from the weak into the strong adsorbed regime is confirmed by analyzing the shape-anisotropy of the dendrimers. We present a mean-field model based on the concept of spacer adsorption which predicts a discontinuous transition of dendrimers due to an excluded volume barrier. The latter results from an increased density of the dendrimer in the flatly adsorbed state which has to be overcome before this state is thermodynamically stable

  3. Adsorption of branched and dendritic polymers onto flat surfaces: A Monte Carlo study

    Sommer, J.-U. [Leibniz Institute of Polymer Research Dresden e. V., 01069 Dresden (Germany); Institute for Theoretical Physics, Technische Universität Dresden, 01069 Dresden (Germany); Kłos, J. S. [Leibniz Institute of Polymer Research Dresden e. V., 01069 Dresden (Germany); Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Mironova, O. N. [Leibniz Institute of Polymer Research Dresden e. V., 01069 Dresden (Germany)

    2013-12-28

    Using Monte Carlo simulations based on the bond fluctuation model we study the adsorption of starburst dendrimers with flexible spacers onto a flat surface. The calculations are performed for various generation number G and spacer length S in a wide range of the reduced temperature τ as the measure of the interaction strength between the monomers and the surface. Our simulations indicate a two-step adsorption scenario. Below the critical point of adsorption, τ{sub c}, a weakly adsorbed state of the dendrimer is found. Here, the dendrimer retains its shape but sticks to the surface by adsorbed spacers. By lowering the temperature below a spacer-length dependent value, τ*(S) < τ{sub c}, a step-like transition into a strongly adsorbed state takes place. In the flatly adsorbed state the shape of the dendrimer is well described by a mean field model of a dendrimer in two dimensions. We also performed simulations of star-polymers which display a simple crossover-behavior in full analogy to linear chains. By analyzing the order parameter of the adsorption transition, we determine the critical point of adsorption of the dendrimers which is located close to the critical point of adsorption for star-polymers. While the order parameter for the adsorbed spacers displays a critical crossover scaling, the overall order parameter, which combines both critical and discontinuous transition effects, does not display simple scaling. The step-like transition from the weak into the strong adsorbed regime is confirmed by analyzing the shape-anisotropy of the dendrimers. We present a mean-field model based on the concept of spacer adsorption which predicts a discontinuous transition of dendrimers due to an excluded volume barrier. The latter results from an increased density of the dendrimer in the flatly adsorbed state which has to be overcome before this state is thermodynamically stable.

  4. Synthesis and study of conjugated polymers containing Di- or Triphenylamine

    Sukwattanasinitt, M.

    1996-06-21

    This thesis consists of two separate parts. The first part addresses the synthesis and study of conjugated polymers containing di- or triphenylamine. Two types of polymers: linear polymers and dendrimers, were synthesized. The polymers were characterized by NMR, IR, UV, GPC, TGA and DSC. Electronic and optical properties of the polymers were studied through the conductivity measurements and excitation- emission spectra. the second part of this thesis deals with a reaction of electron-rich acetylenes with TCNE. The discovery of the reaction from charge transfer complex studies and the investigation of this reaction on various electron-rich acetylenes are presented.

  5. Tailoring the dendrimer core for efficient gene delivery.

    Hu, Jingjing; Hu, Ke; Cheng, Yiyun

    2016-04-15

    Dendrimers have been widely used as non-viral gene vectors due to well-defined chemical structures, high density of cationic charges and ease of surface modification. Although a large number of studies have reported the important roles of dendrimer architecture, component, generation and surface functionality in gene delivery, the effect of dendrimer core on this issue still remains unclear. Recent literatures suggest that a slight alternation in dendrimer core has a profound effect in the transfection efficacy and biocompatibility. In this review, we will discuss the transfection mechanism of dendrimers with different types of cores in respect of flexibility, hydrophobicity and functionality. We hope to open a possibility of designing efficient dendrimers for gene delivery by choosing a proper dendrimer core. As a branch of researches on dendrimers and dendritic polymers, the design of biocompatible and high efficient polymeric gene carriers has attracted increasing attentions during these years. Although the effect of dendrimer generation, species, architecture and surface functionality on gene delivery have been widely reported, the effect of dendrimer core on this issue still remains unclear. Recent literatures suggest that a minor variation on the dendrimer core has a profound effect in the transfection efficacy and biocompatibility. This critical review summarized the dendrimers with different types of cores and discussed the transfection mechanism with particular focus on the flexibility, hydrophobicity, and functionality. It is hoped to provide a new insight to design efficient and safe dendrimer-based gene vectors by choosing a proper core. To the best of our knowledge, this is the first review on the effect of dendrimer core on gene delivery. The findings obtained in this filed are of central importance in the design of efficient polymeric gene vectors. This article will appeal a wide readership such as physical chemist, dendrimer chemist, biological

  6. Glycopeptide dendrimers. Part I

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2008-01-01

    Roč. 14, č. 1 (2008), s. 2-43 ISSN 1075-2617 R&D Projects: GA ČR GA203/03/1362; GA ČR GA203/06/1272; GA MZe QF3115; GA AV ČR KAN200520703 Institutional research plan: CEZ:AV0Z40550506 Keywords : artificial virus * calixarene dendrimers * carbopeptide dendrimers * glycopeptide dendrimers Subject RIV: CC - Organic Chemistry Impact factor: 1.654, year: 2008

  7. Bifunctional Phosphorus Dendrimers and Their Properties.

    Caminade, Anne-Marie; Majoral, Jean-Pierre

    2016-04-23

    Dendrimers are hyperbranched and monodisperse macromolecules, generally considered as a special class of polymers, but synthesized step-by-step. Most dendrimers have a uniform structure, with a single type of terminal function. However, it is often desirable to have at least two different functional groups. This review will discuss the case of bifunctional phosphorus-containing dendrimers, and the consequences for their properties. Besides the terminal functions, dendritic structures may have also a function at the core, or linked off-center to the core, or at the core of dendrons (dendritic wedges). Association of two dendrons having different terminal functions leads to Janus dendrimers (two faces). The internal structure can also possess functional groups on one layer, or linked to one layer, or on several layers. Finally, there are several ways to have two types of terminal functions, besides the case of Janus dendrimers: either each terminal function bears two functions sequentially, or two different functions are linked to each terminal branching point. Examples of each type of structure will be given in this review, as well as practical uses of such sophisticated structures in the fields of fluorescence, catalysis, nanomaterials and biology.

  8. Lattice cluster theory of associating polymers. I. Solutions of linear telechelic polymer chains.

    Dudowicz, Jacek; Freed, Karl F

    2012-02-14

    The lattice cluster theory (LCT) for the thermodynamics of a wide array of polymer systems has been developed by using an analogy to Mayer's virial expansions for non-ideal gases. However, the high-temperature expansion inherent to the LCT has heretofore precluded its application to systems exhibiting strong, specific "sticky" interactions. The present paper describes a reformulation of the LCT necessary to treat systems with both weak and strong, "sticky" interactions. This initial study concerns solutions of linear telechelic chains (with stickers at the chain ends) as the self-assembling system. The main idea behind this extension of the LCT lies in the extraction of terms associated with the strong interactions from the cluster expansion. The generalized LCT for sticky systems reduces to the quasi-chemical theory of hydrogen bonding of Panyioutou and Sanchez when correlation corrections are neglected in the LCT. A diagrammatic representation is employed to facilitate the evaluation of the corrections to the zeroth-order approximation from short range correlations. © 2012 American Institute of Physics

  9. New method for preparing a liquid crystal polymer that exhibits linearly polarized white fluorescence

    Zheng Shijun; Kun, Wang; Kobayashi, Takaomi

    2011-01-01

    With the aim of developing a single-chain white-light-emitting polymer, liquid crystal (LC) polymers with a shish-kebab-type moiety on their cross-conjugated (p-phenylene)s-poly(p-phenylenevinylene)s main chain were synthesized by Gilch polymerization. They were characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and polarizing optical microscopy (POM). 1 H-NMR indicated that the polymers had a shish-kebab structure, which strongly suppressed the formation of structural defects in the polymers. DSC revealed that the polymers had thermotropic LC properties, indicating that the LC polymers were enantiotropic. XRD showed that the polymers had a mesophase, which implies that they were in a smectic LC phase. A polymer with 'kebabs' of 2,5-bis(4'-alkoxyphenyl)benzene was combined with an aligned polyimide film with orientated microgrooves. The polymer main chain was aligned due to the orientation of the 'kebabs' of the uniform cross-conjugated structure. It lay between the kebabs and the 'shish' of the polymer main chains. The aligned polymer main chain emitted yellow light while and the oriented LC side chains emitted blue light emission. These two emissions resulted in linearly polarized white fluorescence.

  10. Increase in Dye:Dendrimer Ratio Decreases Cellular Uptake of Neutral Dendrimers in RAW Cells.

    Vaidyanathan, Sriram; Kaushik, Milan; Dougherty, Casey; Rattan, Rahul; Goonewardena, Sascha N; Banaszak Holl, Mark M; Monano, Janet; DiMaggio, Stassi

    2016-09-12

    Neutral generation 3 poly(amidoamine) dendrimers were labeled with Oregon Green 488 (G3-OG n ) to obtain materials with controlled fluorophore:dendrimer ratios (n = 1-2), a mixture containing mostly 3 dyes per dendrimer, a mixture containing primarily 4 or more dyes per dendrimer ( n = 4+), and a stochastic mixture ( n = 4 avg ). The UV absorbance of the dye conjugates increased linearly as n increased and the fluorescence emission decreased linearly as n increased. Cellular uptake was studied in RAW cells and HEK 293A cells as a function of the fluorophore:dendrimer ratio (n). The cellular uptake of G3-OG n ( n = 3, 4+, 4 avg ) into RAW cells was significantly lower than G3-OG n ( n = 1, 2). The uptake of G3-OG n ( n = 3, 4+, 4 avg ) into HEK 293A cells was not significantly different from G3-OG 1 . Thus, the fluorophore:dendrimer ratio was observed to change the extent of uptake in the macrophage uptake mechanism but not in the HEK 293A cell. This difference in endocytosis indicates the presence of a pathway in the macrophage that is sensitive to hydrophobicity of the particle.

  11. Synthesis, Characterization and Biological Studies of New Linear Thermally Stable Schiff Base Polymers with Flexible Spacers.

    Qureshi, Farah; Khuhawar, Muhammad Yar; Jahangir, Taj Muhammad; Channar, Abdul Hamid

    2016-01-01

    Five new linear Schiff base polymers having azomethine structures, ether linkages and extended aliphatic chain lengths with flexible spacers were synthesized by polycondensation of dialdehyde (monomer) with aliphatic and aromatic diamines. The formation yields of monomer and polymers were obtained within 75-92%. The polymers with flexible spacers of n-hexane were somewhat soluble in acetone, chloroform, THF, DMF and DMSO on heating. The monomer and polymers were characterized by melting point, elemental microanalysis, FT-IR, (1)HNMR, UV-Vis spectroscopy, thermogravimetry (TG), differential thermal analysis (DTA), fluorescence emission, scanning electron microscopy (SEM) and viscosities and thermodynamic parameters measurements of their dilute solutions. The studies supported formation of the monomer and polymers and on the basis of these studies their structures have been assigned. The synthesized polymers were tested for their antibacterial and antifungal activities.

  12. Developmental toxicity of low generation PAMAM dendrimers in zebrafish

    King Heiden, Tisha C.; Dengler, Emelyne; Kao, Weiyuan John; Heideman, Warren; Peterson, Richard E.

    2007-01-01

    Biological molecules and intracellular structures operate at the nanoscale; therefore, development of nanomedicines shows great promise for the treatment of disease by using targeted drug delivery and gene therapies. PAMAM dendrimers, which are highly branched polymers with low polydispersity and high functionality, provide an ideal architecture for construction of effective drug carriers, gene transfer devices and imaging of biological systems. For example, dendrimers bioconjugated with selective ligands such as Arg-Gly-Asp (RGD) would theoretically target cells that contain integrin receptors and show potential for use as drug delivery devices. While RGD-conjugated dendrimers are generally considered not to be cytotoxic, there currently exists little information on the risks that such materials pose to human health. In an effort to compliment and extend the knowledge gleaned from cell culture assays, we have used the zebrafish embryo as a rapid, medium throughput, cost-effective whole-animal model to provide a more comprehensive and predictive developmental toxicity screen for nanomaterials such as PAMAM dendrimers. Using the zebrafish embryo, we have assessed the developmental toxicity of low generation (G3.5 and G4) PAMAM dendrimers, as well as RGD-conjugated forms for comparison. Our results demonstrate that G4 dendrimers, which have amino functional groups, are toxic and attenuate growth and development of zebrafish embryos at sublethal concentrations; however, G3.5 dendrimers, with carboxylic acid terminal functional groups, are not toxic to zebrafish embryos. Furthermore, RGD-conjugated G4 dendrimers are less potent in causing embryo toxicity than G4 dendrimers. RGD-conjugated G3.5 dendrimers do not elicit toxicity at the highest concentrations tested and warrant further study for use as a drug delivery device

  13. Adsorption of branched and dendritic polymers onto flat surfaces: A Monte Carlo study

    Sommer, J.-U.; Kłos, J. S.; Mironova, O. N.

    2013-12-01

    Using Monte Carlo simulations based on the bond fluctuation model we study the adsorption of starburst dendrimers with flexible spacers onto a flat surface. The calculations are performed for various generation number G and spacer length S in a wide range of the reduced temperature τ as the measure of the interaction strength between the monomers and the surface. Our simulations indicate a two-step adsorption scenario. Below the critical point of adsorption, τc, a weakly adsorbed state of the dendrimer is found. Here, the dendrimer retains its shape but sticks to the surface by adsorbed spacers. By lowering the temperature below a spacer-length dependent value, τ*(S) model of a dendrimer in two dimensions. We also performed simulations of star-polymers which display a simple crossover-behavior in full analogy to linear chains. By analyzing the order parameter of the adsorption transition, we determine the critical point of adsorption of the dendrimers which is located close to the critical point of adsorption for star-polymers. While the order parameter for the adsorbed spacers displays a critical crossover scaling, the overall order parameter, which combines both critical and discontinuous transition effects, does not display simple scaling. The step-like transition from the weak into the strong adsorbed regime is confirmed by analyzing the shape-anisotropy of the dendrimers. We present a mean-field model based on the concept of spacer adsorption which predicts a discontinuous transition of dendrimers due to an excluded volume barrier. The latter results from an increased density of the dendrimer in the flatly adsorbed state which has to be overcome before this state is thermodynamically stable.

  14. Dendrimers destabilize proteins in a generation-dependent manner involving electrostatic interactions

    Gichm, Lise; Christensen, Casper; Boas, Ulrik

    2008-01-01

    Dendrimers are well-defined chemical polymers with a characteristic branching pattern that gives rise to attractive features such as antibacterial and antitumor activities as well as drug delivery properties. In addition, dendrimers can solubilize prion protein aggregates at very low concentratio...

  15. Some new aspects of dendrimer applications

    Flomenbom, Ophir; Amir, Roey J.; Shabat, Doron; Klafter, Joseph

    2005-01-01

    Dendrimers are characterized by special features that make them promising candidates for many applications. Here we focus on two such applications: dendrimers as light harvesting antennae, and dendrimers as molecular amplifiers, which may serve as novel platforms for drug delivery. Both applications stem from the unique structure of dendrimers. We present a theoretical framework based on the master equation within which we describe these applications. The quantities of interest are the first passage time (FPT), probability density function (PDF) and its moments. We examine how the FPT PDF and its characteristics depend on the geometric and energetic structures of the dendrimeric system. In particular, we investigate the dependence of the FPT properties on the number of generations (dendrimer size) and the system bias. We present analytical expressions for the FPT PDF for very efficient dendrimeric antennae and for dendrimeric amplifiers. For these cases the mean FPT scales linearly with the system length, and fluctuations around the mean FPT are negligible for large systems. Relationships of the FPT to light harvesting process for other types of system-bias are discussed

  16. Influence of dendrimer's structure on its activity against amyloid fibril formation

    Klajnert, B.; Cortijo-Arellano, M.; Cladera, J.; Bryszewska, M.

    2006-01-01

    Inhibition of fibril assembly is a potential therapeutic strategy in neurodegenerative disorders such as prion and Alzheimer's diseases. Highly branched, globular polymers-dendrimers-are novel promising inhibitors of fibril formation. In this study, the effect of polyamidoamine (PAMAM) dendrimers (generations 3rd, 4th, and 5th) on amyloid aggregation of the prion peptide PrP 185-208 and the Alzheimer's peptide Aβ 1-28 was examined. Amyloid fibrils were produced in vitro and their formation was monitored using the dye thioflavin T (ThT). Fluorescence studies were complemented with electron microscopy. The results show that the higher the dendrimer generation, the larger the degree of inhibition of the amyloid aggregation process and the more effective are dendrimers in disrupting the already existing fibrils. A hypothesis on dendrimer-peptide interaction mechanism is presented based on the dendrimers' molecular structure

  17. Tecto-dendrimers: a study of covalently bound nanospheres

    Welch, Paul M [Los Alamos National Laboratory; Welch, Cynthia F [Los Alamos National Laboratory

    2008-01-01

    We present a computational and theoretical study of the size, shape, and solution properties of tecto-dendrimers. This class of polymer, composed of a central dendrimer with multiple dendrimers attached at its periphery, holds promise for multi-drug delivery and environmental remediation applications. We find (i) that the maximum number of tecto-units that may be attached to the central core varies logarightmically with the ratio of the sizes of the dendrimers, (ii) that their density profiles display a minimum near the junction of the tecto-units with the core, (iii) that a simple expression captures their radius of gyration, (iv) that their intrinsic viscosity will display a maximum as a function of the number of tecto-units attached, and (v) that their sphericity increases with increasing number of attached tecto-units. These results should bear upon both the synthesis and application of these materials.

  18. The influence of polymer architectures on the dewetting behavior of thin polymer films: from linear chains to ring chains.

    Wang, Lina; Xu, Lin; Liu, Binyuan; Shi, Tongfei; Jiang, Shichun; An, Lijia

    2017-05-03

    The dewetting behavior of ring polystyrene (RPS) film and linear polystyrene (LPS) film on silanized Si substrates with different grafting densities and PDMS substrate was investigated. Results showed that polymer architectures greatly influenced the dewetting behavior of the thin polymer film. On the silanized Si substrate with 69% grafting density, RPS chains exhibited stronger adsorption compared with LPS chains, and as a result the wetting layer formed more easily. For LPS films, with a decreased annealing temperature, the stability of the polymer film changed from non-slip dewetting via apparent slip dewetting to apparently stable. However, for RPS films, the polymer film stability switched from apparent slip dewetting to apparently stable. On the silanized Si substrate with 94% grafting density, the chain adsorption became weaker and the dewetting processes were faster than that on the substrate with 69% grafting density at the same experimental temperature for both the LPS and RPS films. Moreover, on the PDMS substrate, LPS films always showed non-slip dewetting, while the dewetting kinetics of RPS films switched from non-slip dewetting to slip dewetting behaviour. Forming the wetting layer strongly influenced the stability and dewetting behavior of the thin polymer films.

  19. Continuous-time quantum walks on multilayer dendrimer networks

    Galiceanu, Mircea; Strunz, Walter T.

    2016-08-01

    We consider continuous-time quantum walks (CTQWs) on multilayer dendrimer networks (MDs) and their application to quantum transport. A detailed study of properties of CTQWs is presented and transport efficiency is determined in terms of the exact and average return probabilities. The latter depends only on the eigenvalues of the connectivity matrix, which even for very large structures allows a complete analytical solution for this particular choice of network. In the case of MDs we observe an interplay between strong localization effects, due to the dendrimer topology, and good efficiency from the linear segments. We show that quantum transport is enhanced by interconnecting more layers of dendrimers.

  20. Pulse radiolysis studies concerning oxidative degradation processes in linear polymers

    Schnabel, Wolfram

    1986-01-01

    On the basis of pulse radiolysis experiments carried out with various polymers in dilute solution three modes of action of molecular oxygen, 0 2 , can be discriminated with respect to main-chain scission: (a) 0 2 acts as a promoter, (b) 0 2 acts as an inhibitor, and (c) 0 2 acts as a fixing agent for main-chain breaks. The promoting mode of action (a) is due to the inhibition of simultaneously occurring intermolecular crosslinking (DNA, polymethylvinylketone) and/or to the combination of peroxyl radicals with the subsequent formation of readily decomposing oxyl radicals (polyethylene oxide, polyacrylamide, polyvinylpyrrolidone, polyribouridylic acid, polyriboadenylic acid, polyribocytidylic acid). The inhibiting mode of action (b) pertains to the reaction of 0 2 with macroradicals that otherwise undergo main-chain rupture (amylose polymethylmethacrylate). Fixing of main-chain ruptures (mode c) becomes important, if macroradicals generated by a very fast rupture of bonds in the main-chain, are prone to recombine quickly. This mode of action was evidenced in the case of polybutenesulfone where main-chain scission involves the extrusion of small segments of the chain. (author)

  1. An intrinsically fluorescent dendrimer as a nanoprobe of cell transport.

    Al-Jamal, Khuloud T; Ruenraroengsak, Pakatip; Hartell, Nicholas; Florence, Alexander T

    2006-07-01

    Dendrimers, spherical or quasi-spherical synthetic polymers in the nano-size range, have found useful applications as prospective carriers in drug and gene delivery. The investigation of dendrimer uptake by cells has been previously achieved by the incorporation of a fluorescent dye to the dendrimer either by chemical conjugation or by physical interaction. Here we describe the synthesis of two intrinsically fluorescent lysine based cationic dendrimers which lack a fluorophore, but which has sufficient fluorescence intensity to be detected at low concentrations. The nomenclature used to describe our compounds results in, for example the 6th generation dendrimer being notated as Gly-Lys(63) (NH2)(64); Gly denotes that the compound has a glycine in the core coupled to 63 lysine branching units (Lys(63)) and that the surface has 64 free amino groups (NH2)(64). The use of these dendrimers in probing transport avoids the need for fluorescent tagging with its attendant problems. The uptake of Gly-Lys(63) (NH2)(64) into Caco-2 cells was followed using confocal microscopy. Being cationic, it first adsorbs to the cell surface, enters the cytoplasm and reaches the nucleus within 35-45 min. Estimates of the diffusion coefficient of the dendrimer within the cell cytoplasm leads to a value of 6.27 ( +/- 0.49) x 10(-11) cm(2) s(-1), which is up to 1000 times lower than the diffusion coefficient of the dendrimer in water. Intrinsically fluorescent dendrimers of different size and charge are useful probes of transport in cells.

  2. Phosphorus dendrimers for nanomedicine.

    Caminade, Anne-Marie

    2017-08-31

    From biomaterials to imaging, and from drug delivery to drugs by themselves, phosphorus-containing dendrimers offer a large palette of biological properties, depending essentially on their types of terminal functions. The most salient examples of phosphorus dendrimers used for the elaboration of bio-chips and of supports for cell cultures, for imaging biological events, and for carrying and delivering drugs or biomacromolecules are presented in this feature article. Several phosphorus dendrimers can be considered also as drugs per se (by themselves) in particular to fight against cancers, neurodegenerative diseases, and inflammation, both in vitro and in vivo. Toxicity assays are also reported.

  3. Dendrimers in drug research

    Boas, Ulrik; Heegaard, Peter M. H.

    2004-01-01

    and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers may be used as drugs...... for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host-guest binding motifs directed towards medical applications is described. Other specific examples...

  4. Understanding constraint release in star/linear polymer blends

    Shivokhin, M. E.

    2014-04-08

    In this paper, we exploit the stochastic slip-spring model to quantitatively predict the stress relaxation dynamics of star/linear blends with well-separated longest relaxation times and we analyze the results to assess the validity limits of the two main models describing the corresponding relaxation mechanisms within the framework of the tube picture (Doi\\'s tube dilation and Viovy\\'s constraint release by Rouse motions of the tube). Our main objective is to understand and model the stress relaxation function of the star component in the blend. To this end, we divide its relaxation function into three zones, each of them corresponding to a different dominating relaxation mechanism. After the initial fast Rouse motions, relaxation of the star is dominated at intermediate times by the "skinny" tube (made by all topological constraints) followed by exploration of the "fat" tube (made by long-lived obstacles only). At longer times, the tube dilation picture provides the right shape for the relaxation of the stars. However, the effect of short linear chains results in time-shift factors that have never been described before. On the basis of the analysis of the different friction coefficients involved in the relaxation of the star chains, we propose an equation predicting these time-shift factors. This allows us to develop an analytical equation combining all relaxation zones, which is verified by comparison with simulation results. © 2014 American Chemical Society.

  5. Dendrimer sensors probed with neutron reflectometry

    Cavaye, Hamish; Smith, Arthur R.G.; Burn, Paul L.; Lo, Shih-Chun; Meredith, Paul; Gentle, Ian R.; James, Michael; Nelson, Andrew

    2009-01-01

    Full text: Oxidative photoluminescence (PL) quenching utilizing conjugated polymers as the sensing has proved to be one of the best of many methods for sensing explosive analytes.[1] However are a number of issues that can make polymers difficult to work with, including complex morphologies reproducibility of syntheses, and the need to include elaborate structures to reduce the packing of the polymer chains. Dendrimers, consisting of a core, dendrons, and surface groups, address these issues by being monodisperse and modular in their design. Determining how analytes are sequestered into thin films is important for solid-state sensors. We show that thin (230 ± 30 A ) and thick (750 ± 50 A) films of a first-generation dendrimer comrised of 2-ethylhexyloxy surface groups, biphenyl-based dendrons, and a 9,9,9',9'-tetra-n-propyl-2,2'-bifluorene core, can rapidly and reversibly detect p-nitrotoll oxidative luminescence quenching. For both the thin and thick films the PL is quenched by just 4 s . Combined PL and neutron reflectometry measurements on pristine and analyte-satura showed that during the adsorption process the films swelled, being on average 4% thicker for thin and thick dendrimer films. At the same time the PL was completely quenched. On removal of the analyte the films returned to their original thickness and scattering length density, and the restored, showing that the sensing process was fully reversible.

  6. Dendrimers in Medicine

    Wu, Linping; Ficker, Mario; Christensen, Jørn Bolstad

    2015-01-01

    Dendrimers are three-dimensional macromolecular structures originating from a central core molecule and surrounded by successive addition of branching layers (generation). These structures exhibit a high degree of molecular uniformity, narrow molecular weight distribution, tunable size and shape ...

  7. Flow-induced correlation effects within a linear chain in a polymer melt

    Stepanyan, R.; Slot, J.J.M.; Molenaar, J.; Tchesnokov, M.A.

    2005-01-01

    A framework for a consistent description of the flow-induced correlation effects within a linear polymer chain in a melt is proposed. The formalism shows how correlations between chain segments in the flow can be incorporated into a hierarchy of distribution functions for tangent vectors. The

  8. Glycopeptide dendrimers. Part II

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2008-01-01

    Roč. 14, č. 1 (2008), s. 44-65 ISSN 1075-2617 R&D Projects: GA ČR GA203/03/1362; GA ČR GA203/06/1272; GA MZe QF3115; GA AV ČR KAN200520703 Institutional research plan: CEZ:AV0Z40550506 Keywords : artificial virus * cascade-release dendrimers * glycopeptide dendrimers * glycoconjugate * glycopeptides Subject RIV: CC - Organic Chemistry Impact factor: 1.654, year: 2008

  9. Noncovalent synthesis of protein dendrimers

    Lempens, E.H.M.; Baal, van I.; Dongen, van J.L.J.; Hackeng, T.M.; Merkx, M.; Meijer, E.W.

    2009-01-01

    The covalent synthesis of complex biomolecular systems such as multivalent protein dendrimers often proceeds with low efficiency, thereby making alternative strategies based on noncovalent chemistry of high interest. Here, the synthesis of protein dendrimers using a strong but noncovalent

  10. Structure of Carbon Nanotube-dendrimer composite

    Vasumathi, V.; Pramanik, Debabrata; Sood, A. K.; Maiti, Prabal K

    2012-01-01

    Using all atomistic molecular dynamics (MD) simulations we report the microscopic picture of the nanotube-dendrimer complex for PAMAM dendrimer of generation 2 to 4 and carbon nanotube of chirality (6,5). We find compact wrapping conformations of dendrimer onto the nanotube surface for all the three generations of PAMAM dendrimer. The degree of wrapping is more for non-protonated dendrimer compared to the protonated dendrimer. For comparison we also study the interaction of another dendrimer,...

  11. Polymerization of a divalent/tetravalent metal-storing atom-mimicking dendrimer

    Albrecht, Ken; Hirabayashi, Yuki; Otake, Masaya; Mendori, Shin; Tobari, Yuta; Azuma, Yasuo; Majima, Yutaka; Yamamoto, Kimihisa

    2016-01-01

    The phenylazomethine dendrimer (DPA) has a layer-by-layer electron density gradient that is an analog of the Bohr atom (atom mimicry). In combination with electron pair mimicry, the polymerization of this atom-mimicking dendrimer was achieved. The valency of the mimicked atom was controlled by changing the chemical structure of the dendrimer. By mimicking a divalent atom, a one-dimensional (1D) polymer was obtained, and by using a planar tetravalent atom mimic, a 2D polymer was obtained. Thes...

  12. Polarization holograms in a bifunctional amorphous polymer exhibiting equal values of photoinduced linear and circular birefringences.

    Provenzano, Clementina; Pagliusi, Pasquale; Cipparrone, Gabriella; Royes, Jorge; Piñol, Milagros; Oriol, Luis

    2014-10-09

    Light-controlled molecular alignment is a flexible and useful strategy introducing novelty in the fields of mechanics, self-organized structuring, mass transport, optics, and photonics and addressing the development of smart optical devices. Azobenzene-containing polymers are well-known photocontrollable materials with large and reversible photoinduced optical anisotropies. The vectorial holography applied to these materials enables peculiar optical devices whose properties strongly depend on the relative values of the photoinduced birefringences. Here is reported a polarization holographic recording based on the interference of two waves with orthogonal linear polarization on a bifunctional amorphous polymer that, exceptionally, exhibits equal values of linear and circular birefringence. The peculiar photoresponse of the material coupled with the holographic technique demonstrates an optical device capable of decomposing the light into a set of orthogonally polarized linear components. The holographic structures are theoretically described by the Jones matrices method and experimentally investigated.

  13. Oligodeoxynucleotide nanostructure formation in the presence of polypropyleneimine dendrimers and their uptake in breast cancer cells

    Chen, Alex M; Santhakumaran, Latha M; Nair, Sandhya K; Amenta, Peter S; Thomas, Thresia; He, Huixin; Thomas, T J

    2006-01-01

    We studied the efficacy of five generations of polypropyleneimine (PPI) dendrimer to provoke nanostructure formation from a 21-nucleotide antisense oligodeoxynucleotide (ODN). Nanostructure formation was observed with all generations of dendrimer by light scattering and microscopic techniques. The efficacy of the dendrimers increased with generation number. Atomic force microscopy (AFM) was used to study the morphology of the structures at different condensation stages. Based on the observed nanostructures, we propose a zipping condensation mechanism, which is very different from the condensation pathways of high molecular weight DNA polymers. Electron microscopy showed the presence of toroidal nanoparticles. Confocal microscopic analysis showed that the nanostructures formed with G-4 and G-5 dendrimers could undergo facile cellular uptake in a breast cancer cell line, MDA-MB-231, whereas nanostructures formed with G-1 to G-3 dendrimers lacked this ability. Nanoparticles formed with G-1 to G-3 dendrimers showed significantly lower zeta potential (5.2-6.5 mV) than those (12-18 mV) of particles formed with G-4 and G-5 dendrimers. These results show that the structure and charge density of the dendrimers are important in ODN nanoparticle formation and cellular transport and that G-4 and G-5 dendrimers are useful in cellular delivery of antisense ODN

  14. Oligodeoxynucleotide nanostructure formation in the presence of polypropyleneimine dendrimers and their uptake in breast cancer cells

    Chen, Alex M [Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102 (United States); Santhakumaran, Latha M [Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States); Nair, Sandhya K [Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States); Amenta, Peter S [Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States); Thomas, Thresia [Department of Environmental and Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States); He, Huixin [Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102 (United States); Thomas, T J [Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States)

    2006-11-14

    We studied the efficacy of five generations of polypropyleneimine (PPI) dendrimer to provoke nanostructure formation from a 21-nucleotide antisense oligodeoxynucleotide (ODN). Nanostructure formation was observed with all generations of dendrimer by light scattering and microscopic techniques. The efficacy of the dendrimers increased with generation number. Atomic force microscopy (AFM) was used to study the morphology of the structures at different condensation stages. Based on the observed nanostructures, we propose a zipping condensation mechanism, which is very different from the condensation pathways of high molecular weight DNA polymers. Electron microscopy showed the presence of toroidal nanoparticles. Confocal microscopic analysis showed that the nanostructures formed with G-4 and G-5 dendrimers could undergo facile cellular uptake in a breast cancer cell line, MDA-MB-231, whereas nanostructures formed with G-1 to G-3 dendrimers lacked this ability. Nanoparticles formed with G-1 to G-3 dendrimers showed significantly lower zeta potential (5.2-6.5 mV) than those (12-18 mV) of particles formed with G-4 and G-5 dendrimers. These results show that the structure and charge density of the dendrimers are important in ODN nanoparticle formation and cellular transport and that G-4 and G-5 dendrimers are useful in cellular delivery of antisense ODN.

  15. Oligodeoxynucleotide nanostructure formation in the presence of polypropyleneimine dendrimers and their uptake in breast cancer cells

    Chen, Alex M.; Santhakumaran, Latha M.; Nair, Sandhya K.; Amenta, Peter S.; Thomas, Thresia; He, Huixin; Thomas, T. J.

    2006-11-01

    We studied the efficacy of five generations of polypropyleneimine (PPI) dendrimer to provoke nanostructure formation from a 21-nucleotide antisense oligodeoxynucleotide (ODN). Nanostructure formation was observed with all generations of dendrimer by light scattering and microscopic techniques. The efficacy of the dendrimers increased with generation number. Atomic force microscopy (AFM) was used to study the morphology of the structures at different condensation stages. Based on the observed nanostructures, we propose a zipping condensation mechanism, which is very different from the condensation pathways of high molecular weight DNA polymers. Electron microscopy showed the presence of toroidal nanoparticles. Confocal microscopic analysis showed that the nanostructures formed with G-4 and G-5 dendrimers could undergo facile cellular uptake in a breast cancer cell line, MDA-MB-231, whereas nanostructures formed with G-1 to G-3 dendrimers lacked this ability. Nanoparticles formed with G-1 to G-3 dendrimers showed significantly lower zeta potential (5.2-6.5 mV) than those (12-18 mV) of particles formed with G-4 and G-5 dendrimers. These results show that the structure and charge density of the dendrimers are important in ODN nanoparticle formation and cellular transport and that G-4 and G-5 dendrimers are useful in cellular delivery of antisense ODN.

  16. Poly (amidoamine) dendrimer-mediated hybrid formulation for combination therapy of ramipril and hydrochlorothiazide.

    Singh, Mayank Kumar; Pooja, Deep; Kulhari, Hitesh; Jain, Sanjay Kumar; Sistla, Ramakrishna; Chauhan, Abhay Singh

    2017-01-01

    We present a dendrimer-based hybrid formulation strategy to explore the potential of poly (amidoamine) PAMAM dendrimers to be used as drug carriers for combination therapy of an anti-hypertensive drug ramipril (RAPL) and a diuretic hydrochlorothiazide (HCTZ). The drug-dendrimer complexes were prepared by phase-equilibration method. The results showed that the solubility of RAPL and HCTZ was dependent on dendrimer concentration and pH of dendrimer solution. The solubility profile of both RAPL and HCTZ dendrimer complexes illustrated a non-linear relationship with dendrimer concentration. At 0.8% (w/v) dendrimer concentration, solubility of RAPL was increased 4.91 folds with amine-terminated while for HCTZ, solubility enhancement was highest (3.72 folds) with carboxy-terminated. The complexes were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis and high performance liquid chromatography. In-vitro drug dissolution performance of pure drugs, individual drug loaded dendrimer formulations and hybrid formulations was studied in USP dissolution medium (pH7.0) and in simulated gastric fluid (pH1.2). Dendrimer mediated formulations showed faster and complete dissolution compared to pure RAPL or HCTZ. Surprisingly, similar pattern of dissolution profile was established with hybrid formulations as compared to individual drug loaded dendrimers. The dendrimer-based hybrid formulations were found to be stable at dark and refrigerated conditions up to 5weeks. Conclusively, the proposed formulation strategy establishes a novel multitasking platform using dendrimer for simultaneous loading and delivery of multiple drugs for pharmaceutical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Fluorescent quantum dot hydrophilization with PAMAM dendrimer

    Potapkin, Dmitry V.; Geißler, Daniel; Resch-Genger, Ute; Goryacheva, Irina Yu.

    2016-05-01

    Polyamidoamine (PAMAM) dendrimers were used to produce CdSe core/multi-shell fluorescent quantum dots (QDs) which are colloidally stable in aqueous solutions. The size, charge, and optical properties of QDs functionalized with the 4th (G4) and 5th (G5) generation of PAMAM were compared with amphiphilic polymer-covered QDs and used as criteria for the evaluation of the suitability of both water solubilization methods. As revealed by dynamic and electrophoretic light scattering (DLS and ELS), the hydrodynamic sizes of the QDs varied from 30 to 65 nm depending on QD type and dendrimer generation, with all QDs displaying highly positive surface charges, i.e., zeta potentials of around +50 mV in water. PAMAM functionalization yielded stable core/multi-shell QDs with photoluminescence quantum yields ( Φ) of up to 45 %. These dendrimer-covered QDs showed a smaller decrease in their Φ upon phase transfer compared with QDs made water soluble via encapsulation with amphiphilic brush polymer bearing polyoxyethylene/polyoxypropylene chains.

  18. Fluorescent quantum dot hydrophilization with PAMAM dendrimer

    Potapkin, Dmitry V., E-mail: potapkindv@gmail.com [Saratov State University, Department of General and Inorganic Chemistry, Chemistry Institute (Russian Federation); Geißler, Daniel, E-mail: daniel.geissler@bam.de; Resch-Genger, Ute, E-mail: ute.resch@bam.de [BAM - Federal Institute for Materials Research and Testing (Germany); Goryacheva, Irina Yu., E-mail: goryachevaiy@mail.ru [Saratov State University, Department of General and Inorganic Chemistry, Chemistry Institute (Russian Federation)

    2016-05-15

    Polyamidoamine (PAMAM) dendrimers were used to produce CdSe core/multi-shell fluorescent quantum dots (QDs) which are colloidally stable in aqueous solutions. The size, charge, and optical properties of QDs functionalized with the 4th (G4) and 5th (G5) generation of PAMAM were compared with amphiphilic polymer-covered QDs and used as criteria for the evaluation of the suitability of both water solubilization methods. As revealed by dynamic and electrophoretic light scattering (DLS and ELS), the hydrodynamic sizes of the QDs varied from 30 to 65 nm depending on QD type and dendrimer generation, with all QDs displaying highly positive surface charges, i.e., zeta potentials of around +50 mV in water. PAMAM functionalization yielded stable core/multi-shell QDs with photoluminescence quantum yields (Φ) of up to 45 %. These dendrimer-covered QDs showed a smaller decrease in their Φ upon phase transfer compared with QDs made water soluble via encapsulation with amphiphilic brush polymer bearing polyoxyethylene/polyoxypropylene chains.

  19. Exciton confinement in organic dendrimer quantum wells for opto-electronic applications

    Lupton, J. M.; Samuel, I. D. W.; Burn, P. L.; Mukamel, S.

    2002-01-01

    Organic dendrimers are a fascinating new class of materials for opto-electronic applications. We present coupled electronic oscillator calculations on novel nanoscale conjugated dendrimers for use in organic light-emitting diodes. Strong confinement of excitations at the center of the dendrimers is observed, which accounts for the dependence of intermolecular interactions and charge transport on the degree of branching of the dendrimer. The calculated absorption spectra are in excellent agreement with the measured data and show that benzene rings are shared between excitations on the linear segments of the hyperbranched molecules. The coupled electronic oscillator approach is ideally suited to treat large dendritic molecules.

  20. Effects of Grafting Density on Block Polymer Self-Assembly: From Linear to Bottlebrush.

    Lin, Tzu-Pin; Chang, Alice B; Luo, Shao-Xiong; Chen, Hsiang-Yun; Lee, Byeongdu; Grubbs, Robert H

    2017-11-28

    Grafting density is an important structural parameter that exerts significant influences over the physical properties of architecturally complex polymers. In this report, the physical consequences of varying the grafting density (z) were studied in the context of block polymer self-assembly. Well-defined block polymers spanning the linear, comb, and bottlebrush regimes (0 ≤ z ≤ 1) were prepared via grafting-through ring-opening-metathesis polymerization. ω-Norbornenyl poly(d,l-lactide) and polystyrene macromonomers were copolymerized with discrete comonomers in different feed ratios, enabling precise control over both the grafting density and molecular weight. Small-angle X-ray scattering experiments demonstrate that these graft block polymers self-assemble into long-range-ordered lamellar structures. For 17 series of block polymers with variable z, the scaling of the lamellar period with the total backbone degree of polymerization (d* ∼ N bb α ) was studied. The scaling exponent α monotonically decreases with decreasing z and exhibits an apparent transition at z ≈ 0.2, suggesting significant changes in the chain conformations. Comparison of two block polymer systems, one that is strongly segregated for all z (System I) and one that experiences weak segregation at low z (System II), indicates that the observed trends are primarily caused by the polymer architectures, not segregation effects. A model is proposed in which the characteristic ratio (C ∞ ), a proxy for the backbone stiffness, scales with N bb as a function of the grafting density: C ∞ ∼ N bb f(z) . The scaling behavior disclosed herein provides valuable insights into conformational changes with grafting density, thus introducing opportunities for block polymer and material design.

  1. Preclinical studies of dendrimer prodrugs.

    Kojima, Chie

    2015-01-01

    Dendrimers are synthetic macromolecules with well-defined structures bearing a wide variety of functional groups on their periphery. These groups can be used to conjugate bioactive molecules such as drugs, ligands and imaging agents. Dendrimer prodrugs can be used to improve the water solubility and pharmacokinetic properties of the corresponding free drugs. This article summarizes preclinical studies pertaining to the use of drug-dendrimer conjugates as dendrimer prodrugs for the treatments of various diseases, including cancer and inflammatory diseases. A wide range of anticancer drugs have been conjugated to dendrimers via biodegradable linkers. The side effects of the parent drugs can be markedly reduced using dendrimer prodrugs, with some drugs showing improved efficacy. Anti-inflammatory agents have also been conjugated to dendrimers and used to treat a number of inflammatory diseases. Drug-dendrimer conjugates are preferable to drug-dendrimer complexes, where the use of degradable linkers is critical to the release of the drug. Polyethylene glycol and/or ligands can be added to a dendrimer prodrug, which is useful for the targeting of affected tissues. Imaging probes can also be incorporated into dendrimer prodrugs for the simultaneous delivery of therapeutic and diagnostic agents as 'theranostics.'

  2. Synthesis and biological evaluation of boronated polyglycerol dendrimers as potential agent for neutron capture therapy

    Silva, Gerald S.; Camillo, Maria A.P.; Higa, Olga Z.; Pugliesi, Reynaldo; Fermamdes, Edson G.R.; Queiroz, Alvaro A.A. de

    2005-01-01

    In this work, the polyglycerol dendrimer (PGLD) generation 5 was used to obtain a boronated macromolecule for boron neutron capture therapy. The PGLD dendrimer was synthesized by the ring opening polymerization of deprotonated glycidol using polyglycerol as core functionality in a step-growth processes denominated divergent synthesis. The PGLD dendritic structure was confirmed by gel permeation chromatography, nuclear magnetic resonance ( 1 H-NMR, 13 C-NMR) and matrix assisted laser desorption/ionization techniques. The synthesized dendrimer presented low dispersion in molecular weights (M w /M n = 1.05) and a degree of branching of 0.82, which characterize the polymer dendritic structure. Quantitative neutron capture radiography was used to investigate the boron-10 enrichment of the polyglycerol dendrimer. The in vitro cytotoxicity to Chinese hamster ovary cells of 10 B-PGLD dendrimer indicate lower cytotoxicity, suggesting that the macromolecule is a biocompatible material. (author)

  3. A bifunctional amorphous polymer exhibiting equal linear and circular photoinduced birefringences.

    Royes, Jorge; Provenzano, Clementina; Pagliusi, Pasquale; Tejedor, Rosa M; Piñol, Milagros; Oriol, Luis

    2014-11-01

    The large and reversible photoinduced linear and circular birefringences in azo-compounds are at the basis of the interest in these materials, which are potentially useful for several applications. Since the onset of the linear and circular anisotropies relies on orientational processes, which typically occur on the molecular and supramolecular length scale, respectively, a circular birefringence at least one order of magnitude lower than the linear one is usually observed. Here, the synthesis and characterization of an amorphous polymer with a dimeric repeating unit containing a cyanoazobenzene and a cyanobiphenyl moiety are reported, in which identical optical linear and circular birefringences are induced for proper light dose and ellipticity. A pump-probe technique and an analytical method based on the Stokes-Mueller formalism are used to investigate the photoinduced effects and to evaluate the anisotropies. The peculiar photoresponse of the polymer makes it a good candidate for applications in smart functional devices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. pH and generation dependent morphologies of PAMAM dendrimers on a graphene substrate.

    Gosika, Mounika; Maiti, Prabal K

    2018-03-07

    The adsorption of PAMAM dendrimers at solid/water interfaces has been extensively studied, and is mainly driven by electrostatic and van der Waals interactions between the substrate and the dendrimers. However, the pH dependence of the adsorption driven predominantly by the van der Waals interactions is poorly explored, although it is crucial for investigating the potentiality of these dendrimers in supercapacitors and surface patterning. Motivated by this aspect, we have studied the adsorption behavior of PAMAM dendrimers of generations 2 (G2) to 5 (G5) with pH and salt concentration variation, on a charge neutral graphene substrate, using fully atomistic molecular dynamics simulations. The instantaneous snapshots from our simulations illustrate that the dendrimers deform significantly from their bulk structures. Based on various structural property calculations, we classify the adsorbed dendrimer morphologies into five categories and map them to a phase diagram. Interestingly, the morphologies we report here have striking analogies with those reported in star-polymer adsorption studies. From the fractional contacts and other structural property analyses we find that the deformations are more pronounced at neutral pH as compared to high and low pH. Higher generation dendrimers resist deformation following the deformation trend, G2 > G3 > G4 > G5 at any given pH level. As the adsorption here is mainly driven by van der Waals interactions, we observe no desorption of the dendrimers as the salt molarity is increased, unlike that reported in the electrostatically driven adsorption studies.

  5. Understanding Effect of Constraint Release Environment on End-to-End Vector Relaxation of Linear Polymer Chains

    Shivokhin, Maksim E.; Read, Daniel J.; Kouloumasis, Dimitris; Kocen, Rok; Zhuge, Flanco; Bailly, Christian; Hadjichristidis, Nikolaos; Likhtman, Alexei E.

    2017-01-01

    of a linear probe chain. For this purpose we first validate the ability of the model to consistently predict both the viscoelastic and dielectric response of monodisperse and binary mixtures of type A polymers, based on published experimental data. We

  6. Recent Advances in Click Chemistry Applied to Dendrimer Synthesis

    Mathieu Arseneault

    2015-05-01

    Full Text Available Dendrimers are monodisperse polymers grown in a fractal manner from a central point. They are poised to become the cornerstone of nanoscale devices in several fields, ranging from biomedicine to light-harvesting. Technical difficulties in obtaining these molecules has slowed their transfer from academia to industry. In 2001, the arrival of the “click chemistry” concept gave the field a major boost. The flagship reaction, a modified Hüisgen cycloaddition, allowed researchers greater freedom in designing and building dendrimers. In the last five years, advances in click chemistry saw a wider use of other click reactions and a notable increase in the complexity of the reported structures. This review covers key developments in the click chemistry field applied to dendrimer synthesis from 2010 to 2015. Even though this is an expert review, basic notions and references have been included to help newcomers to the field.

  7. Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

    Sonam Choudhary

    2017-05-01

    Full Text Available Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed.

  8. Synthesis of a cationic thermoresponsive dendrimer and its self-assembly with apoferritin protein cage

    Välimäki, Salla

    2015-01-01

    The aim of this work was to synthesize cationic dendrimer with a thermoresponsive polymer tail and complex the dendrimer with negatively charged apoferritin protein nanocage. These kind of systems are developed, for example, for biomedical applications. Spermine dendron with atom transfer radical polymerization initiator in focal point was synthesized successfully. Thermoresponsive poly(di(ethylene glycol) methyl ether methacrylate) was in situ polymerized to the dendron to form the therm...

  9. Comparison of Properties among Dendritic and Hyperbranched Poly(ether ether ketones and Linear Poly(ether ketones

    Atsushi Morikawa

    2016-02-01

    Full Text Available Poly(ether ether ketone dendrimers and hyperbranched polymers were prepared from 3,5-dimethoxy-4′-(4-fluorobenzoyldiphenyl ether and 3,5-dihydroxy-4′-(4-fluorobenzoyldiphenyl ether through aromatic nucleophilic substitution reactions. 1-(tert-Butyldimethylsiloxy-3,5-bis(4-fluorobenzoylbenzene was polycondensed with bisphenols, followed by cleavage of the protective group to form linear poly(ether ketones having the same hydroxyl groups in the side chains as the chain ends of the dendrimer and hyperbranched polymers. Their properties, such as solubilities, reduced viscosities, and thermal properties, were compared with one another. Similar comparisons were also carried out among the corresponding methoxy group polymers, and the size of the molecules was shown to affect the properties.

  10. Intracellular Ca2+ release mediates cationic but not anionic poly(amidoamine) (PAMAM) dendrimer-induced tight junction modulation.

    Avaritt, Brittany R; Swaan, Peter W

    2014-09-01

    Poly(amidoamine) (PAMAM) dendrimers show great promise for utilization as oral drug delivery vehicles. These polymers are capable of traversing epithelial barriers, and have been shown to translocate by both transcellular and paracellular routes. While many proof-of-concept studies have shown that PAMAM dendrimers improve intestinal transport, little information exists on the mechanisms of paracellular transport, specifically dendrimer-induced tight junction modulation. Using anionic G3.5 and cationic G4 PAMAM dendrimers with known absorption enhancers, we investigated tight junction modulation in Caco-2 monolayers by visualization and mannitol permeability and compared dendrimer-mediated tight junction modulation to that of established permeation enhancers. [(14)C]-Mannitol permeability in the presence and absence of phospholipase C-dependent signaling pathway inhibitors was also examined and indicated that this pathway may mediate dendrimer-induced changes in permeability. Differences between G3.5 and G4 in tight junction protein staining and permeability with inhibitors were evident, suggesting divergent mechanisms were responsible for tight junction modulation. These dissimilarities are further intimated by the intracellular calcium release caused by G4 but not G3.5. Based on our results, it is apparent that the underlying mechanisms of dendrimer permeability are complex, and the complexities are likely a result of the density and sign of the surface charges of PAMAM dendrimers. The results of this study will have implications on the future use of PAMAM dendrimers for oral drug delivery.

  11. DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

    2004-01-01

    Dendrimer conjugates are presented, which are formed between a dendrimer and a protein solubilising substance. Such dendrimer conjugates are effective in the treatment of protein aggregate-related diseases (e.g. prion-related diseases). The protein solubilising substance and the dendrimer together...

  12. Macromolecular 'size' and 'hardness' drives structure in solvent-swollen blends of linear, cyclic, and star polymers.

    Gartner, Thomas E; Jayaraman, Arthi

    2018-01-17

    In this paper, we apply molecular simulation and liquid state theory to uncover the structure and thermodynamics of homopolymer blends of the same chemistry and varying chain architecture in the presence of explicit solvent species. We use hybrid Monte Carlo (MC)/molecular dynamics (MD) simulations in the Gibbs ensemble to study the swelling of ∼12 000 g mol -1 linear, cyclic, and 4-arm star polystyrene chains in toluene. Our simulations show that the macroscopic swelling response is indistinguishable between the various architectures and matches published experimental data for the solvent annealing of linear polystyrene by toluene vapor. We then use standard MD simulations in the NPT ensemble along with polymer reference interaction site model (PRISM) theory to calculate effective polymer-solvent and polymer-polymer Flory-Huggins interaction parameters (χ eff ) in these systems. As seen in the macroscopic swelling results, there are no significant differences in the polymer-solvent and polymer-polymer χ eff between the various architectures. Despite similar macroscopic swelling and effective interaction parameters between various architectures, the pair correlation function between chain centers-of-mass indicates stronger correlations between cyclic or star chains in the linear-cyclic blends and linear-star blends, compared to linear chain-linear chain correlations. Furthermore, we note striking similarities in the chain-level correlations and the radius of gyration of cyclic and 4-arm star architectures of identical molecular weight. Our results indicate that the cyclic and star chains are 'smaller' and 'harder' than their linear counterparts, and through comparison with MD simulations of blends of soft spheres with varying hardness and size we suggest that these macromolecular characteristics are the source of the stronger cyclic-cyclic and star-star correlations.

  13. Compositional analysis of nitrile terminated poly(propylene imine) dendrimers by high-performance liquid chromatography combined with electrospray mass spectrometry

    van der Wal, S; Mengerink, Y; Brackman, JC; de Brabander, EMM; Jeronimus-Stratingh, CM; Bruins, AP

    1998-01-01

    Separation methods for nitrile terminated poly(propylene imine) dendrimers were developed to monitor and optimize their large scale production. Detailed analyses of defects within a dendrimer generation were performed by HPLC at alkaline pH (sodium hydroxide) on a polymer-based column or at neutral

  14. Exciton localization-delocalization transition in an extended dendrimer

    Pouthier, Vincent, E-mail: vincent.pouthier@univ-fcomte.fr [Institut UTINAM, Université de Franche-Comté, CNRS UMR 6213, 25030 Besançon Cedex (France)

    2013-12-21

    Exciton-mediated quantum state transfer between the periphery and the core of an extended dendrimer is investigated numerically. By mapping the dynamics onto that of a linear chain, it is shown that a localization-delocalization transition arises for a critical value of the generation number G{sub c} ≈ 5. This transition originates in the quantum interferences experienced by the excitonic wave due to the multiple scatterings that arise each time the wave tunnels from one generation to another. These results suggest that only small-size dendrimers could be used for designing an efficient quantum communication protocol.

  15. Exciton localization-delocalization transition in an extended dendrimer

    Pouthier, Vincent

    2013-01-01

    Exciton-mediated quantum state transfer between the periphery and the core of an extended dendrimer is investigated numerically. By mapping the dynamics onto that of a linear chain, it is shown that a localization-delocalization transition arises for a critical value of the generation number G c ≈ 5. This transition originates in the quantum interferences experienced by the excitonic wave due to the multiple scatterings that arise each time the wave tunnels from one generation to another. These results suggest that only small-size dendrimers could be used for designing an efficient quantum communication protocol

  16. Neutron Reflectometry Investigations of the Interaction of DNA-PAMAM Dendrimers with Model Biological Membranes

    Ainalem, M.L.; Rennie, A.R.; Campbell, Richard; Edler, Karen; Nylander, Tommy

    2009-01-01

    The systemic delivery of DNA for gene therapy requires control of DNA compaction by an agent, such a lipid, surfactant or a polymer (e.g. cationic dendrimers) as well as understanding of how this complex interacts with a biological membrane. Poly (amido amine) (PAMAM) dendrimers have been reported to be a promising synthetic gene-transfection agent. We have studied the structure of the complexes formed between DNA and PAMAM dendrimers with SANS, dynamic light scattering and cryo-TEM. Here we noted that the structure of the complex formed strongly depends on the generation of the dendrimer. The results of the adsorption of generation 2 (G2) and 4 (G4) PAMAM dendrimers to surface deposited bilayers, consisting of palmitoyl oleoyl phosphatidyl choline on silicon surface, have been studied using neutron reflectometry (NR). The NR data shows that the dendrimers are able to penetrate the bilayer. However, the complex is less able to penetrate the bilayer, but rather stays on the top of the bilayer. The dendrimers appear slightly flattened on the surface in comparison with their size in bulk as determined by light scattering. We will also report on the interfacial behavior of the DNA-PAMAM complexes at other types of studies of interfaces, important for biomedical applications, where NR has allowed us to determine the layer structure and composition. (author)

  17. Emerging synthetic strategies for core cross-linked star (CCS) polymers and applications as interfacial stabilizers: bridging linear polymers and nanoparticles.

    Chen, Qijing; Cao, Xueteng; Xu, Yuanyuan; An, Zesheng

    2013-10-01

    Core cross-linked star (CCS) polymers become increasingly important in polymer science and are evaluated in many value-added applications. However, limitations exist to varied degrees for different synthetic methods. It is clear that improvement in synthetic efficiency is fundamental in driving this field moving even further. Here, the most recent advances are highlighted in synthetic strategies, including cross-linking with cross-linkers of low solubility, polymerization-induced self-assembly in aqueous-based heterogeneous media, and cross-linking via dynamic covalent bonds. The understanding of CCS polymers is also further refined to advocate their role as an intermediate between linear polymers and polymeric nanoparticles, and their use as interfacial stabilizers is rationalized within this context. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Molecular dynamics study of the structure and interparticle interactions of polyethylene glycol-conjugated PAMAM dendrimers.

    Lee, Hwankyu; Larson, Ronald G

    2009-10-08

    We performed molecular dynamics (MD) simulations of one or two copies of polyethylene glycol of molecular weight 550 (PEG550) and 5000 (PEG5000) daltons, conjugated to generation 3 (G3) to 5 (G5) polyamidoamine (PAMAM) dendrimers with explicit water using a coarse-grained model. We found the radii of gyration of these dendrimer-PEG molecules to be close to those measured in experiments by Hedden and Bauer (Hedden , R. C. ; Bauer , B. J. Macromolecules 2003 , 36 , 1829.). Densely grafted PEG ligands (>50% of the dendrimer surface) extend like brushes, with layer thickness in agreement with theory for starlike polymers. Two dendrimer-PEG complexes in the box drift away from each other, indicating that no aggregation is induced by either short or long PEG chains, conflicting with a recent view that the cytotoxicity of some PEGylated particles might be due to particle aggregation for long PEG lengths.

  19. Optically nonlinear energy transfer in light-harvesting dendrimers

    Andrews, David; Bradshaw, DS

    2004-01-01

    Dendrimeric polymers are the subject of intense research activity geared towards their implementation in nanodevice applications such as energy harvesting systems,organic light-emitting diodes, photosensitizers, low-threshold lasers, and quantum logic elements, etc. A recent development in this area has been the construction of dendrimers specifically designed to exhibit novel forms of optical nonlinearity, exploiting the unique properties of these materials at high levels of photon flux. Sta...

  20. Linear and Nonlinear Rheology Combined with Dielectric Spectroscopy of Hybrid Polymer Nanocomposites for Semiconductive Applications

    Kádár, Roland; Abbasi, Mahdi; Figuli, Roxana; Rigdahl, Mikael; Wilhelm, Manfred

    2017-01-01

    The linear and nonlinear oscillatory shear, extensional and combined rheology-dielectric spectroscopy of hybrid polymer nanocomposites for semiconductive applications were investigated in this study. The main focus was the influence of processing conditions on percolated poly(ethylene-butyl acrylate) (EBA) nanocomposite hybrids containing graphite nanoplatelets (GnP) and carbon black (CB). The rheological response of the samples was interpreted in terms of dispersion properties, filler distortion from processing, filler percolation, as well as the filler orientation and distribution dynamics inside the matrix. Evidence of the influence of dispersion properties was found in linear viscoelastic dynamic frequency sweeps, while the percolation of the nanocomposites was detected in nonlinearities developed in dynamic strain sweeps. Using extensional rheology, hybrid samples with better dispersion properties lead to a more pronounced strain hardening behavior, while samples with a higher volume percentage of fillers caused a drastic reduction in strain hardening. The rheo-dielectric time-dependent response showed that in the case of nanocomposites containing only GnP, the orientation dynamics leads to non-conductive samples. However, in the case of hybrids, the orientation of the GnP could be offset by the dispersing of the CB to bridge the nanoplatelets. The results were interpreted in the framework of a dual PE-BA model, where the fillers would be concentrated mainly in the BA regions. Furthermore, better dispersed hybrids obtained using mixing screws at the expense of filler distortion via extrusion processing history were emphasized through the rheo-dielectric tests. PMID:28336857

  1. Linearly and circularly polarized laser photoinduced molecular order in azo dye doped polymer films

    Saad Bendaoud

    2017-01-01

    Full Text Available Photo-induced behavior of Azo Disperse one (AZD1 doped Poly(Methyl MethAcrylate (PMMA using both linear and circular polarized light is studied. The anisotropy is not erased by the circular polarization light. The circular polarization light combined with relatively long lifetime of the cis state in azo dye doped polymers activate all transverse directions of the angular hole burning through the spot in the film inducing anisotropy. Under circular polarized light, there is no orientation perpendicularly to the helex described by the rotating electric field vector, trans molecules reorients in the propagation direction of the pump beam. The polarization state of the probe beam after propagation through the pumped spot depends strongly on the angle of incidence of both pump and probe beams on the input face. In the case where circular polarized pump and probe beams are under the same angle of incidence, the probe beam “sees” anisotropic film as if it is isotropic. Results of this work shows the possibility to reorient azobenzene-type molecules in two orthogonal directions using alternately linearly and circularly polarized beams.

  2. Which Dendrimer to Attain the Desired Properties? Focus on Phosphorhydrazone Dendrimers.

    Caminade, Anne-Marie; Majoral, Jean-Pierre

    2018-03-09

    Among the six Critical Nanoscale Design Parameters (CNDPs) proposed by Prof. Donald A. Tomalia, this review illustrates the influence of the sixth one, which concerns the elemental composition, on the properties of dendrimers. After a large introduction that summarizes different types of dendrimers that have been compared with PolyAMidoAMine (PAMAM) dendrimers, this review will focus on the properties of positively and negatively charged phosphorhydrazone (PPH) dendrimers, especially in the field of biology, compared with other types of dendrimers, in particular PAMAM dendrimers, as well as polypropyleneimine (PPI), carbosilane, and p-Lysine dendrimers.

  3. Which Dendrimer to Attain the Desired Properties? Focus on Phosphorhydrazone Dendrimers

    Anne-Marie Caminade

    2018-03-01

    Full Text Available Among the six Critical Nanoscale Design Parameters (CNDPs proposed by Prof. Donald A. Tomalia, this review illustrates the influence of the sixth one, which concerns the elemental composition, on the properties of dendrimers. After a large introduction that summarizes different types of dendrimers that have been compared with PolyAMidoAMine (PAMAM dendrimers, this review will focus on the properties of positively and negatively charged phosphorhydrazone (PPH dendrimers, especially in the field of biology, compared with other types of dendrimers, in particular PAMAM dendrimers, as well as polypropyleneimine (PPI, carbosilane, and p-Lysine dendrimers.

  4. A ligand exchange strategy for one-pot sequential synthesis of (hyperbranched polyethylene)-b-(linear polyketone) block polymers.

    Zhang, Zhichao; Ye, Zhibin

    2012-08-18

    Upon the addition of an equimolar amount of 2,2'-bipyridine, a cationic Pd-diimine complex capable of facilitating "living" ethylene polymerization is switched to catalyze "living" alternating copolymerization of 4-tertbutylstyrene and CO. This unique chemistry is thus employed to synthesize a range of well-defined treelike (hyperbranched polyethylene)-b-(linear polyketone) block polymers.

  5. Elucidating and tuning the strain-induced non-linear behavior of polymer nanocomposites: a detailed molecular dynamics simulation study.

    Shen, Jianxiang; Liu, Jun; Gao, Yangyang; Li, Xiaolin; Zhang, Liqun

    2014-07-28

    By setting up a coarse-grained model of polymer nanocomposites, we monitored the change in the elastic modulus as a function of the strain, derived from the stress-strain behavior by determining uniaxial tension and simple shear of two typical spatial distribution states (aggregation and dispersion) of nanoparticles (NPs). In both these cases, we observed that the elastic modulus decreases non-linearly with the increase of strain and reaches a low plateau at larger strains. This phenomenon is similar to the so-called "Payne effect" for elastomer nanocomposites. Particularly, the modulus of the aggregation case is more sensitive to the imposed strain. By examining the structural parameters, such as the number of neighboring NPs, coordination number of NPs, root-mean-squared average force exerted on the NPs, local strain, chain conformations (bridge, dangle, loop, interface bead and connection bead), and the total interaction energy of NP-polymer and NP-NP, we inferred that the underlying mechanism of the aggregation case is the disintegration of the NP network or clusters formed through direct contact; however, for the dispersion case, the non-linear behavior is attributed to the destruction of the NP network or clusters formed through the bridging of adsorbed polymer segments among the NPs. The former physical network is influenced by NP-NP interaction and NP volume fraction, while the latter is influenced by NP-polymer interaction and NP volume fraction. Lastly, we found that for the dispersion case, further increasing the inter-particle distance or grafting NPs with polymer chains can effectively reduce the non-linear behavior due to the decrease of the physical network density. In general, this simulation work, for the first time, establishes the correlation between the micro-structural evolution and the strain-induced non-linear behavior of polymer nanocomposites, and sheds some light on how to reduce the "Payne effect".

  6. Phosphorus dendrimers and photodynamic therapy. Spectroscopic studies on two dendrimer-photosensitizer complexes: Cationic phosphorus dendrimer with rose bengal and anionic phosphorus dendrimer with methylene blue.

    Dabrzalska, Monika; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2015-08-15

    Dendrimers due to their unique architecture may play an important role in drug delivery systems including chemotherapy, gene therapy and recently, photodynamic therapy as well. We investigated two dendrimer-photosensitizer systems in context of potential use of these systems in photodynamic therapy. The mixtures of an anionic phosphorus dendrimer of the second generation and methylene blue were studied by UV-vis spectroscopy while that of a cationic phosphorus dendrimer (third generation) and rose bengal were investigated by spectrofluorimetric methods. Spectroscopic analysis of these two systems revealed the formation of dendrimer-photosensitizer complexes via electrostatic interactions as well as π stacking. The stoichiometry of the rose bengal-cationic dendrimer complex was estimated to be 7:1 and 9:1 for the methylene blue-anionic dendrimer complex. The results suggest that these polyanionic or polycationic phosphorus dendrimers can be promising candidates as carriers in photodynamic therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Substituted Polyacetylenes Prepared with Rh Catalysts: From Linear to Network-Type Conjugated Polymers

    Sedláček, J.; Balcar, Hynek

    2017-01-01

    Roč. 57, č. 1 (2017), s. 31-51 ISSN 1558-3724 Institutional support: RVO:61388955 Keywords : conjugated polymers * polyacetylenes * conjugated polymer networks Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Polymer science Impact factor: 6.459, year: 2016

  8. Multiple Linear Regression Modeling To Predict the Stability of Polymer-Drug Solid Dispersions: Comparison of the Effects of Polymers and Manufacturing Methods on Solid Dispersion Stability.

    Fridgeirsdottir, Gudrun A; Harris, Robert J; Dryden, Ian L; Fischer, Peter M; Roberts, Clive J

    2018-03-29

    Solid dispersions can be a successful way to enhance the bioavailability of poorly soluble drugs. Here 60 solid dispersion formulations were produced using ten chemically diverse, neutral, poorly soluble drugs, three commonly used polymers, and two manufacturing techniques, spray-drying and melt extrusion. Each formulation underwent a six-month stability study at accelerated conditions, 40 °C and 75% relative humidity (RH). Significant differences in times to crystallization (onset of crystallization) were observed between both the different polymers and the two processing methods. Stability from zero days to over one year was observed. The extensive experimental data set obtained from this stability study was used to build multiple linear regression models to correlate physicochemical properties of the active pharmaceutical ingredients (API) with the stability data. The purpose of these models is to indicate which combination of processing method and polymer carrier is most likely to give a stable solid dispersion. Six quantitative mathematical multiple linear regression-based models were produced based on selection of the most influential independent physical and chemical parameters from a set of 33 possible factors, one model for each combination of polymer and processing method, with good predictability of stability. Three general rules are proposed from these models for the formulation development of suitably stable solid dispersions. Namely, increased stability is correlated with increased glass transition temperature ( T g ) of solid dispersions, as well as decreased number of H-bond donors and increased molecular flexibility (such as rotatable bonds and ring count) of the drug molecule.

  9. Linear and Nonlinear Rheology Combined with Dielectric Spectroscopy of Hybrid Polymer Nanocomposites for Semiconductive Applications

    Roland Kádár

    2017-01-01

    Full Text Available The linear and nonlinear oscillatory shear, extensional and combined rheology-dielectric spectroscopy of hybrid polymer nanocomposites for semiconductive applications were investigated in this study. The main focus was the influence of processing conditions on percolated poly(ethylene-butyl acrylate (EBA nanocomposite hybrids containing graphite nanoplatelets (GnP and carbon black (CB. The rheological response of the samples was interpreted in terms of dispersion properties, filler distortion from processing, filler percolation, as well as the filler orientation and distribution dynamics inside the matrix. Evidence of the influence of dispersion properties was found in linear viscoelastic dynamic frequency sweeps, while the percolation of the nanocomposites was detected in nonlinearities developed in dynamic strain sweeps. Using extensional rheology, hybrid samples with better dispersion properties lead to a more pronounced strain hardening behavior, while samples with a higher volume percentage of fillers caused a drastic reduction in strain hardening. The rheo-dielectric time-dependent response showed that in the case of nanocomposites containing only GnP, the orientation dynamics leads to non-conductive samples. However, in the case of hybrids, the orientation of the GnP could be offset by the dispersing of the CB to bridge the nanoplatelets. The results were interpreted in the framework of a dual PE-BA model, where the fillers would be concentrated mainly in the BA regions. Furthermore, better dispersed hybrids obtained using mixing screws at the expense of filler distortion via extrusion processing history were emphasized through the rheo-dielectric tests.

  10. Super-stretchable metallic interconnects on polymer with a linear strain of up to 100%

    Arafat, Yeasir; Dutta, Indranath; Panat, Rahul, E-mail: Rahul.panat@wsu.edu [School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington 99163 (United States)

    2015-08-24

    Metal interconnects in flexible and wearable devices are heterogeneous metal-polymer systems that are expected to sustain large deformation without failure. The principal strategy to make strain tolerant interconnect lines on flexible substrates has comprised of creating serpentine structures of metal films with either in-plane or out-of-plane waves, using porous substrates, or using highly ductile materials such as gold. The wavy and helical serpentine patterns preclude high-density packing of interconnect lines on devices, while ductile materials such as Au are cost prohibitive for real world applications. Ductile copper films can be stretched if bonded to the substrate, but show high level of cracking beyond few tens of % strain. In this paper, we demonstrate a material system consisting of Indium metal film over an elastomer (PDMS) with a discontinuous Cr layer such that the metal interconnect can be stretched to extremely high linear strain (up to 100%) without any visible cracks. Such linear strain in metal interconnects exceeds that reported in literature and is obtained without the use of any geometrical manipulations or porous substrates. Systematic experimentation is carried out to explain the mechanisms that allow the Indium film to sustain the high strain level without failure. The islands forming the discontinuous Cr layer are shown to move apart from each other during stretching without delamination, providing strong adhesion to the Indium film while accommodating the large strain in the system. The Indium film is shown to form surface wrinkles upon release from the large strain, confirming its strong adhesion to PDMS. A model is proposed based upon the observations that can explain the high level of stretch-ability of the Indium metal film over the PDMS substrate.

  11. Preparation of Cu Nanoclusters within Dendrimer Templates

    Zhao, M

    1998-01-01

    ... (16-atom Cu cluster in G4 and 64-atom Cu cluster in G6 dendrimers). The clusters remain trapped within the dendrimers for extended periods of time, do not agglomerate, and do not precipitate. The clusters can also be oxidized to yield dendrimer-encapsulated Cu(2+).

  12. Nanomedicine for prion disease treatment: new insights into the role of dendrimers.

    McCarthy, James M; Appelhans, Dietmar; Tatzelt, Jörg; Rogers, Mark S

    2013-01-01

    Despite their devastating impact, no effective therapeutic yet exists for prion diseases at the symptomatic stage in humans or animals. Progress is hampered by the difficulty in identifying compounds that affect PrP (Sc) and the necessity of any potential therapeutic to gain access to the CNS. Synthetic polymers known as dendrimers are a particularly promising candidate in this area. Studies with cell culture models of prion disease and prion infected brain homogenate have demonstrated that numerous species of dendrimers eliminate PrP (Sc) in a dose and time dependent fashion and specific glycodendrimers are capable of crossing the CNS. However, despite their potential a number of important questions remained unanswered such as what makes an effective dendrimer and how dendrimers eliminate prions intracellularly. In a number of recent studies we have tackled these questions and revealed for the first time that a specific dendrimer can inhibit the intracellular conversion of PrP (C) to PrP (Sc) and that a high density of surface reactive groups is a necessity for dendrimers in vitro anti-prion activity. Understanding how a therapeutic works is a vital component in maximising its activity and these studies therefore represent a significant development in the race to find effective treatments for prion diseases.

  13. Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-05-01

    In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

  14. Nonequilibrium molecular dynamics study of ring polymer melts under shear and elongation flows: A comparison with their linear analogs

    Yoon, Jeongha; Kim, Jinseong; Baig, Chunggi, E-mail: cbaig@unist.ac.kr [Department of Chemical Engineering, School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798 (Korea, Republic of)

    2016-07-15

    We present detailed results for the structural and rheological properties of unknotted and unconcatenated ring polyethylene (PE) melts under shear and elongation flows via direct atomistic nonequilibrium molecular dynamics simulations. Short (C{sub 78}H{sub 156}) and long (C{sub 400}H{sub 800}) ring PE melts were subjected to planar Couette flow (PCF) and planar elongational flow (PEF) across a wide range of strain rates from linear to highly nonlinear flow regimes. The results are analyzed in detail through a direct comparison with those of the corresponding linear polymers. We found that, in comparison to their linear analogs, ring melts possess rather compact chain structures at or near the equilibrium state and exhibit a considerably lesser degree of structural deformation with respect to the applied flow strength under both PCF and PEF. The large structural resistance of ring polymers against an external flow field is attributed to the intrinsic closed-loop configuration of the ring and the topological constraint of nonconcatenation between ring chains in the melt. As a result, there appears to be a substantial discrepancy between ring and linear systems in terms of their structural and rheological properties such as chain orientation, the distribution of chain dimensions, viscosity, flow birefringence, hydrostatic pressure, the pair correlation function, and potential interaction energies. The findings and conclusions drawn in this work would be a useful guide in future exploration of the characteristic dynamical and relaxation mechanisms of ring polymers in bulk or confined systems under flowing conditions.

  15. Positron annihilation study of polyphenylene dendrimers

    Marek, T.; Suevegh, K.; Vertes, A.; Ernst, A.; Bauer, R.; Weil, T.; Wiesler, U.; Klapper, M.; Muellen, K.

    2003-01-01

    The free volume of a series of rigid polyphenylene dendrimers was studied by positron lifetime spectroscopy and the experimental data were compared with results from molecular dynamics calculations. Contrary to dendrimers containing flexible repeat units rigid polyphenylene dendrimers proved to contain large stable 'inner' voids of a distinct size between their dendritic branches. The size of the 'inner' cavities increases with the size of the dendrimer. Due to these voids, polyphenylene dendrimers are potentially attractive with respect to the selective incorporation of guest molecules

  16. Dendrimer based hybrid materials : coexistence of amorphous calcium carbonate and calcite

    Donners, J.J.J.M.; Heywood, B.R.; Meijer, E.W.; Nolte, R.J.M.; Sommerdijk, N.A.J.M.

    1999-01-01

    The crystn. of inorg. materials using polymers as templates is an interesting method to prep. composite materials with unique properties. Poly(propyleneimine) dendrimers are well-defined and highly-branched macromols. with regular and easily modifiable surfaces. Polyhedral aggregates from

  17. Star-shaped Poly(2-oxazoline)s by Dendrimer Endcapping

    Lambermont-Thijs, H.M.L.; Fijten, M.W.M.; Schubert, U.S.; Hoogenboom, R.

    2011-01-01

    The synthesis of star-shaped poly(2-ethyl-2-oxazoline) is reported by direct end-capping of the living polymer chains with dendritic multiamines. The end-capping kinetics after addition of a first generation polypropylenimine dendrimer are discussed based on monitoring by size exclusion

  18. Spatial distribution of intra-molecular water and polymeric components in polyelectrolyte dendrimers revealed by small angle scattering investigations

    Wu, Bin; Li, Xin; Do, Changwoo; Kim, Tae-Hwan; Shew, Chwen-Yang; Liu, Yun; Yang, Jun; Hong, Kunlun; Porcar, Lionel; Chen, Chun-Yu; Liu, Emily L.; Smith, Gregory S.; Herwig, Kenneth W.; Chen, Wei-Ren

    2011-10-01

    An experimental scheme using contrast variation small angle neutron scattering technique is developed to investigate the structural characteristics of amine-terminated poly(amidoamine) dendrimers solutions. Using this methodology, we present the dependence of both the intra-dendrimer water and the polymer distribution on molecular protonation, which can be precisely adjusted by tuning the pH of the solution. Assuming spherical symmetry of the spatial arrangement of the constituent components of dendrimer, and that the atomic ratio of hydrogen-to-deuterium for the solvent residing within the cavities of dendrimer is identical to that for the solvent outside the dendrimer, the intra-dendrimer water distribution along the radial direction is determined. Our result clearly reveals an outward relocation of the peripheral groups, as well as enhanced intra-dendrimer hydration, upon increasing the molecular protonation and, therefore, allows the determination of segmental backfolding in a quantitative manner. The connection between these charge-induced structural changes and our recently observed progressively active segmental dynamics is also discussed.

  19. Direct Synthesis and Morphological Characterization of Gold-Dendrimer Nanocomposites Prepared Using PAMAM Succinamic Acid Dendrimers: Preliminary Study of the Calcification Potential

    E. Vasile

    2014-01-01

    Full Text Available Gold-dendrimer nanocomposites were obtained for the first time by a simple colloidal approach based on the use of polyamidoamine dendrimers with succinamic acid terminal groups and dodecanediamine core. Spherical and highly crystalline nanoparticles with dimensions between 3 nm and 60 nm, and size-polydispersity depending on the synthesis conditions, have been generated. The influence of the stoichiometric ratio and the structural and architectural features of the dendrimers on the properties of the nanocomposites has been described. The self-assembling behaviour of these materials produces gold-dendrimer nanostructured porous networks with variable density, porosity, and composition. The investigations of the reaction systems, by TEM, at two postsynthesis moments, allowed to preliminary establish the control over the properties of the nanocomposite products. Furthermore, this study allowed better understanding of the mechanism of nanocomposite generation. Impressively, in the early stages of the synthesis, the organization of gold inside the dendrimer molecules has been evidenced by micrographs. Growth and ripening mechanisms further lead to nanoparticles with typical characteristics. The potential of such nanocomposite particles to induce calcification when coating a polymer substrate was also investigated.

  20. Direct synthesis and morphological characterization of gold-dendrimer nanocomposites prepared using PAMAM succinamic acid dendrimers: preliminary study of the calcification potential.

    Vasile, E; Serafim, A; Petre, D; Giol, D; Dubruel, P; Iovu, H; Stancu, I C

    2014-01-01

    Gold-dendrimer nanocomposites were obtained for the first time by a simple colloidal approach based on the use of polyamidoamine dendrimers with succinamic acid terminal groups and dodecanediamine core. Spherical and highly crystalline nanoparticles with dimensions between 3 nm and 60 nm, and size-polydispersity depending on the synthesis conditions, have been generated. The influence of the stoichiometric ratio and the structural and architectural features of the dendrimers on the properties of the nanocomposites has been described. The self-assembling behaviour of these materials produces gold-dendrimer nanostructured porous networks with variable density, porosity, and composition. The investigations of the reaction systems, by TEM, at two postsynthesis moments, allowed to preliminary establish the control over the properties of the nanocomposite products. Furthermore, this study allowed better understanding of the mechanism of nanocomposite generation. Impressively, in the early stages of the synthesis, the organization of gold inside the dendrimer molecules has been evidenced by micrographs. Growth and ripening mechanisms further lead to nanoparticles with typical characteristics. The potential of such nanocomposite particles to induce calcification when coating a polymer substrate was also investigated.

  1. Feasibility study of basic characterization of MAGAT polymer gel using CBCT attached in linear accelerator: Preliminary study

    Sathiyaraj, P.; Samuel, E. James jebaseelan

    2018-01-01

    The aim of this study is to evaluate the methacrylic acid, gelatin and tetrakis (hydroxymethyl) phosphonium chloride gel (MAGAT) by cone beam computed tomography (CBCT) attached with modern linear accelerator. To compare the results of standard diagnostic computed tomography (CT) with CBCT, different parameters such as linearity, sensitivity and temporal stability were checked. MAGAT gel showed good linearity for both diagnostic CT and CBCT measurements. Sensitivity and temporal stability were also comparable with diagnostic CT measurements. In both the modalities, the sensitivity of the MAGAT increased to 4 days and decreased till the 10th day of post irradiation. Since all measurements (linearity, sensitivity and temporal stability) from diagnostic CT and CBCT were comparable, CBCT could be a potential tool for dose analysis study for polymer gel dosimeter.

  2. Ordered Layered Dendrimers Constructed from Two Known Dendrimer Families: Inheritance and Emergence of Properties.

    Dib, Hanna; Rebout, Cyrille; Laurent, Régis; Mallet-Ladeira, Sonia; Sournia-Saquet, Alix; Sárosi, Menyhárt B; Hey-Hawkins, Evamarie; Majoral, Jean-Pierre; Delavaux-Nicot, Béatrice; Caminade, Anne-Marie

    2016-07-25

    A new concept is presented, namely the synthesis of dendrimers intrinsically composed in alternation of building blocks pertaining to two known families of dendrimers: phosphorhydrazone dendrimers and triazine-piperazine dendrimers. These mixed dendrimers with layered controlled architecture inherit their easy (31) P NMR characterization and their thermal stability from the phosphorhydrazone family, and their decreased solubility from the triazine-piperazine family. However, they have also their own and original characteristics. Both parent families are white powders, whereas the mixed dendrimers are yellow, orange, or red powders, depending on the generation. DFT calculations were carried out on model dendrons to understand these special color features. Remarkably, these dendrimers incorporating redox-active organic entities allow for the first time the monitoring of the growth of an organic dendrimer by electrochemistry while highlighting an even-odd generation behavior. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Shear-Induced Phase Separation in Aqueous Polymer Solutions: Temperature-Sensitive Microgels and Linear Polymer Chains

    Stieger, M.A.; Richtering, W.

    2003-01-01

    The influence of shear flow on the phase separation of aqueous poly(N-isopropylacrylamide) (PNiPAM) microgel suspensions was investigated by means of rheo-turbidity and rheo-small angle neutron scattering (rheo-SANS) and compared to the behavior of linear PNiPAM macromolecules. The rheological

  4. Dynamical heterogeneities and mechanical non-linearities: Modeling the onset of plasticity in polymer in the glass transition.

    Masurel, R J; Gelineau, P; Lequeux, F; Cantournet, S; Montes, H

    2017-12-27

    In this paper we focus on the role of dynamical heterogeneities on the non-linear response of polymers in the glass transition domain. We start from a simple coarse-grained model that assumes a random distribution of the initial local relaxation times and that quantitatively describes the linear viscoelasticity of a polymer in the glass transition regime. We extend this model to non-linear mechanics assuming a local Eyring stress dependence of the relaxation times. Implementing the model in a finite element mechanics code, we derive the mechanical properties and the local mechanical fields at the beginning of the non-linear regime. The model predicts a narrowing of distribution of relaxation times and the storage of a part of the mechanical energy --internal stress-- transferred to the material during stretching in this temperature range. We show that the stress field is not spatially correlated under and after loading and follows a Gaussian distribution. In addition the strain field exhibits shear bands, but the strain distribution is narrow. Hence, most of the mechanical quantities can be calculated analytically, in a very good approximation, with the simple assumption that the strain rate is constant.

  5. Cylindrical micelles of a POSS amphiphilic dendrimer as nano-reactors for polymerization.

    Weng, Jing-Ting; Yeh, Tso-Fan; Samuel, Ashok Zachariah; Huang, Yi-Fan; Sie, Jyun-Hao; Wu, Kuan-Yi; Peng, Chi-How; Hamaguchi, Hiro-O; Wang, Chien-Lung

    2018-02-15

    A low generation amphiphilic dendrimer, POSS-AD, which has a POSS core and eight amphiphilic arms, was synthesized and used as a nano-reactor to produce well-defined polymer nano-cylinders. Confirmed by small-angle X-ray scattering (SAXS), Raman and NMR spectrometry, monodispersed cylindrical micelles that contain a hydrophilic cavity with a diameter of 2.09 nm and a length of 4.26 nm were produced via co-assembling POSS-AD with hydrophilic liquids, such as H 2 O and HEMA in hydrophobic solvents. Taking the HEMA/POSS-AD cylindrical micelles as nano-reactors, polymerization of HEMA within the micelles results in polymer nano-cylinders (POSS-ADNPs) with a diameter of 2.24 nm and a length of 5.02 nm. The study confirmed that despite the inability to maintain specific shape in solution, low generation dendrimers form well-defined nano-containers or nano-reactors, which relies on co-assembling with hydrophilic guest molecules. These nano-reactors are robust enough to maintain their shape during the polymerization of the guest molecules. Polymer nano-cylinders with dimensions less than 10 nm can thus be produced from the HEMA/POSS-AD micelles. Since the chemical structure of low-generation dendrimers and the contents of the co-assembled nano-reactors can be easily adjusted, the concept holds the potential for the further developments of low-generation amphiphilic dendrimers.

  6. Dendrimers and Dendrons as Versatile Building Blocks for the Fabrication of Functional Hydrogels

    Sadik Kaga

    2016-04-01

    Full Text Available Hydrogels have emerged as a versatile class of polymeric materials with a wide range of applications in biomedical sciences. The judicious choice of hydrogel precursors allows one to introduce the necessary attributes to these materials that dictate their performance towards intended applications. Traditionally, hydrogels were fabricated using either polymerization of monomers or through crosslinking of polymers. In recent years, dendrimers and dendrons have been employed as well-defined building blocks in these materials. The multivalent and multifunctional nature of dendritic constructs offers advantages in either formulation or the physical and chemical properties of the obtained hydrogels. This review highlights various approaches utilized for the fabrication of hydrogels using well-defined dendrimers, dendrons and their polymeric conjugates. Examples from recent literature are chosen to illustrate the wide variety of hydrogels that have been designed using dendrimer- and dendron-based building blocks for applications, such as sensing, drug delivery and tissue engineering.

  7. Synthesis of an amphiphilic dendrimer-like block copolymer and its application on drug delivery

    Wang, Shuaipeng

    2014-10-27

    Dendrimer-like amphiphilic copolymer is a kind of three-dimensional spherical structure polymer. An amphiphilic dendrimer-like diblock copolymer, PEEGE-G2-b-PEO(OH)12, constituted of a hydrophobic poly(ethoxyethyl glycidol ether) inner core and a hydrophilic poly(ethylene oxide) outer layer, has been successfully synthesized by the living anionic ring-opening polymerization method. The intermediates and targeted products were characterized with 1H NMR spectroscopy and gel permeation chromatography. The application on drug delivery of dendrimer-like diblock copolymer PEEGE-G2-b-PEO(OH)12 using DOX as a model drug was also studied. The drug loading content and encapsulation efficiency were found at 13.07% and 45.75%, respectively. In vitro release experiment results indicated that the drug-loaded micelles exhibited a sustained release behavior under acidic media.

  8. Orientation phenomena in chromophore DR1-containing polymer films and their non-linear optical response

    Moencke, Doris; Mountrichas, Grigoris; Pispas, Stergios; Kamitsos, Efstratios I.

    2011-01-01

    The effectiveness of chromophore alignment in polymer films following corona poling can be assessed by the generated second harmonic signal. Optimization of the stability and strength of this nonlinear optical response may improve with a better understanding of the underlying principal order phenomena. Structural analysis by vibrational, optical, and 1 H NMR spectroscopy reveals side chain tacticity, aggregation effects, and changes in orientation as a function of temperature. Co-polymers with the functionalized chromophore Disperse Red 1 methacrylate (MDR1) were prepared for three different methacrylate types. High side chain polarity and short side chain length increase generally chromophore aggregation in films, whereas the very long poly-ether side chains in PMEO based co-polymers are wrapped separately around the DR1 entities. Side chain tacticity depends on space requirements, but also on the capacity of side groups to form OH-bridges. Side chain tacticity might present an additional parameter for the assessment of chromophore aggregation and poling induced alignments. Stepwise heating of co-polymer films causes an increase in the number of random over ordered side chain arrangements. Cross-linking by anhydride formation is observed after heating the methacrylic acid based co-polymer.

  9. Perspective: Dendrimer drugs for infection and inflammation.

    Shaunak, Sunil

    2015-12-18

    Biologists are dissecting complex biological pathways at breath taking speed. It is opening up new opportunities for the therapeutic evaluation of novel dendrimer drugs. This review focuses on studies of small dendrimers decorated with sulfate, phosphonate, N-acetyl-cysteine, glucosamine and mannose in animal model studies of infection and inflammation. It highlights those animal model studies which have demonstrated the most promising dendrimer drug constructs as potential new medicines. The issues relating to their analytical chemistry that are slowing the progress of dendrimer drugs into the clinic are highlighted. It should be possible to solve these with additional analytical expertise because it is small dendrimers with only 16-32 peripheral groups that make for the best infection and inflammation related medicines. Public-private partnerships are now needed to progress these dendrimer drugs into proof-of-concept clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Investigation of migrant-polymer interaction in pharmaceutical packaging material using the linear interaction energy algorithm.

    Feenstra, Peter; Brunsteiner, Michael; Khinast, Johannes

    2014-10-01

    The interaction between drug products and polymeric packaging materials is an important topic in the pharmaceutical industry and often associated with high costs because of the required elaborative interaction studies. Therefore, a theoretical prediction of such interactions would be beneficial. Often, material parameters such as the octanol water partition coefficient are used to predict the partitioning of migrant molecules between a solvent and a polymeric packaging material. Here, we present the investigation of the partitioning of various migrant molecules between polymers and solvents using molecular dynamics simulations for the calculation of interaction energies. Our results show that the use of a model for the interaction between the migrant and the polymer at atomistic detail can yield significantly better results when predicting the polymer solvent partitioning than a model based on the octanol water partition coefficient. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Review Dendrimer : Definisi, Sintesis, Aplikasi Dan Prospektif

    Rahmi, Dwinna

    2013-01-01

    Dendrimer merupakan makrostruktur monodisperse dengan banyak cabang yang homogen dan degree of branching (DB) 100%. Dua cara sintesis dendrimer yaitu convergent dan divergent dilakukan. Convergent dilakukan dengan reaksi kovalen antara dua dan lebih monomer. Divergent dimulai dengan pembentukan inti dilanjutkan dengan pembentukan cabang yang merupakan group fungsional yang aktif. Sejauh ini dendrimer sudah banyak diterapkan pada bidang farmasi yaitu drug delivery dan non farmasi pada proses i...

  12. Effect of Hydrogen Bonding on Linear and Nonlinear Rheology of Entangled Polymer Melts

    Shabbir, Aamir; Goldansaz, Hadi; Hassager, Ole

    2015-01-01

    for a model system of pure poly(n-butyl acrylate), PnBA, homopolymer and four PnBA− poly(acrylic acid), PnBA−PAA, copolymers with different number of AA side groups. The copolymers are synthesized via hydrolysis of the pure PnBA homopolymer. Therefore, all polymers studied have the same backbone length...

  13. Reactive Landing of Dendrimer Ions onto Activated Self-assembled Monolayer Surfaces

    Hu, Qichi; Laskin, Julia

    2014-02-06

    The reactivity of gaseous, amine-terminated polyamidoamine (PAMAM) dendrimer ions with activated self-assembled monolayer (SAM) surfaces terminated with N-hydroxysuccinimidyl ester groups (NHS-SAM) is examined using mass-selected ion deposition combined with in situ infrared reflection absorption spectroscopy (IRRAS). The reaction extent is determined from depletion of the infrared band at 1753 cm-1, corresponding to the stretching vibration of the NHS carbonyl groups following ion deposition. For reaction yields below 10%, NHS band depletion follows a linear dependence on the ion dose. By comparing the kinetics plots obtained for 1,12-dodecanediamine and different generations of dendrimer ions (G0–G3) containing 4, 8, 16, and 32 terminal amino group, we demonstrate that the relative reaction efficiency increases linearly with the number of NH2 groups in the molecule. This finding is rationalized assuming the formation of multiple amide bonds upon collision of higher-generation dendrimers with NHS-SAM. Furthermore, by comparing the NHS band depletion following deposition of [M+4H]4+ ions of the G2 dendrimer at 30, 80, and 120 eV, we demonstrate that the ion’s kinetic energy has no measurable effect on reaction efficiency. Similarly, the ion’s charge state only has a minor effect on the reactive landing efficiency of dendrimer ions. Our results indicate that reactive landing is an efficient approach for highly selective covalent immobilization of complex multifunctional molecules onto organic surfaces terminated with labile functional groups.

  14. Pulling self-interacting linear polymers on a family of fractal lattices embedded in three-dimensional space

    Elezović-Hadžić, S; Živić, I

    2013-01-01

    We have studied the problem of force pulling self-interacting linear polymers situated in fractal containers that belong to the Sierpinski gasket (SG) family of fractals embedded in three-dimensional (3D) space. Each member of this family is labeled with an integer b (2 ≤ b ≤ ∞). The polymer chain is modeled by a self-avoiding walk (SAW) with one end anchored to one of the four boundary walls of the lattice, while the other (floating in the bulk of the fractal) is the position at which the force is acting. By applying an exact renormalization group (RG) method we have established the phase diagrams, including the critical force–temperature dependence, for fractals with b = 2,3 and 4. Also, for the same fractals, in all polymer phases, we examined the generating function G 1 for the numbers of all possible SAWs with one end anchored to the boundary wall. We found that besides the usual power-law singularity of G 1 , governed by the critical exponent γ 1 , whose specific values are worked out for all cases studied, in some regimes the function G 1 displays an essential singularity in its behavior. (paper)

  15. Linear electro-optical behavior of hybrid nanocomposites based on silicon carbide nanocrystals and polymer matrices

    Bouclé, J.; Kassiba, A.; Makowska-Janusik, M.; Herlin-Boime, N.; Reynaud, C.; Desert, A.; Emery, J.; Bulou, A.; Sanetra, J.; Pud, A. A.; Kodjikian, S.

    2006-11-01

    An electro-optical activity has been recently reported for hybrid nanocomposite thin films where inorganic silicon carbide nanocrystals (ncSiC) are incorporated into polymer matrices. The role of the interface SiC polymer is suggested as the origin of the observed second order nonlinear optical susceptibility in the hybrid materials based on poly-(methylmethacrylate) (PMMA) or poly-( N -vinylcarbazole) matrices. In this work, we report an analysis of the electro-optical response of this hybrid system as a function of the ncSiC content and surface state in order to precise the interface effect in the observed phenomenon. Two specific ncSiC samples with similar morphology and different surface states are incorporated in the PMMA matrix. The effective Pockels parameters of the corresponding hybrid nanocomposites have been estimated up to 7.59±0.74pm/V ( 1wt.% of ncSiC in the matrix). The interfacial region ncSiC polymer is found to play the main role in the observed effect. Particularly, the electronic defects on the ncSiC nanocrystal surface modify the interfacial electrical interactions between the two components. The results are interpreted and discussed on the basis of the strong influence of these active centers in the interfacial region at the nanoscale, which are found to monitor the local hyperpolarizabilities and the macroscopic nonlinear optical susceptibilities. This approach allows us to complete the description and understanding of the electro-optical response in the hybrid SiC /polymer systems.

  16. Modelling of the charge carrier mobility in disordered linear polymer materials

    Toman, Petr; Menšík, Miroslav; Bartkowiak, W.; Pfleger, Jiří

    2017-01-01

    Roč. 19, č. 11 (2017), s. 7760-7771 ISSN 1463-9076 R&D Projects: GA ČR(CZ) GA15-05095S Grant - others:AV ČR(CZ) M200501204 Program:M Institutional support: RVO:61389013 Keywords : charge carrier mobility * conjugated polymer * charge transport modelling Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 4.123, year: 2016

  17. Synthesis of hydrazone functionalized epoxy polymers for non-linear optical device applications

    Singh, Rajendra K.

    A series of twelve, thermally crosslinkable, epoxy polymers bearing covalently attached NLO-active hydrazone chromophores were synthesized. The primary focus was on the synthesis of two series of NLO-active hydroxy functionalized hydrazone chromophores. The first series, called the monohydroxy series (Hydrazones I--VI) comprised of six monohydroxy functionalized hydrazones and the second series consisted of six dihydroxy functionalized hydrazones (Hydrazones VII--XII). These hydrazone chromophores were then grafted, via the hydroxy functionality, on to a commercial epoxy polymer to obtain twelve NLO-active soluble prepolymers. The grafting reaction yields multiple secondary hydroxyl sites due to opening of the epoxide rings and these hydroxyl groups were used for further crosslinking by formulating the prepolymers with a blocked polyisocyanate commercial crosslinker. This formulation was spin coated on glass slides to form 2--2.5 m m thick uniform, defect free, transparent films. The films were corona poled, above their Tg, to align the chromophores in a noncentrosymmetric fashion and simultaneously complete the thermal cure that results in a highly crosslinked network. Finally the thermal characteristics of the second order nonlinearity of the twelve polymers are compared to illustrate the key structure-property relationships underlying the performance of the films.

  18. Influence of material non-linearity on the thermo-mechanical response of polymer foam cored sandwich structures - FE modelling and preliminary experiemntal results

    Palleti, Hara Naga Krishna Teja; Thomsen, Ole Thybo; Fruehmann, Richard.K

    In this paper, the polymer foam cored sandwich structures with fibre reinforced composite face sheets will be analyzed using the commercial FE code ABAQUS/Standard® incorporating the material and geometrical non-linearity. Large deformations are allowed which attributes geometric non linearity...

  19. Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy.

    Menjoge, Anupa R; Rinderknecht, Amber L; Navath, Raghavendra S; Faridnia, Masoud; Kim, Chong J; Romero, Roberto; Miller, Richard K; Kannan, Rangaramanujam M

    2011-03-30

    , which is similar to other investigations of large macromolecules, e.g., IgG. These overall findings suggest that entry of drugs conjugated to polymers, i.e., dendrimers, would be limited in their transfer across the human placenta when compared to smaller drug molecules alone, suggesting novel methods for selectively delivering therapeutics to the pregnant woman without significant transfer to the fetus, especially since the half life of the dendrimer in blood is relatively short. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. A polymer, random walk model for the size-distribution of large DNA fragments after high linear energy transfer radiation

    Ponomarev, A. L.; Brenner, D.; Hlatky, L. R.; Sachs, R. K.

    2000-01-01

    DNA double-strand breaks (DSBs) produced by densely ionizing radiation are not located randomly in the genome: recent data indicate DSB clustering along chromosomes. Stochastic DSB clustering at large scales, from > 100 Mbp down to simulations and analytic equations. A random-walk, coarse-grained polymer model for chromatin is combined with a simple track structure model in Monte Carlo software called DNAbreak and is applied to data on alpha-particle irradiation of V-79 cells. The chromatin model neglects molecular details but systematically incorporates an increase in average spatial separation between two DNA loci as the number of base-pairs between the loci increases. Fragment-size distributions obtained using DNAbreak match data on large fragments about as well as distributions previously obtained with a less mechanistic approach. Dose-response relations, linear at small doses of high linear energy transfer (LET) radiation, are obtained. They are found to be non-linear when the dose becomes so large that there is a significant probability of overlapping or close juxtaposition, along one chromosome, for different DSB clusters from different tracks. The non-linearity is more evident for large fragments than for small. The DNAbreak results furnish an example of the RLC (randomly located clusters) analytic formalism, which generalizes the broken-stick fragment-size distribution of the random-breakage model that is often applied to low-LET data.

  1. Dendrimer-based dynamic combinatorial libraries

    Chang, T.; Meijer, E.W.

    2005-01-01

    The aim of this project is to create water-sol. dynamic combinatorial libraries based upon dendrimer-guest complexes. The guest mols. are designed to bind to dendrimers using multiple secondary interactions, such as electrostatics and hydrogen bonding. We have been able to incorporate various guest

  2. Probing the binding of cationic lipids with dendrimers.

    Mandeville, J S; Bourassa, P; Tajmir-Riahi, H A

    2013-01-14

    Polycationic polymers are used extensively in biology to disrupt cell membranes and thus enhance the transport of materials into the cell. We report the bindings of several lipids cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium-propane(DOTAP), dioctadecyldimethylammoniumbromide (DDAB), and dioleoylphosphatidylethanolamine (DOPE) to dendrimers of different compositions such as mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) under physiological conditions. FTIR, UV-visible spectroscopic, methods and molecular modeling were used to analyze the lipid binding mode, the binding constant, and the effects of lipid complexation on the dendrimer structure. The structural analysis showed that lipids bind dendrimers through both hydrophilic and hydrophobic contacts with overall binding constants of K(chol-mPEG-G3) = 1.7 × 10(3) M(-1), K(chol-mPEG-PAMAM-G4) = 2.7 × 10(3) M(-1), K(chol-PAMAM-G4) = 1.0 × 10(3) M(-1), K(DOPE-mPEG-G3) = 1.5 × 10(3) M(-1), K(DOPE-mPEG-PAMAM-G4) = 1.6 × 10(3) M(-1), K(DOPE-PAMAM-G4) = 5.3 × 10(2) M(-1), K(DDAB-mPEG-G3) = 1.5 × 10(3) M(-1), K(DDAB-mPEG-PAMAM-G4) = 1.9 × 10(2) M(-1), K(DDAB-PAMAM-G4) = 7.0 × 10(2) M(-1), K(DOTAP-mPEG-G3) = 1.9 × 10(3) M(-1), K(DOTAP-mPEG-PAMAM-G4) = 1.5 × 10(3) M(-1), and K(DOTAP-PAMAM-G4) = 5.7 × 10(2) M(-1). Weaker interaction was observed as dendrimer cationic charges increased. The free binding energies from docking were -5.15 (cholesterol), -5.79 (DDAB), and -5.36 kcal/mol (DOTAP) with the order of stability DDAB-PAMAM-G-4 > DOTAP-PAMAM-G4 > cholesterol-PAMAM-G4, consistent with the spectroscopic results. Dendrimers might act as carriers to transport lipids in vitro.

  3. Rational design of novel, fluorescent, tagged glutamic acid dendrimers with different terminal groups and in silico analysis of their properties

    Martinho N

    2017-09-01

    Full Text Available Nuno Martinho,1–3 Liana C Silva,1,4 Helena F Florindo,1 Steve Brocchini,2 Mire Zloh,3 Teresa S Barata2 1Research Institute for Medicines (iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; 2Department of Pharmaceutics, UCL School of Pharmacy, London, 3School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK; 4Centro de Química-Física Molecular and IN – Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal Abstract: Dendrimers are hyperbranched polymers with a multifunctional architecture that can be tailored for the use in various biomedical applications. Peptide dendrimers are particularly relevant for drug delivery applications due to their versatility and safety profile. The overall lack of knowledge of their three-dimensional structure, conformational behavior and structure–activity relationship has slowed down their development. Fluorophores are often conjugated to dendrimers to study their interaction with biomolecules and provide information about their mechanism of action at the molecular level. However, these probes can change dendrimer surface properties and have a direct impact on their interactions with biomolecules and with lipid membranes. In this study, we have used computer-aided molecular design and molecular dynamics simulations to identify optimal topology of a poly(L-glutamic acid (PG backbone dendrimer that allows incorporation of fluorophores in the core with minimal availability for undesired interactions. Extensive all-atom molecular dynamic simulations with the CHARMM force field were carried out for different generations of PG dendrimers with the core modified with a fluorophore (nitrobenzoxadiazole and Oregon Green 488 and various surface groups (glutamic acid, lysine and tryptophan. Analysis of structural and topological features of all designed dendrimers provided information about their size, shape

  4. Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers.

    Kojima, Chie; Regino, Celeste; Umeda, Yasuhito; Kobayashi, Hisataka; Kono, Kenji

    2010-01-04

    Dendrimers are a potential drug carrier. Because modification with polyethylene glycol (PEG) is known to improve the blood retention, PEGylated dendrimers have been studied as a useful drug carrier. In this study, three types of PEGylated L-lysine-bearing polyamidoamine dendrimers (PEG2k-Lys-PAMAM (G4), PEG5k-Lys-PAMAM (G4), PEG2k-Lys-PAMAM (G5)) were synthesized, which are composed of a dendrimer of different generations (generations 4 and 5) and PEG chains with different molecular weights (2k and 5k). An acetylated L-lysine-bearing dendrimer was also synthesized as a non-PEGylated dendrimer. Bifunctional diethylenetriaminepentaacetic acid (pSCN-benzyl-DTPA) was bound to the epsilon -amino group of lysine in a dendrimer, to be labeled with radioactive indium-111. These PEGylayed dendrimers showed longer blood retention and lower accumulation in other normal organs such as the kidneys than the non-PEGylated dendrimer. The PEGylated dendrimers with the higher generation and the longer PEG led the greater blood retention.

  5. Understanding Effect of Constraint Release Environment on End-to-End Vector Relaxation of Linear Polymer Chains

    Shivokhin, Maksim E.

    2017-05-30

    We propose and verify methods based on the slip-spring (SSp) model [ Macromolecules 2005, 38, 14 ] for predicting the effect of any monodisperse, binary, or ternary environment of topological constraints on the relaxation of the end-to-end vector of a linear probe chain. For this purpose we first validate the ability of the model to consistently predict both the viscoelastic and dielectric response of monodisperse and binary mixtures of type A polymers, based on published experimental data. We also report the synthesis of new binary and ternary polybutadiene systems, the measurement of their linear viscoelastic response, and the prediction of these data by the SSp model. We next clarify the relaxation mechanisms of probe chains in these constraint release (CR) environments by analyzing a set of "toy" SSp models with simplified constraint release rates, by examining fluctuations of the end-to-end vector. In our analysis, the longest relaxation time of the probe chain is determined by a competition between the longest relaxation times of the effective CR motions of the fat and thin tubes and the motion of the chain itself in the thin tube. This picture is tested by the analysis of four model systems designed to separate and estimate every single contribution involved in the relaxation of the probe\\'s end-to-end vector in polydisperse systems. We follow the CR picture of Viovy et al. [ Macromolecules 1991, 24, 3587 ] and refine the effective chain friction in the thin and fat tubes based on Read et al. [ J. Rheol. 2012, 56, 823 ]. The derived analytical equations form a basis for generalizing the proposed methodology to polydisperse mixtures of linear and branched polymers. The consistency between the SSp model and tube model predictions is a strong indicator of the compatibility between these two distinct mesoscopic frameworks.

  6. Peptide Dendrimer/Lipid Hybrid Systems Are Efficient DNA Transfection Reagents: Structure–Activity Relationships Highlight the Role of Charge Distribution Across Dendrimer Generations

    2013-01-01

    Efficient DNA delivery into cells is the prerequisite of the genetic manipulation of organisms in molecular and cellular biology as well as, ultimately, in nonviral gene therapy. Current reagents, however, are relatively inefficient, and structure–activity relationships to guide their improvement are hard to come by. We now explore peptide dendrimers as a new type of transfection reagent and provide a quantitative framework for their evaluation. A collection of dendrimers with cationic and hydrophobic amino acid motifs (such as KK, KA, KH, KL, and LL) distributed across three dendrimer generations was synthesized by a solid-phase protocol that provides ready access to dendrimers in milligram quantities. In conjunction with a lipid component (DOTMA/DOPE), the best reagent, G1,2,3-KL ((LysLeu)8(LysLysLeu)4(LysLysLeu)2LysGlySerCys-NH2), improves transfection by 6–10-fold over commercial reagents under their respective optimal conditions. Emerging structure–activity relationships show that dendrimers with cationic and hydrophobic residues distributed in each generation are transfecting most efficiently. The trigenerational dendritic structure has an advantage over a linear analogue worth up to an order of magnitude. The success of placing the decisive cationic charge patterns in inner shells rather than previously on the surface of macromolecules suggests that this class of dendrimers significantly differs from existing transfection reagents. In the future, this platform may be tuned further and coupled to cell-targeting moieties to enhance transfection and cell specificity. PMID:23682947

  7. Charge-dependent conformations and dynamics of pamam dendrimers revealed by neutron scattering and molecular dynamics

    Wu, Bin

    Neutron scattering and fully atomistic molecular dynamics (MD) are employed to investigate the structural and dynamical properties of polyamidoamine (PAMAM) dendrimers with ethylenediamine (EDA) core under various charge conditions. Regarding to the conformational characteristics, we focus on scrutinizing density profile evolution of PAMAM dendrimers as the molecular charge of dendrimer increases from neutral state to highly charged condition. It should be noted that within the context of small angle neutron scattering (SANS), the dendrimers are composed of hydrocarbon component (dry part) and the penetrating water molecules. Though there have been SANS experiments that studied the charge-dependent structural change of PAMAM dendrimers, their results were limited to the collective behavior of the aforementioned two parts. This study is devoted to deepen the understanding towards the structural responsiveness of intra-molecular polymeric and hydration parts separately through advanced contrast variation SANS data analysis scheme available recently and unravel the governing principles through coupling with MD simulations. Two kinds of acids, namely hydrochloric and sulfuric acids, are utilized to tune the pH condition and hence the molecular charge. As far as the dynamical properties, we target at understanding the underlying mechanism that leads to segmental dynamic enhancement observed from quasielstic neutron scattering (QENS) experiment previously. PAMAM dendrimers have a wealth of potential applications, such as drug delivery agency, energy harvesting medium, and light emitting diodes. More importantly, it is regarded as an ideal system to test many theoretical predictions since dendrimers conjugate both colloid-like globular shape and polymer-like flexible chains. This Ph.D. research addresses two main challenges in studying PAMAM dendrimers. Even though neutron scattering is an ideal tool to study this PAMAM dendrimer solution due to its matching temporal and

  8. A UV-prepared linear polymer electrolyte membrane for dye-sensitized solar cells

    Imperiyka, M., E-mail: imperiyka@gmail.com [Faculty of Arts and Sciences, Kufra Campus, University of Benghazi, Al Kufrah (Libya); Ahmad, A.; Hanifah, S.A. [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia); Polymer Research Center, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia); Bella, F. [Center for Space Human Robotics @Polito, Istituto Italiano di Tecnologia, Corso Trento 21, 10129 Torino (Italy); Department of Applied Science and Technology – DISAT, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino (Italy)

    2014-10-01

    The effects of LiClO{sub 4} and LiFS{sub 3}SO{sub 3} on poly(glycidyl methacrylate)-based solid polymer electrolyte and its photoelectrochemical performance in a dye sensitized solar cell consisting of FTO/TiO{sub 2}–dye/P(GMA)–LiClO{sub 4}–EC/Pt were investigated. The electrochemical stability of films was studied by cyclic voltammetry (CV). The highest ionic conductivities obtained were 4.2×10{sup −5} and 3.7×10{sup −6} S cm{sup −1} for the film containing 30 wt% LiClO{sub 4} and 25 wt% LiCF{sub 3}SO{sub 3}, respectively. The polymer electrolytes showed electrochemical stability windows up to 3 V and 2.8 V for LiClO{sub 4} and LiCF{sub 3}SO{sub 3}, respectively. The assembled dye-sensitized solar cell showed a sunlight conversion efficiency of 0.679% (J{sub sc}=3 mA cm{sup −2}, V{sub oc}=0.48 V and FF=0.47), under light intensity of 100 mW cm{sup −2}.

  9. Optical absorption and energy transport in compact dendrimers with unsymmetrical branching

    Supritz, C.; Gounaris, V.; Reineker, P.

    2008-01-01

    We investigate the linear optical absorption and the energy transport in compact dendrimers with unsymmetrical branching, using the Frenkel exciton concept. The electron-phonon interaction is taken into account by introducing a heat bath that interacts with the exciton in a stochastic manner

  10. Cationic Polyamidoamine Dendrimers as Modulators of EGFR Signaling In Vitro and In Vivo.

    Saghir Akhtar

    Full Text Available Cationic polyamidoamine (PAMAM dendrimers are branch-like spherical polymers being investigated for a variety of applications in nanomedicine including nucleic acid drug delivery. Emerging evidence suggests they exhibit intrinsic biological and toxicological effects but little is known of their interactions with signal transduction pathways. We previously showed that the activated (fragmented generation (G 6 PAMAM dendrimer, Superfect (SF, stimulated epidermal growth factor receptor (EGFR tyrosine kinase signaling-an important signaling cascade that regulates cell growth, survival and apoptosis- in cultured human embryonic kidney (HEK 293 cells. Here, we firstly studied the in vitro effects of Polyfect (PF, a non-activated (intact G6 PAMAM dendrimer, on EGFR tyrosine kinase signaling via extracellular-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK in cultured HEK 293 cells and then compared the in vivo effects of a single administration (10mg/kg i.p of PF or SF on EGFR signaling in the kidneys of normal and diabetic male Wistar rats. Polyfect exhibited a dose- and time-dependent inhibition of EGFR, ERK1/2 and p38 MAPK phosphorylation in HEK-293 cells similar to AG1478, a selective EGFR inhibitor. Administration of dendrimers to non-diabetic or diabetic animals for 24h showed that PF inhibited whereas SF stimulated EGFR phosphorylation in the kidneys of both sets of animals. PF-mediated inhibition of EGFR phosphorylation as well as SF or PF-mediated apoptosis in HEK 293 cells could be significantly reversed by co-treatment with antioxidants such as tempol implying that both these effects involved an oxidative stress-dependent mechanism. These results show for the first time that SF and PF PAMAM dendrimers can differentially modulate the important EGFR signal transduction pathway in vivo and may represent a novel class of EGFR modulators. These findings could have important clinical implications for the use of PAMAM

  11. Effect of surfactant species and electrophoretic medium composition on the electrophoretic behavior of neutral and water-insoluble linear synthetic polymers in nonaqueous capillary zone electrophoresis.

    Fukai, Nao; Kitagawa, Shinya; Ohtani, Hajime

    2017-07-01

    We have recently demonstrated the separation of neutral and water-insoluble linear synthetic polymers in nonaqueous capillary zone electrophoresis (NACZE) using a cationic surfactant of cetyltrimethylammonium chloride (CTAC). In this study, eight ionic surfactants were investigated for the separation of four synthetic polymers (polystyrene, polymethylmethacrylates, polybutadiene, and polycarbonate); only three surfactants (CTAC, dimethyldioctadecylammonium bromide, and sodium dodecylsulfate) caused their separation. The order of the interaction between the polymers and the surfactants depended on both the surfactant species and the composition of the electrophoretic medium. Their investigation revealed that the separation is majorly affected by the hydrophobic interactions between the polymers and the ionic surfactants. In addition, the electrophoretic behavior of polycarbonate suggested that electrostatic interaction also affects the selectivity of the polymers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Stress and neutron scattering measurements on linear polymer melts undergoing steady elongational flow

    Hassager, Ole; Mortensen, Kell; Bach, Anders

    2012-01-01

    We use small-angle neutron scattering to measure the molecular stretching in polystyrene melts undergoing steady elongational flow at large stretch rates. The radius of gyration of the central segment of a partly deuterated polystyrene molecule is, in the stretching direction, increasing...... exhibited by the linear polystyrene melt....

  13. Uni-axial Elongational Viscosity of Linear and Branched polymer melts

    Hassager, Ole; Nielsen, Jens Kromann; Rasmussen, Henrik Koblitz

    2005-01-01

    About 40 years ago interest in the measurement of elongational viscosity of polymer melts started to grow. Here we present measurements of transient (and steady) uni-axial elongational viscosity, using the FSR, of the following melts: Four narrow MMD polystyrene (PS) samples with weight......-average molar mass Mw in the range of 50k to 390k. Three different bi-disperse samples, mixed from the narrow MMD PS. Two low-density polyethylene (LDPE) melts (Lupolen 1840D and 3020D). A steady-state viscosity was kept for 1-2.5 Hencky strain units in all measurements.The measurements on the bi-disperse PS...... melts have demonstrated that both the transient and steady elongational viscosity is quite sensitive to polydispersity. Bi-disperse PS resembles the behaviour of mono-disperse melts only at elongational rates larger then the inverse of maximal time constant of the smallest molecule. As observed in Boger...

  14. The interplay of morphology and carrier recombination in dendrimer-based organic photovoltaics.

    Shaheen, Sean; Kopidakis, Nikos; Mitchell, William; Rance, William; van de Lagemaat, Jao; Rumbles, Garry

    2007-03-01

    Pi-conjugated dendrimers provide an alternative to polymers in organic photovoltaic devices that allow for systematic study of how the molecular structure affects the morphology of the donor and acceptor components and subsequently how the device operates. The degree of mixing and specific geometry of the donor-acceptor blend play a determining role in the rate of exciton dissociation as well as the efficacy of charge transport out of the active layer. We find that pi-conjugated dendrimers are more miscible with the fullerene-derivative acceptor than their polymeric counterparts, which leads to smaller domains than are commonly found in polymer-fullerene blends. Here we discuss how these differing morphologies affect exciton dissociation, carrier transport, and carrier recombination in the devices.

  15. Adsorption of mixtures of poly(amidoamine) dendrimers and sodium dodecyl sulfate at the air-water interface.

    Arteta, Marianna Yanez; Campbell, Richard A; Nylander, Tommy

    2014-05-27

    We relate the adsorption from mixtures of well-defined poly(amidoamine) (PAMAM) dendrimers of generations 4 and 8 with sodium dodecyl sulfate (SDS) at the air-water interface to the bulk solution properties. The anionic surfactant shows strong attractive interactions with the cationic dendrimers at pH 7, and electrophoretic mobility measurements indicate that the association is primarily driven by electrostatic interactions. Optical density measurements highlight the lack of colloidal stability of the formed bulk aggregates at compositions close to charge neutrality, the time scale of which is dependent on the dendrimer generation. Adsorption at the air-water interface was followed from samples immediately after mixing using a combination of surface tension, neutron reflectometry, and ellipsometry measurements. In the phase separation region for dendrimers of generation 4, we observed high surface tension corresponding to a depleted surfactant solution but only when the aggregates carried an excess of surfactant. Interestingly, these depleted adsorption layers contained spontaneously adsorbed macroscopic aggregates, and these embedded particles do not rearrange to spread monomeric material at the interface. These findings are discussed in relation to the interfacial properties of mixtures involving dendrimers of generation 8 as well as polydisperse linear and hyperbranched polyelectrolytes where there is polyelectrolyte bound to a surfactant monolayer. The results presented here demonstrate the capability of dendrimers to sequester anionic surfactants in a controllable manner, with potential applications as demulsification and antifoaming agents.

  16. Poly(amidoamine) dendrimers on lipid bilayers II: Effects of bilayer phase and dendrimer termination.

    Kelly, Christopher V; Leroueil, Pascale R; Orr, Bradford G; Banaszak Holl, Mark M; Andricioaei, Ioan

    2008-08-07

    The molecular structures and enthalpy release of poly(amidoamine) (PAMAM) dendrimers binding to 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC) bilayers were explored through atomistic molecular dynamics. Three PAMAM dendrimer terminations were examined: protonated primary amine, neutral acetamide, and deprotonated carboxylic acid. Fluid and gel lipid phases were examined to extract the effects of lipid tail mobility on the binding of generation-3 dendrimers, which are directly relevant to the nanoparticle interactions involving lipid rafts, endocytosis, lipid removal, and/or membrane pores. Upon binding to gel phase lipids, dendrimers remained spherical, had a constant radius of gyration, and approximately one-quarter of the terminal groups were in close proximity to the lipids. In contrast, upon binding to fluid phase bilayers, dendrimers flattened out with a large increase in their asphericity and radii of gyration. Although over twice as many dendrimer-lipid contacts were formed on fluid versus gel phase lipids, the dendrimer-lipid interaction energy was only 20% stronger. The greatest enthalpy release upon binding was between the charged dendrimers and the lipid bilayer. However, the stronger binding to fluid versus gel phase lipids was driven by the hydrophobic interactions between the inner dendrimer and lipid tails.

  17. Investigation of Dendrimer-Membrane Interactions

    Mecke, Almut; Hessler, Jessica; Lee, Inhan; Banaszak Holl, Mark; Orr, Bradford; Patri, Anil K.; Baker, J. R.

    2003-03-01

    Modified Polyamidoamine (PAMAM) dendrimers show great promise as targeted drug transport agents. Current research efforts point to the possibility of dramatic improvements to conventional chemotherapy by selectively delivering a therapeutic to antigen bearing tumor cells. In order to better understand the uptake mechanism of such devices into cells we are investigating dendrimer-surface adsorption and dendrimer-membrane interactions using atomic force microscopy, light scattering and computer simulations. Model systems consisting of supported DMPC lipid bilayers have shown interesting results suggesting the shape and architecture of nano-devices play an important role for their biologic activity. We are also investigating the effect of targeted drug vehicles on cells in vitro.

  18. Optically nonlinear energy transfer in light-harvesting dendrimers

    Andrews, David L.; Bradshaw, David S.

    2004-08-01

    Dendrimeric polymers are the subject of intense research activity geared towards their implementation in nanodevice applications such as energy harvesting systems, organic light-emitting diodes, photosensitizers, low-threshold lasers, and quantum logic elements, etc. A recent development in this area has been the construction of dendrimers specifically designed to exhibit novel forms of optical nonlinearity, exploiting the unique properties of these materials at high levels of photon flux. Starting from a thorough treatment of the underlying theory based on the principles of molecular quantum electrodynamics, it is possible to identify and characterize several optically nonlinear mechanisms for directed energy transfer and energy pooling in multichromophore dendrimers. Such mechanisms fall into two classes: first, those where two-photon absorption by individual donors is followed by transfer of the net energy to an acceptor; second, those where the excitation of two electronically distinct but neighboring donor groups is followed by a collective migration of their energy to a suitable acceptor. Each transfer process is subject to minor dissipative losses. In this paper we describe in detail the balance of factors and the constraints that determines the favored mechanism, which include the excitation statistics, structure of the energy levels, laser coherence factors, chromophore selection rules and architecture, possibilities for the formation of delocalized excitons, spectral overlap, and the overall distribution of donors and acceptors. Furthermore, it transpires that quantum interference between different mechanisms can play an important role. Thus, as the relative importance of each mechanism determines the relevant nanophotonic characteristics, the results reported here afford the means for optimizing highly efficient light-harvesting dendrimer devices.

  19. Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity

    Shao, Naimin; Su, Yunzhang; Hu, Jingjing; Zhang, Jiahai; Zhang, Hongfeng; Cheng, Yiyun

    2011-01-01

    Background Polyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug. Methods The dendrimer-phenylbutazone complexes were characterized by 1H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated. Results Aqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines. Conclusion Although the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development. PMID:22267921

  20. Characterization and modeling of performance of Polymer Composites Reinforced with Highly Non-Linear Cellulosic Fibers

    Rozite, L; Joffe, R; Varna, J; Nyström, B

    2012-01-01

    The behaviour of highly non-linear cellulosic fibers and their composite is characterized. Micro-mechanisms occurring in these materials are identified. Mechanical properties of regenerated cellulose fibers and composites are obtained using simple tensile test. Material visco-plastic and visco-elastic properties are analyzed using creep tests. Two bio-based resins are used in this study – Tribest and EpoBioX. The glass and flax fiber composites are used as reference materials to compare with Cordenka fiber laminates.

  1. Characterization and modeling of performance of Polymer Composites Reinforced with Highly Non-Linear Cellulosic Fibers

    Rozite, L.; Joffe, R.; Varna, J.; Nyström, B.

    2012-02-01

    The behaviour of highly non-linear cellulosic fibers and their composite is characterized. Micro-mechanisms occurring in these materials are identified. Mechanical properties of regenerated cellulose fibers and composites are obtained using simple tensile test. Material visco-plastic and visco-elastic properties are analyzed using creep tests. Two bio-based resins are used in this study - Tribest and EpoBioX. The glass and flax fiber composites are used as reference materials to compare with Cordenka fiber laminates.

  2. PHOTOREFRACTIVE POLYMERS

    Morichere, D; Malliaras, G.G; Krasnikov, V.V.; Bolink, H.J; Hadziioannou, G

    The use of polymers as photorefractive materials offers many advantages : flexibility in synthesis, doping, processing and low cost. The required functionalities responsible for photorefractivity, namely charge generation, transport, trapping and linear electrooptic effect are given in the polymer

  3. A review on comparative study of PPI and PAMAM dendrimers

    Kaur, Daljeet; Jain, Keerti; Mehra, Neelesh Kumar; Kesharwani, Prashant; Jain, Narendra K.

    2016-01-01

    Dendrimers are hyperbranched, monodispersed macromolecules with multivalent functional end groups. Dendrimers have been explored as carrier for many drugs like anticancer, antiviral, antimalarial, antiprotozoal, anti tubercular drugs. Although a number of different types of dendrimers containing different core molecules, branching monomers and surface functional groups have been designed till date for drug delivery applications, yet the poly(propyleneimine) (PPI) and poly(amidoamine) (PAMAM) dendrimers have been the most explored dendrimers in this regard. In this review, we have summarized a comparative data on PPI and PAMAM dendrimers particularly relevant to their properties, synthesis, toxicity, biomedical applications and drug delivery attributes.

  4. Light-emitting dendrimer film morphology: A neutron reflectivity study

    Vickers, S. V.; Barcena, H.; Knights, K. A.; Thomas, R. K.; Ribierre, J.-C.; Gambino, S.; Samuel, I. D. W.; Burn, P. L.; Fragneto, Giovanna

    2010-06-01

    We have used neutron reflectivity (NR) measurements to probe the physical structure of phosphorescent dendrimer films. The dendrimers consisted of fac-tris(2-phenylpyridyl)iridium(III) cores, biphenyl-based dendrons (first or second generation), and perdeuterated 2-ethylhexyloxy surface groups. We found that the shape and hydrodynamic radius of the dendrimer were both important factors in determining the packing density of the dendrimers. "Cone" shaped dendrimers were found to pack more effectively than "spherical" dendrimers even when the latter had a smaller radius. The morphology of the films determined by NR was consistent with the measured photoluminescence and charge transporting properties of the materials.

  5. A review on comparative study of PPI and PAMAM dendrimers

    Kaur, Daljeet; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar [ISF College of Pharmacy, Pharmaceutical Nanotechnology Research Laboratory (India); Kesharwani, Prashant [Wayne State University, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences (United States); Jain, Narendra K., E-mail: jnarendr@yahoo.co.in, E-mail: dr.jnarendr@gmail.com [ISF College of Pharmacy, Pharmaceutical Nanotechnology Research Laboratory (India)

    2016-06-15

    Dendrimers are hyperbranched, monodispersed macromolecules with multivalent functional end groups. Dendrimers have been explored as carrier for many drugs like anticancer, antiviral, antimalarial, antiprotozoal, anti tubercular drugs. Although a number of different types of dendrimers containing different core molecules, branching monomers and surface functional groups have been designed till date for drug delivery applications, yet the poly(propyleneimine) (PPI) and poly(amidoamine) (PAMAM) dendrimers have been the most explored dendrimers in this regard. In this review, we have summarized a comparative data on PPI and PAMAM dendrimers particularly relevant to their properties, synthesis, toxicity, biomedical applications and drug delivery attributes.

  6. A novel dendrimer based on poly (L-glutamic acid) derivatives as an efficient and biocompatible gene delivery vector

    Zeng Xin; Pan Shirong; Wang Chi; Wen Yuting; Wu Hongmei; Wang Cuifeng; Wu Chuanbin; Feng Min; Li Jie

    2011-01-01

    Non-viral gene delivery systems based on cationic polymers have faced limitations related to their relative low gene transfer efficiency, cytotoxicity and system instability in vivo. In this paper, a flexible and pompon-like dendrimer composed of poly (amidoamine) (PAMAM) G4.0 as the inner core and poly (L-glutamic acid) grafted low-molecular-weight polyethylenimine (PLGE) as the surrounding multiple arms was synthesized (MGI dendrimer). The novel MGI dendrimer was designed to combine the merits of size-controlled PAMAM G4.0 and the low toxicity and flexible chains of PLGE. In phosphate-buffered saline dispersions the well-defined DNA/MGI complex above a N/P ratio of 30 showed good stability with particle sizes of approximately 200 nm and a comparatively low polydispersity index. However, the particle size of the DNA/25 kDa polyethylenimine (DNA/PEI 25K) complex was larger than 700 nm under the same salt conditions. The shielding of the compact amino groups at the periphery of flexible PAMAM and biocompatible PLGE chains in MGI resulted in a dramatic decrease of the cytotoxicity compared to native PAMAM G4.0 dendrimer. The in vitro transfection efficiency of DNA/MGI dendrimer complex was higher than that of PAMAM G4.0 dendrimer. Importantly, in serum-containing medium, DNA/MGI complexes at their optimal N/P ratio maintained the same high levels of transfection efficiency as in serum-free medium, while the transfection efficiency of native PAMAM G4.0, PEI 25K and Lipofectamine 2000 were sharply decreased. In vivo gene delivery of pVEGF165/MGI complex into balloon-injured rabbit carotid arteries resulted in significant inhibition of restenosis by increasing VEGF165 expression in local vessels. Therefore, the pompon-like MGI dendrimer may be a promising vector candidate for efficient gene delivery in vivo.

  7. Action of amylolytic and pullulytic enzymes from various anaerobic thermophiles on linear and branched glucose polymers

    Koch, R [Goettingen Univ. (Germany, F.R.). Inst. fuer Mikrobiologie; Antranikian, G [Technische Univ. Hamburg-Harburg, Hamburg (Germany, F.R.). Arbeitsbereich Biotechnologie 1

    1990-10-01

    A detailed study has been conducted on the action of starch hydrolyzing enzymes from thermophilic anaerobic bacteria belonging to the genera Clostridium, Thermoanaerobacter and Thermobacteroides. The appearance of multiple bands on polyacrylamide gels with amylolytic as well as pullulytic activities was shown to be a general feature of bacteria investigated. Analysis of the hydrolysis products of each protein band clearly demonstrated the capability of these organisms to hydrolyze {alpha}-1,4-glycosidic bonds in linear oligosaccharides and {alpha}-1,6-glycosidic linkages in pullulan. Furthermore, the enzyme system of thermophilic bacteria investigated was also capable of attacking in the {alpha}-1,6-linkages in branched oligosaccharides. Due to the action of these thermoactive enzymes with multiple specificity an almost complete hydrolysis of raw starch and maltodextrin could be achieved under the same conditions and in one step. (orig.).

  8. Formation of Silver and Gold Dendrimer Nanocomposites

    Balogh, Lajos; Valluzzi, Regina; Laverdure, Kenneth S.; Gido, Samuel P.; Hagnauer, Gary L.; Tomalia, Donald A.

    1999-01-01

    Structural types of dendrimer nanocomposites have been studied and the respective formation mechanisms have been described, with illustration of nanocomposites formed from poly(amidoamine) PAMAM dendrimers and zerovalent metals, such as gold and silver. Structure of {(Au(0)) n- PAMAM} and {(Ag(0)) n- PAMAM} gold and silver dendrimer nanocomposites was found to be the function of the dendrimer structure and surface groups as well as the formation mechanism and the chemistry involved. Three different types of single nanocomposite architectures have been identified, such as internal ('I'), external ('E') and mixed ('M') type nanocomposites. Both the organic and inorganic phase could form nanosized pseudo-continuous phases while the other components are dispersed at the molecular or atomic level either in the interior or on the surface of the template/container. Single units of these nanocomposites may be used as building blocks in the synthesis of nanostructured materials

  9. On Topological Indices of Certain Dendrimer Structures

    Aslam, Adnan; Bashir, Yasir; Ahmad, Safyan; Gao, Wei

    2017-05-01

    A topological index can be considered as transformation of chemical structure in to real number. In QSAR/QSPR study, physicochemical properties and topological indices such as Randić, Zagreb, atom-bond connectivity ABC, and geometric-arithmetic GA index are used to predict the bioactivity of chemical compounds. Dendrimers are highly branched, star-shaped macromolecules with nanometer-scale dimensions. Dendrimers are defined by three components: a central core, an interior dendritic structure (the branches), and an exterior surface with functional surface groups. In this paper we determine generalised Randić, general Zagreb, general sum-connectivity indices of poly(propyl) ether imine, porphyrin, and zinc-Porphyrin dendrimers. We also compute ABC and GA indices of these families of dendrimers.

  10. Vortex-Induced Alignment of a Water Soluble Supramolecular Nanofiber Composed of an Amphiphilic Dendrimer

    Akihiko Tsuda

    2013-06-01

    Full Text Available We have synthesized a novel amphiphilic naphthalene imide bearing a cationic dendrimer wedge (NID. NID molecules in water self-assemble to form a two-dimensional ribbon, which further coils to give a linear supramolecular nanofiber. The sample solution showed linear dichroism (LD upon stirring of the solution, where NID nanofibers dominantly align at the center of vortex by hydrodynamic interaction with the downward torsional flows.

  11. Study of Dendrimers by Topological Indices

    Soleimani Najmeh

    2017-12-01

    Full Text Available In this paper, five degree based topological indices, the first Zagreb (M1, second Zagreb (M2, first multiple Zagreb (PM1, second multiple Zagreb (PM2, and the hyper Zagreb (HM indices of two types of dendrimers are studied. In addition, two distance based topological indices, the total eccentricity (θ and eccentric connectivity (ξc indices of these dendrimers are computed.

  12. Solid polymer/salt electrolytes based on linear poly((N-2-cyanoethyl)ethylenimine)

    Erickson, M.; Frech, R.; Glatzhofer, D.T.

    2003-01-01

    There has been growing interest in the structure, properties, ionic association, and conductivity in poly(acrylonitrile) (PAN)/salt systems and its structural analogues. We have developed a simple procedure to cyanoethylate the nitrogen atoms (>95% by 1 H-NMR) of linear poly(ethylenimine) (PEI) to form poly((N-2-cyanoethyl)ethylenimine) (PCEEI). IR studies indicate that, like PAN, a second nitrile stretching band develops for PCEEI on addition of LiTf, indicating coordination of nitrile groups to Li cations. However, spectroscopic data on the triflate ions indirectly suggest that, unlike PAN/LiTf systems, PCEEI systems contain significant proportions of 'free' Li cations at high LiTf concentrations. Initial results indicate the RT ionic conductivity in the PCEEI systems is on the order of 10 -8 S cm -1 at a composition of N:Li=6:1 and was found to be largely independent of LiTf concentration over a range of sample concentrations. The nature of the relative concentrations of ionic species of LiTf in PCEEI was determined with infrared spectroscopy. Results of room temperature and variable temperature complex impedance measurements are presented

  13. DNA condensation by partially acetylated poly(amido amine) dendrimers: effects of dendrimer charge density on complex formation.

    Yu, Shi; Li, Ming-Hsin; Choi, Seok Ki; Baker, James R; Larson, Ronald G

    2013-09-03

    The ability of poly(amido amine) (or PAMAM) dendrimers to condense semiflexible dsDNA and penetrate cell membranes gives them great potential in gene therapy and drug delivery but their high positive surface charge makes them cytotoxic. Here, we describe the effects of partial neutralization by acetylation on DNA condensation using light scattering, circular dichroism, and single molecule imaging of dendrimer-DNA complexes combed onto surfaces and tethered to those surfaces under flow. We find that DNA can be condensed by generation-five (G5) dendrimers even when the surface charges are more than 65% neutralized, but that such dendrimers bind negligibly when an end-tethered DNA is stretched in flow. We also find that when fully charged dendrimers are introduced by flow to end-tethered DNA, all DNA molecules become equally highly coated with dendrimers at a rate that becomes very fast at high dendrimer concentration, and that dendrimers remain bound during subsequent flow of dendrimer-free buffer. These results suggest that the presence of dendrimer-free DNA coexisting with dendrimer-bound DNA after bulk mixing of the two in solution may result from diffusion-limited irreversible dendrimer-DNA binding, rather than, or in addition to, the previously proposed cooperative binding mechanism of dendrimers to DNA.

  14. DNA Condensation by Partially Acetylated Poly(amido amine Dendrimers: Effects of Dendrimer Charge Density on Complex Formation

    Ronald G. Larson

    2013-09-01

    Full Text Available The ability of poly(amido amine (or PAMAM dendrimers to condense semiflexible dsDNA and penetrate cell membranes gives them great potential in gene therapy and drug delivery but their high positive surface charge makes them cytotoxic. Here, we describe the effects of partial neutralization by acetylation on DNA condensation using light scattering, circular dichroism, and single molecule imaging of dendrimer-DNA complexes combed onto surfaces and tethered to those surfaces under flow. We find that DNA can be condensed by generation-five (G5 dendrimers even when the surface charges are more than 65% neutralized, but that such dendrimers bind negligibly when an end-tethered DNA is stretched in flow. We also find that when fully charged dendrimers are introduced by flow to end-tethered DNA, all DNA molecules become equally highly coated with dendrimers at a rate that becomes very fast at high dendrimer concentration, and that dendrimers remain bound during subsequent flow of dendrimer-free buffer. These results suggest that the presence of dendrimer-free DNA coexisting with dendrimer-bound DNA after bulk mixing of the two in solution may result from diffusion-limited irreversible dendrimer-DNA binding, rather than, or in addition to, the previously proposed cooperative binding mechanism of dendrimers to DNA.

  15. New dendrimer - peptide host - guest complexes : towards dendrimers as peptide carriers

    Boas, U.; Sontjens, S.H.M.; Jensen, K.J.; Christensen, J.B.; Meijer, E.W.

    2002-01-01

    Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions

  16. Design of dendrimer-based drug delivery nanodevices with enhanced therapeutic efficacies

    Kannan, Rangaramanujam

    2007-03-01

    Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorable, `peripheral' functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug delivery. They have significant potential compared to liposomes and nanoparticles, because of the reduced macrophage update, increased cellular transport, and the ability to modulate the local environment through functional groups. We are developing nanodevices based on dendritic systems for drug delivery, that contain a high drug payload, ligands, and imaging agents, resulting in `smart' drug delivery devices that can target, deliver, and signal. In collaboration with the Children's Hospital of Michigan, Karmanos Cancer Institute, and College of Pharmacy, we are testing the in vitro and in vivo response of these nanodevices, by adapting the chemistry for specific clinical applications such as asthma and cancer. These materials are characterized by UV/Vis spectroscopy, flow cytometry, fluorescence/confocal microscopy, and appropriate animal models. Our results suggest that: (1) We can prepare drug-dendrimer conjugates with drug payloads of greater than 50%, for a variety of drugs; (2) The dendritic polymers are capable of transporting and delivering drugs into cells faster than free drugs, with superior therapeutic efficiency. This can be modulated by the surface functionality of the dendrimer; (3) For chemotherapy drugs, the conjugates are a factor of 6-20 times more effective even in drug-resistant cell lines; (4) For corticosteroidal drugs, the dendritic polymers provide higher drug residence times in the lung, allowing for passive targeting. The ability of the drug-dendrimer-ligand conjugates to target specific asthma and cancer cells is currently being explored using in vitro and in vivo animal models.

  17. Brief Timelapse on Dendrimer Chemistry: Advances, Limitations, and Expectations

    Ornelas, Catia

    2015-01-01

    , with a critical analysis on the expectations, limitations, advances, current challenges and future directions. Dendrimer timelapse demonstrates constant evolution in dendrimer chemistry enabling their application in nanomedicine, protein mimic, catalysis

  18. pH responsiveness of dendrimer-like poly(ethylene oxide)s.

    Feng, Xiaoshuang; Taton, Daniel; Borsali, Redouane; Chaikof, Elliot L; Gnanou, Yves

    2006-09-06

    Poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA), two polymers known to form pH-sensitive aggregates through noncovalent interactions, were assembled in purposely designed architecture -a dendrimer-like PEO scaffold carrying short inner PAA chains-to produce unimolecular systems that exhibit pH responsiveness. Because of the particular placement of the PAA chains within the dendrimer-like structure, intermolecular complexation between acrylic acid (AA) and ethylene oxide (EO) units-and thus macroscopic aggregation or even mesoscopic micellization-could be avoided in favor of the sole intramolecular complexation. The sensitivity of such interactions to pH was exploited to generate dendrimer-like PEOs that reversibly shrink and expand with the pH. Such PAA-carrying dendrimer-like PEOs were synthesized in two main steps. First, a fifth-generation dendrimer-like PEO was obtained by combining anionic ring-opening polymerization (AROP) of ethylene oxide from a tris-hydroxylated core and selective branching reactions of PEO chain ends. To this end, an AB(2)C-type branching agent was designed: the latter includes a chloromethyl (A) group for its covalent attachment to the arm ends, two geminal hydroxyls (B(2)) protected in the form of a ketal ring for the growth of subsequent PEO generations by AROP, and a vinylic (C) double bonds for further functionalization of the interior of dendrimer-like PEOs. Reiteration of AROP and derivatization of PEO branches allowed us to prepare a dendrimer-like PEO of fourth generation with a total molar mass of 52,000 g x mol(-1), containing 24 external hydroxyl functions and 21 inner vinylic groups in the interior. A fifth generation of PEO chains was generated from this parent dendrimer-like PEO of fourth generation using a "conventional" AB(2)-type branching agent, and 48 PEO branches could be grown by AROP. The 48 outer hydroxy-end groups of the fifth-generation dendrimer-like PEO obtained were subsequently quantitatively

  19. New dendrimer - Peptide host - Guest complexes: Towards dendrimers as peptide carriers

    Boas, Ulrik; Sontjens, S.H.M.; Jensen, Knud Jørgen

    2002-01-01

    Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions...... between the dendrimer outer shell tertiary amines and the C-terminal carboxylic acid of the peptide, and also through host-urea to peptide-amide hydrogen bonding. The hydrogen-bonding nature of the peptide dendrimer interactions was further confirmed by using Fourier transform IR spectroscopy, for which...... the NH- and CO-stretch signals of the peptide amide moieties shift towards lower wave-numbers upon complexation with the dendrimer. Spatial analysis of the complexes with NOESY spectroscopy generally shows close proximity of the N-terminal Boc group of the peptide to the peripheral adamantyl groups...

  20. New organic photorefractive material composed of a charge-transporting dendrimer and a stilbene chromophore

    Bai, Jaeil; Ducharme, Stephen; Leonov, Alexei G.; Lu, Liu; Takacs, James M.

    1999-10-01

    In this report, we introduce new organic photorefractive composites consisting of charge transporting den-drimers highly doped with a stilbene nonlinear optic chromophore, The purpose of making these composites is to improve charge transport, by reducing inhomogeneity when compared to ordinary polymer-based systems. Because the structure of this material gives us freedom to control the orientation of charge transport agents synthetically, we can study the charge transport mechanism more systematically than in polymers. We discuss this point and present the characterization results for this material.

  1. PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

    2004-01-01

    A method for the synthesis of dendrimer conjugates having a well-defined chemical structure, comprising one or more carbohydrate moieties and one or more immunomodulating substances coupled to a dendrimer, is presented. First, the carbohydrate is bound to the dendrimer in a chemoselective manner...... conjugates and their use in vaccination, production of antibodies, high throughput screening, diagnostic assays and libraries....

  2. Oligothia dendrimers for the formation of gold nanoparticles

    d'Aleo, A.; Williams, R.M.; Osswald, F.; Edamana, P.; Hahn, U.; van Heyst, J.; Tichelaar, F.D.; Voegtle, F.; De Cola, L.

    2004-01-01

    The synthesis and characterization of oligothia dendrimers and their use for the formation of gold nanoparticles is described. The role played by these dendrimers in controlling the stability and size of the particles is discussed. It is shown that the generation of the dendrimers, as well as the

  3. Preliminary biological evaluation of a urea-functionalized dendrimer

    Stephan, H.; Syhre, R.; Spies, H.; Johannsen, B.; Zessin, J.; Steinbach, J.; Klein, L.; Werner, N.; Voegtle, F.

    2002-01-01

    A new third generation ethylurea-functionalized polypropyleneamine dendrimer was prepared. After labelling this dendrimer with 11-carbon the biodistribution in rats was studied. The highest level of radioactivity was found in the liver (30-35% ID). The 11 C-labelled dendrimer was well tolerated by the rats. (orig.)

  4. DNA assisted self-assembly of PAMAM dendrimers.

    Mandal, Taraknath; Kumar, Mattaparthi Venkata Satish; Maiti, Prabal K

    2014-10-09

    We report DNA assisted self-assembly of polyamidoamine (PAMAM) dendrimers using all atom Molecular Dynamics (MD) simulations and present a molecular level picture of a DNA-linked PAMAM dendrimer nanocluster, which was first experimentally reported by Choi et al. (Nano Lett., 2004, 4, 391-397). We have used single stranded DNA (ssDNA) to direct the self-assembly process. To explore the effect of pH on this mechanism, we have used both the protonated (low pH) and nonprotonated (high pH) dendrimers. In all cases studied here, we observe that the DNA strand on one dendrimer unit drives self-assembly as it binds to the complementary DNA strand present on the other dendrimer unit, leading to the formation of a DNA-linked dendrimer dimeric complex. However, this binding process strongly depends on the charge of the dendrimer and length of the ssDNA. We observe that the complex with a nonprotonated dendrimer can maintain a DNA length dependent inter-dendrimer distance. In contrast, for complexes with a protonated dendrimer, the inter-dendrimer distance is independent of the DNA length. We attribute this observation to the electrostatic complexation of a negatively charged DNA strand with the positively charged protonated dendrimer.

  5. Modulation of Quorum Sensing in a Gram-Positive Pathogen by Linear Molecularly Imprinted Polymers with Anti-infective Properties.

    Motib, Anfal; Guerreiro, Antonio; Al-Bayati, Firas; Piletska, Elena; Manzoor, Irfan; Shafeeq, Sulman; Kadam, Anagha; Kuipers, Oscar; Hiller, Luisa; Cowen, Todd; Piletsky, Sergey; Andrew, Peter W; Yesilkaya, Hasan

    2017-12-22

    We describe the development, characterization, and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as an anti-infective by blocking the quorum sensing (QS) mechanism and so abrogating the virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches, no cross-linker is used. This results in soluble low-molecular-weight oligomers that can act as a therapeutic agent in vitro and in vivo. The LMIP was characterized by mass spectrometry to determine its monomer composition. Fragments identified were then aligned along the peptide template by computer modeling to predict the possible monomer sequence of the LMIP. These findings provide a proof of principle that LMIPs can be used to block QS, thus setting the stage for the development of LMIPs a novel drug-discovery platform and class of materials to target Gram-positive pathogens. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Low potential stable glucose detection at dendrimers modified polyaniline nanotubes

    Alessandra Nogueira Santos

    2010-03-01

    Full Text Available The utilization of nanostructured materials for development of biosensors is a growing field in medical diagnostics. In this work a glucose biosensor based on bioactive polyglycerol (PGLD and chitosan dendrimers (CHD was developed. PGLD and CHD were bioconjugated with the enzyme glucose oxidase (GOx to obtain dendrimers with glucose sensing properties. Polyaniline nanotubes (PANINT´s were used as electron mediator due to their high ability to promote electron-transfer reactions involving GOx. The PGLD-GOx and CHD-GOx were entrapped in PANINT´s during template electrochemical polymerization of aniline. The prepared PGLD-GOx/PANINT´s and CHD-GOx/PANINT´s biosensors exhibit a strong and stable amperometric response to glucose even at a low potential of +100 mV. The based PGLD-GOx/PANINT´s and CHD-GOx/PANINT´s biosensors showed a good performance in glucose concentrations range in human blood. A comparison of the sensitivities to glucose showed that both biosensors have a linearity range between 0.02 and 10 mM, though PGLD-GOx/PANINT´s is more sensitive (10.41 vs. 7.04 nA.mM-1. The difference in the biosensor behavior and the high sensitivity of the PGLD-GOx/PANINT´s may be due to the specific organization of GOx layer at surface of the modifier macromolecule PGLD and their distribution in PANINT´s. The enzyme affinity for the substrate, K Mapp remains quite good after GOx immobilization on PGLD and CHD dendrimers and entrapment of the bioconjugates in PANINT´s.

  7. On the ability of PAMAM dendrimers and dendrimer/DNA aggregates to penetrate POPC model biomembranes.

    Ainalem, Marie-Louise; Campbell, Richard A; Khalid, Syma; Gillams, Richard J; Rennie, Adrian R; Nylander, Tommy

    2010-06-03

    Poly(amido amine) (PAMAM) dendrimers have previously been shown, as cationic condensing agents of DNA, to have high potential for nonviral gene delivery. This study addresses two key issues for gene delivery: the interaction of the biomembrane with (i) the condensing agent (the cationic PAMAM dendrimer) and (ii) the corresponding dendrimer/DNA aggregate. Using in situ null ellipsometry and neutron reflection, parallel experiments were carried out involving dendrimers of generations 2 (G2), 4 (G4), and 6 (G6). The study demonstrates that free dendrimers of all three generations were able to traverse supported palmitoyloleoylphosphatidylcholine (POPC) bilayers deposited on silica surfaces. The model biomembranes were elevated from the solid surfaces upon dendrimer penetration, which offers a promising new way to generate more realistic model biomembranes where the contact with the supporting surface is reduced and where aqueous cavities are present beneath the bilayer. The largest dendrimer (G6) induced partial bilayer destruction directly upon penetration, whereas the smaller dendrimers (G2 and G4) leave the bilayer intact, so we propose that lower generation dendrimers have greater potential as transfection mediators. In addition to the experimental observations, coarse-grained simulations on the interaction between generation 3 (G3) dendrimers and POPC bilayers were performed in the absence and presence of a bilayer-supporting negatively charged surface that emulates the support. The simulations demonstrate that G3 is transported across free-standing POPC bilayers by direct penetration and not by endocytosis. The penetrability was, however, reduced in the presence of a surface, indicating that the membrane transport observed experimentally was not driven solely by the surface. The experimental reflection techniques were also applied to dendrimer/DNA aggregates of charge ratio = 0.5, and while G2/DNA and G4/DNA aggregates interact with POPC bilayers, G6/DNA

  8. Selective cytotoxicity of PAMAM G5 core–PAMAM G2.5 shell tecto-dendrimers on melanoma cells

    Schilrreff P

    2012-07-01

    Full Text Available Priscila Schilrreff,1 Cecilia Mundiña-Weilenmann,2 Eder Lilia Romero,1 Maria Jose Morilla11Programa de Nanomedicinas, Universidad Nacional de Quilmes, Buenos Aires, Argentina; 2Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, La Plata, ArgentinaBackground: The controlled introduction of covalent linkages between dendrimer building blocks leads to polymers of higher architectural order known as tecto-dendrimers. Because of the few simple steps involved in their synthesis, tecto-dendrimers could expand the portfolio of structures beyond commercial dendrimers, due to the absence of synthetic drawbacks (large number of reaction steps, excessive monomer loading, and lengthy chromatographic separations and structural constraints of high-generation dendrimers (reduction of good monodispersity and ideal dendritic construction due to de Gennes dense-packing phenomenon. However, the biomedical uses of tecto-dendrimers remain unexplored. In this work, after synthesizing saturated shell core–shell tecto-dendrimers using amine-terminated polyamidoamine (PAMAM generation 5 (G5 as core and carboxyl-terminated PAMAM G2.5 as shell (G5G2.5 tecto-dendrimers, we surveyed for the first time the main features of their interaction with epithelial cells.Methods: Structural characterization of G5G2.5 was performed by polyacrylamide gel electrophoresis, matrix-assisted laser desorption time-of-flight mass spectrometry, and microscopic techniques; their hydrodynamic size and Z-potential was also determined. Cellular uptake by human epidermal keratinocytes, colon adenocarcinoma, and epidermal melanoma (SK-Mel-28 cells was determined by flow cytometry. Cytotoxicity was determined by mitochondrial activity, lactate dehydrogenase release, glutathione depletion, and apoptosis/necrosis measurement.Results: The resultant 60%–67% saturated shell, 87,000-dalton G5G2.5 (mean molecular weight interacted with cells in a significantly different

  9. Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii

    Petit, Anne-Noelle, E-mail: anne-noelle.petit@ec.gc.ca [Environment Canada, 105 McGill Street, Montreal, Quebec H2Y 2E7 (Canada); Eullaffroy, Philippe [Laboratoire Plantes, Pesticides et Developpement Durable, EA 2069, URVVC, BP 1039, Universite de Reims Champagne-Ardenne, 51687 Reims Cedex 2 (France); Debenest, Timothee; Gagne, Francois [Environment Canada, 105 McGill Street, Montreal, Quebec H2Y 2E7 (Canada)

    2010-10-15

    In recent decades, a new class of polymeric materials, PAMAM dendrimers, has attracted marked interest owing to their unique nanoscopic architecture and their hopeful perspectives in nanomedicine and therapeutics. However, the potential release of dendrimers into the aquatic environment raises the issue about their toxicity on aquatic organisms. Our investigation sought to estimate the toxicity of cationic PAMAM dendrimers on the green alga, Chlamydomonas reinhardtii. Algal cultures were exposed to different concentrations (0.3-10 mg L{sup -1}) of low dendrimer generations (G2, G4 and G5) for 72 h. Potential adverse effects on Chlamydomonas were assessed using esterase activity (cell viability), photosynthetic O{sub 2} evolution, pigments content and chlorophyll a fluorescence transient. According to the median inhibitory concentration (IC{sub 50}) appraised from esterase activity, toxicity on cell viability decreased with dendrimer generation number (2, 3 and 5 mg L{sup -1} for G2, G4 and G5 dendrimers, respectively). Moreover, the three generations of dendrimers did not induce the same changes in the photosynthetic metabolism of the green alga. O{sub 2} evolution was stimulated in cultures exposed to the lowest generations tested (i.e. G2 and G4) whereas no significant effects were observed with G5. In addition, total chlorophyll content was increased after G2 treatment at 2.5 mg L{sup -1}. Finally, G2 and G4 had positive effects on photosystem II (PSII): the amount of active PSII reaction centers, the primary charge separation and the electron transport between Q{sub A} and Q{sub B} were all increased inducing activation of the photosynthetic electron transport chain. These changes resulted in stimulation of full photosynthetic performance.

  10. Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii

    Petit, Anne-Noelle; Eullaffroy, Philippe; Debenest, Timothee; Gagne, Francois

    2010-01-01

    In recent decades, a new class of polymeric materials, PAMAM dendrimers, has attracted marked interest owing to their unique nanoscopic architecture and their hopeful perspectives in nanomedicine and therapeutics. However, the potential release of dendrimers into the aquatic environment raises the issue about their toxicity on aquatic organisms. Our investigation sought to estimate the toxicity of cationic PAMAM dendrimers on the green alga, Chlamydomonas reinhardtii. Algal cultures were exposed to different concentrations (0.3-10 mg L -1 ) of low dendrimer generations (G2, G4 and G5) for 72 h. Potential adverse effects on Chlamydomonas were assessed using esterase activity (cell viability), photosynthetic O 2 evolution, pigments content and chlorophyll a fluorescence transient. According to the median inhibitory concentration (IC 50 ) appraised from esterase activity, toxicity on cell viability decreased with dendrimer generation number (2, 3 and 5 mg L -1 for G2, G4 and G5 dendrimers, respectively). Moreover, the three generations of dendrimers did not induce the same changes in the photosynthetic metabolism of the green alga. O 2 evolution was stimulated in cultures exposed to the lowest generations tested (i.e. G2 and G4) whereas no significant effects were observed with G5. In addition, total chlorophyll content was increased after G2 treatment at 2.5 mg L -1 . Finally, G2 and G4 had positive effects on photosystem II (PSII): the amount of active PSII reaction centers, the primary charge separation and the electron transport between Q A and Q B were all increased inducing activation of the photosynthetic electron transport chain. These changes resulted in stimulation of full photosynthetic performance.

  11. Temperature-sensitive elastin-mimetic dendrimers: Effect of peptide length and dendrimer generation to temperature sensitivity.

    Kojima, Chie; Irie, Kotaro; Tada, Tomoko; Tanaka, Naoki

    2014-06-01

    Dendrimers are synthetic macromolecules with unique structure, which are a potential scaffold for peptides. Elastin is one of the main components of extracellular matrix and a temperature-sensitive biomacromolecule. Previously, Val-Pro-Gly-Val-Gly peptides have been conjugated to a dendrimer for designing an elastin-mimetic dendrimer. In this study, various elastin-mimetic dendrimers using different length peptides and different dendrimer generations were synthesized to control the temperature dependency. The elastin-mimetic dendrimers formed β-turn structure by heating, which was similar to the elastin-like peptides. The elastin-mimetic dendrimers exhibited an inverse phase transition, largely depending on the peptide length and slightly depending on the dendrimer generation. The elastin-mimetic dendrimers formed aggregates after the phase transition. The endothermal peak was observed in elastin-mimetic dendrimers with long peptides, but not with short ones. The peptide length and the dendrimer generation are important factors to tune the temperature dependency on the elastin-mimetic dendrimer. Copyright © 2013 Wiley Periodicals, Inc.

  12. Conformational Effects in Non-Stoichiometric Complexes of Two Hyperbranched Molecules with a Linear Polyelectrolyte

    Alexey Lyulin

    2012-01-01

    Full Text Available We report results from Brownian dynamics computer simulations of systems comprised by two terminally charged hyperbranched molecules preferentially branched in the periphery, with an oppositely charged linear chain of varying length. Comparison of the findings from the present study to stoichiometric counterparts and to analogous dendrimer-based complexes, reveal that the presence of the second hyperbranched molecule incurs significant changes in the conformational characteristics of both components of the complex. Instead of step-like changes in the average size and shape of the hyperbranched component that were noted in the previously studied stoichiometric systems, a rather smooth change is observed upon increase of the length of the linear component. In addition, a markedly different behavior is also noticed in the conformational characteristics of the linear chain when compared to that in similar dendrimer-based systems. The above findings are consistent with the higher degree of deformability of the peripherally branched molecules which allow appropriate rearrangements in shape in order to accommodate the favorable Coulombic interactions between the two components of the complex. This behavior offers new insight towards the design of more efficient hyperbranched-based systems which can take advantage of the multifunctionality and the structural properties of the highly branched polymer components.

  13. Photoinduced Charge Transport Spectra for Porphyrin and Naphthalene Derivative-based Dendrimers

    Park, J. H.; Wu, Y.; Parquette, J. R.; Epstein, A. J.

    2006-03-01

    Dendrimers are important chemical structures for harvesting charge. We prepared model dendrimers using two porphyrin derivatives and a naphthalene derivative. Films of these porphyrin derivatives have a strong Soret band (˜430nm) and four significant Q-bands; the naphthalene derivative has strong absorption at 365 and 383nm. Two kinds of photovoltaic cell structures [ITO/BaytronP/(thick or thin) dendrimer/Al] are constructed to investigate the optical response spectra of dendrimers under electric potential(V) on the cell (range from -1V to 2V). To obtain pure optical responses, incident light is modulated with an optical chopper and a lock-in amplifier is used to measure current (IAC) and phase (θ). For the excitation of the Soret band, IAC and θ do not change substantially with change of sign and amplitude of V. For Q-bands and naphthalene absorption bands, θ nearly follows the polarity of V on the cells and IAC is linear with V. Hence, IAC is nearly ohmic for Q- band although there are shifts due to built-in-potential. IAC for Soret band is almost same for thick and thin active layer cells. In contrast, IAC increases with thickness increase for Q bands. Mechanisms of photogeneration and charge transport will be discussed.

  14. Tailoring silver nanoparticle construction using dendrimer templated silica networks

    Liu Xiaojun; Kakkar, Ashok

    2008-01-01

    We have examined the role of the internal environment of dendrimer templated silica networks in tailoring the construction of silver nanoparticle assemblies. Silica networks from which 3,5-dihydroxybenzyl alcohol based dendrimer templates have been completely removed, slowly wet with an aqueous solution of silver acetate. The latter then reacts with internal silica silanol groups, leading to chemisorption of silver ions, followed by the growth of silver oxide nanoparticles. Silica network constructed using generation 4 dendrimer contains residual dendrimer template, and mixes with aqueous silver acetate solution easily. Upon chemisorption, silver ions get photolytically reduced to silver metal under a stabilizing dendrimer environment, leading to the formation of silver metal nanoparticles

  15. PAMAM dendrimer with 4-carbomethoxypyrrolidone - In vitro assessment of neurotoxicity

    Janaszewska, Anna; Studzian, Maciej; Petersen, Johannes Fabritius

    2015-01-01

    Cytotoxicity of cationic amino-terminated PAMAM dendrimer and modified PAMAM-pyrrolidone dendrimer was compared. LDH assay and cell visualization technique were employed. Mouse embryonic hippocampal cells (mHippoE-18) were used. The experiments were performed in FBS-deprived medium. Pyrrolidone......-modification significantly diminished toxicity of PAMAM dendrimer. The absence of FBS did not reveal significant impact on the toxic effect. Results from LDH assay and MTT test were in good consistency. Low cytotoxicity of PAMAM-pyrrolidone dendrimer increases reliability of the results showing a small impact...... of this dendrimer on cell viability....

  16. Poly(amido amine) dendrimers in oral delivery.

    Yellepeddi, Venkata K; Ghandehari, Hamidreza

    2016-01-01

    Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed.

  17. Fluorescent properties of novel dendrimer dyes based on thiazole orange

    Fei Xuening; Gu Yingchun; Lan Yunquan; Shi Bin

    2011-01-01

    In this paper, polyamidoamine (PAMAM) dendrimers with active amino group of some generations (G=0.5-2) were prepared from commercial aminoacetaldehyde diethyl acetal by the divergent method. After that, thiazole orange (TO) with -COOH was incorporated with dendrimers of G=1 and 2 to afford novel dendrimer-TO dyes. The fluorescent properties studies showed that the fluorescent intensity of the same concentration of dendrimer-TO (G=2) was higher than that of the dendrimer-TO (G=1), and both of them were much stronger than free TO with -COOH. There was a fluorescent enhancement of the dendrimer dyes compared with free dye. The dendrimer dyes were of well-defined chemical structure,with little aggregation and self-quenching as well as good fluorescence properties of good stability, high intensity and sensitivity, which could be used in labeling cancer cells and further in diagnosis and detection of early-stage tumors. - Highlights: → A kind of dendrimer probe based on TO was designed and synthesized. → Dendrimers showed an obvious fluorescence enhancement compared to free dye. → Dendrimers labeled with BSA also showed fluorescence enhancement. → Dendrimers may be used in diagnosis and detection of early-stage tumors.

  18. Interaction between viologen-phosphorus dendrimers and α-synuclein

    Milowska, Katarzyna; Grochowina, Justyna; Katir, Nadia; El Kadib, Abdelkrim; Majoral, Jean-Pierre; Bryszewska, Maria; Gabryelak, Teresa

    2013-01-01

    In this study the interaction between viologen-phosphorus dendrimers and α-synuclein (ASN) was examined. Polycationic viologen-phosphorus dendrimers (two positive charges per viologen unit) are novel compounds with relatively unknown properties. The influence of these viologen dendrimers on ASN was tested using fluorimetric and circular dichroism methods. ASN contains four tyrosine residues; therefore, the influence of dendrimers on protein molecular conformation by measuring the changes in the ASN fluorescence in the presence of dendrimers was evaluated. The interaction of dendrimers with free L-tyrosine was also monitored. Results show that viologen-phosphorus dendrimers interact with ASN; they quenched the fluorescence of ASN as well as free tyrosine by dynamic and static ways. However, the quenching was not accompanied by modifications in the ASN secondary structure. - Highlights: ► Interaction between viologen-phosphorus dendrimers and α-synuclein (ASN) was investigated. ► Viologen-phosphorus dendrimers can quench the fluorescence of tyrosine in ASN. ► Dendrimers caused red-shift in maximum of fluorescence. ► Viologen-phosphorus dendrimers did not change the secondary structure of ASN.

  19. Brief Timelapse on Dendrimer Chemistry: Advances, Limitations, and Expectations

    Ornelas, Catia

    2015-12-09

    © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Dendrimers are well-defined branched macromolecules that have been studied for a wide variety of applications. Possibility to add multiple functionalities in precise locations of the dendritic structure generated great expectations for the application of dendrimers in nanomedicine, however, the number of dendrimer-based formulations that advance to clinical studies has been somewhat deceiving. This is partially due to the nonreproducible pharmokinetic behavior observed for multifunctional dendrimers synthesized through the random-statistical approach that leads to mixtures of products. Therefore, it is crucial to develop multifunctional dendrimers with well-defined structures in order to increase the chances of meeting the clinical expectations placed on dendrimers. This talent article will give an overview of the dendrimer field, discussing the application of dendrimers in nanomedicine, light-harvesting systems, sensing and catalysis, with a critical analysis on the expectations, limitations, advances, current challenges and future directions. Dendrimer timelapse demonstrates constant evolution in dendrimer chemistry enabling their application in nanomedicine, protein mimic, catalysis, light harvesting systems, and sensing. Increasing the variety of functionalities in dendrimers located at precise sites of the dendritic backbone result in versatile multifunctional nanomaterials that in the future might approach the conceptual nanobots.

  20. Interaction between viologen-phosphorus dendrimers and {alpha}-synuclein

    Milowska, Katarzyna, E-mail: milowska@biol.uni.lodz.pl [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland); Grochowina, Justyna [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland); Katir, Nadia [Laboratoire de Chimie de Coordination CNRS, 205 route de Narbonne, 31077 Toulouse (France); El Kadib, Abdelkrim [Institute of Nanomaterials and Nanotechnology (INANOTECH)-MAScIR (Moroccan Foundation for Advanced Science, Innovation and Research), ENSET, Avenue de I' Armee Royale, Madinat El Irfane, 10100 Rabat (Morocco); Majoral, Jean-Pierre [Laboratoire de Chimie de Coordination CNRS, 205 route de Narbonne, 31077 Toulouse (France); Bryszewska, Maria; Gabryelak, Teresa [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland)

    2013-02-15

    In this study the interaction between viologen-phosphorus dendrimers and {alpha}-synuclein (ASN) was examined. Polycationic viologen-phosphorus dendrimers (two positive charges per viologen unit) are novel compounds with relatively unknown properties. The influence of these viologen dendrimers on ASN was tested using fluorimetric and circular dichroism methods. ASN contains four tyrosine residues; therefore, the influence of dendrimers on protein molecular conformation by measuring the changes in the ASN fluorescence in the presence of dendrimers was evaluated. The interaction of dendrimers with free L-tyrosine was also monitored. Results show that viologen-phosphorus dendrimers interact with ASN; they quenched the fluorescence of ASN as well as free tyrosine by dynamic and static ways. However, the quenching was not accompanied by modifications in the ASN secondary structure. - Highlights: Black-Right-Pointing-Pointer Interaction between viologen-phosphorus dendrimers and {alpha}-synuclein (ASN) was investigated. Black-Right-Pointing-Pointer Viologen-phosphorus dendrimers can quench the fluorescence of tyrosine in ASN. Black-Right-Pointing-Pointer Dendrimers caused red-shift in maximum of fluorescence. Black-Right-Pointing-Pointer Viologen-phosphorus dendrimers did not change the secondary structure of ASN.

  1. One-, two- and three-photon spectroscopy of π-conjugated dendrimers: cooperative enhancement and coherent domains

    Drobizhev, M.; Rebane, A.; Suo, Z.; Spangler, C.W.

    2005-01-01

    We use wavelength tunable femtosecond pulses to measure intrinsic (simultaneous) two-photon absorption (2PA) and three-photon absorption (3PA) molecular cross section in two series of π-conjugated dendrimers built of identical 4,4'-bis(diphenylamino) stilbene (BDPAS) and 4,4'-bis(diphenylamino) distyrylbenzene (BDPADSB) repeat units. Record large 2PA cross sections, σ 2 =10 -46 cm 4 s are obtained for the largest second-generation BDPAS-based dendrimer, as well as zeroth-generation 4-arm BDPADSB-based dendrimer. In both series, maximum 2PA cross section increases nonlinearly with the number of π-electrons, whereas for higher generations this dependence turns to linear one. 3PA cross section also increases nonlinearly with the size of the system in the series of BDPAS-based molecules, amounting a record large value, σ 3 =10 -79 cm 6 s 2 , for the largest, second-generation dendrimer. We interpret these results in terms of direct inter-branch conjugation, which facilitates cooperative enhancement of the nonlinear-optical response. We propose a simple model which allows us to determine the effective size of coherent domains (extent of conjugation), which, in turn, determines the optimum dendrimer size for most efficient nonlinear response

  2. Pharmaceutical and biomedical potential of surface engineered dendrimers.

    Satija, Jitendra; Gupta, Umesh; Jain, Narendra Kumar

    2007-01-01

    Dendrimers are hyperbranched, globular, monodisperse, nanometric polymeric architecture, having definite molecular weight, shape, and size (which make these an inimitable and optimum carrier molecule in pharmaceutical field). Dendritic architecture is having immense potential over the other carrier systems, particularly in the field of drug delivery because of their unique properties, such as structural uniformity, high purity, efficient membrane transport, high drug pay load, targeting potential, and good colloidal, biological, and shelf stability. Despite their enormous applicability in different areas, the inherent cytotoxicity, reticuloendothelial system (RES) uptake, drug leakage, immunogenicity, and hemolytic toxicity restricted their use in clinical applications, which is primarily associated with cationic charge present on the periphery due to amine groups. To overcome this toxic nature of dendrimers, some new types of nontoxic, biocompatible, and biodegradable dendrimers have been developed (e.g., polyester dendrimer, citric acid dendrimer, arginine dendrimer, carbohydrate dendrimers, etc.). The surface engineering of parent dendrimers is graceful and convenient strategy, which not only shields the positive charge to make this carrier more biomimetic but also improves the physicochemical and biological behavior of parent dendrimers. Thus, surface modification chemistry of parent dendrimers holds promise in pharmaceutical applications (such as solubilization, improved drug encapsulation, enhanced gene transfection, sustained and controlled drug release, intracellular targeting) and in the diagnostic field. Development of multifunctional dendrimer holds greater promise toward the biomedical applications because a number of targeting ligands determine specificity in the same manner as another type of group would secure stability in biological milieu and prolonged circulation, whereas others facilitate their transport through cell membranes. Therefore, as a

  3. Uses of Dendrimers for DNA Microarrays

    Jean-Pierre Majoral

    2006-08-01

    Full Text Available Biosensors such as DNA microarrays and microchips are gaining an increasingimportance in medicinal, forensic, and environmental analyses. Such devices are based onthe detection of supramolecular interactions called hybridizations that occur betweencomplementary oligonucleotides, one linked to a solid surface (the probe, and the other oneto be analyzed (the target. This paper focuses on the improvements that hyperbranched andperfectly defined nanomolecules called dendrimers can provide to this methodology. Twomain uses of dendrimers for such purpose have been described up to now; either thedendrimer is used as linker between the solid surface and the probe oligonucleotide, or thedendrimer is used as a multilabeled entity linked to the target oligonucleotide. In the firstcase the dendrimer generally induces a higher loading of probes and an easier hybridization,due to moving away the solid phase. In the second case the high number of localized labels(generally fluorescent induces an increased sensitivity, allowing the detection of smallquantities of biological entities.

  4. Structural properties of dendrimer-colloid mixtures

    Lenz, Dominic A; Blaak, Ronald; Likos, Christos N

    2012-01-01

    We consider binary mixtures of colloidal particles and amphiphilic dendrimers of the second generation by means of Monte Carlo simulations. By using the effective interactions between monomer-resolved dendrimers and colloids, we compare the results of simulations of mixtures stemming from a full monomer-resolved description with the effective two-component description at different densities, composition ratios, colloid diameters and interaction strengths. Additionally, we map the two-component system onto an effective one-component model for the colloids in the presence of the dendrimers. Simulations based on the resulting depletion potentials allow us to extend the comparison to yet another level of coarse graining and to examine under which conditions this two-step approach is valid. In addition, a preliminary outlook into the phase behavior of this system is given. (paper)

  5. Nonlinear Optical and Time-Resolved Properties of Novel Organic Dendrimers and Dendrimer Metal

    Goodson, T., III

    2004-01-01

    .... We found in particular that gold-metal dendrimer nanocomposites have very strong optical limiting properties that may be useful for eye and sensor protection devices in the visible and near Infrared spectral regions...

  6. Dendrimers for Vaccine and Immunostimulatory Uses

    Heegaard, Peter M. H.; Boas, Ulrik; Sørensen, Nanna Skall

    2010-01-01

    for efficient immunostimulating compounds (adjuvants) that can increase the efficiency of vaccines, as dendrimers can provide molecularly defined multivalent scaffolds to produce highly defined conjugates with small molecule immunostimulators and/or antigens. The review gives an overview on the use...... of dendrimers as molecularly defined carriers/presenters of small antigens, including constructs that have built-in immunostimulatory (adjuvant) properties, and as stand-alone adjuvants that can be mixed with antigens to provide efficient vaccine formulations. These approaches allow the preparation...... of molecularly defined vaccines with highly predictable and specific properties and enable knowledge-based vaccine design substituting the traditional empirically based approaches for vaccine development and production....

  7. Structure of DNA-Functionalized Dendrimer Nanoparticles

    Kumar, Mattaparthi Venkata Satish; Maiti, Prabal K

    2012-01-01

    Atomistic molecular dynamics simulations have been carried out to reveal the characteristic features of ethylenediamine (EDA) cored protonated poly amido amine (PAMAM) dendrimers of generation 3 (G3) and 4 (G4) that are functionalized with single stranded DNAs (ssDNAs). The four ssDNA strands that are attached via alkythiolate [-S (CH2)6-] linker molecule to the free amine groups on the surface of the PAMAM dendrimers observed to undergo a rapid conformational change during the 25 ns long sim...

  8. Antibody-dendrimer conjugates: the number, not the size of the dendrimers, determines the immunoreactivity.

    Wängler, C; Moldenhauer, G; Eisenhut, M; Haberkorn, U; Mier, W

    2008-04-01

    Radioimmunotherapy using antibodies with favorable tumor targeting properties and high binding affinity is increasingly applied in cancer therapy. The potential of this valuable cancer treatment modality could be further improved by increasing the specific activity of the labeled proteins. This can be done either by coupling a large number of chelators which leads to a decreased immunoreactivity or by conjugating a small number of multimeric chelators. In order to systematically investigate the influence of conjugations on immunoreactivity with respect to size and number of the conjugates, the anti-EGFR antibody hMAb425 was reacted with PAMAM dendrimers of different size containing up to 128 chelating agents per conjugation site. An improved dendrimer synthesis protocol was established to obtain compounds of high homogeneity suitable for the formation of defined protein conjugates. The quantitative derivatization of the PAMAM dendrimers with DOTA moieties and the characterization of the products by isotopic dilution titration using (111)In/(nat)In are shown. The DOTA-containing dendrimers were conjugated with high efficiency to hMAb425 by applying Sulfo-SMCC as cross-linking agent and a 10- to 25-fold excess of the thiol-containing dendrimers. The determination of the immunoreactivities of the antibody-dendrimer conjugates by FACS analysis revealed a median retained immunoreactivity of 62.3% for 1.7 derivatization sites per antibody molecule, 55.4% for 2.8, 27.9% for 5.3, and 17.1% for 10.0 derivatization sites per antibody but no significant differences in immunoreactivity for different dendrimer sizes. These results show that the dendrimer size does not influence the immunoreactivity of the derivatized antibody significantly over a wide molecular weight range, whereas the number of derivatization sites has a crucial effect.

  9. Practical computational toolkits for dendrimers and dendrons structure design

    Martinho, Nuno; Silva, Liana C.; Florindo, Helena F.; Brocchini, Steve; Barata, Teresa; Zloh, Mire

    2017-09-01

    Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.

  10. Generation dependent cancer targeting potential of poly(propyleneimine) dendrimer.

    Kesharwani, Prashant; Tekade, Rakesh K; Jain, Narendra K

    2014-07-01

    Dendrimer-mediated delivery of bioactive is a successful and widely explored concept. This paper desribes comparative data pertaining to generation dependent cancer targeting propensity of Poly(propyleneimine) (PPI) dendrimers. This debut report reportsthe drug targeting and antciancer potential of different dendrimer generations. PPI dendrimers of different generations (3.0G, 4.0G and 5.0G) were synthesized and loaded with Melphalan. Results from loading, hemolysis, hematologic, cytotoxicty and flow cytometry assay depicted that as the generation of dendrimer increased from fourth to fifth, the only parameter i.e. toxicty is increased exponentionally. However, others parameters, i.e. loading, sustained release behavior, and targeting efficacy increased negligibly. Kaplan-Meier survival curves clearly depicted comparable therapeutic potential of PPI4M with PPI5M. In vivo investigations in Balb/c mice again favored 4.0G PPI dendrimer to be preferable nanocarrier for anticancer drug delivery owing to analogous anticancer potential. The outcomes of the investigation evidently projects 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer in respect of its drug delivery benefit as well as superior biocompatibility. Thus, much against the common belief, 4.0G PPI dendrimers may be considered to be optimum in respect of drug delivery precluding the use of much more toxic 5.0G PPI dendrimer, which offers no benefit over 4.0G. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Nature of the effective interaction between dendrimers

    Mandal, Taraknath; Dasgupta, Chandan; Maiti, Prabal K.

    2014-01-01

    We have performed fully atomistic classical molecular dynamics simulations to calculate the effective interaction between two polyamidoamine dendrimers. Using the umbrella sampling technique, we have obtained the potential of mean force (PMF) between the dendrimers and investigated the effects of protonation level and dendrimer size on the PMF. Our results show that the interaction between the dendrimers can be tuned from purely repulsive to partly attractive by changing the protonation level. The PMF profiles are well-fitted by the sum of an exponential and a Gaussian function with the weight of the exponential function dominating over that of the Gaussian function. This observation is in disagreement with the results obtained in previous analytic [C. Likos, M. Schmidt, H. Löwen, M. Ballauff, D. Pötschke, and P. Lindner, Macromolecules 34, 2914 (2001)] and coarse-grained simulation [I. Götze, H. Harreis, and C. Likos, J. Chem. Phys. 120, 7761 (2004)] studies which predicted the effective interaction to be Gaussian

  12. Nature of the effective interaction between dendrimers

    Mandal, Taraknath, E-mail: taraknath@physics.iisc.ernet.in; Dasgupta, Chandan, E-mail: cdgupta@physics.iisc.ernet.in; Maiti, Prabal K., E-mail: maiti@physics.iisc.ernet.in [Centre for Condensed Matter Theory, Physics Department, Indian Institute of Science, Bangalore-560012 (India)

    2014-10-14

    We have performed fully atomistic classical molecular dynamics simulations to calculate the effective interaction between two polyamidoamine dendrimers. Using the umbrella sampling technique, we have obtained the potential of mean force (PMF) between the dendrimers and investigated the effects of protonation level and dendrimer size on the PMF. Our results show that the interaction between the dendrimers can be tuned from purely repulsive to partly attractive by changing the protonation level. The PMF profiles are well-fitted by the sum of an exponential and a Gaussian function with the weight of the exponential function dominating over that of the Gaussian function. This observation is in disagreement with the results obtained in previous analytic [C. Likos, M. Schmidt, H. Löwen, M. Ballauff, D. Pötschke, and P. Lindner, Macromolecules 34, 2914 (2001)] and coarse-grained simulation [I. Götze, H. Harreis, and C. Likos, J. Chem. Phys. 120, 7761 (2004)] studies which predicted the effective interaction to be Gaussian.

  13. Fluorescent Self-Assembled Polyphenylene Dendrimer Nanofibers

    Liu, Daojun; Feyter, Steven De; Cotlet, Mircea; Wiesler, Uwe-Martin; Weil, Tanja; Herrmann, Andreas; Müllen, Klaus; Schryver, Frans C. De

    2003-01-01

    A second-generation polyphenylene dendrimer 1 self-assembles into nanofibers on various substrates such as HOPG, silicon, glass, and mica from different solvents. The investigation with noncontact atomic force microscopy (NCAFM) and scanning electron microscopy (SEM) shows that the morphology of the

  14. Transport and Biodistribution of Dendrimers Across Human Fetal Membranes: Implications for Intravaginal Administration of Dendrimers

    Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kannan, Sujatha; Kim, Chong Jai; Romero, Roberto; Kannan, Rangaramanujam M.

    2010-01-01

    Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly(amidoamine)) dendrimers, across human fetal membrane (using a side-by-side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size~ 400 Da) and fluorophore-tagged G4-PAMAM dendrimers (~ 16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF-MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a five hour period, the dendrimer transport across all the three membranes was less than transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10-7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10-8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5 to 4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be

  15. A polyamidoamine dendrimer-streptavidin supramolecular architecture for biosensor development.

    Soda, N; Arotiba, O A

    2017-12-01

    A novel polyamidoamine dendrimer-streptavidin supramolecular architecture suitable as a versatile platform for biosensor development is reported. The dendrimer was electrodeposited on a glassy carbon electrode via cyclic voltammetry. The dendrimer electrode was further modified with streptavidin by electrostatic attraction upon drop coating. The platform i.e. the dendrimer-streptavidin modified electrode was electrochemically interrogated in phosphate buffer, ferrocyanide and H 2 O 2 . The dendrimer-streptavidin platform was used in the preparation of a simple DNA biosensor as a proof of concept. The supramolecular architecture of dendrimer-streptavidin was stable, electroactive and thus lends itself as a versatile immobilisation layer for any biotinylated bioreceptors in biosensor development. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. The structure of carbosilane dendrimers of higher generations

    Rogachev, A.V.; Kuklin, A.I.; Chernyj, A.Yu.; Ozerin, A.N.; Muzafarov, A.M.; Tatarinova, E.A.; Gordelij, V.I.

    2008-01-01

    Using small-angle neutron scattering method, we investigate the structure of carbosilane dendrimers of the ninth generation with a four-function core and butyl terminal groups. It is shown that the dendrimers in question are monodispersive objects having anisometric form. The values of the partial volume and the mean scattering length density are determined with the contrast variation method. The studied dendrimers exhibit the same size and distribution of the scattering length density. It is found that about 20% of the interior dendrimer volume is permeable to a solvent. Performing a Monte Carlo simulation, we reconstruct the spatial distribution of scattering length density over the dendrimers and reveal changing of the excluded volume for different contrasts. The spatial structure features of carbosilane dendrimers of higher generations are discussed

  17. Charge transport in highly efficient iridium cored electrophosphorescent dendrimers

    Markham, Jonathan P. J.; Samuel, Ifor D. W.; Lo, Shih-Chun; Burn, Paul L.; Weiter, Martin; Bässler, Heinz

    2004-01-01

    Electrophosphorescent dendrimers are promising materials for highly efficient light-emitting diodes. They consist of a phosphorescent core onto which dendritic groups are attached. Here, we present an investigation into the optical and electronic properties of highly efficient phosphorescent dendrimers. The effect of dendrimer structure on charge transport and optical properties is studied using temperature-dependent charge-generation-layer time-of-flight measurements and current voltage (I-V) analysis. A model is used to explain trends seen in the I-V characteristics. We demonstrate that fine tuning the mobility by chemical structure is possible in these dendrimers and show that this can lead to highly efficient bilayer dendrimer light-emitting diodes with neat emissive layers. Power efficiencies of 20 lm/W were measured for devices containing a second-generation (G2) Ir(ppy)3 dendrimer with a 1,3,5-tris(2-N-phenylbenzimidazolyl)benzene electron transport layer.

  18. A blue-emitting CdS/dendrimer nanocomposite

    Sooklal, K.; Murphy, C.J.; Hanus, L.H.; Ploehn, H.J.

    1998-01-01

    CdS/dendrimer nanocomposites that emit blue light are formed by the arrested precipitation of nanometer-scale CdS quantum dots in the presence of starburst (poly(aminoamine)) dendrimers as the stabilizing host. The authors report a strong photoluminescence with emission maxima at about 450 nm. The optoelectronic properties of the CdS clusters are shown to be sensitive to synthesis conditions, including dendrimer type, solvent type, and the concentration of dendrimer and other solutes. Thin films of these materials prepared by solution casting retain the optoelectronic properties of the parent solutions. (orig.)

  19. Optical absorption and energy transfer processes in dendrimers

    Reineker, P.; Engelmann, A.; Yudson, V.I.

    2004-01-01

    For dendrimers of various sizes the energy transfer and the optical absorption is investigated theoretically. The molecular subunits of a dendrimer are modeled as two-level systems. The electronic interaction between them is described via transfer integrals and the influence of vibrational degrees of freedom is taken into account in a first approach using a stochastic model. We discuss the time dependence of the energy transport and show that rim states of the dendrimer dominate the absorption spectra, that in general the electronic excitation energy is concentrated on peripheric molecules, and that the energetically lowest absorption peak is redshifted with increasing dendrimer size due to delocalization of the electronic excitation

  20. Comparison of the internalization of targeted dendrimers and dendrimer-entrapped gold nanoparticles into cancer cells.

    Shi, Xiangyang; Wang, Su He; Lee, Inhan; Shen, Mingwu; Baker, James R

    2009-11-01

    Dendrimer-based nanotechnology significantly advances the area of targeted cancer imaging and therapy. Herein, we compared the difference of surface acetylated fluorescein isocyanate (FI) and folic acid (FA) modified generation 5 (G5) poly(amidoamine) dendrimers (G5.NHAc-FI-FA), and dendrimer-entrapped gold nanoparticles with similar modifications ([(Au(0))(51.2)-G5.NHAc-FI-FA]) in terms of their specific internalization to FA receptor (FAR)-overexpressing cancer cells. Confocal microscopic studies show that both G5.NHAc-FI-FA and [(Au(0))(51.2-)G5.NHAc-FI-FA] exhibit similar internalization kinetics regardless of the existence of Au nanoparticles (NPs). Molecular dynamics simulation of the two different nanostructures reveals that the surface area and the FA moiety distribution from the center of the geometry are slightly different. This slight difference may not be recognized by the FARs on the cell membrane, consequently leading to similar internalization kinetics. This study underlines the fact that metal or inorganic NPs entrapped within dendrimers interact with cells in a similar way to that of dendrimers lacking host NPs. 2009 Wiley Periodicals, Inc.

  1. Liquid Crystalline Dendrimers. 1. Synthesis of Five Generations of Carbosilane Liquid Crystalline Dendrimers with Terminal Cyanobiphenyl Groups

    Shibaev, V

    1998-01-01

    Using the controlled layer by layer experimental technique via reiterative sequence of chemical reactions carbosilane LC dendrimers with terminal cyanobiphenyl mesogenic groups of generations 1 - 5 were synthesized...

  2. Host-guest chemistry of dendrimer-drug complexes. 6. Fully acetylated dendrimers as biocompatible drug vehicles using dexamethasone 21-phosphate as a model drug.

    Yang, Kun; Weng, Liang; Cheng, Yiyun; Zhang, Hongfeng; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen

    2011-03-17

    Fully acetylated poly(amidoamine) (PAMAM) dendrimer was proposed as a biocompatible drug vehicle using dexamethasone 21-phosphate (Dp21) as a model drug. NMR techniques including (1)H NMR and 2D NOE NMR were used to characterize the host-guest chemistry of acetylated dendrimer/Dp21 and cationic dendrimer/Dp21 complexes. The pH-dependent micellization, complexation, and inclusion behaviors of Dp21 were observed in the presence of acetylated and cationic PAMAM dendrimers. Acetylated dendrimer only encapsulates Dp21 at acidic conditions, while cationic dendrimer can host Dp21 at both acidic and neutral conditions. The orientation of Dp21 molecules in the dendrimer cavities depends on the quaternization degree of tertiary amine groups of dendrimer and the protonation ratio of phosphate group of Dp21. A distinctive pH-dependent release behavior of Dp21 from the acetylated and nonacetylated dendritic matrix was observed: Dp21 exhibits a much slower release rate from acetylated dendrimer at lower pH conditions and a much faster release rate from nonacetylated dendrimer with decreasing pH values. Cytotoxicity studies further confirmed the biocompatibility of acetylated dendrimers, which are much safer in the delivery of therapeutics for the treatment of various diseases than nonacetylated dendrimers. The dendrimer-drug binding and release mechanisms provide a new insight for the design and optimization of biocompatible dendrimer-based drug delivery systems. © 2011 American Chemical Society

  3. Thin film properties of triphenylamine-cored dendrimers: A molecular approach to control aggregation

    Vamvounis, George, E-mail: g.vamvounis@uq.edu.au; Pivrikas, Almantas; Shaw, Paul E.; Burn, Paul L.

    2013-12-02

    The solid-state photophysical and charge transport properties of two first-generation dendrimers are presented. The dendrimers are comprised of a triphenylamine core, dendrons containing a phenyl branching unit with thiophene (Dendrimer 1) or bithiophene (Dendrimer 2) moieties, and dodecyl surface groups. For Dendrimer 1, the excited state is located within the center of the dendrimer giving rise to a moderate solid-state photoluminescence quantum yield (Φ{sub pl}) (0.13) and significant charge trapping, with both observations due to the degree of overlap of the main electroactive chromophores on adjacent dendrimers. For Dendrimer 2, the excited state is located within the dendron and in the solid-state this leads to a strongly red-shifted and weakened emission (Φ{sub pl} ∼ 0.02) due to strong intermolecular chromophore interactions. For films of Dendrimer 2 the charge mobility was higher than Dendrimer 1 but was still limited by a low density of strongly interacting electroactive chromophores. The pronounced difference between the solid-state properties of the two dendrimers is simply engineered by the addition of an extra thiophene in each of the dendrons. - Highlights: • Photophysical and charge-transport properties of two dendrimers are investigated. • Excited-state is on the center for Dendrimer 1 and on the dendron for Dendrimer 2. • Film quantum yield of luminescence is higher for Dendrimer 1. • Dendrimer 1 displays greater charge trapping at high fields.

  4. Quaternized Polyamidoamine Dendrimers as Novel Gene Delivery System: Relationship between Degree of Quaternization and Their Influences

    Lee, Jung Hoon; Lim, Yong beom; Choi, Joon Sig; Choi, Myung Un; Yang, Chul Hak; Park, Jong Sang

    2003-01-01

    Quaternary ammonium groups were introduced to Starburst polyamidoamine (PAMAM) dendrimers for a gene carrier. These quaternary dendritic carriers exhibited reduced cytotoxicity on 293T cells compared to parent dendrimers examined and their transfection efficiency were similar with parent dendrimers. Quaternization could be a promising tool to improve properties of dendrimers as a gene delivery carrier

  5. Thin film properties of triphenylamine-cored dendrimers: A molecular approach to control aggregation

    Vamvounis, George; Pivrikas, Almantas; Shaw, Paul E.; Burn, Paul L.

    2013-01-01

    The solid-state photophysical and charge transport properties of two first-generation dendrimers are presented. The dendrimers are comprised of a triphenylamine core, dendrons containing a phenyl branching unit with thiophene (Dendrimer 1) or bithiophene (Dendrimer 2) moieties, and dodecyl surface groups. For Dendrimer 1, the excited state is located within the center of the dendrimer giving rise to a moderate solid-state photoluminescence quantum yield (Φ pl ) (0.13) and significant charge trapping, with both observations due to the degree of overlap of the main electroactive chromophores on adjacent dendrimers. For Dendrimer 2, the excited state is located within the dendron and in the solid-state this leads to a strongly red-shifted and weakened emission (Φ pl ∼ 0.02) due to strong intermolecular chromophore interactions. For films of Dendrimer 2 the charge mobility was higher than Dendrimer 1 but was still limited by a low density of strongly interacting electroactive chromophores. The pronounced difference between the solid-state properties of the two dendrimers is simply engineered by the addition of an extra thiophene in each of the dendrons. - Highlights: • Photophysical and charge-transport properties of two dendrimers are investigated. • Excited-state is on the center for Dendrimer 1 and on the dendron for Dendrimer 2. • Film quantum yield of luminescence is higher for Dendrimer 1. • Dendrimer 1 displays greater charge trapping at high fields

  6. Investigation on electromechanical properties of a muscle-like linear actuator fabricated by bi-film ionic polymer metal composites

    Sun, Zhuangzhi; Zhao, Gang; Qiao, Dongpan; Song, Wenlong

    2017-12-01

    Artificial muscles have attracted great attention for their potentials in intelligent robots, biomimetic devices, and micro-electromechanical system. However, there are many performance bottlenecks restricting the development of artificial muscles in engineering applications, e.g., the little blocking force and short working life. Focused on the larger requirements of the output force and the lack characteristics of the linear motion, an innovative muscle-like linear actuator based on two segmented IPMC strips was developed to imitate linear motion of artificial muscles. The structures of the segmented IPMC strip of muscle-like linear actuator were developed and the established mathematical model was to determine the appropriate segmented proportion as 1:2:1. The muscle-like linear actuator with two segmented IPMC strips assemble by two supporting link blocks was manufactured for the study of electromechanical properties. Electromechanical properties of muscle-like linear actuator under the different technological factors were obtained to experiment, and the corresponding changing rules of muscle-like linear actuators were presented to research. Results showed that factors of redistributed resistance and surface strain on both end-sides were two main reasons affecting the emergence of different electromechanical properties of muscle-like linear actuators.

  7. Linear side chains in benzo[1,2-b:4,5-b′]dithiophene-thieno[3,4-c] pyrrole-4,6-dione polymers direct self-assembly and solar cell performance

    Cabanetos, Clement; El Labban, Abdulrahman; Bartelt, Jonathan A.; Douglas, Jessica D.; Mateker, William R.; Frechet, Jean; McGehee, Michael D.; Beaujuge, Pierre

    2013-01-01

    role that linear side-chain substituents play in poly(benzo[1,2-b:4,5-b′]dithiophene-thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers for bulk heterojunction (BHJ) solar cell applications. We show that replacing branched side chains by linear ones

  8. Dendrimer effects on peptide and protein fibrillation

    Heegaard, Peter M. H.; Boas, Ulrik; Otzen, Daniel E.

    2007-01-01

    involved in a range of serious and irreversibly progressive pathological conditions (protein-misfolding diseases). Interesting as this may be, the interaction of dendrimers with such generic peptidic aggregates also offers a new perspective on the molecular mechanisms governing assembly and disassembly......, they offer numerous possibilities for interactions with and responses to biological macromolecules and biostructures including cell membranes and proteins. By way of their multiple functional surface groups, they allow the design of surfaces carrying a multitude of biological motifs and/or charges giving...... rise to quite significant biological and physico-chemical effects. Here we describe the surprising ability of dendrimers to interact with and perturb polypeptide conformations, particularly efficiently towards amyloid structures; that is, the structures of highly insoluble polypeptide aggregates...

  9. Carbon 13 nuclear magnetic resonance chemical shifts empiric calculations of polymers by multi linear regression and molecular modeling

    Da Silva Pinto, P.S.; Eustache, R.P.; Audenaert, M.; Bernassau, J.M.

    1996-01-01

    This work deals with carbon 13 nuclear magnetic resonance chemical shifts empiric calculations by multi linear regression and molecular modeling. The multi linear regression is indeed one way to obtain an equation able to describe the behaviour of the chemical shift for some molecules which are in the data base (rigid molecules with carbons). The methodology consists of structures describer parameters definition which can be bound to carbon 13 chemical shift known for these molecules. Then, the linear regression is used to determine the equation significant parameters. This one can be extrapolated to molecules which presents some resemblances with those of the data base. (O.L.). 20 refs., 4 figs., 1 tab

  10. Piezoelectric sensor for sensitive determination of metal ions based on the phosphate-modified dendrimer

    Wang, S. H.; Shen, C. Y.; Lin, Y. M.; Du, J. C.

    2016-08-01

    Heavy metal ions arising from human activities are retained strongly in water; therefore public water supplies must be monitored regularly to ensure the timely detection of potential problems. A phosphate-modified dendrimer film was investigated on a quartz crystal microbalance (QCM) for sensing metal ions in water at room temperature in this study. The chemical structures and sensing properties were characterized by Fourier transform infrared spectroscopy and QCM measurement, respectively. This phosphate-modified dendrimer sensor can directly detect metal ions in aqueous solutions. This novel sensor was evaluated for its capacity to sense various metal ions. The sensor exhibited a higher sensitivity level and shorter response time to copper(II) ions than other sensors. The linear detection range of the prepared QCM based on the phosphate-modified dendrimer was 0.0001 ∼ 1 μM Cu(II) ions (R2 = 0.98). The detection properties, including sensitivity, response time, selectivity, reusability, maximum adsorption capacity, and adsorption equilibrium constants, were also investigated.

  11. Combining metadynamics simulation and experiments to characterize dendrimers in solution

    Pavan, G.M.; Barducci, A.; Albertazzi, L.; Parrinello, M.

    2013-01-01

    We report a combined theoretical-experimental approach to characterize dendrimers and Polyethylene Glycol (PEG)-dendrimer hybrids in solution. Well-tempered metadynamics simulation allows for an exhaustive sampling of the conformational fluctuations in solution. In contrast to classical molecular

  12. Composition consisting of a dendrimer and an active substance

    1995-01-01

    The invention relates to a composition consisting of a dendrimer provided with blocking agents and an active substance occluded in the dendrimer. According to the invention a blocking agent is a compound which is sterically of sufficient size, which readily enters into a chemical bond with the

  13. Molecular dynamic analysis of the structure of dendrimers

    Canetta, E.; Maino, G. E-mail: maino@bologna.enea.it

    2004-01-01

    We present main results of molecular dynamics simulations that we have carried out in order to investigate structural properties of polyamidoamine (PAMAM) dendrimers. Obtained data confirm the PAMAM dendrimer structure proposed by experiments, performed by means of X-ray scattering (SAXS) and quasi-elastic light scattering (QELS) techniques.

  14. Molecular dynamic analysis of the structure of dendrimers

    Canetta, E.; Maino, G.

    2004-01-01

    We present main results of molecular dynamics simulations that we have carried out in order to investigate structural properties of polyamidoamine (PAMAM) dendrimers. Obtained data confirm the PAMAM dendrimer structure proposed by experiments, performed by means of X-ray scattering (SAXS) and quasi-elastic light scattering (QELS) techniques

  15. Dendrimer D5 is a vector for peptide transport to brain cells.

    Sarantseva, S V; Bolshakova, O I; Timoshenko, S I; Kolobov, A A; Schwarzman, A L

    2011-02-01

    Dendrimers are a new class of nonviral vectors for gene or drug transport. Dendrimer capacity to penetrate through the blood-brain barrier remaines little studied. Biotinylated polylysine dendrimer D5, similarly to human growth hormone biotinylated fragment covalently bound to D5 dendrimer, penetrates through the blood-brain barrier and accumulates in Drosophila brain after injection into the abdomen. Hence, D5 dendrimer can serve as a vector for peptide transport to brain cells.

  16. Dendrimers as Potential Therapeutic Tools in HIV Inhibition

    Xiangbo Li

    2013-07-01

    Full Text Available The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. In this review, we discuss the application of dendrimers as both therapeutic agents and non-viral vectors of chemical agents and genes for HIV treatment. On the one hand, dendrimers with functional end groups combine with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of HIV to the host cell. Some of the dendrimers are capable of intruding into the cell and interfere with the later stages of HIV replication as well. On the other hand, dendrimers are also able to transfer chemical drugs and genes into the host cells, which conspicuously increase the anti-HIV activity of these materials. Dendrimers as therapeutic tools provide a potential treatment for HIV infection.

  17. Facile Preparation of Hybrid Zinc Porphyrin Dendrimer Using Coordination Complex

    Choi, Go-Eun; Shin, Eun Ju [Sunchon National University, Suncheon (Korea, Republic of)

    2016-03-15

    Porphyrins and metalloporphyrins have been investigated extensively due to their important role in natural photosynthesis, strong absorption in visible region, good light-harvesting properties, unique photophysical and electrochemical properties, and the development of simple synthetic routes for various derivatives. Dendrimers have globular structure with branches of repeating units and wide diversity of the architecture because their size, shape, and functionalities can be tailored. Numerous dendrimers have been designed and synthesized for various applications ranging from catalyst to drug delivery. Both pyridine dendrons Py-PD and Py-AD were successfully coordinated at axial position on central zinc metal cation in zinc porphyrin dendrimers ZnP-AD, ZnP-AD2, or ZnP-AD4. Therefore, it was proven that the formation of axial coordination complex between metal-centered dendrimer and ligand-containing dendron provides another facile method for the preparation of new hybrid dendrimer.

  18. Star Polymers.

    Ren, Jing M; McKenzie, Thomas G; Fu, Qiang; Wong, Edgar H H; Xu, Jiangtao; An, Zesheng; Shanmugam, Sivaprakash; Davis, Thomas P; Boyer, Cyrille; Qiao, Greg G

    2016-06-22

    Recent advances in controlled/living polymerization techniques and highly efficient coupling chemistries have enabled the facile synthesis of complex polymer architectures with controlled dimensions and functionality. As an example, star polymers consist of many linear polymers fused at a central point with a large number of chain end functionalities. Owing to this exclusive structure, star polymers exhibit some remarkable characteristics and properties unattainable by simple linear polymers. Hence, they constitute a unique class of technologically important nanomaterials that have been utilized or are currently under audition for many applications in life sciences and nanotechnologies. This article first provides a comprehensive summary of synthetic strategies towards star polymers, then reviews the latest developments in the synthesis and characterization methods of star macromolecules, and lastly outlines emerging applications and current commercial use of star-shaped polymers. The aim of this work is to promote star polymer research, generate new avenues of scientific investigation, and provide contemporary perspectives on chemical innovation that may expedite the commercialization of new star nanomaterials. We envision in the not-too-distant future star polymers will play an increasingly important role in materials science and nanotechnology in both academic and industrial settings.

  19. Transport and biodistribution of dendrimers across human fetal membranes: implications for intravaginal administration of dendrimer-drug conjugates.

    Menjoge, Anupa R; Navath, Raghavendra S; Asad, Abbas; Kannan, Sujatha; Kim, Chong J; Romero, Roberto; Kannan, Rangaramanujam M

    2010-06-01

    Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly (amidoamine)) dendrimers, across human fetal membrane (using a side by side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size approximately 400 Da) and fluorophore-tagged G(4)-PAMAM dendrimers (approximately 16 kDa). The fluorophore-tagged G(4)-PAMAM dendrimers were synthesized and characterized using (1)H NMR, MALDI TOF MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a 5 h period, the dendrimer transport across all the three membranes was less than dendrimer (5.8 x 10(-8) cm(2)/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5-4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother

  20. The use of Gauss-Hermite quadrature in the determination of the molecular weight distribution of linear polymers by rheometry

    T. M. Farias

    2013-12-01

    Full Text Available The molecular weight distribution (MWD and its parameters are of the fundamental importance in the characterization of polymers. Therefore, the development of techniques for faster MWD determination is a relevant issue. This paper aims at implementing one of the relaxation models from double reptation theory proposed in the literature and analyzing the numeric strategy for the evaluation of the integrals appearing in the relaxation model. The inverse problem, i.e., the determination of the MWD from rheological data using a specified relaxation model and an imposed distribution function was approximated. Concerning the numerical strategy for the evaluation of the integrals appearing in the relaxation models, the use of Gauss-Hermite quadrature using a new change of variables was proposed. In the test of samples of polyethylene with polydispersities less than 10, the application of this methodology led to MWD curves which provided a good fit of the experimental SEC data.

  1. Linear side chains in benzo[1,2-b:4,5-b′]dithiophene-thieno[3,4-c] pyrrole-4,6-dione polymers direct self-assembly and solar cell performance

    Cabanetos, Clement

    2013-03-27

    While varying the size and branching of solubilizing side chains in π-conjugated polymers impacts their self-assembling properties in thin-film devices, these structural changes remain difficult to anticipate. This report emphasizes the determining role that linear side-chain substituents play in poly(benzo[1,2-b:4,5-b′]dithiophene-thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers for bulk heterojunction (BHJ) solar cell applications. We show that replacing branched side chains by linear ones in the BDT motifs induces a critical change in polymer self-assembly and backbone orientation in thin films that correlates with a dramatic drop in solar cell efficiency. In contrast, we show that for polymers with branched alkyl-substituted BDT motifs, controlling the number of aliphatic carbons in the linear N-alkyl-substituted TPD motifs is a major contributor to improved material performance. With this approach, PBDTTPD polymers were found to reach power conversion efficiencies of 8.5% and open-circuit voltages of 0.97 V in BHJ devices with PC71BM, making PBDTTPD one of the best polymer donors for use in the high-band-gap cell of tandem solar cells. © 2013 American Chemical Society.

  2. SNAP dendrimers: multivalent protein display on dendrimer-like DNA for directed evolution.

    Kaltenbach, Miriam; Stein, Viktor; Hollfelder, Florian

    2011-09-19

    Display systems connect a protein with the DNA encoding it. Such systems (e.g., phage or ribosome display) have found widespread application in the directed evolution of protein binders and constitute a key element of the biotechnological toolkit. In this proof-of-concept study we describe the construction of a system that allows the display of multiple copies of a protein of interest in order to take advantage of avidity effects during affinity panning. To this end, dendrimer-like DNA is used as a scaffold with docking points that can join the coding DNA with multiple protein copies. Each DNA construct is compartmentalised in water-in-oil emulsion droplets. The corresponding protein is expressed, in vitro, inside the droplets as a SNAP-tag fusion. The covalent bond between DNA and the SNAP-tag is created by reaction with dendrimer-bound benzylguanine (BG). The ability to form dendrimer-like DNA straightforwardly from oligonucleotides bearing BG allowed the comparison of a series of templates differing in size, valency and position of BG. In model selections the most efficient constructs show recoveries of up to 0.86 % and up to 400-fold enrichments. The comparison of mono- and multivalent constructs suggests that the avidity effect enhances enrichment by up to fivefold and recovery by up to 25-fold. Our data establish a multivalent format for SNAP-display based on dendrimer-like DNA as the first in vitro display system with defined tailor-made valencies and explore a new application for DNA nanostructures. These data suggest that multivalent SNAP dendrimers have the potential to facilitate the selection of protein binders especially during early rounds of directed evolution, allowing a larger diversity of candidate binders to be recovered. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Scaling Behavior of Dendritic Nanoparticle Mobility in Semidilute Polymer Solutions

    Kort, de D.W.; Rombouts, W.H.; Hoeben, F.J.M.; Janssen, H.M.; As, van H.; Duynhoven, van J.P.M.

    2015-01-01

    In our studies on particle mobility in polymer solutions, we have investigated and determined self-diffusion coefficients of nanoparticles in semidilute solutions of poly(ethylene glycol) (PEG, Mw = 6, 20, 35, and 100 kDa). Specially designed PEGylated dendrimers with well-defined sizes (dh =

  4. Determination of the linear coefficient of thermal expansion in polymer films at the nanoscale: influence of the composition of EVA copolymers and the molecular weight of PMMA.

    González-Benito, J; Castillo, E; Cruz-Caldito, J F

    2015-07-28

    Nanothermal-expansion of poly(ethylene-co-vinylacetate), EVA, and poly(methyl methacrylate), PMMA, in the form of films was measured to finally obtain linear coefficients of thermal expansion, CTEs. The simple deflection of a cantilever in an atomic force microscope, AFM, was used to monitor thermal expansions at the nanoscale. The influences of: (a) the structure of EVA in terms of its composition (vinylacetate content) and (b) the size of PMMA chains in terms of the molecular weight were studied. To carry out this, several polymer samples were used, EVA copolymers with different weight percents of the vinylacetate comonomer (12, 18, 25 and 40%) and PMMA polymers with different weight average molecular weights (33.9, 64.8, 75.600 and 360.0 kg mol(-1)). The dependencies of the vinyl acetate weight fraction of EVA and the molecular weight of PMMA on their corresponding CTEs were analyzed to finally explain them using new, intuitive and very simple models based on the rule of mixtures. In the case of EVA copolymers a simple equation considering the weighted contributions of each comonomer was enough to estimate the final CTE above the glass transition temperature. On the other hand, when the molecular weight dependence is considered the free volume concept was used as novelty. The expansion of PMMA, at least at the nanoscale, was well and easily described by the sum of the weighted contributions of the occupied and free volumes, respectively.

  5. Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

    Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

    2014-10-06

    The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Viologen-Phosphorus Dendrimers Inhibit α-Synuclein Fibrillation.

    Milowska, Katarzyna; Grochowina, Justyna; Katir, Nadia; El Kadib, Abdelkrim; Majoral, Jean-Pierre; Bryszewska, Maria; Gabryelak, Teresa

    2013-03-04

    Inhibition of α-synuclein (ASN) fibril formation is a potential therapeutic strategy in Parkinson's disease and other synucleinopathies. The aim of this study was to examine the role of viologen-phosphorus dendrimers in the α-synuclein fibrillation process and to assess the structural changes in α-synuclein under the influence of dendrimers. ASN interactions with phosphonate and pegylated surface-reactive viologen-phosphorus dendrimers were examined by measuring the zeta potential, which allowed determining the number of dendrimer molecules that bind to the ASN molecule. The fibrillation kinetics and the structural changes were examined using ThT fluorescence and CD spectroscopy. Depending on the concentration of the used dendrimer and the nature of the reactive groups located on the surface, ASN fibrillation kinetics can be significantly reduced, and even, in the specific case of phosphonate dendrimers, the fibrillation can be totally inhibited at low concentrations. The presented results indicate that viologen-phosphorus dendrimers are able to inhibit ASN fibril formation and may be used as fibrillar regulating agents in neurodegenerative disorders.

  7. Nanoscale effects in dendrimer-mediated targeting of neuroinflammation.

    Nance, Elizabeth; Zhang, Fan; Mishra, Manoj K; Zhang, Zhi; Kambhampati, Siva P; Kannan, Rangaramanujam M; Kannan, Sujatha

    2016-09-01

    Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Transepithelial and endothelial transport of poly (amidoamine) dendrimers.

    Kitchens, Kelly M; El-Sayed, Mohamed E H; Ghandehari, Hamidreza

    2005-12-14

    This article summarizes our efforts to evaluate the potential of poly (amidoamine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the permeability of a series of cationic PAMAM-NH2 (G0-G4) dendrimers across Caco-2 cell monolayers was evaluated as a function of dendrimer generation, concentration, and incubation time. The influence of dendrimer surface charge on the integrity, paracellular permeability, and viability of Caco-2 cell monolayers was monitored by measuring the transepithelial electrical resistance (TEER), 14C-mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively. Microvascular extravasation of PAMAM-NH2 dendrimers in relation to their size, molecular weight, and molecular geometry is also discussed. Results of these studies show that transepithelial transport and microvascular extravasation of PAMAM dendrimers are dependent on their structural features including molecular size, molecular geometry, and surface chemistry. These results suggest that by optimizing the size and surface charge of PAMAM dendrimers, it is possible to develop oral delivery systems based on these carriers for targeted drug delivery.

  9. Synergistic activity profile of carbosilane dendrimer G2-STE16 in combination with other dendrimers and antiretrovirals as topical anti-HIV-1 microbicide.

    Sepúlveda-Crespo, Daniel; Lorente, Raquel; Leal, Manuel; Gómez, Rafael; De la Mata, Francisco J; Jiménez, José Luis; Muñoz-Fernández, M Ángeles

    2014-04-01

    Polyanionic carbosilane dendrimers represent opportunities to develop new anti-HIV microbicides. Dendrimers and antiretrovirals (ARVs) acting at different stages of HIV replication have been proposed as compounds to decrease new HIV infections. Thus, we determined the potential use of our G2-STE16 carbosilane dendrimer in combination with other carbosilane dendrimers and ARVs for the use as topical microbicide against HIV-1. We showed that these combinations obtained 100% inhibition and displayed a synergistic profile against different HIV-1 isolates in our model of TZM.bl cells. Our results also showed their potent activity in the presence of an acidic vaginal or seminal fluid environment and did not activate an inflammatory response. This study is the first step toward exploring the use of different anionic carbosilane dendrimers in combination and toward making a safe microbicide. Therefore, our results support further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicide. This paper describes the first steps toward the use of anionic carbosilane dendrimers in combination with antivirals to address HIV-1, paving the way to further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicides. © 2014.

  10. Energy transfer to xanthene dyes in dansylated POPAM dendrimers

    Aumanen, Jukka; Korppi-Tommola, Jouko

    2011-12-01

    Excitation energy transfer (EET) in host-guest complexes of dansylated POPAM dendrimers and xanthene dyes have been studied by transient absorption spectroscopy. EET from dansyl periphery to guests: rose bengal, eosin, or fluorescein, showed non-exponential behaviour as a result of distribution of donor-acceptor distances. Time constants range from 100 fs to 8 ps, independent of the dye and the dendrimer generation. Experiments suggested that in dendrimers binding more than one guest, EET among the guests becomes effective. Guest-host and guest-guest interactions induce non-radiative relaxation channels making excitation decays of the guests clearly faster in complexes than in solution.

  11. The effect of dendrimer on cotton dyeability with direct dyes

    Khakzar Bafrooei F.

    2014-01-01

    Full Text Available Pretreatment of cotton fabric with poly(propylene imine dendrimer enhanced its colour strength using C.I. Direct Red 81 and C.I. Direct Blue 78. Application of this dendrimer and the direct dye simultaneously on cotton fabric by the exhaust and the continuous dyeing method were studied; slight improvements in the dyeing results were obtained. Pretreatment of the cotton fabric with dendrimer in an emulsion form using the pad-dry method followed by continuous dyeing markedly increased the colour strength. In addition, level dyeing was obtained, and no negative effects on the fastness properties of the dyes used were observed.

  12. Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

    Ceña-Diez R

    2016-05-01

    Full Text Available Rafael Ceña-Diez,1–4,* Pilar García-Broncano,1–5,* Francisco Javier de la Mata,4,6 Rafael Gómez,4,6 Mª Ángeles Muñoz-Fernández1–4 1Hospital General Universitario Gregorio Marañon, 2Instituto de Investigación Sanitaria Gregorio Marañon, 3Spanish HIV HGM Biobank, 4Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, 5Laboratory of Viral Infection and Immunity, National Center of Microbiology, Health Institute of Carlos III, Majadahonda, 6Department of Organic Chemistry and Inorganic Chemistry, University of Alcalá, Alcalá de Henares, Madrid, Spain *These authors contributed equally to this work Abstract: The development of a safe and effective microbicide to prevent the sexual transmission of human immunodeficiency virus (HIV-1 is urgently needed. Unfortunately, the majority of microbicides, such as poly(L-lysine-dendrimers, anionic polymers, or antiretrovirals, have proved inactive or even increased the risk of HIV infection in clinical trials, most probably due to the fact that these compounds failed to prevent semen-exposed HIV infection. We showed that G2-S16 dendrimer exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4/CCR5 interaction and providing a barrier to infection for long periods, confirming its multifactorial and nonspecific ability. Previously, we demonstrated that topical administration of G2-S16 prevents HIV transmission in humanized BLT mice without irritation or vaginal lesions. Here, we demonstrated that G2-S16 is active against mock- and semen-exposed HIV-1 and could be a promising microbicide against HIV infection. Keywords: G2-S16, dendrimer, HIV-1, SEVI, microbicide, antiretrovirals

  13. Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery.

    Hu, Jingjing; Su, Yunzhang; Zhang, Hongfeng; Xu, Tongwen; Cheng, Yiyun

    2011-12-01

    In this study, dendrimers was synthesized by introducing functional groups into the interior pockets of fully acetylated dendrimers. NMR techniques including COSY and 2D-NOESY revealed the molecular structures of the synthesized dendrimers and the encapsulation of guest molecule such as methotrexate within their interior pockets. The synthesized polymeric nanocarriers showed much lower cytotoxicity on two cell lines than cationic dendrimers, and exhibited better performance than fully acetylated dendrimers in the sustained release of methotrexate. The results provided a new strategy in the design of non-toxic dendrimers with high performance in the delivery of anti-cancer drugs for clinical applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Atomistic computer simulations on multi-loaded PAMAM dendrimers: a comparison of amine- and hydroxyl-terminated dendrimers

    Badalkhani-Khamseh, Farideh; Ebrahim-Habibi, Azadeh; Hadipour, Nasser L.

    2017-12-01

    Poly(amidoamine) (PAMAM) dendrimers have been extensively studied as delivery vectors in biomedical applications. A limited number of molecular dynamics (MD) simulation studies have investigated the effect of surface chemistry on therapeutic molecules loading, with the aim of providing insights for biocompatibility improvement and increase in drug loading capacity of PAMAM dendrimers. In this work, fully atomistic MD simulations were employed to study the association of 5-Fluorouracil (5-FU) with amine (NH2)- and hydroxyl (OH)-terminated PAMAM dendrimers of generations 3 and 4 (G3 and G4). MD results show a 1:12, 1:1, 1:27, and 1:4 stoichiometry, respectively, for G3NH2-FU, G3OH-FU, G4NH2-FU, and G4OH-FU complexes, which is in good agreement with the isothermal titration calorimetry results. The results obtained showed that NH2-terminated dendrimers assume segmented open structures with large cavities and more drug molecules can encapsulate inside the dendritic cavities of amine terminated dendrimers. However, OH-terminated have a densely packed structure and therefore, 5-FU drug molecules are more stable to locate close to the surface of the dendrimers. Intermolecular hydrogen bonding analysis showed that 5-FU drug molecules have more tendency to form hydrogen bonds with terminal monomers of OH-terminated dendrimers, while in NH2-terminated these occur both in the inner region and the surface. Furthermore, MM-PBSA analysis revealed that van der Waals and electrostatic energies are both important to stabilize the complexes. We found that drug molecules are distributed uniformly inside the amine and hydroxyl terminated dendrimers and therefore, both dendrimers are promising candidates as drug delivery systems for 5-FU drug molecules.

  15. Dual stimuli-sensitive dendrimers: Photothermogenic gold nanoparticle-loaded thermo-responsive elastin-mimetic dendrimers.

    Fukushima, Daichi; Sk, Ugir Hossain; Sakamoto, Yasuhiro; Nakase, Ikuhiko; Kojima, Chie

    2015-08-01

    Dendrimers are synthetic macromolecules with unique structures that can work as nanoplatforms for both photothermogenic gold nanoparticles (AuNPs) and thermosensitive elastin-like peptides (ELPs) with valine-proline-glycine-valine-glycine (VPGVG) repeats. In this study, photothermogenic AuNPs were loaded into thermo-responsive elastin-mimetic dendrimers (dendrimers conjugating ELPs at their periphery) to produce dual stimuli-sensitive nanoparticles. Polyamidoamine G4 dendrimers were modified with acetylated VPGVG and (VPGVG)2, and the resulting materials were named ELP1-den and ELP2-den, respectively. The AuNPs were prepared by the reduction of Au ions using a dendrimer-nanotemplated method. The AuNP-loaded elastin-mimetic dendrimers exhibited photothermal properties. ELP1-den and ELP2-den showed similar temperature-dependent changes in their conformations. Phase transitions were observed at around 55°C and 35°C for the AuNP-loaded ELP1-den and AuNP-loaded ELP2-den, respectively, but not for the corresponding PEGylated dendrimer. In contrast to the AuNP-loaded PEGylated dendrimer, AuNP-loaded ELP2-den readily associated with cells and induced efficient photocytotoxicity at 37°C. The cell association and the photocytotoxicity properties of AuNP-loaded ELP2-den could be controlled by temperature. These results therefore suggest that dual stimuli-sensitive dendrimer nanoparticles of this type could be used for photothermal therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Propagation of PAMAM dendrimers on the carbon fiber surface by in situ polymerization: a novel methodology for fiber/matrix composites

    Zhang, R.L.; Gao, B.; Zhang, J.; Cui, H.Z.; Li, D.W.

    2015-01-01

    Graphical abstract: - Highlights: • The manuscript has the following obvious new contributions. • A facile strategy to generating dendrimers onto carbon fibers to functionalize conventional carbon fibers was reported. The density and type of the functional groups on the fiber surface can be easily adjusted by changing the reaction conditions. • The hierarchical reinforcement formed using this novel method improved the composite interface bonding through supplying sufficient chemical bonding and strong mechanical interlocking. • We can generate dendrimers with different side groups (unsaturated groups or hydroxyl groups, and others) and chain length to meet the requirements according to different matrices and applications. - Abstract: A facile strategy for generating dendrimers onto carbon fibers, in order to functionalize them, was reported. Dendrimers were propagated on the surface of carbon fibers by in situ polymerization with Michael addition. The changes in morphology, surface composition and surface energy, which were studied by atomic force microscope (AFM), dynamic contact angle analysis test (DCAT) and x-ray photoelectron microscopy (XPS), were related to the interfacial performance of model composites. In addition, the level of fiber-matrix adhesion was determined by the interlaminar shear strength (ILSS) test. Experimental results indicated that some dendritic polymer was successfully grown on the fiber surface through the chemical reaction, and this significantly enhanced the interfacial bonding of the carbon fiber composites.

  17. Solid phase microextraction of diclofenac using molecularly imprinted polymer sorbent in hollow fiber combined with fiber optic-linear array spectrophotometry.

    Pebdani, Arezou Amiri; Shabani, Ali Mohammad Haji; Dadfarnia, Shayessteh; Khodadoust, Saeid

    2015-08-05

    A simple solid phase microextraction method based on molecularly imprinted polymer sorbent in the hollow fiber (MIP-HF-SPME) combined with fiber optic-linear array spectrophotometer has been applied for the extraction and determination of diclofenac in environmental and biological samples. The effects of different parameters such as pH, times of extraction, type and volume of the organic solvent, stirring rate and donor phase volume on the extraction efficiency of the diclofenac were investigated and optimized. Under the optimal conditions, the calibration graph was linear (r(2)=0.998) in the range of 3.0-85.0 μg L(-1) with a detection limit of 0.7 μg L(-1) for preconcentration of 25.0 mL of the sample and the relative standard deviation (n=6) less than 5%. This method was applied successfully for the extraction and determination of diclofenac in different matrices (water, urine and plasma) and accuracy was examined through the recovery experiments. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Solid phase microextraction of diclofenac using molecularly imprinted polymer sorbent in hollow fiber combined with fiber optic-linear array spectrophotometry

    Pebdani, Arezou Amiri; Shabani, Ali Mohammad Haji; Dadfarnia, Shayessteh; Khodadoust, Saeid

    2015-08-01

    A simple solid phase microextraction method based on molecularly imprinted polymer sorbent in the hollow fiber (MIP-HF-SPME) combined with fiber optic-linear array spectrophotometer has been applied for the extraction and determination of diclofenac in environmental and biological samples. The effects of different parameters such as pH, times of extraction, type and volume of the organic solvent, stirring rate and donor phase volume on the extraction efficiency of the diclofenac were investigated and optimized. Under the optimal conditions, the calibration graph was linear (r2 = 0.998) in the range of 3.0-85.0 μg L-1 with a detection limit of 0.7 μg L-1 for preconcentration of 25.0 mL of the sample and the relative standard deviation (n = 6) less than 5%. This method was applied successfully for the extraction and determination of diclofenac in different matrices (water, urine and plasma) and accuracy was examined through the recovery experiments.

  19. Variations of structures and solid-state conductivity of isomeric silver(I) coordination polymers having linear and V-shaped thiophene-centered ditriazole ligands

    Hu, Bin; Geng, Jiao; Zhang, Lie; Huang, Wei

    2014-01-01

    A pair of new linear and V-shaped acceptor–donor–acceptor (A−D−A) thiophene-centered ditriazole structural isomers, i.e., 2,5-di(1H-1,2,4-triazol-1-yl)thiophene (L 1 ) and 3,4-di(1H-1,2,4-triazol-1-yl)thiophene (L 2 ), has been synthesized and characterized. They are used as μ 2 -bridging ligands to prepare a pair of silver(I) coordination polymers formulated as [Ag(L 1 )(NO 3 )] n (1) and [Ag(L 2 )(NO 3 )] n (2), which are also structural isomers at the supramolecular level. X-ray single-crystal diffraction analyses for 1 and 2 reveal that they exhibit the same one-dimensional (1D) coordination polymers but different structural architectures because of the distinguishable shape and configuration of isomeric ligands (L 1 and L 2 ) and the alterations of the coordination numbers. More interestingly, compared with the free ligands, 1D silver(I) polymeric isomers 1 and 2 show significant enhancement of solid-state conductivity to different extents (1.42×10 4 and 2.17×10 3 times), where 6.96 times' enhancement of solid-state conductivity from 1 to 2 has been observed. The formation of Ag–N coordinative bonds and the configurational discrepancy of L 1 and L 2 are believed to play important roles in facilitating the electron transport between molecules, which can also be supported by Density Function Theory calculations of their band gaps. - Graphical abstract: A pair of linear and V-shaped isomeric thiophene-centered ditriazole ligands (L 1 ) and L 2 are used to prepare a pair of silver(I) polymeric isomers (1 and 2), where significant enhancement of solid-state conductivity to different extents are observed originating from the distinguishable shape and configuration of isomeric ligands. - Highlights: • A pair of linear and V-shaped thiophene-centered ditriazole structural isomers is prepared. • They are used as µ 2 -bridging ligands to prepare a pair of silver(I) polymeric isomers. • Significant enhancement of solid-state conductivity is observed

  20. Novel Synchronous Linear and Rotatory Micro Motors Based on Polymer Magnets with Organic and Inorganic Insulation Layers

    Andreas WALDSCHIK

    2008-12-01

    Full Text Available In this work, we report on the development of several synchronous motors with rotatory or linear movements. The synchronous micro motors are brushless DC motors or stepper motors with electrically controlled commutation consisting of a stator and a rotor. The rotor is mounted onto the stator and is adjusted by an integrated guidance. Inside the stator different coil systems are realized, like double layer sector coils or special nested coils. The coil systems can be controlled by three or six phases depending on the operational mode. Furthermore, inorganic insulation layers were used in order to reduce the thickness of the system. By this means four layers of electrical conductors can be realized especially for the 2D devices. The smallest diameter of the rotatory motor is 1 mm and could be successfully driven.

  1. Stabilization of Lipid Membranes With Dendritic Polymers

    2004-12-01

    Langmuir - Blodgett (Takamato, et al., 2001) and solution techniques (Johnson, et al., 2002). However, BLMs are too unstable to be used to make effective...J.A., Ivanova, A.T., Schwartz, D.K., Yang, T., and Cremer, P.S., 2001: Stable Ordering in Langmuir - Blodgett Films, Science, 293, 1292-1295. Tully...Various dendrimers and hyperbranched polymers were evaluated. In addition, lipids with different head groups were used to probe the underlying

  2. Engineering of dendrimer surfaces to enhance transepithelial transport and reduce cytotoxicity.

    Jevprasesphant, Rachaneekorn; Penny, Jeffrey; Attwood, David; McKeown, Neil B; D'Emanuele, Antony

    2003-10-01

    To evaluate the cytotoxicity, permeation, and transport mechanisms of PAMAM dendrimers and surface-modified cationic PAMAM dendrimers using monolayers of the human colon adenocarcinoma cell line, Caco-2. Cytotoxicity was determined using the MTT assay. The effect of dendrimers on monolayer integrity was determined from measurements of transepithelial electrical resistance (TEER) and [14C]mannitol apparent permeability coefficient (Papp). The Papp of dendrimers through monolayers was measured in both the apical (A)-to-basolateral (B) and B --> A directions at 4 degrees C and 37 degrees C and also in the presence and absence of ethylenediamine tetraacetic acid (EDTA) and colchicine. The cytotoxicity and permeation of dendrimers increased with both concentration and generation. The cytotoxicity of cationic dendrimers (G2, G3, G4) was greater than that of anionic dendrimers (G2.5, G3.5) but was reduced by conjugation with lauroyl chloride: the least cytotoxic conjugates were those with six attached lauroyl chains. At 37 degrees C the Papp of cationic dendrimers was higher than that of anionic dendrimers and, in general, increased with the number of attached lipid chains. Cationic dendrimers decreased TEER and significantly increased the Papp of mannitol. Modified dendrimers also reduced TEER and caused a more marked increase in the Papp of mannitol. The Papp values of dendrimers and modified dendrimers were higher in the presence of EDTA, lower in the presence of colchicine, and lower at 4 degrees C than at 37 degrees C. The properties of dendrimers may be significantly modified by surface engineering. Conjugation of cationic PAMAM dendrimers with lauroyl chloride decreased their cytotoxicity and increased their permeation through Caco-2 cell monolayers. Both PAMAM dendrimers and lauroyl-PAMAM dendrimer conjugates can cross epithelial monolayers by paracellular and transcellular pathways.

  3. Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation.

    Kulhari, Hitesh; Pooja, Deep; Singh, Mayank K; Chauhan, Abhay S

    2015-02-01

    Abstract Cisplatin is mainly used in the treatment of ovarian, head and neck and testicular cancer. Poor solubility and non-specific interactions causes hurdles in the development of successful cisplatin formulation. There were few reports on poly(amidoamine) (PAMAM) dendrimer-cisplatin complexes for anticancer treatment. But the earlier research was mainly focused on therapeutic effect of PAMAM dendrimer-cisplatin complex, with less attention paid on the formulation development of these complexes. Objective of the present study is to optimize and validate the carboxylate-terminated, EDA core PAMAM dendrimer-based cisplatin formulation with respect to various variables such as dendrimer core, generation, drug entrapment, purification, yield, reproducibility, stability, storage and in-vitro release. Dendrimer-cisplatin complex was prepared by an efficient method which significantly increases the % platinum (Pt) content along with the product yield. Dendrimers showed reproducible (∼27%) platinum loading by weight. Variation in core and generations does not produce significant change in the % Pt content. Percentage Pt content of dendrimeric formulation increases with increase in drug/dendrimer mole ratio. Formulation with low drug/dendrimer mole ratio showed delayed release compared to the higher drug/dendrimer mole ratio; these dendrimer formulations are stable in room temperature. In vitro release profiles of the stored dendrimer-cisplatin samples showed comparatively slow release of cisplatin, which may be due to formation of strong bond between cisplatin and dendrimer. This study will contribute to create a fine print for the formulation development of PAMAM dendrimer-cisplatin complexes.

  4. Smart dendrimer-based nanogel for enhancing 5-fluorouracil ...

    Author for correspondence (nckhoavnn@yahoo.com) chemical properties of the ..... accounting for 90% of loaded 5-FU from dialysis membrane, whereas ... of the NIPAM layer-coated dendrimer contributed to control the drug sustainably from ...

  5. Preparation and evaluation of peptide-dendrimer-paclitaxel ...

    Tropical Journal of Pharmaceutical Research April 2017; 16 (4): 737-742 ... conjugates for treatment of heterogeneous stage 1 non- small cell lung ... Keywords: Paclitaxel, Lung cancer, Non-small cell lung cancer, Dendrimer, Peptide, PAMAM.

  6. Formulation and Development of Dendrimer-Based Transdermal ...

    Shandong Traditional Chinese Medicine University, Jinan 250012, China ... system for the management of some diseased conditions. Keywords: Dendrimers ... anti-inflammatory and analgesic activity [3]. ..... Cost-effective management of.

  7. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

    2013-01-01

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

  8. Thermodynamic properties of a liquid crystal carbosilane dendrimer

    Samosudova, Ya. S.; Markin, A. V.; Smirnova, N. N.; Ogurtsov, T. G.; Boiko, N. I.; Shibaev, V. P.

    2016-11-01

    The temperature dependence of the heat capacity of a first-generation liquid crystal carbosilane dendrimer with methoxyphenyl benzoate end groups is studied for the first time in the region of 6-370 K by means of precision adiabatic vacuum calorimetry. Physical transformations are observed in this interval of temperatures, and their standard thermodynamic characteristics are determined and discussed. Standard thermodynamic functions C p ° ( T), H°( T) - H°(0), S°( T) - S°(0), and G°( T) - H°(0) are calculated from the obtained experimental data for the region of T → 0 to 370 K. The standard entropy of formation of the dendrimer in the partially crystalline state at T = 298.15 K is calculated, and the standard entropy of the hypothetic reaction of its synthesis at this temperature is estimated. The thermodynamic properties of the studied dendrimer are compared to those of second- and fourth-generation liquid crystal carbosilane dendrimers with the same end groups studied earlier.

  9. Dendrimer advances for the central nervous system delivery of therapeutics.

    Xu, Leyuan; Zhang, Hao; Wu, Yue

    2014-01-15

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included.

  10. Host-guest chemistry of dendrimer-drug complexes. 4. An in-depth look into the binding/encapsulation of guanosine monophosphate by dendrimers.

    Hu, Jingjing; Fang, Min; Cheng, Yiyun; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen

    2010-06-03

    In the present study, we investigated the host-guest chemistry of dendrimer/guanosine monophosphate (GMP) and present an in-depth look into the binding/encapsulation of GMP by dendrimers using NMR studies. (1)H NMR spectra showed a significant downfield shift of methylene protons in the outmost layer of the G5 dendrimer, indicating the formation of ion pairs between cationic amine groups of dendrimer and anionic phosphate groups of GMP. Chemical shift titration results showed that the binding constant between G5 dendrimer and GMP is 17,400 M(-1) and each G5 dendrimer has 107 binding sites. The binding of GMP to dendrimers prevents its aggregation in aqueous solutions and thereby enhances its stability. Nuclear Overhauser effect measurements indicated that a GMP binding and encapsulation balance occurs on the surface and in the interior of dendrimer. The binding/encapsulation transitions can be easily tailored by altering the surface and interior charge densities of the dendrimer. All these findings provide a new insight into the host-guest chemistry of dendrimer/guest complexes and may play important roles in the study of dendrimer/DNA aggregates by a "bottom-up" strategy.

  11. The synthesis and characterization of biotin-silver-dendrimer nanocomposites as novel bioselective labels

    Maly, J; Lampova, H; Semeradtova, A; Stofik, M [Faculty of Science, University of J E Purkynje, 40096 Usti nad Labem (Czech Republic); Kovacik, L, E-mail: malyjalga@seznam.c [Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague (Czech Republic)

    2009-09-23

    This paper presents a synthesis of a novel nanoparticle label with selective biorecognition properties based on a biotinylated silver-dendrimer nanocomposite (AgDNC). Two types of labels, a biotin-AgDNC (bio-AgDNC) and a biotinylated AgDNC with a poly(ethylene)glycol spacer (bio-PEG-AgDNC), were synthesized from a generation 7 (G7) hydroxyl-terminated ethylenediamine-core-type (2-carbon core) PAMAM dendrimer (DDM) by an N,N'-dicyclohexylcarbodiimide (DDC) biotin coupling and a NaBH{sub 4} silver reduction method. Synthesized conjugates were characterized by several analytical methods, such as UV-vis, FTIR, AFM, TEM, ELISA, HABA assay and SPR. The results show that stable biotinylated nanocomposites can be formed either with internalized silver nanoparticles (AgNPs) in a DMM polymer backbone ('type I') or as externally protected ('type E'), depending on the molar ratio of the silver/DMM conjugate and type of conjugate. Furthermore, the selective biorecognition function of the biotin is not affected by the AgNPs' synthesis step, which allows a potential application of silver nanocomposite conjugates as biospecific labels in various bioanalytical assays, or potentially as fluorescence cell biomarkers. An exploitation of the presented label in the development of electrochemical immunosensors is anticipated.

  12. Synthesis and characterization of polyglycerols dendrimers for applications in tissue engineering biological

    Passos, E.D.; Queiroz, A.A.A. de

    2014-01-01

    Full text: Introduction: Over the last twenty years is the growing development in the manufacture of synthetic scaffold in tissue engineering applications. These new materials are based on polyglycerol dendrimers (PGLD's). PGLD's are highly functional polymers with hydroxymethyl side groups, fulfill all structural prerequisites to replace poly(ethylene glycol)s in medical applications. Furthermore, since these materials are based on naturally occurring compounds that degrades over time in the body and can be safely excreted. The objective of this work was the synthesis, physicochemical, biological characterization of HPGL's with potential use as scaffolds in tissue engineering. HPGL's with oligomeric cores, of diglycerol triglycerol and tetraglycerol was used. Theoretical and Experimental Simulation Details: The synthesis of PGLD procedures involves the etherification of glycerol through anionic polymerization of glycidol. The PGLD's were characterized by chromatographic techniques (SEC and HPLC), spectroscopic (FTIR, 1H-NMR and 13C - NMR) electrochemical (zeta potential) and thermal analysis (DSC and TGA) techniques. The structure- activity relationships (SAR's) of compound prototype and its analogs were studied to determine the generation number (G) of the molecule responsible for the biological activity on the adhesion and cell proliferation process. A detailed study of the structure of PGLD's of G=0-4 was performed using the Hyperchem 7. 5 and Gromacs 4 software packages. The biocompatibility studies were studied by scanning electron microscopy (SEM) and fluorescence microscopy (EPF) technique after PGLD (G=0-4) blood contact. The overall electro-negativity/total charge density, dipole moment, frontier orbital's (HOMO - LUMO) and electrostatic potential maps (EPM) were calculated. The most stable form of the resulting compounds was determined by estimating the hydration energy and energy conformation. Results and Discussion: The techniques SEM and EPF

  13. Kinetics of oriented crystallization of polymers in the linear stress-orientation range in the series expansion approach

    L. Jarecki

    2018-04-01

    Full Text Available An analytical formula is derived for the oriented crystallization coefficient governing kinetics of oriented crystallization under uniaxial amorphous orientation in the entire temperature range. A series expansion approach is applied to the free energy of crystallization in the Hoffman-Lauritzen kinetic model of crystallization at accounting for the entropy of orientation of the amorphous chains. The series expansion coefficients are calculated for systems of Gaussian chains in linear stress-orientation range. Oriented crystallization rate functions are determined basing on the ‘proportional expansion’ approach proposed by Ziabicki in the steady-state limit. Crystallization kinetics controlled by separate predetermined and sporadic primary nucleation is considered, as well as the kinetics involving both nucleation mechanisms potentially present in oriented systems. The involvement of sporadic nucleation in the transformation kinetics is predicted to increase with increasing amorphous orientation. Example computations illustrate the dependence of the calculated functions on temperature and amorphous orientation, as well as qualitative agreement of the calculations with experimental results.

  14. Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

    Kanika Madaan

    2014-01-01

    Full Text Available Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity.

  15. Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

    Madaan, Kanika; Kumar, Sandeep; Poonia, Neelam; Lather, Viney; Pandita, Deepti

    2014-01-01

    Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity. PMID:25035633

  16. Biological properties of water-soluble phosphorhydrazone dendrimers

    Anne-Marie Caminade

    2013-01-01

    Full Text Available Dendrimers are hyperbranched and perfectly defined macromolecules, constituted of branches emanating from a central core in an iterative fashion. Phosphorhydrazone dendrimers constitute a special family of dendrimers, possessing one phosphorus atom at each branching point. The internal structure of these dendrimers is hydrophobic, but hydrophilic terminal groups can induce the solubility of the whole structure in water. Indeed, the properties of these compounds are mainly driven by the type of terminal groups their bear; this is especially true for the biological properties. For instance, positively charged terminal groups are efficient for transfection experiments, as drug carriers, as anti-prion agents, and as inhibitor of the aggregation of Alzheimer's peptides, whereas negatively charged dendrimers have anti-HIV properties and can influence the human immune system, leading to anti-inflammatory properties usable against rheumatoid arthritis. This review will give the most representative examples of the biological properties of water-soluble phosphorhydrazone dendrimers, organized depending on the type of terminal groups they bear.

  17. Biphasic interactions between a cationic dendrimer and actin.

    Ruenraroengsak, Pakatip; Florence, Alexander T

    2010-12-01

    Gene delivery systems face the problem not only of the route toward the cell and tissues in question, but also of the molecularly crowded environment of both the cytoplasm and the nucleus itself. One of the physical barriers in the cytoplasm for diffusing nanoparticles is an actin network. Here, we describe the finding that a self-fluorescent sixth generation cationic dendrimer (6 nm in diameter) interacts reversibly and possibly electrostatically with actin filaments in vitro. Not only does this interaction slow the diffusion of the dendrimer but it also affects actin polymerization in a biphasic manner. At low concentrations the dendrimer behaves like a G-binding actin protein, retarding actin polymerization, whereas at high concentrations the dendrimer acts as a nucleating protein accelerating the polymerization. Thus in vivo the diffusion of a dendrimer carrier such as this has both physical and chemical elements: by decreasing polymerization it might accelerate its own transport, and by enhancing actin polymerization retard it. This finding suggests that such a dendrimer may have a role as an anticancer agent through its inhibitory effect on actin polymerization.

  18. In vitro evaluation of dendrimer prodrugs for oral drug delivery.

    Najlah, Mohammad; Freeman, Sally; Attwood, David; D'Emanuele, Antony

    2007-05-04

    Dendrimer-based prodrugs were used to enhance the transepithelial permeability of naproxen, a low solubility model drug. The stability of the dendrimer-naproxen link was assessed. Naproxen was conjugated to G0 polyamidoamine (PAMAM) dendrimers either by an amide bond or an ester bond. The stability of G0 prodrugs was evaluated in 80% human plasma and 50% rat liver homogenate. The cytotoxicity of conjugates towards Caco-2 cells was determined and the transport of the conjugates across Caco-2 monolayers (37 degrees C) was reported. In addition, one lauroyl chain (L) was attached to the surface group of G0 PAMAM dendrimer of the diethylene glycol ester conjugate (G0-deg-NAP) to enhance permeability. The lactic ester conjugate, G0-lact-NAP, hydrolyzed slowly in 80% human plasma and in 50% rat liver homogenate (t(1/2)=180 min). G0-deg-NAP was hydrolyzed more rapidly in 80% human plasma (t(1/2)=51 min) and was rapidly cleaved in 50% liver homogenate (t(1/2)=4.7 min). The conjugates were non-toxic when exposed to Caco-2 cells for 3h. Permeability studies showed a significant enhancement in the transport of naproxen when conjugated to dendrimers; L-G0-deg-NAP yielding the highest permeability. Dendrimer-based prodrugs with appropriate linkers have potential as carriers for the oral delivery of low solubility drugs such as naproxen.

  19. Exciton Transport Simulations in Phenyl Cored Thiophene Dendrimers

    Kim, Kwiseon; Erkan Kose, Muhammet; Graf, Peter; Kopidakis, Nikos; Rumbles, Garry; Shaheen, Sean E.

    2009-03-01

    Phenyl cored 3-arm and 4-arm thiophene dendrimers are promising materials for use in photovoltaic devices. It is important to understand the energy transfer mechanisms in these molecules to guide the synthesis of novel dendrimers with improved efficiency. A method is developed to estimate the exciton diffusion lengths for the dendrimers and similar chromophores in amorphous films. The approach exploits Fermi's Golden Rule to estimate the energy transfer rates for an ensemble of bimolecular complexes in random orientations. Using Poisson's equation to evaluate Coulomb integrals led to efficient calculation of excitonic couplings between the transition densities. Monte-Carlo simulations revealed the dynamics of energy transport in the dendrimers. Experimental exciton diffusion lengths of the dendrimers range 10 ˜ 20 nm, increasing with the size of the dendrimer. Simulated diffusion lengths correlate well with experiments. The chemical structure of the chromophore, the shape of the transition densities and the exciton lifetime are found to be the most important factors that determine the exciton diffusion length in amorphous films.

  20. Gene Transfer in Eukaryotic Cells Using Activated Dendrimers

    Dennig, Jörg

    Gene transfer into eukaryotic cells plays an important role in cell biology. Over the last 30 years a number of transfection methods have been developed to mediate gene transfer into eukaryotic cells. Classical methods include co-precipitation of DNA with calcium phosphate, charge-dependent precipitation of DNA with DEAE-dextran, electroporation of nucleic acids, and formation of transfection complexes between DNA and cationic liposomes. Gene transfer technologies based on activated PAMAM-dendrimers provide another class of transfection reagents. PAMAM-dendrimers are highly branched, spherical molecules. Activation of newly synthesized dendrimers involves hydrolytic removal of some of the branches, and results in a molecule with a higher degree of flexibility. Activated dendrimers assemble DNA into compact structures via charge interactions. Activated dendrimer - DNA complexes bind to the cell membrane of eukaryotic cells, and are transported into the cell by non-specific endocytosis. A structural model of the activated dendrimer - DNA complex and a potential mechanism for its uptake into cells will be discussed.

  1. Ultrafast Dynamics of Dansylated POPAM Dendrimers and Energy Transfer in their Dye Complexes

    Aumanen, J.; Kesti, T.; Sundström, V.; Vögtle, F.; Korppi-Tommola, J.

    We have studied internal dynamics of dansylated poly(propyleneamine) dendrimers of different generations in solution and excitation energy transfer from dansyl chromophores to xanthene dyes that form van der Waals complexes with the dendrimers

  2. Molecular boxes on a molecular printboard: encapsulation of anionic dyes in immobilized dendrimers

    Onclin, S.; Huskens, Jurriaan; Ravoo, B.J.; Reinhoudt, David

    2005-01-01

    Fifth-generation poly(propylene imine) dendrimers, modified with 64 apolar adamantyl groups, have been immobilized on cyclodextrin host monolayers (molecular printboards) on glass by supramolecular microcontact printing. The immobilized dendrimers retain their guest-binding properties and function

  3. Electrical switching and memory phenomena observed in redox-gradient dendrimer sandwich devices

    Li, JianChang; Blackstock, Silas C.; Szulczewski, Greg J.

    2005-01-01

    We report on the fabrication of dendrimer sandwich devices with electrical switching and memory properties. The storage media is consisted of a redox-gradient dendrimer layer sandwiched in organic barrier thin films. The dendrimer layer acts as potential well where redox-state changes and consequent electrical transitions of the embedded dendrimer molecules are expected to be effectively triggered and retained, respectively. Experimental results indicated that electrical switching could be re...

  4. Permeability of surface modified polyamidoamine (PAMAM) dendrimers across Caco-2 cell monolayers

    Yellepeddi, Venkata K.; Pisal, Dipak S.; Kumar, Ajay; Kaushik, Radhey S.; Hildreth, Michael B.; Guan, Xiangming; Palakurthi, Srinath

    2007-01-01

    Aim of this study was to prepare polyamine-conjugated PAMAM dendrimers and study their permeability across Caco-2 cell monolayers. Polyamines, namely, arginine and ornithine were conjugated to the amine terminals of the G4 PAMAM dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (Papp) for the PAMAM dendrimers increased by conjugating the dendrimers with both of the polyamines. The enhancement in permeability was depe...

  5. Synthesis and optical properties of water-soluble biperylene-based dendrimers.

    Shao, Pin; Jia, Ningyang; Zhang, Shaojuan; Bai, Mingfeng

    2014-05-30

    We report the synthesis and photophysical properties of three biperylene-based dendrimers, which show red fluorescence in water. A fluorescence microscopy study demonstrated uptake of biperylene-based dendrimers in living cells. Our results indicate that these biperylene-based dendrimers are promising candidates in fluorescence imaging applications with the potential as therapeutic carriers.

  6. A selective glucose sensor: the cooperative effect of monoboronic acid-modified poly(amidoamine) dendrimers.

    Tsai, Ching-Hua; Tang, Yi-Hsuan; Chen, Hui-Ting; Yao, Yi-Wen; Chien, Tun-Cheng; Kao, Chai-Lin

    2018-05-01

    Selective glucose binding was identified through five generations of monoboronic acid-functionalized PAMAM dendrimers. The best selectivity obtained when using G3 dendrimers (1b) generated 71.1, 94.9, and 1309 times stronger binding than when using galactose, fructose, and lactose, respectively. Further experiments using dendrimer analogues and glucose derivatives suggested that two nearby monoboronic acids cooperatively bound one glucose.

  7. Investigation of interactions between dendrimer-coated magnetite nanoparticles and bovine serum albumin

    Pan Bifeng; Gao Feng; Ao Limei

    2005-01-01

    We investigated the interactions between dendrimer-coated magnetite nanoparticles (MNPs) and the protein serum albumin. The investigation was based on the fluorescence quenching of tryptophan residue of serum albumin after binding with the dendrimer-coated magnetite nanoparticles. The extent of the interactions between bovine serum albumin and dendrimer-coated MNPs strongly depends on their surface groups and pH value

  8. Build-up enhancement of photoluminescence from phenylazomethine bismuth dendrimer using Bi(OTf)3

    Kambe, Tetsuya; Imaoka, Shotaro; Imaoka, Takane; Yamamoto, Kimihisa

    2018-05-01

    Metal assembly to a dendrimer can provide various functionalities based on the branched structure. Here, we researched assembly phenomena of bismuth salts in the phenylazomethine dendrimer and achieved enhancement of emission intensity per metal unit by using Bi(OTf)3. This enhancement suggested increasing of Bi-N coordination bonds derived from the bismuth units in the dendrimer.

  9. Transport of surface engineered polyamidoamine (PAMAM) dendrimers across IPEC-J2 cell monolayers.

    Pisal, Dipak S; Yellepeddi, Venkata K; Kumar, Ajay; Palakurthi, Srinath

    2008-11-01

    The aim of our study was to prepare arginine-and ornithine-conjugated Polyamidoamine (PAMAM) dendrimers and study their permeability across IPEC-J2 cell monolayers, a new intestinal cell line model for drug absorption studies. Arginine and ornithine were conjugated to the amine terminals of the PAMAM(G4) dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (P(app)) for the PAMAM dendrimers increased by conjugating the dendrimers with both of these polyamines. The enhancement in permeability was dependent on the dendrimer concentration and duration of incubation. Correlation between monolayer permeability and the decrease in transepithelial electrical resistance (TEER) with the PAMAM dendrimers and the polyamine-conjugated dendrimers suggests that paracellular transport is one of the mechanisms of transport across the epithelial cells. Cytotoxicity of these surface-modified dendrimers was evaluated in IPEC-J2 cells by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were insignificantly more toxic than PAMAM dendrimer as well as ornithine-conjugated dendrimers. Though investigations on the possible involvement of other transport mechanisms are in progress, results of the present study suggest the potential of dendrimer-polyamine conjugates as the carriers for antigen/drug delivery through the oral mucosa.

  10. Interactions of poly(amidoamine) dendrimers with human serum albumin: binding constants and mechanisms.

    Giri, Jyotsnendu; Diallo, Mamadou S; Simpson, André J; Liu, Yi; Goddard, William A; Kumar, Rajeev; Woods, Gwen C

    2011-05-24

    The interactions of nanomaterials with plasma proteins have a significant impact on their in vivo transport and fate in biological fluids. This article discusses the binding of human serum albumin (HSA) to poly(amidoamine) [PAMAM] dendrimers. We use protein-coated silica particles to measure the HSA binding constants (K(b)) of a homologous series of 19 PAMAM dendrimers in aqueous solutions at physiological pH (7.4) as a function of dendrimer generation, terminal group, and core chemistry. To gain insight into the mechanisms of HSA binding to PAMAM dendrimers, we combined (1)H NMR, saturation transfer difference (STD) NMR, and NMR diffusion ordered spectroscopy (DOSY) of dendrimer-HSA complexes with atomistic molecular dynamics (MD) simulations of dendrimer conformation in aqueous solutions. The binding measurements show that the HSA binding constants (K(b)) of PAMAM dendrimers depend on dendrimer size and terminal group chemistry. The NMR (1)H and DOSY experiments indicate that the interactions between HSA and PAMAM dendrimers are relatively weak. The (1)H NMR STD experiments and MD simulations suggest that the inner shell protons of the dendrimers groups interact more strongly with HSA proteins. These interactions, which are consistently observed for different dendrimer generations (G0-NH(2)vs G4-NH(2)) and terminal groups (G4-NH(2)vs G4-OH with amidoethanol groups), suggest that PAMAM dendrimers adopt backfolded configurations as they form weak complexes with HSA proteins in aqueous solutions at physiological pH (7.4).

  11. Synthesis and Catalytic Evaluation of Dendrimer-Encapsulated Cu Nanoparticles: An Undergraduate Experiment Exploring Catalytic Nanomaterials

    Feng, Z. Vivian; Lyon, Jennifer L.; Croley, J. Sawyer; Crooks, Richard M.; Vanden Bout, David A.; Stevenson, Keith J.

    2009-01-01

    Copper nanoparticles were synthesized using generation 4 hydroxyl-terminated (G4-OH) poly(amidoamine) (PAMAM) dendrimers as templates. The synthesis is conducted by coordinating copper ions with the interior amines of the dendrimer, followed by chemical reduction to form dendrimer-encapsulated copper nanoparticles (Cu-DEN). The catalytic…

  12. Stopped-flow kinetic studies of poly(amidoamine) dendrimer-calf thymus DNA to form dendriplexes.

    Dey, Debabrata; Kumar, Santosh; Maiti, Souvik; Dhara, Dibakar

    2013-11-07

    Poly(amidoamine) (PAMAM) dendrimers are known to be highly efficient nonviral carriers in gene delivery. Dendrimer-mediated transfection is known to be a function of the dendrimer to DNA charge ratio as well as the size of the dendrimer. In the present study, the binding kinetics of four PAMAM dendrimers (G1, G2, G3, and G4) with calf thymus DNA (CT-DNA) has been studied using stopped-flow fluorescence spectroscopy. The effect of dendrimer-to-DNA charge ratio and dendrimer generation on the binding kinetics was investigated. In most cases, the results of dendrimer-CT-DNA binding can be explained by a two-step reaction mechanism: a rapid electrostatic binding between the dendrimer and DNA, followed by a conformational change of the dendrimer-DNA complex that ultimately leads to DNA condensation. It was observed that the charge ratio on the dendrimer and the DNA phosphate groups, as well as the dendrimer generation (size), has a marked effect on the kinetics of binding between the DNA and the dendrimers. The rate constant (k'1) of the first step was much higher compared to that of the second step (k'2), and both were found to increase with an increase in dendrimer concentration. Among the four generations of dendrimers, G4 exhibited significantly faster binding kinetics compared to the three smaller generation dendrimers.

  13. Inhibition of the norepinephrine transporter by χ-conotoxin dendrimers.

    Wan, Jingjing; Brust, Andreas; Bhola, Rebecca F; Jha, Prerna; Mobli, Mehdi; Lewis, Richard J; Christie, Macdonald J; Alewood, Paul F

    2016-05-01

    Peptide dendrimers are a novel class of macromolecules of emerging interest with the potential of delayed renal clearance due to their molecular size and enhanced activity due to the multivalency effect. In this work, an active analogue of the disulfide-rich χ-conotoxin χ-MrIA (χ-MrIA), a norepinephrine reuptake (norepinephrine transporter) inhibitor, was grafted onto a polylysine dendron. Dendron decoration was achieved by employing copper-catalyzed alkyne-azide cycloaddition with azido-PEG chain-modified χ-MrIA analogues, leading to homogenous 4-mer and 8-mer χ-MrIA dendrimers with molecular weights ranging from 8 to 22 kDa. These dendrimers were investigated for their impact on peptide secondary structure, in vitro functional activity, and potential anti-allodynia in vivo. NMR studies showed that the χ-MrIA tertiary structure was maintained in the χ-MrIA dendrimers. In a functional norepinephrine transporter reuptake assay, χ-MrIA dendrimers showed slightly increased potency relative to the azido-PEGylated χ-MrIA analogues with similar potency to the parent peptide. In contrast to χ-MrIA, no anti-allodynic action was observed when the χ-MrIA dendrimers were administered intrathecally in a rat model of neuropathic pain, suggesting that the larger dendrimer structures are unable to diffuse through the spinal column tissue and reach the norepinephrine transporter. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  14. Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer

    Li K

    2013-07-01

    Full Text Available Kangan Li,1,4,5,* Shihui Wen,2,* Andrew C Larson,4,5 Mingwu Shen,2 Zhuoli Zhang,4,5 Qian Chen,3 Xiangyang Shi,2,3 Guixiang Zhang1 1Department of Radiology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, People’s Republic of China; 4Departments of Radiology and Biomedical Engineering, Northwestern University, Chicago, IL, USA; 5Robert H Lurie Comprehensive Cancer Center, Chicago, IL, USA *These authors contributed equally to this work Abstract: Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP as a dual-modality contrast agent for magnetic resonance (MR/computed tomography (CT imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine dendrimers modified with gadolinium chelate (DOTA-NHS and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results

  15. Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo.

    Malik, N; Wiwattanapatapee, R; Klopsch, R; Lorenz, K; Frey, H; Weener, J W; Meijer, E W; Paulus, W; Duncan, R

    2000-03-01

    Dendrimers are highly branched macromolecules of low polydispersity that provide many exciting opportunities for design of novel drug-carriers, gene delivery systems and imaging agents. They hold promise in tissue targeting applications, controlled drug release and moreover, their interesting nanoscopic architecture might allow easier passage across biological barriers by transcytosis. However, from the vast array of structures currently emerging from synthetic chemistry it is essential to design molecules that have real potential for in vivo biological use. Here, polyamidoamine (PAMAM, Starburst), poly(propyleneimine) with either diaminobutane or diaminoethane as core, and poly(ethylene oxide) (PEO) grafted carbosilane (CSi-PEO) dendrimers were used to study systematically the effect of dendrimer generation and surface functionality on biological properties in vitro. Generally, dendrimers bearing -NH(2) termini displayed concentration- and in the case of PAMAM dendrimers generation-dependent haemolysis, and changes in red cell morphology were observed after 1 h even at low concentrations (10 microg/ml). At concentrations below 1 mg/ml CSi-PEO dendrimers and those dendrimers with carboxylate (COONa) terminal groups were neither haemolytic nor cytotoxic towards a panel of cell lines in vitro. In general, cationic dendrimers were cytotoxic (72 h incubation), displaying IC(50) values=50-300 microg/ml dependent on dendrimer-type, cell-type and generation. Preliminary studies with polyether dendrimers prepared by the convergent route showed that dendrimers with carboxylate and malonate surfaces were not haemolytic at 1 h, but after 24 h, unlike anionic PAMAM dendrimers they were lytic. Cationic 125I-labelled PAMAM dendrimers (gen 3 and 4) administered intravenously (i.v.) to Wistar rats ( approximately 10 microg/ml) were cleared rapidly from the circulation (<2% recovered dose in blood at 1 h). Anionic PAMAM dendrimers (gen 2.5, 3.5 and 5.5) showed longer circulation

  16. The application of poly(amidoamine dendrimers for modification of jute yarns: Preparation and dyeing properties

    Ali Akbar Zolriasatein

    2015-03-01

    Full Text Available In this study, poly(amidoamine (PAMAM G-2 dendrimer was used for jute yarn. Fourier transform infrared spectroscopy (FT-IR revealed that all carbonyl groups of jute fibers reacted with amino groups of polyamidoamine dendrimers. SEM observation indicated the good dispersion PAMAM dendrimers. Jute yarns pretreated with PAMAM dendrimer displayed markedly enhanced color strength with reactive dyes, even when dyeing had been carried out in the absence of electrolyte or alkali. Dendrimer-treated jute yarn showed much better light-fastness than untreated jute yarn.

  17. Transepithelial Transport of PEGylated Anionic Poly(amidoamine) Dendrimers: Implications for Oral Drug Delivery

    Sweet, Deborah M.; Kolhatkar, Rohit B.; Ray, Abhijit; Swaan, Peter; Ghandehari, Hamidreza

    2009-01-01

    The purpose of this work was to assess the impact of PEGylation on transepithelial transport of anionic poly(amidoamine) dendrimers. Cytotoxicity, uptake and transport across Caco-2 cells of PEGylated G3.5 and G4.5 PAMAM dendrimers were studied. Methoxy polyethylene glycol (750 Da) was conjugated to carboxylic acid-terminated PAMAM dendrimers at feed ratios of 1, 2 and 4 PEG per dendrimer. Compared to the control, PEGylation of anionic dendrimers did not significantly alter cytotoxicity up to...

  18. Energy transfer dynamics in Light-Harvesting Dendrimers

    Melinger, Joseph S.; McMorrow, Dale; Kleiman, Valeria D.

    2002-03-01

    We explore energy transfer dynamics in light-harvesting phenylacetylene symmetric and asymmetric dendrimers. Femtosecond pump-probe spectroscopy is used to probe the ultrafast dynamics of electronic excitations in these dendrimers. The backbone of the macromolecule consists of branches of increasing conjugation length, creating an energy gradient, which funnels energy to an accepting perylene trap. In the case of the symmetric dendrimer (nanostar), the energy transfer efficiency is known to approach nearly unity, although the nature and timescale of the energy transfer process is still unknown. For the asymmetric dendrimers, energy transfer efficiencies are very high, with the possibility of more complex transfer processes. We experimentally monitor the transport of excitons through the light-harvesting dendrimer. The transients show a number of components, with timescales ranging from <300fs to several tens of picoseconds, revealing the complex photophysics taking place in these macromolecules. We interpret our results in terms of the Förster mechanism in which energy transfer occurs through dipole-dipole interactions.

  19. Cationic PAMAM dendrimers as pore-blocking binary toxin inhibitors.

    Förstner, Philip; Bayer, Fabienne; Kalu, Nnanya; Felsen, Susanne; Förtsch, Christina; Aloufi, Abrar; Ng, David Y W; Weil, Tanja; Nestorovich, Ekaterina M; Barth, Holger

    2014-07-14

    Dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. Here we identified poly(amido amine) (PAMAM) dendrimers as novel blockers for the pore-forming B components of the binary anthrax toxin (PA63) and Clostridium botulinum C2 toxin (C2IIa). These pores are essential for delivery of the enzymatic A components of the internalized toxins from endosomes into the cytosol of target cells. We demonstrate that at low μM concentrations cationic PAMAM dendrimers block PA63 and C2IIa to inhibit channel-mediated transport of the A components, thereby protecting HeLa and Vero cells from intoxication. By channel reconstitution and high-resolution current recording, we show that the PAMAM dendrimers obstruct transmembrane PA63 and C2IIa pores in planar lipid bilayers at nM concentrations. These findings suggest a new potential role for the PAMAM dendrimers as effective polyvalent channel-blocking inhibitors, which can protect human target cells from intoxication with binary toxins from pathogenic bacteria.

  20. Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

    Hubbard, Dallin; Enda, Michael; Bond, Tanner; Moghaddam, Seyyed Pouya Hadipour; Conarton, Josh; Scaife, Courtney; Volckmann, Eric; Ghandehari, Hamidreza

    2015-11-02

    Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

  1. Mechanism of PAMAM Dendrimers Internalization in Hippocampal Neurons.

    Vidal, Felipe; Vásquez, Pilar; Díaz, Carola; Nova, Daniela; Alderete, Joel; Guzmán, Leonardo

    2016-10-03

    Polyamidoamine (PAMAM) dendrimers are hyperbranched macromolecules which have been described as one of the most promising drug nanocarrier systems. A key process to understand is their cellular internalization mechanism because of its direct influence on their intracellular distribution, association with organelles, entry kinetics, and cargo release. Despite that internalization mechanisms of dendrimers have been studied in different cell types, in the case of neurons they are not completely described. Considering the relevance of central nervous system (CNS) diseases and neuropharmacology, the aim of this report is to describe the molecular internalization mechanism of different PAMAM-based dendrimer systems in hippocampal neurons. Four dendrimers based on fourth generation PAMAM with different surface properties were studied: unmodified G4, with a positively charged surface; PP50, with a substitution of the 50% of amino surface groups with polyethylene glycol neutral groups; PAc, with a substitution of the 30% of amino surface groups with acrylate anionic groups; and PFO, decorated with folic acid groups in a 25% of total terminal groups. Confocal images show that both G4 and PFO are able to enter the neurons, but not PP50 and PAc. Colocalization study with specific endocytosis markers and specific endocytosis inhibitor assay demonstrate that clathrin-mediated endocytosis would be the main internalization mechanism for G4, whereas clathrin- and caveolae-mediated endocytosis would be implicated in PFO internalization. These results show the existence of different internalization mechanisms for PAMAM dendrimers in neurons and the possibility to control their internalization properties with specific chemical modifications.

  2. Skin Delivery of EGCG and Silibinin: Potential of Peptide Dendrimers for Enhanced Skin Permeation and Deposition.

    Shetty, Pallavi Krishna; Manikkath, Jyothsna; Tupally, Karnaker; Kokil, Ganesh; Hegde, Aswathi R; Raut, Sushil Y; Parekh, Harendra S; Mutalik, Srinivas

    2017-08-01

    The aim of the present study was to evaluate the ability of the peptide dendrimers to facilitate transdermal delivery of antioxidants, silibinin, and epigallocatechin-3-gallate (EGCG). Drug-peptide dendrimer complexes were prepared and evaluated for their ability to permeate across the skin. The data revealed the ready formation of complexes between drug and peptide dendrimer in a molar ratio of 1:1. In vitro permeation studies using excised rat skin and drug-peptide dendrimer complexes showed highest values for cumulative drug permeation at the end of 12 h (Q 12 ), with corresponding permeability coefficient (Kp) and enhancement ratio values also determined at this time point. With silibinin, 3.96-, 1.81-, and 1.06-fold increase in skin permeation was observed from silibinin-peptide dendrimer complex, simultaneous application of silibinin + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. With EGCG, 9.82-, 2.04-, and 1.72-fold increase in skin permeation was observed from EGCG-peptide dendrimer complex, simultaneous application of EGCG + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. The present study demonstrates the application of peptide dendrimers in effectively delivering antioxidants such as EGCG and silibinin into the skin, thus offering the potential to provide antioxidant effects when delivered via appropriately formulated topical preparations.

  3. Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes.

    Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

    2015-11-14

    Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.

  4. Transepithelial transport of PEGylated anionic poly(amidoamine) dendrimers: implications for oral drug delivery.

    Sweet, Deborah M; Kolhatkar, Rohit B; Ray, Abhijit; Swaan, Peter; Ghandehari, Hamidreza

    2009-08-19

    The purpose of this work was to assess the impact of PEGylation on transepithelial transport of anionic poly(amidoamine) dendrimers. Cytotoxicity, uptake and transport across Caco-2 cells of PEGylated G3.5 and G4.5 PAMAM dendrimers were studied. Methoxy polyethylene glycol (750 Da) was conjugated to carboxylic acid-terminated PAMAM dendrimers at feed ratios of 1, 2 and 4 PEG per dendrimer. Compared to the control, PEGylation of anionic dendrimers did not significantly alter cytotoxicity up to a concentration of 0.1 mM. PEGylation of G3.5 dendrimers significantly decreased cellular uptake and transepithelial transport while PEGylation of G4.5 dendrimers led to a significant increase in uptake, but also a significant decrease in transport. Dendrimer PEGylation reduced the opening of tight junctions as evidenced by confocal microscopy techniques. Modulation of the tight junctional complex correlated well with changes in PEGylated dendrimer transport and suggests that anionic dendrimers are transported primarily through the paracellular route. PEGylated dendrimers show promise in oral delivery applications where increased functionality for drug conjugation and release is desired.

  5. Molecular analysis of interactions between dendrimers and asymmetric membranes at different transport stages.

    He, XiaoCong; Qu, ZhiGuo; Xu, Feng; Lin, Min; Wang, JiuLing; Shi, XingHua; Lu, TianJian

    2014-01-07

    Studying dendrimer-biomembrane interactions is important for understanding drug and gene delivery. In this study, coarse-grained molecular dynamics simulations were performed to investigate the behaviors of polyamidoamine (PAMAM) dendrimers (G4 and G5) as they interacted with asymmetric membranes from different sides of the bilayer, thus mimicking different dendrimer transport stages. The G4 dendrimer could insert into the membrane during an equilibrated state, and the G5 dendrimer could induce pore formation in the membrane when the dendrimers interacted with the outer side (outer interactions) of an asymmetric membrane [with 10% dipalmitoyl phosphatidylserine (DPPS) in the inner leaflet of the membrane]. During the interaction with the inner side of the asymmetric membrane (inner interactions), the G4 and G5 dendrimers only adsorbed onto the membrane. As the membrane asymmetry increased (e.g., increased DPPS percentage in the inner leaflet of the membrane), the G4 and G5 dendrimers penetrated deeper into the membrane during the outer interactions and the G4 and G5 dendrimers were adsorbed more tightly onto the membrane for the inner interactions. When the DPPS content reached 50%, the G4 dendrimer could completely penetrate through the membrane from the outer side to the inner side. Our study provides molecular understanding and reference information about different dendrimer transport stages during drug and gene delivery.

  6. Immobilization of dendrimers on Si-C linked carboxylic acid-terminated monolayers on silicon(111)

    Boecking, Till; Wong, Elicia L.S.; James, Michael; Watson, Jolanta A.; Brown, Christopher L.; Chilcott, Terry C.; Barrow, Kevin D.; Coster, Hans G.L.

    2006-01-01

    Poly(amidoamine) dendrimers were attached to activated undecanoic acid monolayers, covalently linked to smooth silicon surfaces via Si-C bonds. The resulting ultra-thin dendrimer films were characterized by X-ray photoelectron spectroscopy (XPS), X-ray reflectometry (XR) and atomic force microscopy (AFM). XPS results suggested amide bond formation between the dendrimer and the surface carboxylic acid groups. XR yielded thicknesses of 10 A for the alkyl region of the undecanoic acid monolayer and 12 A for the dendrimer layer, considerably smaller than the diameter of these spherical macromolecules in solution. This was consistent with AFM images showing collapsed dendrimers on the surface. It was concluded that the deformation arose from a large number of amine groups on the surface of each dendrimer reacting efficiently with the activated surface, whereby the dendrimers can deform to fill voids while spreading over the activated surface to form a homogeneous macromolecular layer

  7. Host-guest chemistry of dendrimer-drug complexes: 7. Formation of stable inclusions between acetylated dendrimers and drugs bearing multiple charges.

    Fang, Min; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen; Cheng, Yiyun

    2012-03-15

    Drug molecules bearing multiple charges usually form precipitates with cationic dendrimers, which presents a challenge during the preparation of dendrimer inclusions for these drugs. In the present study, fully acetylated polyamidoamine (PAMAM) dendrimers were proposed as stable vehicles for drug molecules bearing two negative charges such as Congo red and indocyanine green. NMR techniques including (1)H NMR and (1)H-(1)H NOESY were used to characterize the host-guest chemistry of acetylated dendrimer and these guest molecules. The cationic PAMAM dendrimer was found to form a precipitate with Congo red and indocyanine green, but the acetylated one avoided the formation of cross-linking structures in aqueous solutions. NOESY studies revealed the encapsulation of Congo red and indocyanine green within the interior cavities of PAMAM dendrimers at mild acidic conditions and acetylated dendrimers show much stronger ability to encapsulate the guest molecules than cationic ones. Also, UV-vis-NIR studies suggest that acetylated dendrimers significantly improve the photostability of indocyanine green and prevent the formation of indocyanine green J-aggregates in aqueous solutions. The present study provides a new insight into dendrimer-based host-guest systems, especially for those guest molecules bearing multiple charges. © 2012 American Chemical Society

  8. Dendrimer-based biosensor for chemiluminescent detection of DNA hybridization

    Liu, P.; Hun, X.; Qing, H.

    2011-01-01

    We report on a highly sensitive chemiluminescent (CL) biosensor for the sequence-specific detection of DNA using a novel bio barcode DNA probe modified with gold nanoparticles that were covered with a dendrimer. The modified probe is composed of gold nanoparticles, a dendrimer, the CL reagent, and the DNA. The capture probe DNA was immobilized on magnetic beads covered with gold. It first hybridizes with the target DNA and then with one terminal end of the signal DNA on the barcoded DNA probe. CL was generated by adding H 2 O 2 and Co(II) ions as the catalyst. The immobilization of dendrimer onto the gold nanoparticles can significantly enhance sensitivity and gives a detection limit of 6 fmol L -1 of target DNA. (author)

  9. On Topological Indices of Certain Families of Nanostar Dendrimers.

    Husin, Mohamad Nazri; Hasni, Roslan; Arif, Nabeel Ezzulddin; Imran, Muhammad

    2016-06-24

    A topological index of graph G is a numerical parameter related to G which characterizes its molecular topology and is usually graph invariant. In the field of quantitative structure-activity (QSAR)/quantitative structure-activity structure-property (QSPR) research, theoretical properties of the chemical compounds and their molecular topological indices such as the Randić connectivity index, atom-bond connectivity (ABC) index and geometric-arithmetic (GA) index are used to predict the bioactivity of different chemical compounds. A dendrimer is an artificially manufactured or synthesized molecule built up from the branched units called monomers. In this paper, the fourth version of ABC index and the fifth version of GA index of certain families of nanostar dendrimers are investigated. We derive the analytical closed formulas for these families of nanostar dendrimers. The obtained results can be of use in molecular data mining, particularly in researching the uniqueness of tested (hyper-branched) molecular graphs.

  10. On Topological Indices of Certain Families of Nanostar Dendrimers

    Mohamad Nazri Husin

    2016-06-01

    Full Text Available A topological index of graph G is a numerical parameter related to G which characterizes its molecular topology and is usually graph invariant. In the field of quantitative structure-activity (QSAR/quantitative structure-activity structure-property (QSPR research, theoretical properties of the chemical compounds and their molecular topological indices such as the Randić connectivity index, atom-bond connectivity (ABC index and geometric-arithmetic (GA index are used to predict the bioactivity of different chemical compounds. A dendrimer is an artificially manufactured or synthesized molecule built up from the branched units called monomers. In this paper, the fourth version of ABC index and the fifth version of GA index of certain families of nanostar dendrimers are investigated. We derive the analytical closed formulas for these families of nanostar dendrimers. The obtained results can be of use in molecular data mining, particularly in researching the uniqueness of tested (hyper-branched molecular graphs.

  11. Dendrimer-magnetic nanostructure: a Monte Carlo simulation

    Jabar, A.; Masrour, R.

    2017-11-01

    In this paper, the magnetic properties of ternary mixed spins (σ,S,q) Ising model on a dendrimer nanostructure are studied using Monte Carlo simulations. The ground state phase diagrams of dendrimer nanostructure with ternary mixed spins σ = 1/2, S = 1 and q = 3/2 Ising model are found. The variation of the thermal total and partial magnetizations with the different exchange interactions, the external magnetic fields and the crystal fields have been also studied. The reduced critical temperatures have been deduced. The magnetic hysteresis cycles have been discussed. In particular, the corresponding magnetic coercive filed values have been deduced. The multiples hysteresis cycles are found. The dendrimer nanostructure has several applications in the medicine.

  12. Structural properties of star-like dendrimers in solution

    Rathgeber, S.; Gast, A.P.; Hedrick, J.L.

    2002-01-01

    We measured the form factor of star-like poly-ε-caprolactone dendrimers under good solvent conditions with small-angle neutron scattering (SANS). The parameters varied in the experiment were the dendrimer generation g=1,2,3 and the number of segments between the branching units n=5,10,15,20. The results are discussed in the frame work of the Beaucage model from which we cannot only derive the radius of gyration R g of the dendrimers but also their fractal dimensions. Decreasing the number of spacer units between the branching points results in a strong stretching of the dendrons. The fractal dimension increases monotonically with increasing generation and spacer number between the limit expected for a low-functionality star P∼5/3 (loose, polymeric structure) and that expected for a high-functionality star P∼3 (compact shape). (orig.)

  13. Hydrogel of Ketoconazole and PAMAM Dendrimers: Formulation and Antifungal Activity

    Elzbieta Tryniszewska

    2012-04-01

    Full Text Available Ketoconazole (KET, an imidazole derivative with well-known antifungal properties, is lipophilic and practically insoluble in water, therefore its clinical use has some practical disadvantages. The aim of the present study was to investigate the influence of PAMAM-NH2 and PAMAM-OH dendrimers generation 2 and generation 3 on the solubility and antifungal activity of KET and to design and evaluate KET hydrogel with PAMAM dendrimers. It was shown that the surface charge of PAMAM dendrimers strongly affects their influence on the improvement of solubility and antifungal activity of KET. The MIC and MFC values obtained by broth dilution method indicate that PAMAM-NH2 dendrimers significantly (up to 16-fold increased the antifungal activity of KET against Candida strains (e.g., in culture Candida albicans 1103059/11 MIC value was 0.008 μg/mL and 0.064 μg/mL, and MFC was 2 μg/mL and 32 μg/mL for KET in 10 mg/mL solution of PAMAM-NH2 G2 and pure KET, respectively. Antifungal activity of designed KET hydrogel with PAMAM-NH2 dendrimers measured by the plate diffusion method was definitely higher than pure KET hydrogel and than commercial available product. It was shown that the improvement of solubility and in the consequence the higher KET release from hydrogels seems to be a very significant factor affecting antifungal activity of KET in hydrogels containing PAMAM dendrimers.

  14. Liquid-crystalline dendrimer Cu(II) complexes and Cu(0) nanoclusters based on the Cu(II) complexes: An electron paramagnetic resonance investigation

    Domracheva, N. E.; Mirea, A.; Schwoerer, M.; Torre-Lorente, L.; Lattermann, G.

    2007-07-01

    New nanostructured materials, namely, the liquid-crystalline copper(II) complexes that contain poly(propylene imine) dendrimer ligands of the first (ligand 1) and second (ligand 2) generations and which have a columnar mesophase and different copper contents (x = Cu/L), are investigated by EPR spectroscopy. The influence of water molecules and nitrate counterions on the magnetic properties of complex 2 (x = 7.3) is studied. It is demonstrated that water molecules can extract some of the copper ions from dendrimer complexes and form hexaaqua copper complexes with free ions. The dimer spectra of fully hydrated complex 2 (x = 7.3) are observed at temperatures T dendrimer copper(II) complex. The temperature-induced valence tautomerism attended by electron transport is revealed for the first time in blue dendrimer complexes 1 (x = 1.9) with a dimer structure. The activation energy for electron transport is estimated to be 0.35 meV. The coordination of the copper ion site (NO4) and the structural arrangement of green complexes 1 (x = 1.9) in the columnar mesophase are determined. Complexes of this type form linear chains in which nitrate counterions serve as bridges between copper centers. It is revealed that green complexes 1 (x = 1.9) dissolved in isotropic inert solvents can be oriented in the magnetic field (B 0 = 8000 G). The degree of orientation of these complexes is rather high (S z = 0.76) and close to that of systems with a complete ordering (S z = 1) in the magnetic field. Copper(0) nanoclusters prepared by reduction of complex 2 (x = 7.3) in two reducing agents (NaBH4, N2H4 · H2O) are examined. A model is proposed for a possible location of Cu(0) nanoclusters in a dendrimer matrix.

  15. Natural and Synthetic Polymers as Inhibitors of Drug Efflux Pumps

    2007-01-01

    Inhibition of efflux pumps is an emerging approach in cancer therapy and drug delivery. Since it has been discovered that polymeric pharmaceutical excipients such as Tweens® or Pluronics® can inhibit efflux pumps, various other polymers have been investigated regarding their potential efflux pump inhibitory activity. Among them are polysaccharides, polyethylene glycols and derivatives, amphiphilic block copolymers, dendrimers and thiolated polymers. In the current review article, natural and synthetic polymers that are capable of inhibiting efflux pumps as well as their application in cancer therapy and drug delivery are discussed. PMID:17896100

  16. Understanding Peptide Dendrimer Interactions with Model Cell Membrane Mimics

    Lind, Tania Kjellerup

    few new drugs have been marketed over the last decades, making it impossible to keep pace with the disturbing levels of multi-drug resistant bacteria. Research in the area of novel drugs, which are less prone to induce resistance, and in-depth knowledge on their uptake mechanisms is thus of paramount...... fusion method, which presents improved means for studying drug-membrane interactions in the future. The interaction mechanism of a family of dendrimers was examined and in particular one dendrimer (BALY) was extensively studied by the combined use of quartz crystal microbalance, atomic force microscopy...

  17. The neighbourhood polynomial of some families of dendrimers

    Nazri Husin, Mohamad; Hasni, Roslan

    2018-04-01

    The neighbourhood polynomial N(G,x) is generating function for the number of faces of each cardinality in the neighbourhood complex of a graph and it is defined as (G,x)={\\sum }U\\in N(G){x}|U|, where N(G) is neighbourhood complex of a graph, whose vertices of the graph and faces are subsets of vertices that have a common neighbour. A dendrimers is an artificially manufactured or synthesized molecule built up from branched units called monomers. In this paper, we compute this polynomial for some families of dendrimer.

  18. M-Polynomial and Related Topological Indices of Nanostar Dendrimers

    Mobeen Munir

    2016-09-01

    Full Text Available Dendrimers are highly branched organic macromolecules with successive layers of branch units surrounding a central core. The M-polynomial of nanotubes has been vastly investigated as it produces many degree-based topological indices. These indices are invariants of the topology of graphs associated with molecular structure of nanomaterials to correlate certain physicochemical properties like boiling point, stability, strain energy, etc. of chemical compounds. In this paper, we first determine M-polynomials of some nanostar dendrimers and then recover many degree-based topological indices.

  19. Dynamics simulation of a π-conjugated light-harvesting dendrimer II: phenylene-based dendrimer (phDG2)

    Kodama, Yasunobu; Ishii, Soh; Ohno, Kaoru

    2009-01-01

    We investigate the light-harvesting property of a π-conjugated dendrimer, phenylene-based dendrimer (phDG2), by carrying out a semi-classical Ehrenfest dynamics simulation based on the time-dependent density functional theory. Similar to our previous study of star-shaped stilbenoid phthalocyanine (SSS1Pc), phDG2 shows electron and hole transfer from the periphery to the core through a π-conjugated network when an electron is selectively excited in the periphery. The one-way electron and hole transfer occurs more easily in dendrimers with planar structure than in those with steric hindrance because π-conjugation is well maintained in the planar structure. The present results explain recent experiments by Akai et al (2005 J. Lumin. 112 449).

  20. Synthesis of Poly(3,4,5-trihydroxybenzoate) dendrimers from Polyphenols and Their Chemiluminescence

    Jung, Dai Il; Song, Ju Hyun; Shin, Eun Hye; Kim, Yun Young; Lee, Do Hun; Choi, Soon Kyu; Hahn, Jung Tai

    2010-01-01

    Polyphenol dendrimers were synthesized to obtain a strong CL compound, and their CL intensities were found to be considerably stronger than the CL intensity of GA. The esterification of the hydroxyl groups of GA in the dendrimer was very effective in developing a strong CL. Further, the relationship between the CL intensity and structure of polyphenol dendrimers must be clarified to understand the reason behind the strong light emission of high-per-branch compounds such as poly(3,4,5-trihydroxybenzoate ester) dendrimers. Polyphenol CL dendrimers can be used for a wide variety of CL assays by utilizing the hydroxyl groups of the polyphenol for forming a hydrogen bond with oxygen in the analyte structure. Dendrimer chemistry is rapidly expanding both for fundamental reasons as well as due to requirements in technological applications. A recent interesting development in dendrimer chemistry concerns the coordination of metal ions by interior branches or exterior units. Dendrimers containing photoactive units are particularly interesting for two reasons: (1) cooperation among the photoactive components can allow the dendrimer to perform specific functions, and (2) changes in the properties of photoactive components can be exploited to monitor the participation of dendrimers in chemical processes

  1. Fabrication of dendrimer-releasing lipidic nanoassembly for cancer drug delivery.

    Sun, Qihang; Ma, Xinpeng; Zhang, Bo; Zhou, Zhuxian; Jin, Erlei; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J; Radosz, Maciej; Sun, Weilin

    2016-06-24

    An inherent dilemma in the use of nanomedicines for cancer drug delivery is their limited penetration into tumors due to their large size. We have demonstrated that dendrimer/lipid nanoassemblies can solve this problem by means of tumor-triggered disassembly and the release of small (several nanometers) dendrimers to facilitate tumor penetration. Herein, we report a general strategy for the fabrication of nanoassemblies from hydrophobic and hydrophilic dendrimers with phospholipids. Hydrophobic dendrimers could assemble with lipids via hydrophobic interactions, whereas hydrophilic dendrimers could only assemble with lipids in the presence of anionic surfactants via both electrostatic and hydrophobic interactions. The nanoassemblies of hydrophobic dendrimers/lipids were found to be capable of stripping off their lipid layers via fusion with the cell membrane and then intracellular or extracellular release of dendrimers, whereas the nanoassemblies of hydrophilic dendrimers/lipids were internalized via endocytosis and then released their dendrimers inside the cells. Therefore, these dendrimer/lipid nanoassemblies could be used for the delivery of different cancer drugs.

  2. Fluorophore:dendrimer ratio impacts cellular uptake and intracellular fluorescence lifetime.

    Dougherty, Casey A; Vaidyanathan, Sriram; Orr, Bradford G; Banaszak Holl, Mark M

    2015-02-18

    G5-NH2-TAMRAn (n = 1-4, 5+, and 1.5(avg)) were prepared with n = 1-4 as a precise dye:dendrimer ratio, 5+ as a mixture of dendrimers with 5 or more dye per dendrimer, and 1.5(avg) as a Poisson distribution of dye:dendrimer ratios with a mean of 1.5 dye per dendrimer. The absorption intensity increased sublinearly with n whereas the fluorescence emission and lifetime decreased with an increasing number of dyes per dendrimer. Flow cytometry was employed to quantify uptake into HEK293A cells. Dendrimers with 2-4 dyes were found to have greater uptake than dendrimer with a single dye. Fluorescence lifetime imaging microscopy (FLIM) showed that the different dye:dendrimer ratio alone was sufficient to change the fluorescence lifetime of the material observed inside cells. We also observed that the lifetime of G5-NH2-TAMRA5+ increased when present in the cell as compared to solution. However, cells treated with G5-NH2-TAMRA1.5(avg) did not exhibit the high lifetime components present in G5-NH2-TAMRA1 and G5-NH2-TAMRA5+. In general, the effects of the dye:dendrimer ratio on fluorescence lifetime were of similar magnitude to environmentally induced lifetime shifts.

  3. Interaction of PAMAM dendrimers with bovine insulin depends on nanoparticle end-groups

    Nowacka, Olga; Milowska, Katarzyna; Bryszewska, Maria

    2015-01-01

    We have looked at the interactions between polyamidoamine (PAMAM) dendrimers with different terminal groups (−COOH, −NH 2 , −OH) and bovine insulin. The influence of PAMAM dendrimers on insulin was tested by measuring zeta potential and fluorescence quenching. The secondary structure of insulin in the presence of dendrimers was examined by circular dichroism. The effect of dendrimers on dithiotreitol-induced aggregation of insulin was investigated by spectrophotometry. Dendrimers quenched the fluorescence of insulin, but did not change its secondary structure. Thus dendrimers neither induce hormone aggregation nor inhibit the aggregation process induced by dithiotreitol (DTT), except at 0.01 µmol/l. Dendrimers–insulin interactions are mainly electrostatic. - Highlight: • The interactions between PAMAM dendrimers and insulin were investigated. • The PAMAM dendrimers can quench the fluorescence of insulin. • The PAMAM dendrimers did not change the secondary structure of insulin. • Dendrimers did not induce aggregation of hormone. • Dendrimers–insulin interaction is mainly electrostatic

  4. Collagen targeting using multivalent protein-functionalized dendrimers

    Breurken, M.; Lempens, E.H.M.; Temming, R.P.; Helms, B.A.; Meijer, E.W.; Merkx, M.

    2011-01-01

    Collagen is an attractive marker for tissue remodeling in a variety of common disease processes. Here we report the preparation of protein dendrimers as multivalent collagen targeting ligands by native chemical ligation of the collagen binding protein CNA35 to cysteine-functionalized dendritic

  5. SANS contrast variation on a dendrimer host-guest complex

    Kleppinger, R.; Mortensen, K.; Meijer, E.W.

    2002-01-01

    Small-angle neutron scattering (SANS) technique was used to study the configurational changes in an oligoethyleneoxy-functionalized poly(propyleneimine) dendrimer (host) when forming complexes with rose bengal (guest). Guinier fits to the scattering data recorded at max. contrast indicated a

  6. Interaction of porphyrins with PAMAM dendrimers in aqueous solution

    Kubát, Pavel; Lang, Kamil; Zelinger, Zdeněk

    2007-01-01

    Roč. 131, - (2007), s. 200-205 ISSN 0167-7322 R&D Projects: GA ČR GA203/04/0426 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z40320502 Keywords : porphyrin * PAMAM dendrimer * aggragation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.982, year: 2007

  7. Charge and energy transports via poly-phenylacetylene based dendrimers

    Shin, Yongwoo; Li, Minghai; Lin, Xi

    2010-03-01

    Poly-Phenylacetylene (PPA) is widely used in photoconductivity, photoluminescence, and light harvesting applications. In this work, we investigate the charge and exciton transport energetics and mechanisms in the PPA-based dendrimers using our recently developed adapted Su-Schrieffer-Heeger (SSH) model Hamiltonians and ab initio Hartree-Fock (HF) calculations. We found both doping and photo-excitation lead to the formation of optical phonon dressed pi electron states, namely the self-localized polarons, in the energy gap. Independent from their origins, these polarons can be self-trapped at multiple lattice locations along the PPA chain, and migrate from one to the next with an activation barrier of ˜0.006 eV, slightly higher than the corresponding barrier found in trans-polyacetylene. The PPA-based dendrimers can be constructed via the meta-positions of phenyl rings. In this case, we found the dendrimer junctions form attractive potential wells for both polarons and excitons, and the width and height of these junction potential wells can be controlled by the geometry of the dendrimers.

  8. Control of mobility in molecular organic semiconductors by dendrimer generation

    Lupton, J. M.; Samuel, I. D.; Beavington, R.; Frampton, M. J.; Burn, P. L.; Bässler, H.

    2001-04-01

    Conjugated dendrimers are of interest as novel materials for light-emitting diodes. They consist of a luminescent chromophore at the core with highly branched conjugated dendron sidegroups. In these materials, light emission occurs from the core and is independent of generation. The dendron branching controls the separation between the chromophores. We present here a family of conjugated dendrimers and investigate the effect of dendron branching on light emission and charge transport. We apply a number of transport measurement techniques to thin films of a conjugated dendrimer in a light-emitting diode configuration to determine the effect of chromophore spacing on charge transport. We find that the mobility is reduced by two orders of magnitude as the size of the molecule doubles with increased branching or dendrimer generation. The degree of branching allows a unique control of mobility by molecular structure. An increase in chromophore separation also results in a reduction of intermolecular interactions, which reduces the red emission tail in film photoluminescence. We find that the steady-state charge transport is well described by a simple device model incorporating the effect of generation, and use the materials to shed light on the interpretation of transient electroluminescence data. We demonstrate the significance of the ability to tune the mobility in bilayer devices, where a more balanced charge transport can be achieved.

  9. Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity

    Monika Dabrzalska

    2017-02-01

    Full Text Available The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer—methylene blue (MB. As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

  10. Dendrimer-coated magnetic particles for radionuclide separation

    Grüttner, Cordula; Böhmer, Volker; Casnati, Alessandro; Dozol, Jean-Francois; Reinhoudt, David; Reinoso garcia, M.M.; Rudershausen, Sandra; Teller, Joachim; Ungaro, Rocco; Verboom, Willem; Wang, Pingshan

    2005-01-01

    Magnetic particles were synthesised for radionuclide removal from nuclear wastes by magnetic separation. Dendrimers with terminal amino groups attached to the particle surface were used to bind chelating groups for lanthanides and actinides. This led to a 50–400-fold increase of the distribution

  11. Exploiting the Physicochemical Properties of Dendritic Polymers for Environmental and Biological Applications

    Bhattacharya, Priyanka; Geitner, Nicholas K.; Sarupria, Sapna; Ke, Pu Chun

    2013-04-07

    In this Perspective we first examine the rich physicochemical properties of dendritic polymers for hosting cations, anions, and polyaromatic hydrocarbons. We then extrapolate these conceptual discussions to the use of dendritic polymers for humic acid antifouling, oil dispersion, copper sensing, and fullerenol remediation. In addition, we review the state-of-the-art of dendrimer research and elaborate on their 10 implications for water purification, environmental remediation, nanomedicine, and energy harvesting.

  12. Dendrimer and an active substance occluded in the dendrimer : a process for the preparation thereof and a process for releasing the active substance

    1998-01-01

    The invention relates to a dendrimer composition in which an effective number of the terminal functionalities are provided with blocking agents, and at least one active substance species is occluded in the dendrimer. A blocking agent is a sufficiently sterically sized compound which readily enters

  13. Host-guest chemistry of dendrimer-drug complexes. 2. Effects of molecular properties of guests and surface functionalities of dendrimers.

    Hu, Jingjing; Cheng, Yiyun; Wu, Qinglin; Zhao, Libo; Xu, Tongwen

    2009-08-06

    The host-guest chemistry of dendrimer-drug complexes is investigated by NMR techniques, including (1)H NMR and 2D-NOESY studies. The effects of molecular properties of drug molecules (protonation ability and spatial steric hindrance of charged groups) and surface functionalities of dendrimers (positively charged amine groups and negatively charged carboxylate groups) on the host-guest interactions are discussed. Different interaction mechanisms between dendrimers and drug molecules are proposed on the basis of NMR results. Primary amine- and secondary amine-containing drugs preferentially bind to negatively charged dendrimers by strong electrostatic interactions, whereas tertiary amine and quaternary ammonium-containing drugs have weak binding ability with dendrimers due to relatively low protonation ability of the tertiary amine group and serious steric hindrance of the quaternary ammonium group. Positively charged drugs locate only on the surface of negatively charged dendrimers, whereas negatively charged drugs locate both on the surface and in the interior cavities of positively charged dendrimers. The host-guest chemistry of dendrimer-drug complexes is promising for the development of new drug delivery systems.

  14. Understanding the Structure-Function Relationships of Dendrimers in Environmental and Biomedical Applications

    Wang, Bo

    We are living an era wherein nanoparticles (NPs) have been widely applied in our lives. Dendrimers are special polymeric NPs with unique physiochemical properties, which have been intensely explored for a variety of applications. Current studies on dendrimers are bottlenecked by insufficient understandings of their structure and dynamic behaviors from a molecular level. With primarily computational approaches supplemented by many other experimental technics, this dissertation aims to establish structure-function relationships of dendrimers in environmental and biomedical applications. More specifically, it thoroughly investigates the interactions between dendrimers and different biomolecules including carbon-based NPs, metal-based NPs, and proteins/peptides. Those results not only provide profound knowledge for evaluating the impacts of dendrimers on environmental and biological systems but also facilitate designing next-generation functional polymeric nanomaterials. The dissertation is organized as following. Chapter 1 provides an overview of current progresses on dendrimer studies, where methodology of Discrete Molecular Dynamics (DMD), my major research tool, is also introduced. Two directions of utilizing dendrimers will be discussed in following chapters. Chapter 2 will focus on environmental applications of dendrimers, where two back-to-back studies are presented. I will start from describing some interesting observations from experiments i.e. dendrimers dispersed model oil molecules. Then, I will reveal why surface chemistries of dendrimers lead to different remediation efficiencies by computational modelings. Finally, I will demonstrate different scenarios of dendrimer-small molecules association. Chapter 3 is centered on dendrimers in the biomedical applications including two subtopics. In the first topic, we will discuss dendrimers as surfactants that modulating the interactions between proteins and NPs. Some fundamental concepts regarding to NPs

  15. Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

    Wang, Jianxin Steven

    The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in

  16. Extremely efficient catalysis of carbon-carbon bond formation using "click" dendrimer-stabilized palladium nanoparticles.

    Astruc, Didier; Ornelas, Cátia; Diallo, Abdou K; Ruiz, Jaime

    2010-07-20

    This article is an account of the work carried out in the authors' laboratory illustrating the usefulness of dendrimer design for nanoparticle palladium catalysis. The "click" synthesis of dendrimers constructed generation by generation by 1-->3 C connectivity, introduces 1,2,3-triazolyl ligands insides the dendrimers at each generation. Complexation of the ligands by Pd(II) followed by reduction to Pd(0) forms dendrimer-stabilized Pd nanoparticles (PdNPs) that are extremely reactive in the catalysis of olefin hydrogenation and C-C bond coupling reactions. The stabilization can be outer-dendritic for the small zeroth-generation dendrimer or intra-dendritic for the larger first- and second-generation dendrimers. The example of the Miyaura-Suzuki reaction that can be catalyzed by down to 1 ppm of PdNPs with a "homeopathic" mechanism (the less, the better) is illustrated here, including catalysis in aqueous solvents.

  17. Interaction of phosphorus dendrimers with HIV peptides—Fluorescence studies of nano-complexes formation

    Ciepluch, Karol, E-mail: ciepluch@biol.uni.lodz.pl [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland); Ionov, Maksim [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland); Majoral, Jean-Pierre [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 Route de Narbonne, F-31077 Toulouse cedex 4 (France); Muñoz-Fernández, Maria Angeles [Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Bryszewska, Maria [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland)

    2014-04-15

    In this study, dendrimers emerge as an alternative approach for delivery of HIV peptides to dendritic cells. Gp160, NH-EIDNYTNTIYTLLEE-COOH; P24, NH-DTINEEAAEW-COOH and Nef, NHGMDDPEREVLEWRFDSRLAF-COOH peptides were complexed with two types of positively charged phosphorus-containing dendrimers (CPD). Fluorescence polarization, dynamic light scattering, transmission and electron microscopy (TEM) techniques were chosen to evaluate the dendriplexes stability. We were able to show that complexes were stable in time and temperature. This is crucial for using these peptide/dendrimer nano-complexes in a new vaccine against HIV-1 infection. -- Highlights: • The phosphorus dendrimers as nanocarriers of HIV-peptides are proposed. • The complexes of dendrimers and HIV-peptides were stable in time, temperature. • The results convince that phosphorus dendrimers could be consider as anti-HIV vaccine candidates.

  18. Interaction of phosphorus dendrimers with HIV peptides—Fluorescence studies of nano-complexes formation

    Ciepluch, Karol; Ionov, Maksim; Majoral, Jean-Pierre; Muñoz-Fernández, Maria Angeles; Bryszewska, Maria

    2014-01-01

    In this study, dendrimers emerge as an alternative approach for delivery of HIV peptides to dendritic cells. Gp160, NH-EIDNYTNTIYTLLEE-COOH; P24, NH-DTINEEAAEW-COOH and Nef, NHGMDDPEREVLEWRFDSRLAF-COOH peptides were complexed with two types of positively charged phosphorus-containing dendrimers (CPD). Fluorescence polarization, dynamic light scattering, transmission and electron microscopy (TEM) techniques were chosen to evaluate the dendriplexes stability. We were able to show that complexes were stable in time and temperature. This is crucial for using these peptide/dendrimer nano-complexes in a new vaccine against HIV-1 infection. -- Highlights: • The phosphorus dendrimers as nanocarriers of HIV-peptides are proposed. • The complexes of dendrimers and HIV-peptides were stable in time, temperature. • The results convince that phosphorus dendrimers could be consider as anti-HIV vaccine candidates

  19. Electrostatic Swelling and Conformational Variation Observed in High-Generation Polyelectrolyte Dendrimers

    Butler, Paul D.; Chen, Wei-Ren; Herwig, Kenneth W.; Hong, Kunlun; Liu, Yun; Porcar, L.; Shew, Chwen-Yang; Smith, Gregory Scott; Chen, Hsin-Lung; Chen, Chun-Yu; Li, Xin; Liu, Emily

    2010-01-01

    A coordinated study combining small angle neutron scattering (SANS) and small angle x-ray scattering (SAXS) measurements was conducted to investigate the structural characteristics of aqueous (D2O) generation 7 and 8 (G7 and G8) PAMAM dendrimer solutions as a function of molecular protonation at room temperature. The change in intra-molecular conformation was clearly exhibited in the data analysis by separating the variation in the inter-molecular correlation. Our results unambiguously demonstrate an increased molecular size and evolved intra-molecular density profile upon increasing the molecular protonation. This is contrary to the existing understanding that in higher generation polyelectrolyte dendrimers, steric crowding stiffens the local motion of dendrimer segments exploring additional available intra-dendrimer volume and therefore inhibits the electrostatic swelling. Our observation is relevant to elucidation of the general microscopic picture of polyelectrolyte dendrimer structure, as well as the development of dendrimer-based packages with based on the stimuli-responsive principle.

  20. pH controlled gating of toxic protein pores by dendrimers

    Mandal, Taraknath; Kanchi, Subbarao; Ayappa, K. G.; Maiti, Prabal K.

    2016-06-01

    Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent bacterial strains, on a target cell membrane is a challenging and active area of research. Here we demonstrate that PAMAM dendrimers can act as effective pH controlled gating devices once the pore has been formed. We have used fully atomistic molecular dynamics (MD) simulations to characterize the cytolysin A (ClyA) protein pores modified with fifth generation (G5) PAMAM dendrimers. Our results show that the PAMAM dendrimer, in either its protonated (P) or non-protonated (NP) states can spontaneously enter the protein lumen. Protonated dendrimers interact strongly with the negatively charged protein pore lumen. As a consequence, P dendrimers assume a more expanded configuration efficiently blocking the pore when compared with the more compact configuration adopted by the neutral NP dendrimers creating a greater void space for the passage of water and ions. To quantify the effective blockage of the protein pore, we have calculated the pore conductance as well as the residence times by applying a weak force on the ions/water. Ionic currents are reduced by 91% for the P dendrimers and 31% for the NP dendrimers. The preferential binding of Cl- counter ions to the P dendrimer creates a zone of high Cl- concentration in the vicinity of the internalized dendrimer and a high concentration of K+ ions in the transmembrane region of the pore lumen. In addition to steric effects, this induced charge segregation for the P dendrimer effectively blocks ionic transport through the pore. Our investigation shows that the bio-compatible PAMAM dendrimers can potentially be used to develop therapeutic protocols based on the pH sensitive gating of pores formed by pore forming toxins to mitigate bacterial infections.Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent

  1. Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

    L. Fernández

    2011-12-01

    Full Text Available The improvement of aqueous solubility of methyl (5-[propylthio]-1H-benzimidazol-2-yl carbamate, albendazole (ABZ using polyamidoamine (PAMAM dendrimers as solubility enhancers was investigated. Full generation PAMAM dendrimers with amine terminal groups, (G3, with hydroxyl terminal groups (G3OH and half generation PAMAM dendrimers with carboxylate terminal groups (G2.5 and G3.5, were chosen for this study. The nature of dendrimer-ABZ association was investigated by UV absorption, fluorescence emission measurements and by ¹H-NMR spectroscopy. The results obtained show that these polymeric structures have the capacity to enhance the solubility of ABZ, both lipophilic and specific hydrogen bond interactions contributing to the guest-host association. Although all studied dendrimers have hydrophobic internal nanoenvironments with similar dimensions, their surfaces differ significantly and the nature and the localization of the interactions involved in ABZ-dendrimer association depend on the type of terminal groups.

  2. Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

    Fernandez, L.; Sigal, E.; Santo, M.; Otero, L.; Silber, J. J.

    2011-01-01

    The improvement of aqueous solubility of methyl (5-[propylthio]-1H-benzimidazole-2-yl) carbamate, albendazole (ABZ) using polyamidoamine (PAMAM) dendrimers as solubility enhancers was investigated. Full generation PAMAM dendrimers with amine terminal groups, (G3), with hydroxyl terminal groups (G3OH) and half generation PAMAM dendrimers with carboxylate terminal groups (G2.5 and G3.5), were chosen for this study. The nature of dendrimer-ABZ association was investigated by UV absorption, fluorescence emission measurements and by 1 H-NMR spectroscopy. The results obtained show that these polymeric structures have the capacity to enhance the solubility of ABZ, both lipophilic and specific hydrogen bond interactions contributing to the guest-host association. Although all studied dendrimers have hydrophobic internal nanoenvironments with similar dimensions, their surfaces differ significantly and the nature and the localization of the interactions involved in ABZ-dendrimer association depend on the type of terminal groups. (author)

  3. Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

    Fernandez, L.; Sigal, E.; Santo, M., E-mail: msanto@exa.unrc.edu.ar [Departamento de Fisica, Facultad de Ciencias Exactas Fisicoquimicas y Naturales, Universidad Nacional de Rio Cuarto (Argentina); Otero, L.; Silber, J. J. [Departamento de Quimica. Facultad de Ciencias Exactas Fisicoquimicas y Naturales, Universidad Nacional de Rio Cuarto, Rio Cuarto (Argentina)

    2011-10-15

    The improvement of aqueous solubility of methyl (5-[propylthio]-1H-benzimidazole-2-yl) carbamate, albendazole (ABZ) using polyamidoamine (PAMAM) dendrimers as solubility enhancers was investigated. Full generation PAMAM dendrimers with amine terminal groups, (G3), with hydroxyl terminal groups (G3OH) and half generation PAMAM dendrimers with carboxylate terminal groups (G2.5 and G3.5), were chosen for this study. The nature of dendrimer-ABZ association was investigated by UV absorption, fluorescence emission measurements and by {sup 1}H-NMR spectroscopy. The results obtained show that these polymeric structures have the capacity to enhance the solubility of ABZ, both lipophilic and specific hydrogen bond interactions contributing to the guest-host association. Although all studied dendrimers have hydrophobic internal nanoenvironments with similar dimensions, their surfaces differ significantly and the nature and the localization of the interactions involved in ABZ-dendrimer association depend on the type of terminal groups. (author)

  4. Short- and long-term cytotoxic effects of doxorubicin conjugates with dendrimers and vector protein on MCF-7/MDR1 chemoresistant breast cancer cells

    Zamulaeva, I. A.; Matchuk, O. N.; Churyukina, K. A.; Kudryavtzev, V. A.; Yabbarov, N. G.; Nikolskaya, E. D.; Zhunina, O. A.; Kondrasheva, I. G.; Severin, E. S.

    2017-09-01

    The dendritic polymers (dendrimers) are perspective nanocontainers for targeted transport of anticancer drugs to tumor cells. We used polyamidoamine dendrimers of the second generation (G2) covalently conjugated with doxorubicin (Dox) and vector protein - recombinant third domain (3D) of alpha-fetoprotein. The objects of the study were MCF-7/MDR1 breast cancer cells, which demonstrated resistance to traditional anticancer agents due to high expression of P-glycoprotein. Effects of free Dox, G2 dendrimers loaded with Dox (G2-Dox), or conjugates of dendrimers with the vector protein and Dox (3D-G2-Dox) were assessed by the criteria of surviving cell number and clonogenic activity 24 hours and 11 days after treatment with the agents at Dox concentration of 2.5 μM, correspondingly. Flow cytometry was used to evaluate accumulation of Dox immediately after the treatment with the agents and removal of Dox during 24 hours of incubation in agent-free medium following by the treatment. Intracellular localization of Dox was studied using laser scanning microscopy. 3D-G2-Dox demonstrated the highest accumulation and the weakest removal from the cells in comparison with all other agents. The use of free Dox, G2-Dox, or 3D-G2-Dox resulted in a significant decrease in number of surviving cells by approximately 25-30% compared to the control (p ≤ 0.01). However, the most pronounced decrease in the clonogenic ability of cells was observed in the 3D-G2-Dox group (to 19% compared to the control, p < 0.01). Taking into account the previously obtained data on the extremely low 3D-G2-Dox accumulation in normal cells, it can be concluded that further development of 3D-G2-Dox as a possible anticancer drug is a promising way to overcome multiple drug resistance with minimal impact on normal cells.

  5. Substrate-Triggered Exosite Binding: Synergistic Dendrimer/Folic Acid Action for Achieving Specific, Tight-Binding to Folate Binding Protein.

    Chen, Junjie; van Dongen, Mallory A; Merzel, Rachel L; Dougherty, Casey A; Orr, Bradford G; Kanduluru, Ananda Kumar; Low, Philip S; Marsh, E Neil G; Banaszak Holl, Mark M

    2016-03-14

    Polymer-ligand conjugates are designed to bind proteins for applications as drugs, imaging agents, and transport scaffolds. In this work, we demonstrate a folic acid (FA)-triggered exosite binding of a generation five poly(amidoamine) (G5 PAMAM) dendrimer scaffold to bovine folate binding protein (bFBP). The protein exosite is a secondary binding site on the protein surface, separate from the FA binding pocket, to which the dendrimer binds. Exosite binding is required to achieve the greatly enhanced binding constants and protein structural change observed in this study. The G5Ac-COG-FA1.0 conjugate bound tightly to bFBP, was not displaced by a 28-fold excess of FA, and quenched roughly 80% of the initial fluorescence. Two-step binding kinetics were measured using the intrinsic fluorescence of the FBP tryptophan residues to give a KD in the low nanomolar range for formation of the initial G5Ac-COG-FA1.0/FBP* complex, and a slow conversion to the tight complex formed between the dendrimer and the FBP exosite. The extent of quenching was sensitive to the choice of FA-dendrimer linker chemistry. Direct amide conjugation of FA to G5-PAMAM resulted in roughly 50% fluorescence quenching of the FBP. The G5Ac-COG-FA, which has a longer linker containing a 1,2,3-triazole ring, exhibited an ∼80% fluorescence quenching. The binding of the G5Ac-COG-FA1.0 conjugate was compared to poly(ethylene glycol) (PEG) conjugates of FA (PEGn-FA). PEG2k-FA had a binding strength similar to that of FA, whereas other PEG conjugates with higher molecular weight showed weaker binding. However, no PEG conjugates gave an increased degree of total fluorescence quenching.

  6. In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates

    Mohammad Najlah

    2017-10-01

    Full Text Available The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM dendrimers as drug carriers of naproxen (NAP, a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L, a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen.

  7. RNA secondary structures in a polymer-zeta model how foldings should be shaped for sparsification to establish a linear speedup

    Jin, Emma Yu; Nebel, M. E.

    2016-01-01

    that the corresponding conditional probabilities behave according to a polymer-zeta probability model. We show that even if some of the structural parameters exhibit an almost realistic behavior on average, the expected shape of a folding in that model must be assumed to highly differ from those observed in nature. More...... sparsification) may reduce the runtime to n2 on average, assuming that nucleotides of distance d form a hydrogen bond (i.e. are paired) with probability (Formula Presented.) for some constants b > 0, c > 1. The latter is called the polymer-zeta model and plays a crucial role in speeding up the above mentioned...... algorithm. In this paper we discuss the application of the polymer-zeta property for the analysis of sparsification, showing that it must be applied conditionally on first and last positions to pair. Afterwards, we will investigate the combinatorics of RNA secondary structures assuming...

  8. Quantitative assessment of surface functionality effects on microglial uptake and retention of PAMAM dendrimers

    Liaw, Kevin; Gök, Ozgul; DeRidder, Louis B.; Kannan, Sujatha; Kannan, Rangaramanujam M.

    2018-04-01

    Dendrimers are a promising class of polymeric nanoparticles for delivery of therapeutics and diagnostics. Polyamidoamine (PAMAM) dendrimers have shown significant efficacy in many animal models, with performance dependent on surface functionalities. Understanding the effects of end groups on biological interactions is critical for rational design of dendrimer-mediated therapies. In this study, we quantify the cellular trafficking kinetics (endocytosis and exocytosis) of generation 4 neutral (D4-OH), cationic (D4-NH2), anionic (D3.5-COOH), and generation 6 neutral (D6-OH) PAMAM dendrimers to investigate the nanoscale effects of surface functionality and size on cellular interactions. Resting and LPS-activated microglia were studied due to their central roles in dendrimer therapies for central nervous system disorders. D4-OH exhibits greater cellular uptake and lower retention than the larger D6-OH. D4-OH and D3.5-COOH exhibit similar trafficking kinetics, while D4-NH2 exhibits significant membrane interactions, resulting in faster cell association but lower internalization. Cationic charge may also enhance vesicular escape for greater cellular retention and preferential partitioning to nuclei. LPS activation further improves uptake of dendrimers, with smaller and cationic dendrimers experiencing the greatest increases in uptake compared to resting microglia. These studies have implications for the dependence of trafficking pathway on dendrimer properties and inform the design of dendrimer constructs tailored to specific therapeutic needs. Cationic dendrimers are ideal for delivering genetic materials to nuclei, but toxicity may be a limiting factor. Smaller, neutral dendrimers are best suited for delivering high levels of therapeutics in acute neuroinflammation, while larger or cationic dendrimers provide robust retention for sustained release of therapeutics in longer-term diseases.

  9. Surface, core, and structure modifications of phosphorus-containing dendrimers. Influence on the thermal stability

    Turrin , Cédric-Olivier; Maraval , Valérie; Leclaire , Julien; Dantras , Eric; Lacabanne , Colette; Caminade , Anne-Marie; Majoral , Jean-Pierre

    2003-01-01

    International audience; Three new series of phosphorus-containing dendrimers are described. Their solubility depends on the type of end groups they bear. Perfluoroalkyl chains give dendrimers soluble in chlorofluorocarbons, whereas guanidinium and pyridinium derivatives give watersoluble compounds. The thermal stability of these compounds, as well as of 19 other dendrimers of various generations, having various cores, or various end groups, or branching points is studied. The main feature of ...

  10. Switching the selectivity of a polyglycerol dendrimer monomolecularly imprinted with D-(−)-fructose

    Hashidzume, Akihito; Zimmerman, Steven C.

    2009-01-01

    A polyglycerol dendrimer unimolecularly imprinted with D-(−)-fructose (Fru) was synthesized. The dendrimer formed adducts with several monosaccharides, Fru, D-(+)-galactose, D-(+)-glucose, D-(+)-mannose, and methyl-α-D-mannopyranoside (MMan), by removal of four water molecules. The dendrimer preferred Fru in the absence of N,N,N′,N′-tetramethylmethylenediamine (TMDAM), whereas it preferred MMan in the presence of TMDAM.

  11. Characterization of an engineered cellulose based membrane by thiol dendrimer for heavy metals removal

    Algarra, Manuel; Vázquez, María Isabel; Alonso, Beatriz S.; Casado, Carmen Mª.; Casado, Juan; Benavente, Juana

    2014-01-01

    Diaminobutane based poly(propyleneimine) dendrimer functionalized with sixteen thiol groups, DAB-3-(SH)16, was successfully embeded in a swollen cellulosic support in order to achieve an easily handle engineered membrane. The membrane was characterised by physicochemical, electrical and transport measurements, and the effect of the dendrimer was established by comparing these results with those obtained for the original cellulosic support. Results show that dendrimer inclusion improves the me...

  12. Trapping time statistics and efficiency of transport of optical excitations in dendrimers

    Heijs, D.J.; Malyshev, V.A.; Knoester, J.

    2004-01-01

    We theoretically study the trapping time distribution and the efficiency of the excitation energy transport in dendritic systems. Trapping of excitations, created at the periphery of the dendrimer, on a trap located at its core, is used as a probe of the efficiency of the energy transport across the dendrimer. The transport process is treated as incoherent hopping of excitations between nearest-neighbor dendrimer units and is described using a rate equation. We account for radiative and non-r...

  13. Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications.

    Esfand, R; Tomalia, D A.

    2001-04-01

    Poly(amidoamine) (PAMAM) dendrimers are the first complete dendrimer family to be synthesized, characterized and commercialized. Based on this extensive activity, they are recognized as a unique new class of synthetic nanostructures. Dendrimers allow the precise control of size, shape and placement of functional groups that is desirable for many life science applications. From this perspective, this review focuses on crucial properties of biomimetic dendrimers that will broaden the potential for their use as macromolecular vectors in novel drug delivery and biomedical applications.

  14. Magnetic properties of dendrimer structures with different coordination numbers: A Monte Carlo study

    Masrour, R.; Jabar, A.

    2016-01-01

    We investigate the magnetic properties of Cayley trees of large molecules with dendrimer structure using Monte Carlo simulations. The thermal magnetization and magnetic susceptibility of a dendrimer structure are given with different coordination numbers, Z=3, 4, 5 and different generations g=3 and 2. The variation of magnetizations with the exchange interactions and crystal fields have been given of this system. The magnetic hysteresis cycles have been established. - Highlights: • The dendrimer structure is investigated using Monte Carlo simulations. • The transition temperatures are obtained for different coordination numbers and generations. • The magnetic hysteresis cycle has been established. • The dendrimer structure exhibit the superparamagnetic behavior.

  15. Effect of solvent-controlled aggregation on the intrinsic emission properties of PAMAM dendrimers

    Jasmine, Maria J.; Kavitha, Manniledam; Prasad, Edamana

    2009-01-01

    Solvent-induced aggregation and its effect on the intrinsic emission properties of amine, hydroxy and carboxylate terminated, poly(amidoamine) (PAMAM) dendrimers have been investigated in glycerol, ethylene glycol, methanol, ethylene diamine and water. Altering the solvent medium induces remarkable changes in the intrinsic emission properties of the PAMAM dendrimers at identical concentration. Upon excitation at 370 nm, amine terminated PAMAM dendrimer exhibits an intense emission at 470 nm in glycerol, ethylene glycol as well as glycerol-water mixtures. Conversely, weak luminescence is observed for hydroxy and carboxylate terminated PAMAM dendrimers in the same solvent systems. When the solvent is changed to ethylene diamine, hydroxy terminated PAMAM exhibits intense blue emission at 425 nm. While the emission intensity is varied when the solvent milieu is changed, excited state lifetime values of PAMAM dendrimers remain independent of the solvent used. UV-visible absorption and dynamic light scattering (DLS) experiments confirm the formation of solvent-controlled dendrimer aggregates in the systems. Comparison of the fluorescence and DLS data reveals that the size distribution of the dendrimer aggregates in each solvent system is distinct, which control the intrinsic emission intensity from PAMAM dendrimers. The experimental results suggest that intrinsic emission intensity from PAMAM dendrimers can be regulated by proper selection of solvents at neutral conditions and room temperature

  16. Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement.

    Shadrack, Daniel M; Mubofu, Egid B; Nyandoro, Stephen S

    2015-11-04

    The biomedical potential of flavonoids is normally restricted by their low water solubility. However, little has been reported on their encapsulation into polyamidoamine (PAMAM) dendrimers to improve their biomedical applications. Generation four (G4) PAMAM dendrimer containing ethylenediaminetetraacetic acid core with acrylic acid and ethylenediamine as repeating units was synthesized by divergent approach and used to encapsulate a flavonoid tetramethylscutellarein (TMScu, 1) to study its solubility and in vitro release for potential bioactivity enhancement. The as-synthesized dendrimer and the dendrimer-TMScu complex were characterized by spectroscopic and spectrometric techniques. The encapsulation of 1 into dendrimer was achieved by a co-precipitation method with the encapsulation efficiency of 77.8% ± 0.69% and a loading capacity of 6.2% ± 0.06%. A phase solubility diagram indicated an increased water solubility of 1 as a function of dendrimer concentration at pH 4.0 and 7.2. In vitro release of 1 from its dendrimer complex indicated high percentage release at pH 4.0. The stability study of the TMScu-dendrimer at 0, 27 and 40 °C showed the formulations to be stable when stored in cool and dark conditions compared to those stored in light and warmer temperatures. Overall, PAMAM dendrimer-G4 is capable of encapsulating 1, increasing its solubility and thus could enhance its bioactivity.

  17. Optimization of dendrimer structure for sentinel lymph node imaging: Effects of generation and terminal group.

    Niki, Yuichiro; Ogawa, Mikako; Makiura, Rie; Magata, Yasuhiro; Kojima, Chie

    2015-11-01

    The detection of the sentinel lymph node (SLN), the first lymph node draining tumor cells, is important in cancer diagnosis and therapy. Dendrimers are synthetic macromolecules with highly controllable structures, and are potent multifunctional imaging agents. In this study, 12 types of dendrimer of different generations (G2, G4, G6, and G8) and different terminal groups (amino, carboxyl, and acetyl) were prepared to determine the optimal dendrimer structure for SLN imaging. Radiolabeled dendrimers were intradermally administrated to the right footpads of rats. All G2 dendrimers were predominantly accumulated in the kidney. Amino-terminal, acetyl-terminal, and carboxyl-terminal dendrimers of greater than G4 were mostly located at the injection site, in the blood, and in the SLN, respectively. The carboxyl-terminal dendrimers were largely unrecognized by macrophages and T-cells in the SLN. Finally, SLN detection was successfully performed by single photon emission computed tomography imaging using carboxyl-terminal dendrimers of greater than G4. The early detection of tumor cells in the sentinel draining lymph nodes (SLN) is of utmost importance in terms of determining cancer prognosis and devising treatment. In this article, the authors investigated various formulations of dendrimers to determine the optimal one for tumor detection. The data generated from this study would help clinicians to fight the cancer battle in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Magnetic properties of dendrimer structures with different coordination numbers: A Monte Carlo study

    Masrour, R., E-mail: rachidmasrour@hotmail.com; Jabar, A.

    2016-11-01

    We investigate the magnetic properties of Cayley trees of large molecules with dendrimer structure using Monte Carlo simulations. The thermal magnetization and magnetic susceptibility of a dendrimer structure are given with different coordination numbers, Z=3, 4, 5 and different generations g=3 and 2. The variation of magnetizations with the exchange interactions and crystal fields have been given of this system. The magnetic hysteresis cycles have been established. - Highlights: • The dendrimer structure is investigated using Monte Carlo simulations. • The transition temperatures are obtained for different coordination numbers and generations. • The magnetic hysteresis cycle has been established. • The dendrimer structure exhibit the superparamagnetic behavior.

  19. Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review

    Liu, Jie; Gray, Warren D.; Davis, Michael E.; Luo, Ying

    2012-01-01

    Dendrimers comprise a category of branched materials with diverse functions that can be constructed with defined architectural and chemical structures. When decorated with bioactive ligands made of peptides and saccharides through peripheral chemical groups, dendrimer conjugates are turned into nanomaterials possessing attractive binding properties with the cognate receptors. At the cellular level, bioactive dendrimer conjugates can interact with cells with avidity and selectivity, and this function has particularly stimulated interests in investigating the targeting potential of dendrimer materials for the design of drug delivery systems. In addition, bioactive dendrimer conjugates have so far been studied for their versatile capabilities to enhance stability, solubility and absorption of various types of therapeutics. This review presents a brief discussion on three aspects of the recent studies to use peptide- and saccharide-conjugated dendrimers for drug delivery: (i) synthesis methods, (ii) cell- and tissue-targeting properties and (iii) applications of conjugated dendrimers in drug delivery nanodevices. With more studies to elucidate the structure–function relationship of ligand–dendrimer conjugates in transporting drugs, the conjugated dendrimers hold promise to facilitate targeted delivery and improve drug efficacy for discovery and development of modern pharmaceutics. PMID:23741608

  20. Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.

    Sadekar, S; Ghandehari, H

    2012-05-01

    This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer-drug conjugates, as a function of physicochemical properties will further need to be assessed. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

    Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

    2013-09-01

    Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH2 and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was 11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC50 values in ovarian cancer cells when compared with carboxylate surface dendrimers ( p cisplatin complexes resulted in a 7.0-fold increase ( p cisplatin chemotherapy of ovarian cancer.

  2. Polymer nanocomposites: polymer and particle dynamics

    Kim, Daniel

    2012-01-01

    Polymer nanocomposites containing nanoparticles smaller than the random coil size of their host polymer chains are known to exhibit unique properties, such as lower viscosity and glass transition temperature relative to the neat polymer melt. It has been hypothesized that these unusual properties result from fast diffusion of the nanostructures in the host polymer, which facilitates polymer chain relaxation by constraint release and other processes. In this study, the effects of addition of sterically stabilized inorganic nanoparticles to entangled cis-1,4-polyisoprene and polydimethylsiloxane on the overall rheology of nanocomposites are discussed. In addition, insights about the relaxation of the host polymer chains and transport properties of nanoparticles in entangled polymer nanocomposites are presented. The nanoparticles are found to act as effective plasticizers for their entangled linear hosts, and below a critical, chemistry and molecular-weight dependent particle volume fraction, lead to reduced viscosity, glass transition temperature, number of entanglements, and polymer relaxation time. We also find that the particle motions in the polymer host are hyperdiffusive and at the nanoparticle length scale, the polymer host acts like a simple, ideal fluid and the composites\\' viscosity rises with increasing particle concentration. © 2012 The Royal Society of Chemistry.

  3. Particle emission from polymer-doped water ice matrices induced by non-linear absorption of laser light at 1064 nm

    Purice, A.; Schou, Jørgen; Dinescu, M.

    2006-01-01

    Emission of PEG (polyethylene glycol) molecules and ions from an ice target induced by laser irradiation in the infrared (IR) regime at 1064 nm was studied. Matrices of 1 wt% PEG flash-frozen solutions were used for polymer deposition with MAPLE (matrix assisted pulsed laser evaporation). Even...

  4. Synthesis and characterization of polyglycerols dendrimers for applications in tissue engineering biological

    Passos, E.D.; Queiroz, A.A.A. de [Universidade Federal de Itajuba (UNIFEI), MG (Brazil)

    2014-07-01

    Full text: Introduction: Over the last twenty years is the growing development in the manufacture of synthetic scaffold in tissue engineering applications. These new materials are based on polyglycerol dendrimers (PGLD's). PGLD's are highly functional polymers with hydroxymethyl side groups, fulfill all structural prerequisites to replace poly(ethylene glycol)s in medical applications. Furthermore, since these materials are based on naturally occurring compounds that degrades over time in the body and can be safely excreted. The objective of this work was the synthesis, physicochemical, biological characterization of HPGL's with potential use as scaffolds in tissue engineering. HPGL's with oligomeric cores, of diglycerol triglycerol and tetraglycerol was used. Theoretical and Experimental Simulation Details: The synthesis of PGLD procedures involves the etherification of glycerol through anionic polymerization of glycidol. The PGLD's were characterized by chromatographic techniques (SEC and HPLC), spectroscopic (FTIR, 1H-NMR and 13C - NMR) electrochemical (zeta potential) and thermal analysis (DSC and TGA) techniques. The structure- activity relationships (SAR's) of compound prototype and its analogs were studied to determine the generation number (G) of the molecule responsible for the biological activity on the adhesion and cell proliferation process. A detailed study of the structure of PGLD's of G=0-4 was performed using the Hyperchem 7. 5 and Gromacs 4 software packages. The biocompatibility studies were studied by scanning electron microscopy (SEM) and fluorescence microscopy (EPF) technique after PGLD (G=0-4) blood contact. The overall electro-negativity/total charge density, dipole moment, frontier orbital's (HOMO - LUMO) and electrostatic potential maps (EPM) were calculated. The most stable form of the resulting compounds was determined by estimating the hydration energy and energy conformation. Results and

  5. Methotrexate loaded polyether-copolyester dendrimers for the treatment of gliomas: enhanced efficacy and intratumoral transport capability.

    Dhanikula, Renu Singh; Argaw, Anteneh; Bouchard, Jean-Francois; Hildgen, Patrice

    2008-01-01

    Therapeutic benefit in glial tumors is often limited due to low permeability of delivery systems across the blood-brain barrier (BBB), drug resistance, and poor penetration into the tumor tissue. In an attempt to overcome these hurdles, polyether-copolyester (PEPE) dendrimers were evaluated as drug carriers for the treatment of gliomas. Dendrimers were conjugated to d-glucosamine as the ligand for enhancing BBB permeability and tumor targeting. The efficacy of methotrexate (MTX)-loaded dendrimers was established against U87 MG and U 343 MGa cells. Permeability of rhodamine-labeled dendrimers and MTX-loaded dendrimers across the in vitro BBB model and their distribution into avascular human glioma tumor spheroids was also studied. Glucosylated dendrimers were found to be endocytosed in significantly higher amounts than nonglucosylated dendrimers by both the cell lines. IC 50 of MTX after loading in dendrimers was lower than that of the free MTX, suggesting that loading MTX in PEPE dendrimers increased its potency. Similar higher activity of MTX-loaded glucosylated and nonglucosylated dendrimers was found in the reduction of tumor spheroid size. These MTX-loaded dendrimers were able to kill even MTX-resistant cells highlighting their ability to overcome MTX resistance. In addition, the amount of MTX-transported across BBB was three to five times more after loading in the dendrimers. Glucosylation further increased the cumulative permeation of dendrimers across BBB and hence increased the amount of MTX available across it. Glucosylated dendrimers distributed through out the avascular tumor spheroids within 6 h, while nonglucosylated dendrimers could do so in 12 h. The results show that glucosamine can be used as an effective ligand not only for targeting glial tumors but also for enhanced permeability across BBB. Thus, glucosylated PEPE dendrimers can serve as potential delivery system for the treatment of gliomas.

  6. Transcorneal iontophoresis of dendrimers: PAMAM corneal penetration and dexamethasone delivery.

    Souza, Joel G; Dias, Karina; Silva, Silas A M; de Rezende, Lucas C D; Rocha, Eduardo M; Emery, Flavio S; Lopez, Renata F V

    2015-02-28

    Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain therapeutic concentrations. Fourth generation polyamidoamine (PAMAM) dendrimers are semi-rigid nanoparticles with surface groups that are easily modified. These dendrimers are known to modulate tight junctions, increase paracellular transport of small molecules and be translocated across epithelial barriers, exhibiting high uptake by different cell lines. The first aim of this study was to investigate the effect of iontophoresis on PAMAM penetration and distribution into the cornea. The second aim was to evaluate, ex vivo and in vivo, the effect of these dendrimers in dexamethasone (Dex) transcorneal iontophoresis. Anionic (PAMAM G3.5) and cationic (PAMAM G4) dendrimers were labeled with fluorescein isothiocyanate (FITC), and their distribution in the cornea was investigated using confocal microscopy after ex vivo anodal and cathodal iontophoresis for various application times. The particle size distribution and zeta potential of the dendrimers in an isosmotic solution were determined using dynamic light scattering and Nanoparticle Tracking Analysis (NTA), where the movement of small particles and the formation of large aggregates, from 5 to 100 nm, could be observed. Transcorneal iontophoresis increased the intensity and depth of PAMAM-FITC fluorescence in the cornea, suggesting improved transport of the dendrimers across the epithelium toward the stroma. PAMAM complexes with Dex were characterized by (13)C-NMR, (1)H-NMR and DOSY. PAMAM G3.5 and PAMAM G4 increased the aqueous solubility of Dex by 10.3 and 3.9-fold, respectively; however, the particle size distribution and zeta potential remained unchanged. PAMAM G3.5 decreased the Dex diffusion coefficient 48-fold compared with PAMAM G4. The ex vivo studies showed that iontophoresis increased the amount of Dex that penetrated into the cornea by 2.9, 5.6 and 3.0-fold for Dex, Dex-PAMAM G4 and Dex-PAMAM G3

  7. Polymer containing functional end groups is base for new polymers

    Hirshfield, S. M.

    1971-01-01

    Butadiene is polymerized with lithium-p-lithiophenoxide to produce linear polymer containing oxy-lithium group at one end and active carbon-lithium group at other end. Living polymers represent new approach to preparation of difunctional polymers in which structural features, molecular weight, type and number of end groups are controlled.

  8. In Silico Characterization of the Binding Affinity of Dendrimers to Penicillin-Binding Proteins (PBPs): Can PBPs be Potential Targets for Antibacterial Dendrimers?

    Ahmed, Shaimaa; Vepuri, Suresh B; Ramesh, Muthusamy; Kalhapure, Rahul; Suleman, Nadia; Govender, Thirumala

    2016-04-01

    We have shown that novel silver salts of poly (propyl ether) imine (PETIM) dendron and dendrimers developed in our group exhibit preferential antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus. This led us to examine whether molecular modeling methods could be used to identify the key structural design principles for a bioactive lead molecule, explore the mechanism of binding with biological targets, and explain their preferential antibacterial activity. The current article reports the conformational landscape as well as mechanism of binding of generation 1 PETIM dendron and dendrimers to penicillin-binding proteins (PBPs) in order to understand the antibacterial activity profiles of their silver salts. Molecular dynamics at different simulation protocols and conformational analysis were performed to elaborate on the conformational features of the studied dendrimers, as well as to create the initial structure for further binding studies. The results showed that for all compounds, there were no significant conformational changes due to variation in simulation conditions. Molecular docking calculations were performed to investigate the binding theme between the studied dendrimers and PBPs. Interestingly, in significant accordance with the experimental data, dendron and dendrimer with aliphatic cores were found to show higher activity against S. aureus than the dendrimer with an aromatic core. The latter showed higher activity against MRSA. The findings from this computational and molecular modeling report together with the experimental results serve as a road map toward designing more potent antibacterial dendrimers against resistant bacterial strains.

  9. Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

    Pryor JB

    2014-04-01

    Full Text Available Joseph B Pryor,1 Bryan J Harper,1 Stacey L Harper1,21Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA; 2School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR, USAAbstract: Dendrimers are well-defined, polymeric nanomaterials currently being investigated for biomedical applications such as medical imaging, gene therapy, and tissue targeted therapy. Initially, higher generation (size dendrimers were of interest because of their drug carrying capacity. However, increased generation was associated with increased toxicity. The majority of studies exploring dendrimer toxicity have focused on a small range of materials using cell culture methods, with few studies investigating the toxicity across a wide range of materials in vivo. The objective of the present study was to investigate the role of surface charge and generation in dendrimer toxicity using embryonic zebrafish (Danio rerio as a model vertebrate. Due to the generational and charge effects observed at the cellular level, higher generation cationic dendrimers were hypothesized to be more toxic than lower generation anionic or neutral dendrimers with the same core composition. Polyamidoamine (PAMAM dendrimers elicited significant morbidity and mortality as generation was decreased. No significant adverse effects were observed from the suite of thiophosphoryl dendrimers studied. Exposure to ≥50 ppm cationic PAMAM dendrimers G3-amine, G4-amine, G5-amine, and G6-amine caused 100% mortality by 24 hours post-fertilization. Cationic PAMAM G6-amine at 250 ppm was found to be statistically more toxic than both neutral PAMAM G6-amidoethanol and anionic PAMAM G6-succinamic acid at the same concentration. The toxicity observed within the suite of varying dendrimers provides evidence that surface charge may be the best indicator of dendrimer toxicity. Dendrimer class and generation are other potential

  10. RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells.

    He, Xuedan; Alves, Carla S; Oliveira, Nilsa; Rodrigues, João; Zhu, Jingyi; Bányai, István; Tomás, Helena; Shi, Xiangyang

    2015-01-01

    Development of multifunctional nanoscale drug-delivery systems for targeted cancer therapy still remains a great challenge. Here, we report the synthesis of cyclic arginine-glycine-aspartic acid (RGD) peptide-conjugated generation 5 (G5) poly(amidoamine) dendrimers for anticancer drug encapsulation and targeted therapy of cancer cells overexpressing αvβ3 integrins. In this study, amine-terminated G5 dendrimers were used as a platform to be sequentially modified with fluorescein isothiocyanate (FI) via a thiourea linkage and RGD peptide via a polyethylene glycol (PEG) spacer, followed by acetylation of the remaining dendrimer terminal amines. The developed multifunctional dendrimer platform (G5.NHAc-FI-PEG-RGD) was then used to encapsulate an anticancer drug doxorubicin (DOX). We show that approximately six DOX molecules are able to be encapsulated within each dendrimer platform. The formed complexes are water-soluble, stable, and able to release DOX in a sustained manner. One- and two-dimensional NMR techniques were applied to investigate the interaction between dendrimers and DOX, and the impact of the environmental pH on the release rate of DOX from the dendrimer/DOX complexes was also explored. Furthermore, cell biological studies demonstrate that the encapsulation of DOX within the G5.NHAc-FI-PEG-RGD dendrimers does not compromise the anticancer activity of DOX and that the therapeutic efficacy of the dendrimer/DOX complexes is solely related to the encapsulated DOX drug. Importantly, thanks to the role played by RGD-mediated targeting, the developed dendrimer/drug complexes are able to specifically target αvβ3 integrin-overexpressing cancer cells and display specific therapeutic efficacy to the target cells. The developed RGD peptide-targeted multifunctional dendrimers may thus be used as a versatile platform for targeted therapy of different types of αvβ3 integrin-overexpressing cancer cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Polyamidoamine dendrimer-based binders for high-loading lithium–sulfur battery cathodes

    Bhattacharya, Priyanka; Nandasiri, Manjula I.; Lv, Dongping; Schwarz, Ashleigh M.; Darsell, Jens T.; Henderson, Wesley A.; Tomalia, Donald A.; Liu, Jun; Zhang, Ji-Guang; Xiao, Jie

    2016-01-01

    Lithium-sulfur (Li-S) batteries are regarded as one of the most promising candidates for next generation energy storage systems because of their ultra high theoretical specific energy. To realize the practical application of Li-S batteries, however, a high S active material loading is essential (>70 wt% in the carbon-sulfur (C-S) composite cathode and >2 mg cm-2 in the electrode). A critical challenge to achieving this high capacity in practical electrodes is the dissolution of the longer lithium polysulfide reaction intermediates in the electrolyte (resulting in loss of active material from the cathode and contamination of the anode due to the polysulfide shuttle mechanism). The binder material used for the cathode is therefore crucial as this is a key determinant of the bonding interactions between the active material (S) and electronic conducting support (C), as well as the maintenance of intimate contact between the electrode materials and current collector. The battery performance can thus be directly correlated with the choice of binder, but this has received only minimal attention in the relevant Li-S battery published literature. Here, we investigated the application of polyamidoamine (PAMAM) dendrimers as functional binders in Li-S batteries—a class of materials which has been unexplored for electrode design. By using dendrimers, it is demonstrated that high S loadings (>4 mg cm-2) can be easily achieved using "standard" (not specifically tailored) materials and simple processing methods. An exceptional electrochemical cycling performance was obtained (as compared to cathodes with conventional linear polymeric binders such as carboxymethyl cellulose (CMC) and styrene-butadiene rubber (SBR)) with >100 cycles and 85-98% capacity retention, thus demonstrating the significant utility of this new binder architecture which exhibits critical physicochemical properties and flexible nanoscale design parameters (CNDP's).

  12. Natural dendrimers: Synthesis and in vitro characterization of glycogen-cysteamine conjugates.

    Perrone, Mara; Lopedota, Angela; Liberati, Elisa; Russo, Vincenzo; Cutrignelli, Annalisa; Laquintana, Valentino; de Sousa, Irene Pereira; Franco, Massimo; Tongiani, Serena; Denora, Nunzio; Bernkop-Schnürch, Andreas

    2017-06-01

    The aim of this study was to synthesize, characterize and evaluate the mucoadhesive properties of the first thiolated hyperbranched natural polysaccharide with biodegradability and biocompatibility features. In detail, glycogen-cysteamine conjugates were synthesized through a first step of oxidative ring opening applying increasing concentrations of sodium periodate, to obtain polymers with different degrees of oxidation, and a second step of reductive amination with a constant amount of cysteamine. The obtained glycogen-cysteamine conjugates were characterized regarding their content of free and total thiol groups by Ellman's assay, biocompatibility, swelling/erosion behavior, rheological synergism and mucoadhesive properties in comparison to the unmodified glycogen. The higher the concentration of periodate was, the higher was the content of total thiol groups being in the range of 255.7±12-1194.5±82μmol/g, biocompatibility remained unaffected by these structural changes. On the contrary, the mucoadhesive properties, evaluated by tensile, rheological synergism and rotating cylinder studies, appear to be influenced by the thiol groups concentration on the glycogen. In particular the glycogen-cysteamine conjugate exhibiting the highest degree of thiolation showed a 79-fold increase in viscosity over a time period of 8h, as well as, remained attached on freshly excised porcine mucosa 32-fold longer than the unmodified polymer. The higher was the amount of conjugated thiol groups, the higher was the water absorption capacity of glycogen-cysteamine tablets in Simulated Intestinal Fluid pH 6.8 (SIF). The introduction of thiol moieties on polymer changed the characteristics of the polysaccharide by improving mucoadhesion properties. Therefore, this work represents the first study describing thiolated natural dendrimers as potential platform useful to realize appropriate mucoadhesive nanocarrier systems suitable to prolong mucosal residence time. Copyright © 2017

  13. On-Demand Bioadhesive Dendrimers with Reduced Cytotoxicity

    Feng Gao

    2018-03-01

    Full Text Available Tissue adhesives based on polyamidoamine (PAMAM dendrimer, grafted with UV-sensitive aryldiazirine (PAMAM-g-diazirine are promising new candidates for light active adhesion on soft tissues. Diazirine carbene precursors form interfacial and intermolecular covalent crosslinks with tissues after UV light activation that requires no premixing or inclusion of free radical initiators. However, primary amines on the PAMAM dendrimer surface present a potential risk due to their cytotoxic and immunological effects. PAMAM-g-diazirine formulations with cationic pendant amines converted into neutral amide groups were evaluated. In vitro toxicity is reduced by an order of magnitude upon amine capping while retaining bioadhesive properties. The in vivo immunological response to PAMAM-g-diazirine formulations was found to be optimal in comparison to standard poly(lactic-co-glycolic acid (PLGA thin films.

  14. Photoinduced electron transfer between benzyloxy dendrimer phthalocyanine and benzoquinone

    Zhang, Tiantian; Ma, Dongdong; Pan, Sujuan; Wu, Shijun; Jiang, Yufeng; Zeng, Di; Yang, Hongqin; Peng, Yiru

    2016-10-01

    Photo-induced electron transfer (PET) is an important and fundamental process in natural photosynthesis. To mimic such interesting PET process, a suitable donor and acceptor couple were properly chosen. Dendrimer phthalocyanines and their derivatives have emerged as promising materials for artificial photosynthesis systems. In this paper, the electron transfer between the light harvest dendrimer phthalocyanine (donor) and the 1,4-benzoquinone (acceptor) was studied by UV/Vis and fluorescence spectroscopic methods. It was found that fluorescence of phthalocyanine was quenched by benzoquinone (BQ) via excited state electron transfer, from the phthalocyanine to the BQ upon excitation at 610 nm. The Stern-Volmer constant (KSV) of electron transfer was calculated. Our study suggests that this dendritic phthalocyanine is an effective new electron donor and transmission complex and could be used as a potential artificial photosynthesis system.

  15. Current-voltage characteristics of dendrimer light-emitting diodes

    Stevenson, S G; Samuel, I D W; Staton, S V; Knights, K A; Burn, P L; Williams, J H T; Walker, Alison B

    2010-01-01

    We have investigated current-voltage (I-V) characteristics of unipolar and bipolar organic diodes that use phosphorescent dendrimers as the emissive organic layer. Through simulation of the measured I-V characteristics we were able to determine the device parameters for each device structure studied, leading to a better understanding of injection and transport behaviour in these devices. It was found that the common practice of assuming injection barriers are equal to the difference between bare electrode work functions and molecular orbital levels is unsuitable for the devices considered here, particularly for gold contacts. The studies confirm that different aromatic units in the dendrons can give significant differences in the charge transporting properties of the dendrimers.

  16. Current-voltage characteristics of dendrimer light-emitting diodes

    Stevenson, S. G.; Samuel, I. D. W.; Staton, S. V.; Knights, K. A.; Burn, P. L.; Williams, J. H. T.; Walker, Alison B.

    2010-09-01

    We have investigated current-voltage (I-V) characteristics of unipolar and bipolar organic diodes that use phosphorescent dendrimers as the emissive organic layer. Through simulation of the measured I-V characteristics we were able to determine the device parameters for each device structure studied, leading to a better understanding of injection and transport behaviour in these devices. It was found that the common practice of assuming injection barriers are equal to the difference between bare electrode work functions and molecular orbital levels is unsuitable for the devices considered here, particularly for gold contacts. The studies confirm that different aromatic units in the dendrons can give significant differences in the charge transporting properties of the dendrimers.

  17. Current-voltage characteristics of dendrimer light-emitting diodes

    Stevenson, S G; Samuel, I D W [Organic Semiconductor Centre, SUPA, School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9SS (United Kingdom); Staton, S V; Knights, K A; Burn, P L [Department of Chemistry, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA (United Kingdom); Williams, J H T; Walker, Alison B, E-mail: a.b.walker@bath.ac.u [Department of Physics, University of Bath, Bath, BA2 7AY (United Kingdom)

    2010-09-29

    We have investigated current-voltage (I-V) characteristics of unipolar and bipolar organic diodes that use phosphorescent dendrimers as the emissive organic layer. Through simulation of the measured I-V characteristics we were able to determine the device parameters for each device structure studied, leading to a better understanding of injection and transport behaviour in these devices. It was found that the common practice of assuming injection barriers are equal to the difference between bare electrode work functions and molecular orbital levels is unsuitable for the devices considered here, particularly for gold contacts. The studies confirm that different aromatic units in the dendrons can give significant differences in the charge transporting properties of the dendrimers.

  18. Wiring of heme enzymes by methylene-blue labeled dendrimers

    Álvarez-Martos, Isabel; Shahdost-fard, Faezeh; Ferapontova, Elena

    2017-01-01

    Redox-modified branched 3D dendrimeric nanostructures may be considered as perspective wires for electrical connection between redox enzymes and electrodes. Here, we studied electron transfer (ET) reactions and bioelectrocatalysis of heme-containing horseradish peroxidase (HRP) and heme- and moli......Redox-modified branched 3D dendrimeric nanostructures may be considered as perspective wires for electrical connection between redox enzymes and electrodes. Here, we studied electron transfer (ET) reactions and bioelectrocatalysis of heme-containing horseradish peroxidase (HRP) and heme......- and molibdopterin-containing sulfite oxidase (SOx), wired to gold by the methylene blue (MB)-labeled polyamidoamine (PAMAM) dendrimers. The enzymes’ electrochemical transformation and bioelectrocatalytic function could be followed at both unlabeled and MB-labeled dendrimer-modified electrodes with the formal redox......, optimization of bioelectrocatalysis of complex intermembrane and, possibly, membrane enzymes....

  19. Biological properties of new viologen-phosphorus dendrimers.

    Ciepluch, Karol; Katir, Nadia; El Kadib, Abdelkrim; Felczak, Aleksandra; Zawadzka, Katarzyna; Weber, Monika; Klajnert, Barbara; Lisowska, Katarzyna; Caminade, Anne-Marie; Bousmina, Mostapha; Bryszewska, Maria; Majoral, Jean Pierre

    2012-03-05

    Some biological properties of eight dendrimers incorporating both phosphorus linkages and viologen units within their cascade structure or at the periphery were investigated for the first time. In particular cytotoxicity, hemotoxicity, and antimicrobial and antifungal activity of these new macromolecules were examined. Even if for example all these species exhibited good antimicrobial properties, it was demonstrated that their behavior strongly depends on several parameters as their size and molecular weight, the number of viologen units and the nature of the terminal groups.

  20. Blue Light Emitting Polyphenylene Dendrimers with Bipolar Charge Transport Moieties

    Guang Zhang

    2016-10-01

    Full Text Available Two light-emitting polyphenylene dendrimers with both hole and electron transporting moieties were synthesized and characterized. Both molecules exhibited pure blue emission solely from the pyrene core and efficient surface-to-core energy transfers when characterized in a nonpolar environment. In particular, the carbazole- and oxadiazole-functionalized dendrimer (D1 manifested a pure blue emission from the pyrene core without showing intramolecular charge transfer (ICT in environments with increasing polarity. On the other hand, the triphenylamine- and oxadiazole-functionalized one (D2 displayed notable ICT with dual emission from both the core and an ICT state in highly polar solvents. D1, in a three-layer organic light emitting diode (OLED by solution processing gave a pure blue emission with Commission Internationale de l’Éclairage 1931 CIE xy = (0.16, 0.12, a peak current efficiency of 0.21 cd/A and a peak luminance of 2700 cd/m2. This represents the first reported pure blue dendrimer emitter with bipolar charge transport and surface-to-core energy transfer in OLEDs.

  1. Blue Light Emitting Polyphenylene Dendrimers with Bipolar Charge Transport Moieties.

    Zhang, Guang; Auer-Berger, Manuel; Gehrig, Dominik W; Blom, Paul W M; Baumgarten, Martin; Schollmeyer, Dieter; List-Kratochvil, E J W; Müllen, Klaus

    2016-10-20

    Two light-emitting polyphenylene dendrimers with both hole and electron transporting moieties were synthesized and characterized. Both molecules exhibited pure blue emission solely from the pyrene core and efficient surface-to-core energy transfers when characterized in a nonpolar environment. In particular, the carbazole- and oxadiazole-functionalized dendrimer ( D1 ) manifested a pure blue emission from the pyrene core without showing intramolecular charge transfer (ICT) in environments with increasing polarity. On the other hand, the triphenylamine- and oxadiazole-functionalized one ( D2 ) displayed notable ICT with dual emission from both the core and an ICT state in highly polar solvents. D1 , in a three-layer organic light emitting diode (OLED) by solution processing gave a pure blue emission with Commission Internationale de l'Éclairage 1931 CIE xy = (0.16, 0.12), a peak current efficiency of 0.21 cd/A and a peak luminance of 2700 cd/m². This represents the first reported pure blue dendrimer emitter with bipolar charge transport and surface-to-core energy transfer in OLEDs.

  2. Structural analysis of binding functionality of folic acid-PEG dendrimers against folate receptor.

    Sampogna-Mireles, Diana; Araya-Durán, Ingrid D; Márquez-Miranda, Valeria; Valencia-Gallegos, Jesús A; González-Nilo, Fernando D

    2017-03-01

    Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-α) overexpression. Incorporation of polyethylene glycol (PEG) can enhance dendrimers solubility and pharmacokinetics, but ligand-receptor binding must not be affected. In this work we characterized, at atomic level, the binding functionality of conventional site-specific dendrimers conjugated with FA with PEG 750 or PEG 3350 as a linker. After Molecular Dynamics simulation, we observed that both PEG's did not interfere over ligand-receptor binding functionality. Although binding kinetics could be notably affected, the folate fragment from both dendrimers remained exposed to the solvent before approaching selectively to FR-α. PEG 3350 provided better solubility and protection from enzymatic degradation to the dendrimer than PEG 750. Also, FA-PEG3350 dendrimer showed a slightly better interaction with FR-α than FA-PEG750 dendrimer. Therefore, theoretical evidence supports that both dendrimers are suitable as drug delivery systems for cancer therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Electron Transfer in Methylene-Blue-Labeled G3 Dendrimers Tethered to Gold

    Álvarez-Martos, Isabel; Kartashov, Andrey; Ferapontova, Elena

    2016-01-01

    , and their dependence on the dendrimer surface packing, contribute to both mechanistic pathways. Electrical wiring of horse-radish peroxidase and hexose oxidase by using MB-labeled dendrimers allowed the bioelectrocatalytic reduction of H2O2 and oxidation of glucose by these enzymes. The demonstrated electrical...

  4. Structural Distortion of Dendrimers on Gold Surfaces: A Tapping-Mode AFM Investigation

    Hierlemann, A

    1998-01-01

    .... The individual dendrimer molecules forming a monolayer were clearly imaged. Upon exposure to hexadecanethiol, the shapes of individual dendrimers change and they become taller and narrower as more stable thiol-Au bonds replace some of the amine-Au bonds...

  5. Proton-conductive materials formed by coumarin photocrosslinked ionic liquid crystal dendrimers

    Concellon, A.; Liang, T.; Schenning, A.P.H.J.; Luis Serrano, J.; Romero, P.; Marcos, M.

    2018-01-01

    In this work, we have successfully examined for the first time the use of ionic dendrimers as building blocks for the preparation of 1D and 2D proton conductive materials. For this purpose, a new family of liquid crystalline dendrimers has been synthesized by ionic self-assembly of poly(amidoamine)

  6. Molecular dynamics study of charged dendrimers in salt-free solution : effect of counterions

    Gurtovenko, A.A.; Lyulin, S.V.; Karttunen, M.E.J.; Vattulainen, I.

    2006-01-01

    Polyamidoamine dendrimers, being protonated under physiological conditions, represent a promising class of nonviral, nanosized vectors for drug and gene delivery. We performed extensive molecular dynamics simulations of a generic model dendrimer in a salt-free solution with dendrimer’s terminal

  7. Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview.

    Mignani, Serge; El Kazzouli, Saïd; Bousmina, Mosto; Majoral, Jean-Pierre

    2013-10-01

    Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Paramagnetic NMR investigation of dendrimer-based host-guest interactions.

    Fei Wang

    Full Text Available In this study, the host-guest behavior of poly(amidoamine (PAMAM dendrimers bearing amine, hydroxyl, or carboxylate surface functionalities were investigated by paramagnetic NMR studies. 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO derivatives were used as paramagnetic guest molecules. The results showed that TEMPO-COOH significantly broaden the ¹H NMR peaks of amine- and hydroxyl-terminated PAMAM dendrimers. In comparison, no paramagnetic relaxation enhancement (PRE was observed between TEMPO-NH₂, TEMPO-OH and the three types of PAMAM dendrimers. The PRE phenomenon observed is correlated with the encapsulation of TEMPO-COOH within dendrimer pockets. Protonation of the tertiary amine groups within PAMAM dendrimers plays an important role during this process. Interestingly, the absence of TEMPO-COOH encapsulation within carboxylate-terminated PAMAM dendrimer is observed due to the repulsion of TEMPO-COO- anion and anionic dendrimer surface. The combination of paramagnetic probes and ¹H NMR linewidth analysis can be used as a powerful tool in the analysis of dendrimer-based host-guest systems.

  9. Molecular dynamics simulation of coarse-grained poly(L-lysine) dendrimers.

    Rahimi, Ali; Amjad-Iranagh, Sepideh; Modarress, Hamid

    2016-03-01

    Poly(L-lysine) (PLL) dendrimer are amino acid based macromolecules and can be used as drug delivery agents. Their branched structure allows them to be functionalized by various groups to encapsulate drug agents into their structure. In this work, at first, an attempt was made on all-atom simulation of PLL dendrimer of different generations. Based on all-atom results, a course-grained model of this dendrimer was designed and its parameters were determined, to be used for simulation of three generations of PLL dendrimer, at two pHs. Similar to the all-atom, the coarse-grained results indicated that by increasing the generation, the dendrimer becomes more spherical. At pH 7, the dendrimer had larger size, whereas at pH 12, due to back folding of branching chains, they had the tendency to penetrate into the inner layers. The calculated radial probability and radial distribution functions confirm that at pH 7, the PLL dendrimer has more cavities and as a result it can encapsulate more water molecules into its inner structure. By calculating the moment of inertia and the aspect ratio, the formation of spherical structure for PLL dendrimer was confirmed.

  10. Photo-physical and structural interactions between viologen phosphorus-based dendrimers and human serum albumin

    Ciepluch, Karol; Katir, Nadia; El Kadib, Abdelkrim; Weber, Monika; Caminade, Anne-Marie; Bousmina, Mostapha; Pierre Majoral, Jean; Bryszewska, Maria

    2012-01-01

    This work deals with photo-physical and structural interactions between viologen phosphorus dendrimers and human serum albumin (HSA). Viologens are derivatives of 4,4′-bipyridinium salts. Aiming to rationalize the parameters governing such interactions eight types of these polycationic dendrimers in which the generation, the number of charges, the nature of the core and of the terminal groups vary from one to another, were designed and used. The influence of viologen-based dendrimers' on human serum albumin has been investigated. The photo-physical interactions of the two systems have been monitored by fluorescence quenching of free L-tryptophan and of HSA tryptophan residue. Additionally, using circular dichroism (CD) the effect of dendrimers on the secondary structure of albumin was measured. The obtained results show that viologen dendrimers interact with human serum albumin quenching its fluorescence either by collisional (dynamic) way or by forming complexes in a ground state (static quenching). In some cases the quenching is accompanied by changes of the secondary structure of HSA. - Highlights: ► Photo-physical interactions between viologen phosphorus dendrimers and human serum albumin (HSA) were investigated. ► The viologen dendrimers can quench the fluorescence of tryptophan in HSA. ► CD spectra to explain the changes in secondary structure of albumin after exposition of dendrimers.

  11. Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.

    Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

    2015-01-01

    Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

  12. Transport of dendrimer nanocarriers through epithelial cells via the transcellular route.

    Jevprasesphant, Rachaneekorn; Penny, Jeffrey; Attwood, David; D'Emanuele, Antony

    2004-06-18

    The mechanism of transport of G3 PAMAM and surface-modified (with lauroyl chains) G3 PAMAM dendrimer nanocarriers across Caco-2 cell monolayers has been investigated. Flow-cytometry studies following quenching of extracellular fluorescence demonstrated the cellular internalisation of dendrimers. Optical sectioning of cells incubated with fluorescein isothiocyanate (FITC)-conjugated dendrimer and lauroyl-dendrimer using confocal laser scanning microscopy revealed colocalisation of a marker for cell nuclei (4',6-diamidino-2-phenylindole, DAPI) and FITC fluorescence, also suggesting cellular internalisation of dendrimers. Transmission electron microscopic analyses of cells incubated with gold-labelled G3 PAMAM dendrimers confirmed endocytosis-mediated cellular internalisation when dendrimers were applied to the apical domain of Caco-2 cells. These findings are in agreement with our previous studies using Caco-2 cell monolayers that showed a significant decrease of dendrimer uptake in the presence of colchicine (endocytosis inhibitor) and when temperature was reduced from 37 to 4 degrees C. Copyright 2004 Elsevier B.V.

  13. Diglycolamide-functionalized dendrimers : Studies on Americium(III) pertraction from radioactive waste

    Ansari, Seraj A.; Mohapatra, Prasanta K.; Leoncini, Andrea; Huskens, Jurriaan; Verboom, Willem

    2017-01-01

    Diglycolamide (DGA)-functionalized poly(propylene imine) diaminobutane dendrimers were evaluated as the carrier in supported liquid membranes (SLMs) for selective recovery of trivalent actinides over uranium. The 0, 1st, and 2nd generation dendrimers with 2, 4, and 8 DGA moieties, termed as LI, LII,

  14. Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

    Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

    2017-12-01

    Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

  15. Regional Morphology and Transport of PAMAM Dendrimers Across Isolated Rat Intestinal Tissue.

    Hubbard, Dallin; Bond, Tanner; Ghandehari, Hamidreza

    2015-12-01

    Intestinal permeability of PAMAM dendrimers has been observed, giving rationale for their use in oral drug delivery as potential carriers of associated molecules. This study assessed the apparent permeability coefficients (Papp) of dendrimers across isolated rat intestinal regional mucosae, along with estimation of the maximum non-toxic concentration. Caco-2 monolayers were also used to assess the comparative Papp values between isolated mucosae and cell culture models. Concentrations from 0.1 to 10 mM of anionic and cationic dendrimers were tested in mucosae to assess their Papp, membrane TEER, [(14)C]-mannitol Papp, and histology. 0.1 mM concentrations of dendrimers were assessed over 120 min in Caco-2 cell monolayers as concentrations above that were cytotoxic. Jejunal transport of dendrimers was higher than transport in colonic epithelium. Monolayer Papp values of dendrimers were comparable to those of jejunal mucosae. Mucosae exposed to dendrimer concentrations of 10 mM for 120 min caused significant reduction in TEER and changes in tissue morphology; however, G3.5 was the only analogue that caused significant TEER reduction and morphological changes at 1 mM concentrations. Transport in jejunal mucosae appears to be the greatest indicating that the small intestinal will be the most likely region to target for oral drug delivery using PAMAM dendrimers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Photo-physical and structural interactions between viologen phosphorus-based dendrimers and human serum albumin

    Ciepluch, Karol, E-mail: ciepluch@biol.uni.lodz.pl [Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90-236 Lodz (Poland); Katir, Nadia [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 route de Narbonne, F-31077 Toulouse cedex 4 (France); Institute of Nanomaterials and Nanotechnology (INANOTECH)-MAScIR (Moroccan Foundation for Advanced Science, Innovation and Research), ENSET, Avenue de l' Armee Royale, Madinat El Irfane, 10100 Rabat (Morocco); El Kadib, Abdelkrim [Institute of Nanomaterials and Nanotechnology (INANOTECH)-MAScIR (Moroccan Foundation for Advanced Science, Innovation and Research), ENSET, Avenue de l' Armee Royale, Madinat El Irfane, 10100 Rabat (Morocco); Weber, Monika [Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90-236 Lodz (Poland); Caminade, Anne-Marie [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 route de Narbonne, F-31077 Toulouse cedex 4 (France); Bousmina, Mostapha [Hassan II Academy of Sciences and Technology, Avenue MVI, Km4, 10220 Rabat (Morocco); Pierre Majoral, Jean [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 route de Narbonne, F-31077 Toulouse cedex 4 (France); Hassan II Academy of Sciences and Technology, Avenue MVI, Km4, 10220 Rabat (Morocco); Bryszewska, Maria [Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90-236 Lodz (Poland)

    2012-06-15

    This work deals with photo-physical and structural interactions between viologen phosphorus dendrimers and human serum albumin (HSA). Viologens are derivatives of 4,4 Prime -bipyridinium salts. Aiming to rationalize the parameters governing such interactions eight types of these polycationic dendrimers in which the generation, the number of charges, the nature of the core and of the terminal groups vary from one to another, were designed and used. The influence of viologen-based dendrimers' on human serum albumin has been investigated. The photo-physical interactions of the two systems have been monitored by fluorescence quenching of free L-tryptophan and of HSA tryptophan residue. Additionally, using circular dichroism (CD) the effect of dendrimers on the secondary structure of albumin was measured. The obtained results show that viologen dendrimers interact with human serum albumin quenching its fluorescence either by collisional (dynamic) way or by forming complexes in a ground state (static quenching). In some cases the quenching is accompanied by changes of the secondary structure of HSA. - Highlights: Black-Right-Pointing-Pointer Photo-physical interactions between viologen phosphorus dendrimers and human serum albumin (HSA) were investigated. Black-Right-Pointing-Pointer The viologen dendrimers can quench the fluorescence of tryptophan in HSA. Black-Right-Pointing-Pointer CD spectra to explain the changes in secondary structure of albumin after exposition of dendrimers.

  17. Functionalized Poly(propylene imine) Dendrimers as Novel Phase Transfer Catalyst in Supercritical Cabon Dioxide

    Goetheer, E.L.V.; Baars, M.W.P.L.; Broeke, van den L.J.P.; Meijer, E.W.; Keurentjes, J.T.F.

    2000-01-01

    Perfluoro-functionalized poly(propylene imine) dendrimers have been used as reactive extractants for anionic species and as phase transfer catalysts for two types of reactions. Different generations of dendrimers have been used for applications in carbon dioxide. First, the reactive extraction of

  18. Synthesis and protonation behavior of carboxylate-functionalized poly(propylene imine) dendrimers

    Duijvenbode, van R.C.; Rajanayagam, A.; Koper, G.J.M.; Baars, M.W.P.L.; Waal, de B.F.M.; Meijer, E.W.; Borkovec, M.

    2000-01-01

    Five generations of carboxylate-functionalized poly(propyleneimine) dendrimers have been synthesized starting from a double Michael addition of amine-functionalized poly(propyleneimine) dendrimers to methyl acrylate followed by basic hydrolysis using LiOH in a water/methanol mixture. The dendritic

  19. Amplified amperometric aptasensor for selective detection of protein using catalase-functional DNA-PtNPs dendrimer as a synergetic signal amplification label.

    Zhang, Juan; Yuan, Yali; biXie, Shun; Chai, Yaqin; Yuan, Ruo

    2014-10-15

    In this work, we present a new strategy to construct an electrochemical aptasensor for sensitive detection of platelet-derived growth factor BB (PDGF-BB) based on the synergetic amplification of a three-dimensional (3D) nanoscale catalase (CAT) enzyme-functional DNA-platinum nanoparticles (PtNPs) dendrimer through autonomous layer-by-layer assembly. Firstly, polyamidoaminedendrimer (PAMAM) with a hyper-branched and three-dimensional structure was served as nanocarriers to coimmobilize a large number of PDGF-BB binding aptamer (PBA II) and ssDNA 1 (S1) to form PBA II-PAMAM-S1 bioconjugate. In the presence of PDGF-BB, the bioconjugate was self-assembled on the electrode by sandwich assay. Following that, the carried S1 propagated a chain reaction of hybridization events between CAT-PtNPs-S1 and CAT-PtNPs-ssDNA 2 (S2) to form a 3D nanoscale CAT-functional PtNPs-DNA dendrimer, which successfully immobilized substantial CAT enzyme and PtNPs with superior catalysis activity. In this process, the formed negatively charged double-helix DNA could cause the intercalation of hexaammineruthenium(III) chloride (RuHex) into the groove via electrostatic interactions. Thus, numerous RuHex redox probes and CAT were decorated inside/outside of the dendrimer. In the presence of H2O2 in electrolytic cell, the synergistic reaction of CAT and PtNPs towards electrocatalysis could further amplify electrochemical signal. Under optimal condition, the CAT-PtNPs-DNA dendrimer-based sensing system presented a linear dependence between the reduction peak currents and logarithm of PDGF-BB concentrations in the range of 0.00005-35 nM with a relatively low detection limit of 0.02 pM. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Polymer films

    Granick, Steve; Sukhishvili, Svetlana A.

    2004-05-25

    A film contains a first polymer having a plurality of hydrogen bond donating moieties, and a second polymer having a plurality of hydrogen bond accepting moieties. The second polymer is hydrogen bonded to the first polymer.

  1. Atomic level insights into realistic molecular models of dendrimer-drug complexes through MD simulations

    Jain, Vaibhav; Maiti, Prabal K.; Bharatam, Prasad V.

    2016-09-01

    Computational studies performed on dendrimer-drug complexes usually consider 1:1 stoichiometry, which is far from reality, since in experiments more number of drug molecules get encapsulated inside a dendrimer. In the present study, molecular dynamic (MD) simulations were implemented to characterize the more realistic molecular models of dendrimer-drug complexes (1:n stoichiometry) in order to understand the effect of high drug loading on the structural properties and also to unveil the atomistic level details. For this purpose, possible inclusion complexes of model drug Nateglinide (Ntg) (antidiabetic, belongs to Biopharmaceutics Classification System class II) with amine- and acetyl-terminated G4 poly(amidoamine) (G4 PAMAM(NH2) and G4 PAMAM(Ac)) dendrimers at neutral and low pH conditions are explored in this work. MD simulation analysis on dendrimer-drug complexes revealed that the drug encapsulation efficiency of G4 PAMAM(NH2) and G4 PAMAM(Ac) dendrimers at neutral pH was 6 and 5, respectively, while at low pH it was 12 and 13, respectively. Center-of-mass distance analysis showed that most of the drug molecules are located in the interior hydrophobic pockets of G4 PAMAM(NH2) at both the pH; while in the case of G4 PAMAM(Ac), most of them are distributed near to the surface at neutral pH and in the interior hydrophobic pockets at low pH. Structural properties such as radius of gyration, shape, radial density distribution, and solvent accessible surface area of dendrimer-drug complexes were also assessed and compared with that of the drug unloaded dendrimers. Further, binding energy calculations using molecular mechanics Poisson-Boltzmann surface area approach revealed that the location of drug molecules in the dendrimer is not the decisive factor for the higher and lower binding affinity of the complex, but the charged state of dendrimer and drug, intermolecular interactions, pH-induced conformational changes, and surface groups of dendrimer do play an

  2. Poly(Propylene Imine Dendrimers and Amoxicillin as Dual-Action Antibacterial Agents

    Natalia Wrońska

    2015-10-01

    Full Text Available Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX against reference strains of common Gram-negative pathogens, alone and in combination with poly(propylene imine (PPI dendrimers, or derivatives thereof, in which 100% of the available hydrogen atoms are substituted with maltose (PPI 100%malG3. The concentrations of dendrimers used remained in the range non-toxic to eukaryotic cells. The results indicate that PPI dendrimers significantly enhance the antibacterial effect of amoxicillin alone, allowing antibiotic doses to be reduced. It is important to reduce doses of amoxicillin because its widespread use in medicine could lead to the development of bacterial resistance and environmental pollution. This is the first report on the combined antibacterial activity of PPI surface-modified maltose dendrimers and amoxicillin.

  3. Trapping time statistics and efficiency of transport of optical excitations in dendrimers

    Heijs, Dirk-Jan; Malyshev, Victor A.; Knoester, Jasper

    2004-09-01

    We theoretically study the trapping time distribution and the efficiency of the excitation energy transport in dendritic systems. Trapping of excitations, created at the periphery of the dendrimer, on a trap located at its core, is used as a probe of the efficiency of the energy transport across the dendrimer. The transport process is treated as incoherent hopping of excitations between nearest-neighbor dendrimer units and is described using a rate equation. We account for radiative and nonradiative decay of the excitations while diffusing across the dendrimer. We derive exact expressions for the Laplace transform of the trapping time distribution and the efficiency of trapping, and analyze those for various realizations of the energy bias, number of dendrimer generations, and relative rates for decay and hopping. We show that the essential parameter that governs the trapping efficiency is the product of the on-site excitation decay rate and the trapping time (mean first passage time) in the absence of decay.

  4. Rheology of Supramolecular Polymers

    Shabbir, Aamir

    Supramolecular polymers are a broad class of materials that include all polymerscapable of associating via secondary interactions. These materials represent an emerging class of systems with superior versatility compared to classical polymers with applications in food stuff, coatings, cost...... efficient processes or biomedical areas. Design and development of supramolecular polymers using ionic, hydrogen bonding or transition metal complexes with tailored properties requires deep understanding of dynamics both in linear and non-linear deformations. While linear rheology is important to understand...... the dynamics under equilibrium conditions, extensional rheology is relevant during the processing or in the usage of polymers utilizing supramolecular associations for example, acrylic based pressure sensitive adhesives are subjected to extensional deformations during the peeling where strain hardening...

  5. The adsorption-desorption transition of double-stranded DNA interacting with an oppositely charged dendrimer induced by multivalent anions.

    Jiang, Yangwei; Zhang, Dong; Zhang, Yaoyang; Deng, Zhenyu; Zhang, Linxi

    2014-05-28

    The adsorption-desorption transition of DNA in DNA-dendrimer solutions is observed when high-valence anions, such as hexavalent anions, are added to the DNA-dendrimer solutions. In the DNA-dendrimer solutions with low-valence anions, dendrimers bind tightly with the V-shaped double-stranded DNA. When high-valence anions, such as pentavalent or hexavalent anions, are added to the DNA-dendrimer solutions, the double-stranded DNA chains can be stretched straightly and the dendrimers are released from the double-stranded DNA chains. In fact, adding high-valence anions to the solutions can change the charge spatial distribution in the DNA-dendrimer solutions, and weaken the electrostatic interactions between the positively charged dendrimers and the oppositely charged DNA chains. Adsorption-desorption transition of DNA is induced by the overcharging of dendrimers. This investigation is capable of helping us understand how to control effectively the release of DNA in gene/drug delivery because an effective gene delivery for dendrimers includes non-covalent DNA-dendrimer binding and the effective release of DNA in gene therapy.

  6. Organic Light-Emitting Diodes Using Multifunctional Phosphorescent Dendrimers with Iridium-Complex Core and Charge-Transporting Dendrons

    Tsuzuki, Toshimitsu; Shirasawa, Nobuhiko; Suzuki, Toshiyasu; Tokito, Shizuo

    2005-06-01

    We report a novel class of light-emitting materials for use in organic light-emitting diodes (OLEDs): multifunctional phosphorescent dendrimers that have a phosphorescent core and dendrons based on charge-transporting building blocks. We synthesized first-generation and second-generation dendrimers consisting of a fac-tris(2-phenylpyridine)iridium [Ir(ppy)3] core and hole-transporting phenylcarbazole-based dendrons. Smooth amorphous films of these dendrimers were formed by spin-coating them from solutions. The OLEDs using the dendrimer exhibited bright green or yellowish-green emission from the Ir(ppy)3 core. The OLEDs using the film containing a mixture of the dendrimer and an electron-transporting material exhibited higher efficiency than those using the neat dendrimer film. The external quantum efficiency of OLEDs using the film containing a mixture of the first-generation dendrimer and an electron-transporting material was as high as 7.6%.

  7. Size-controlled gold nanoparticles obtained from electrodeposited amidoferrocenylpoly(propyleneimine) dendrimer-templates for the electrochemical sensing of dopamine

    Villena, Carlos; Bravo, Marta; Alonso, Beatriz; Casado, Carmen M.; Losada, José; García Armada, M. Pilar

    2017-10-01

    Nanometer-scale gold particles exhibit size-dependent electronic properties with important sensing and biosensing applications. In the same way, a lot of analytes show some type of surface-sensitive reaction and the electrode material has a strong influence on the catalytic activity. In this work we study the kinetics and electrochemistry of electrodes with size controlled gold nanoparticles, obtained by electrodeposited amidoferrocenylpoly(propyleneimine) dendrimers of two generations as templates, and the kinetics and the analytical response to the oxidation of dopamine. We demonstrate that the four-types of modified electrodes show good catalytic responses toward the oxidation of dopamine via different processes in relation with the absence or presence of gold nanoparticles and their size. The best response was obtained with the largest nanoparticles, obtained with the first generation dendrimer-template at 0.3 V vs. SCE, with three linear ranges (0-70, 70-600 and 600-1000 μM), with sensitivities 585.7; 466.0 and 314.3 μA/mM cm2, and limit of detection of 0.01 μM. The effect of interfering substances has been studied by differential pulse voltammetry and the developed sensor has been successfully used for the determination of dopamine in a commercial dopamine hydrochloride injection and in spiked Human urine.

  8. Hybrid graphene oxide/DAB-Am-16 dendrimer: Preparation, characterization chemical reactivity and their electrocatalytic detection of L-Dopamine

    Do Carmo, Devaney Ribeiro; Fernandes, Daniela Silvestrini

    2017-09-01

    Graphene oxide (GO) was chemically modified with a poly(propylene)imine Generation 3.0 dendrimer (DAB-Am-16). The characterization, structure and properties of hybrid graphene oxide/DAB-Am-16 dendrimer was studied by Raman spectroscopy, Fourier-Transforming Infrared Spectroscopy (FT-IR), X-Ray Photoelectron Spectroscopic (XPS), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Thermogravimetric analysis. After functionalized the hybrid material (GOD) can interact with copper and subsequently with hexacyanoferrate (III) ions (GODHCu). The GODHCu incorporated into a graphite paste electrode (20% w/w) was applied to an electrocatalytic detection of neurotransmitter L-dopamine using differential pulse voltammetry. The analytical curve showed a linear response in the concentration range from 1.0 × 10-7 to 1.0 × 10-5 mol L-1 with a corresponding equation Y(A) = 1.706 × 10-5 + 0.862 [L-dopamine] and a correlation coefficient r2 = 0.998. The detection limit was 6.36 × 10-7 mol L-1 with a relative standard deviation of ±4% (n = 3) and an amperometric sensitivity of 0.862 A/mol L-1.

  9. Enhanced Intestinal Permeability of Bufalin by a Novel Bufalin-Peptide-Dendrimer Inclusion through Caco-2 Cell Monolayer

    Chi-on Chan

    2017-11-01

    Full Text Available Bufalin (BFL has excellent physiological activities such as defending tumors, improving cardiac function, and so on. However, due to its poor water-solubility and bioavailability, the clinical application of BFL remains limited. In order to improve bioavailability of BFL, in our previous research, a novel peptide-dendrimer (PD was synthesized and applied to encapsulate BFL. In the present study, we investigate the absorption property and mechanism of BFL in free form and BFL-peptide-dendrimer inclusion (BPDI delivery system by using the Caco-2 cell monolayer model in vitro. The apparent permeability coefficient (Papp values of BFL in free or BPDI form were over 1.0 × 10−6 cm/s. Meanwhile, their almost equal bi-directional transport and linear transport percentage with time and concentration course indicated that BFL in both forms was absorbed mainly through passive diffusion. The most important result is that the Papp values of BFL increased about three-fold more BPDI than those of its free form, which indicated the intestinal permeability of BFL could be improved while BFL was encapsulated in BPDI form. Therefore, PD encapsulation may be a potential delivery system to increase the bioavailability of BFL.

  10. Physicochemical and biological properties of self-assembled antisense/poly(amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio

    Nomani, Alireza; Haririan, Ismaeil; Rahimnia, Ramin; Fouladdel, Shamileh; Gazori, Tarane; Dinarvand, Rassoul; Omidi, Yadollah; Azizi, Ebrahim

    2010-01-01

    To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine) dendrimer (PAMAM) dendrimer and a short-stranded DNA (antisense oligonucleotide), multiple methods were used to characterize these nanoparticles including photon correlation spectroscopy (PCS); zeta potential measurement; and atomic force microscopy (AFM). PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller mol...

  11. Diverse assemblies of the (4,4) grid layers exemplified in Zn(II)/Co(II) coordination polymers with dual linear ligands

    Liu, Guang-Zhen; Li, Xiao-Dong; Xin, Ling-Yun; Li, Xiao-Ling; Wang, Li-Ya

    2013-01-01

    Diverse (4,4) grid layers are exemplified in five two-dimensional coordination polymers with dual µ 2 -bridged ligands, namely, ([Zn(cbaa)(bpp)]·H 2 O) n (1), [Zn 2 (cbaa) 2 (bpy)] n (2), [Co 2 (cbaa) 2 (bpp) 2 ] n (3), [Co(cbaa)(bpp)] n (4), and [Co(bdaa)(bpp)(H 2 O) 2 ] n (5) (H 2 cbaa=4-carboxybenzeneacetic acid, bpp=1,3-di(4-pyridyl)propane, bpy=4,4′-bipyridyl, and H 2 bdaa=1,4-benzenediacrylic acid). For 1, two (4,4) grid layers with [ZnN 2 O 2 ] tetrahedron as the node are held together by lattice water forming a H-bonding bilayer. Individual (4,4) grid layer in 2 is based on (Zn 2 (OCO) 4 ) paddlewheel unit as the node. Two (4,4) grid layers with (Co 2 O(OCO) 2 ) dimer as the node are covalently interconnected by organic ligands affording a thick bilayer of 3 with new framework topology. The different entanglements between two coincident (4,4) grid layers with [CoN 2 O 4 ] octahedron as the node leads to two 2D→2D interpenetrated structures for 4 and 5. Furthermore, fluorescent properties of 1 and 2 as well as magnetic properties of 3 are investigated. - Graphical abstract: Diverse assemblies of the (4,4) grid layers with different network nodes forms five coordination polymers that are well characterized by IR, TGA, element analysis, fluorescent and magnetic measurement. - Highlights: • Diverse assemblies of the (4,4) grid layers with different structural units as the nodes. • A new topology type with the uninodal 6-connected net of (4 12 .5 2 .6) is found. • Intense fluorescence emissions with a rare blue-shift of 55 nm compared to free carboxylate ligand

  12. Detection of parathyroid hormone using an electrochemical impedance biosensor based on PAMAM dendrimers.

    Özcan, Hakkı Mevlüt; Sezgintürk, Mustafa Kemal

    2015-01-01

    This paper presents a novel hormone-based impedimetric biosensor to determine parathyroid hormone (PTH) level in serum for diagnosis and monitoring treatment of hyperparathyroidism, hypoparathyroidism and thyroid cancer. The interaction between PTH and the biosensor was investigated by an electrochemical method. The biosensor was based on the gold electrode modified by 12-mercapto dodecanoic (12MDDA). Antiparathyroid hormone (anti-PTH) was covalently immobilized on to poly amidoamine dendrimer (PAMAM) which was bound to a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) couple, self-assembled monolayer structure from one of the other NH2 sites. The immobilization of anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscope techniques. After the optimization studies of immobilization materials such as 12MDDA, EDC-NHS, PAMAM, and glutaraldehyde, the performance of the biosensor was investigated in terms of linearity, sensitivity, repeatability, and reproducibility. PTH was detected within a linear range of 10-60 fg/mL. Finally the described biosensor was used to monitor PTH levels in artificial serum samples. © 2015 American Institute of Chemical Engineers.

  13. Rational design of dendrimer/lipid nanoassemblies in drug delivery for cancer chemotherapy

    Sun, Qihang

    Nanocarriers can minimize the side effects and improve therapeutic efficacy of anticancer drugs. Although some success has been achieved via active or passive drug delivery to tumor cells, the known nanocarriers are far from satisfying therapeutic efficacy expectations. This is because they usually fail in one of the four crucial requirements, that is, to retain drug in blood circulation but release it reliably in tumor cells and to be stealthy in transport in circulation and tumor tissue but sticky upon arrival at the tumor cell. Therefore, the goal of this work is to fabricate nanoassemblies of dendrimers and lipids to address all these challenges. Particularly, nanoassemblies designed and prepared in this work are illustrated to improve the tumor tissue penetration. Examples of dendrimers synthesized in this work are water-insoluble, pH-dependent water-insoluble and water-soluble biodegradable polyester dendrimers. These dendrimers are shown to be encapsulated by commonly used fusogenic and long-circulating lipids to form reliable nanoassemblies. The dendrimer/lipid nanocarriers are used to demonstrate a cascade drug delivery. They are expected to be stable in circulation, due to their appropriately large size, but to release the drug-loaded dendrimers in tumor tissue. The released dendrimers carrying drugs are much smaller and hence expected to have a much deeper penetration throughout the tumor tissue.

  14. Synergistic effect of amino acids modified on dendrimer surface in gene delivery.

    Wang, Fei; Wang, Yitong; Wang, Hui; Shao, Naimin; Chen, Yuanyuan; Cheng, Yiyun

    2014-11-01

    Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single-functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple-functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Development of a Topical Resveratrol Formulation for Commercial Applications Using Dendrimer Nanotechnology.

    Pentek, Tyler; Newenhouse, Eric; O'Brien, Brennin; Chauhan, Abhay Singh

    2017-01-14

    Resveratrol (RSV) is well known for its anti-oxidant and anti-aging properties. However, resveratrol is insoluble in water and has stability issues. Recently, efforts were placed to prepare a resveratrol-based advanced anti-aging topical product but it contains harsh organic solvents and oils that could be harmful to the human body and the environment. Hence, we propose the use of a multifunctional dendrimer to solve the solubility and stability issues of resveratrol. A dendrimer-resveratrol complex was prepared, optimized and tested for solubility enhancement, stability in solution and cream dosage forms. We have also developed a high performance liquid chromatography method to measure the resveratrol within the final product. PAMAM dendrimers increased the solubility and stability of resveratrol in water and semisolid dosage forms. Therefore, this product would be water based 'green' formulation devoid of harsh organic solvents and oils and can be safely applied to the skin. Additionally, we have shown that the dendrimer helped to increase overall RSV loading and skin penetration of resveratrol. The dendrimer-RSV formulation was successfully scaled up towards commercialization. Dendrimer with RSV has led to an innovation in anti-aging cream and solutions that could be commercially marketed. Dendrimer-RSV complex could also be added to other product forms for additional purposes and applications.

  16. Assess the Intra-molecular Cavity in PAMAM Dendrimers by Small Angle Neutron Scattering

    Chen, Wei-Ren

    2008-01-01

    In this report, we present a contrast variation small angle neutron scattering (SANS) study of a series of neutral PAMAM dendrimer in aqueous solutions using three different generations (G4-6) at a concentration of about 10 mg/ml. Varying the solvent hydrogen-deuterium ratio, the scattering contributions from the water molecules and the constituent components of PAMAM dendrimer can be determined. Using an analytical model of the scattering cross section I(Q) incorporating the effect of water penetration, we have quantified the intra-molecular space of PAMAM dendrimer by evaluating the number of guest water molecules and we draw a direct comparison to computational predictions. As expected, the overall available internal cavity was seen to increase as a function of increasing dendrimer generation. However, the fraction of water accessible volume in the internal cavity of a dendrimer was found to remain invariant for the three generation PAMAM dendrimers studied in this report. We have also estimated the average water density inside a dendrimer, which is found to be higher than that of bulk water

  17. Tautomeric forms of PPI dendrimers functionalized with 4-(4′-ethoxybenzoyloxy)salicylaldehyde chromophores

    Franckevičius, M.; Vaišnoras, R.; Marcos, M.; Serrano, J.L.; Gruodis, A.; Galikova, N.; Gulbinas, V.

    2012-01-01

    Highlights: ► SA chromophore groups are formed by bonding terminal groups to PPI dendrimers. ► SA chromophore groups reveal four most stable tautomeric forms. ► Tautomeric properties of SA groups depend on the dendrimer generation and solvent. ► Aggregation of SA chromophores facilitates formation of the trans-keto tautomers. ► Fluorescence of PPI SA dendrimers is attributed to nπ ∗ states of keto tautomers. -- Abstract: Bonding of the promesogenic unit derived from 4-(4′-ethoxybenzoyloxy)salicylaldehyde to the amino terminated PPI dendrimer chains results in formation of the salicylidenimine chromophore groups. Absorption and fluorescence investigations of the dendrimer solutions supported by the quantum chemistry calculations revealed that the chromophore groups may exist in enol and keto tautomeric forms with relative concentrations depending on the dendrimer generation and solvent. The dendrimer fluorescence is attributed to nπ ∗ states of keto tautomers which may also be formed from excited enol tautomers.

  18. Analysis of the spatial structure of rigid polyphenylene dendrimers by small-angle neutron scattering

    Rosenfeldt, S.; Dingenouts, N.; Poetschke, D.; Ballauff, M.; Berresheim, A.J.; Muellen, K.; Lindner, P.; Saalwaechter, K.

    2005-01-01

    The analysis of the spatial structure of a rigid polyphenylene dendrimer G4-M of fourth generation by small-angle neutron scattering (SANS) is presented. This dendrimer is composed of phenyl units and is therefore devoid of any flexible unit. The scattering intensity of dilute solutions of the dendrimer was measured by SANS at different contrast which was adjusted by mixtures of protonated and deuterated toluene. Hence, the method of contrast variation could be applied and the data yield the scattering function extrapolated to infinite contrast. The comparison of this data with simulations demonstrates that the scaffold of the dendrimer is rigid as expected from its chemical structure. The positions of the various units setting up consecutive shells of the dendrimer are relatively well localized and the entire structure cannot be modeled in terms of spherically symmetric models. No backfolding of the terminal groups can occur and the model calculations demonstrate that higher generations of this dendritic scaffold must exhibit a dense shell and a congestion of the terminal groups. This finding is directly corroborated by recent solid-state NMR data. All results show that the rigid dendrimer investigated here presents the first example for a dendritic structure whose segment density does not have its maximum at the center. Rigid scaffolds are therefore the only way to achieve the goal of a 'dense-shell' dendrimer whereas flexible scaffolds leads invariably to the 'dense-core' case

  19. Development of TREN dendrimers over mesoporous SBA-15 for CO2 adsorption

    Bhagiyalakshmi, Margandan; Park, Sang Do; Cha, Wang Seog; Jang, Hyun Tae

    2010-01-01

    Mesoporous SBA-15 was synthesized using rice husk ash (RHA) as the silica source and their defective Si-OH groups were grafted with tris(2-aminoethyl) amine (TREN) dendrimers generation through step-wise growth technique. The X-ray diffraction (XRD) and nitrogen adsorption/desorption results of parent SBA-15 obtained from RHA, suggests its resemblance with SBA-15 synthesized using conventional silica sources. Furthermore, the nitrogen adsorption/desorption results of SBA-15/TREN dendrimer generations (G1-G3) illustrates the growth of dendrimer inside the mesopores of SBA-15 and their CO 2 adsorption capacity was determined at 25 deg. C. The maximum CO 2 adsorption capacity of 5-6 and 7-8 wt% over second and third dendrimer generation was observed which is discernibly higher than the reported melamine and PAMAM dendrimers. The experimental CO 2 adsorption capacity was found to be less than theoretically calculated CO 2 adsorption capacity due to inter and intra molecular amidation as result of steric hindrance during the dendrimer growth. These SBA-15/TREN dendrimer generations also exhibit thermal stability up to 350 deg. C and CO 2 adsorption capacity remains unaltered upon seven consecutive runs.

  20. PEGylation of polylysine dendrimers improves absorption and lymphatic targeting following SC administration in rats.

    Kaminskas, Lisa M; Kota, Jagannath; McLeod, Victoria M; Kelly, Brian D; Karellas, Peter; Porter, Christopher Jh

    2009-12-03

    Polylysine dendrimers have potential as highly flexible, biodegradable nanoparticular carriers that may also promote lymphatic transport. The current study was undertaken to determine the impact of PEGylation on the absorption and lymphatic transport of polylysine dendrimers modified by surface derivatisation with PEG (200, 570 or 2000Da) or 4-benzene sulphonate following SC or IV dosing. PEGylation led to the PEG(200) derived dendrimer being rapidly and completely absorbed into the blood after SC administration, however only 3% of the administered dose was recovered in pooled thoracic lymph over 30h. Increasing the PEG chain length led to a systematic decrease in absorption into the blood and an enhancement of the proportion recovered in the lymphatics (up to 29% over 30h). For the PEG(570) and PEG(2000) derived dendrimers, indirect access to the lymph via equilibration across the capillary beds also appeared to play a role in lymphatic targeting after both IV and SC dosing. In contrast, the anionic benzene sulphonate-capped dendrimer was not well absorbed from the SC injection site (26% bioavailability) into either the blood or the lymph. The data suggest that PEGylated poly-L-lysine dendrimers are well absorbed from SC injection sites and that the extent of lymphatic transport may be enhanced by increasing the size of the PEGylated dendrimer complex.

  1. Effect of generation on the electronic properties of light-emitting dendrimers

    Burn, Paul L.; Halim, Mounir; Pillow, Jonathan N. G.; Samuel, Ifor D. W.

    1999-12-01

    We have compared the optical and electronic properties of a series of porphyrin centered dendrimers containing stilbene dendrons. The first and second generation dendrimers could be spin-coated from solution to form good quality thin films. Incorporation into single layer light-emitting diodes gave red-light emission with maximum external quantum efficiencies of 0.02% and 0.04% for the first and second generation dendrimers respectively. We have determined by photoluminescence studies that energy can be transferred efficiently from the stilbene dendrons to the porphyrin core and that PL emission is from the core. Cyclic voltammetry studies on the dendrimers show that the reductions are porphyrin centered with the dendrons only affecting the rate of heterogeneous electron transfer between the electrode and the dendrimers. This suggests that charge mobility within a dendrimer film in an LED will be affected by the porphyrin edge to porphyrin edge distance. We have studied the hydrodynamic radii of the dendrimers by gel permeation chromatography and found as expected that the average porphyrin edge to dendron edge distance increases with generation. This is consistent with the slowing of heterogeneous electron transfer observed in the cyclic voltammetry on increasing the generation number and suggests that the dendrons are interleaved in the solid state to facilitate charge transport.

  2. Transepithelial transport of PAMAM dendrimers across isolated rat jejunal mucosae in ussing chambers.

    Hubbard, Dallin; Ghandehari, Hamidreza; Brayden, David J

    2014-08-11

    Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.5 and amine-terminated G4 PAMAM dendrimers was assessed using isolated rat jejunal mucosae mounted in Ussing chambers. The 1 mM FITC-labeled dendrimers were added to the apical side of mucosae. Apparent permeability coefficients (Papp) from the apical to the basolateral side were significantly increased for FITC when conjugated to G3.5 PAMAM dendrimer compared to FITC alone. Minimal signs of toxicity were observed when mucosae were exposed to both dendrimers with respect to transepithelial electrical resistance changes, carbachol-induced short circuit current stimulation, and histological changes. [(14)C]-mannitol fluxes were not altered in the presence of 1 mM dendrimers, suggesting that the paracellular pathway was not affected at this concentration in this model. These results give insight into the mechanism of PAMAM dendrimer transepithelial rat jejunal transport, as well as toxicological considerations important for oral drug delivery.

  3. Cholesterol-conjugated supramolecular assemblies of low generations polyamidoamine dendrimers for enhanced EGFP plasmid DNA transfection

    Golkar, Nasim; Samani, Soliman Mohammadi; Tamaddon, Ali Mohammad, E-mail: amtamadon@gmail.com [Shiraz University of Medical Sciences, Department of Pharmaceutics, School of Pharmacy (Iran, Islamic Republic of)

    2016-05-15

    Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and {sup 1}H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (<50 µg/ml) depending on the dendrimer generation and cholesterol/amine mole ratio. Cholesterol conjugation resulted in higher resistance of the condensed plasmid DNA in a competition assay with heparin sulfate. Also, the transfection efficiency was determined higher for the cholesterol conjugates than unmodified dendrimers in HepG2 cells, showing the highest for G2-Chol at 40 % degree of cholesterol modification (G2-Chol{sub 40 %}) among various dendrimer generations. Interestingly, such conjugate showed a complete protection of plasmid against serum nucleases. Our results confirmed that the cholesterol conjugation to PAMAM dendrimers of low generations bearing little cytotoxicity improves their several physicochemical and biological characteristics required for an enhanced delivery of plasmid DNA into cells.

  4. Phosphorus Dendrimers as Carriers of siRNA—Characterisation of Dendriplexes

    Jean-Pierre Majoral

    2013-04-01

    Full Text Available There are many types of dendrimers used as nanomolecules for gene delivery but there is still an ongoing search for ones that are able to effectively deliver drugs to cells. The possibility of gene silencing using siRNA gives hope for effective treatment of numerous diseases. The aim of this work was to investigate in vitro biophysical properties of dendriplexes formed by siRNA and cationic phosphorus dendrimers of 3rd and 4th generation. First, using the ethidium bromide intercalation method, it was examined whether dendrimers have an ability to form complexes with siRNA. Next, the characterisation of dendriplexes formed at different molar ratios was carried out using biophysical methods. The effects of zeta potential, size and changes of siRNA conformation on the complexation with dendrimers were examined. It was found that both phosphorus dendrimers interacted with siRNA. The zeta potential values of dendriplexes ranged from negative to positive and the hydrodynamic diameter depended on the number of dendrimer molecules in the complex. Furthermore, using circular dichroism spectroscopy it was found that cationic phosphorus dendrimers changed only slightly the shape of siRNA CD spectra, thus they did not induce significant changes in the nucleic acid secondary structure during complex formation.

  5. Functionalized linear and cyclic polyolefins

    Tuba, Robert; Grubbs, Robert H.

    2018-02-13

    This invention relates to methods and compositions for preparing linear and cyclic polyolefins. More particularly, the invention relates to methods and compositions for preparing functionalized linear and cyclic polyolefins via olefin metathesis reactions. Polymer products produced via the olefin metathesis reactions of the invention may be utilized for a wide range of materials applications. The invention has utility in the fields of polymer and materials chemistry and manufacture.

  6. Multifunctional Dendrimer-templated Antibody Presentation on Biosensor Surfaces for Improved Biomarker Detection.

    Han, Hye Jung; Kannan, Rangaramanujam M; Wang, Sunxi; Mao, Guangzhao; Kusanovic, Juan Pedro; Romero, Roberto

    2010-02-08

    Dendrimers, with their well-defined globular shape and a high density of functional groups, are ideal nanoscale materials for templating sensor surfaces. This work exploits dendrimers as a versatile platform for capturing biomarkers with improved sensitivity and specificity. Synthesis, characterization, fabrication, and functional validation of the dendrimer-based assay platform are described. Bifunctional hydroxyl/thiol functionalized G4-polyamidoamine (PAMAM) dendrimer is synthesized and immobilized on to the polyethylene-glycol (PEG)-functionalized assay plate by coupling PEG-maleimide and dendrimer thiol groups. Simultaneously, part of the dendrimer thiol groups are converted to hydrazide functionalities. The resulting dendrimer-modified surface is coupled to the capture antibody in the Fc region of the oxidized antibody. This preserves the orientation flexibility of the antigen binding region (Fv) of the antibody. To validate the approach, the fabricated plates are further used as a solid phase for developing a sandwich type ELISA to detect IL-6 and IL-1β, important biomarkers for early stages of chorioamnionitis. The dendrimer-modified plate provides assays with significantly enhanced sensitivity, lower nonspecific adsorption, and a detection limit of 0.13 pg ml -1 for IL-6 luminol detection and 1.15 pg ml -1 for IL-1β TMB detection, which are significantly better than those for the traditional ELISA. The assays were validated in human serum samples from normal (non-pregnant) woman and pregnant women with pyelonephritis. The specificity and the improved sensitivity of the dendrimer-based capture strategy could have significant implications for the detection of a wide range of cytokines and biomarkers since the capture strategy could be applied to multiplex microbead assays, conductometric immunosensors and field effect biosensors.

  7. Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

    Narsireddy A

    2015-11-01

    Full Text Available Amreddy Narsireddy,1 Kurra Vijayashree,2 Mahesh G Adimoolam,1 Sunkara V Manorama,1 Nalam M Rao21CSIR – Indian Institute of Chemical Technology, 2CSIR – Centre for Cellular and Molecular Biology, Hyderabad, IndiaAbstract: Challenges in photodynamic therapy (PDT include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl-21H,23H-porphine [PS] and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine dendrimer (G4 was conjugated with a PS and a nitrilotriacetic acid (NTA group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.Keywords: photodynamic therapy, dendrimers, nanoparticle, targeted delivery, Affibody, xenograft animal model

  8. Synthesis and Characterization of Poly(Amidoamine Dendrimers Encapsulatd 198Au Nanoparticles

    R. Ritawidya1,2

    2012-12-01

    Full Text Available Brachytherapy or internal radiotherapy is one of many methods used for treatment of cancer. This modality requires an agent with radionuclides that emits  or β particle with a proper energy. 198Au (99% β max = 0.96 MeV and t1/2 = 2.69 days is one of radionuclides that has been considered to be effective for the above-mentioned purpose. The purpose of this research was to synthesis and characterize poly(amidoamine (PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles as a new brachytherapy agent. PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles was successfully synthesized by a bottom-up method using sodium borohydride as a reductor. Purification was then performed by a size exclusion chromatography in order to separate large Au nanoparticles that were formed outside the cavity of PAMAM G3.0 dendrimers. Prior to the synthesis of PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles, the synthetic procedure was first established by using a non-radioactive Au. The PAMAM G3.0 dendrimers encapsulated Au nanoparticles produced was then characterized by using an UV-Vis spectroscopy, a transmission electron microscopy (TEM, particle size analyzer (PSA, and an atomic absorption spectroscopy (AAS. Characterization results revealed that PAMAM G3.0 dendrimers encapsulated Au nanoparticles that were prepared from a reaction mixture of PAMAM G3.0 dendrimers and Au HAuCl4 with mol ratio of 2.8, was found to be a proper formula. It produced PAMAM G3.0 dendrimers encapsulated Au nanoparticles with diameter of 1.743 nm, spheris, uniform and drug loading value of 26.34%. This formula was then used in synthesis using radioactive Au, 198Au. Characterization results of PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles gave a radiochemical purity of 99.4% and zero charge.

  9. Diverse assemblies of the (4,4) grid layers exemplified in Zn(II)/Co(II) coordination polymers with dual linear ligands

    Liu, Guang-Zhen; Li, Xiao-Dong; Xin, Ling-Yun; Li, Xiao-Ling [College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang, Henan 471022 (China); Wang, Li-Ya, E-mail: wlya@lynu.edu.cn [College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang, Henan 471022 (China); College of Chemistry and Pharmacy Engineering, Nanyang Normal University, Nanyang, Henan 473061 (China)

    2013-07-15

    Diverse (4,4) grid layers are exemplified in five two-dimensional coordination polymers with dual µ{sub 2}-bridged ligands, namely, ([Zn(cbaa)(bpp)]·H{sub 2}O){sub n} (1), [Zn{sub 2}(cbaa){sub 2}(bpy)]{sub n} (2), [Co{sub 2}(cbaa){sub 2}(bpp){sub 2}]{sub n} (3), [Co(cbaa)(bpp)]{sub n} (4), and [Co(bdaa)(bpp)(H{sub 2}O){sub 2}]{sub n} (5) (H{sub 2}cbaa=4-carboxybenzeneacetic acid, bpp=1,3-di(4-pyridyl)propane, bpy=4,4′-bipyridyl, and H{sub 2}bdaa=1,4-benzenediacrylic acid). For 1, two (4,4) grid layers with [ZnN{sub 2}O{sub 2}] tetrahedron as the node are held together by lattice water forming a H-bonding bilayer. Individual (4,4) grid layer in 2 is based on (Zn{sub 2}(OCO){sub 4}) paddlewheel unit as the node. Two (4,4) grid layers with (Co{sub 2}O(OCO){sub 2}) dimer as the node are covalently interconnected by organic ligands affording a thick bilayer of 3 with new framework topology. The different entanglements between two coincident (4,4) grid layers with [CoN{sub 2}O{sub 4}] octahedron as the node leads to two 2D→2D interpenetrated structures for 4 and 5. Furthermore, fluorescent properties of 1 and 2 as well as magnetic properties of 3 are investigated. - Graphical abstract: Diverse assemblies of the (4,4) grid layers with different network nodes forms five coordination polymers that are well characterized by IR, TGA, element analysis, fluorescent and magnetic measurement. - Highlights: • Diverse assemblies of the (4,4) grid layers with different structural units as the nodes. • A new topology type with the uninodal 6-connected net of (4{sup 12}.5{sup 2}.6) is found. • Intense fluorescence emissions with a rare blue-shift of 55 nm compared to free carboxylate ligand.

  10. Photoinduced Electron Transfer of PAMAM Dendrimer-Zinc(II) Porphyrin Associates at Polarized Liquid|Liquid Interfaces.

    Nagatani, Hirohisa; Sakae, Hiroki; Torikai, Taishi; Sagara, Takamasa; Imura, Hisanori

    2015-06-09

    The heterogeneous photoinduced electron-transfer reaction of the ion associates between NH2-terminated polyamidoamine (PAMAM) dendrimers and 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato zinc(II) (ZnTPPS(4-)) was studied at the polarized water|1,2-dichloroethane (DCE) interface. The positive photocurrent arising from the photoreduction of ZnTPPS(4-) by a lipophilic quencher, decamethylferrocene, in the interfacial region was significantly enhanced by the ion association with the PAMAM dendrimers. The photocurrent response of the dendrimer-ZnTPPS(4-) associates was dependent on the pH condition and on the generation of dendrimer. A few cationic additives such as polyallylamine and n-octyltrimethyammonium were also examined as alternatives to the PAMAM dendrimer, but the magnitude of the photocurrent enhancement was rather small. The high photoreactivity of the dendrimer-ZnTPPS(4-) associates was interpreted mainly as a result of the high interfacial concentration of photoreactive porphyrin units associated stably with the dendrimer which was preferably adsorbed at the polarized water|DCE interface. The photochemical data observed in the second and fourth generation PAMAM dendrimer systems demonstrated that the higher generation dendrimer which can incorporate a porphyrin molecule more completely in the interior is less efficient for the photocurrent enhancement at the interface. These results indicated that the photoreactivity of ionic reactant at a polarized liquid|liquid interface can readily be modified via ion association with the charged dendrimer.

  11. Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

    Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath, E-mail: palakurthi@tamhsc.edu [Texas A and M Health Science Center, Irma Lerma Rangel College of Pharmacy (United States)

    2013-09-15

    Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH{sub 2} and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was {approx}11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC{sub 50} values in ovarian cancer cells when compared with carboxylate surface dendrimers (p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase (p < 0.05) in expression of apoptotic genes (Bcl2, Bax, p53) and 13.2- to 27.1-fold increase (p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

  12. Synthesis and in-vitro cytotoxicity of dendrimer cytostatic conjugates

    Scutaru, Ana Maria

    2011-01-01

    Bendamustine and melphalan are nitrogen mustard derivatives from the group of alkylating agents and are used for the treatment of various cancers such as chronic lymphocytic leukemia (CLL) or breast cancer. However their use is limited by numerous side effects. Therefore, 1,3,5-tris(3-aminopropyl)benzene (G0) and the G1 analogous 1,3,5-tris[3,5-bis(3-aminopropyl)-N-propylbenzamide]benzene were chosen to synthesize cytostatic-dendrimer conjugates and to achieve ‘tumor targeting' through the EP...

  13. Study of the complexation of oxacillin in 1-(4-Carbomethoxypyrrolidone)-terminated PAMAM dendrimers

    Hansen, Jon Stefan; Ficker, Mario; Petersen, Johannes Fabritius

    2013-01-01

    The complexation of oxacillin to three generations of 1-(4-carbomethoxypyrrolidone)-terminated PAMAM dendrimers was studied with NMR in CD3OD and CDCl3. The stochiometries, which were determined from Job plots, were found to be both solvent- and generation-dependent. The dissociation constants (Kd......) and Gibbs energies for complexation of oxacillin into the 1-(4-carbomethoxypyrrolidone)-terminated PAMAM dendrimer hosts were determined by (1)H NMR titrations and showed weaker binding of oxacillin upon increasing the size (generation) of the dendrimer....

  14. Enhancement of Muramyldipeptide (MDP) Immunostimulatory Activity by Controlled Multimerization on Dendrimers

    Sørensen, Nanna Skall; Boas, Ulrik; Heegaard, Peter M. H.

    2011-01-01

    Peptidoglycan is a widespread bacterial PAMP molecule and a powerful initiator of innate immune responses. It consists of repeating units of MDP, which as a monomer is only weakly immunostimulatory. Here, MDP-coupled dendrimers were prepared and investigated for stimulation of pig blood mononuclear...... cells. Compared to monomeric MDP, MDP-dendrimers induced a markedly enhanced production of IL-12 p40, IL-1β and IL-6 and completely down-regulated surface expression of B7 and MHC class II. These results suggest a possible novel strategy based on controlled multimerization of minimal PAMP motifs...... on dendrimers for preparing molecularly defined immunostimulators with predictable bioactivities....

  15. Dendrimer encapsulated Silver nanoparticles as novel catalysts for reduction of aromatic nitro compounds

    Asharani, I. V.; Thirumalai, D.; Sivakumar, A.

    2017-11-01

    Polyethylene glycol (PEG) core dendrimer encapsulated silver nanoparticles (AgNPs) were synthesized through normal chemical reduction method, where dendrimer acts as reducing and stabilizing agent. The encapsulated AgNPs were well characterized using TEM, DLS and XPS techniques. The synthesized AgNPs showed excellent catalytic activity towards the reduction of aromatic nitro compounds with sodium borohydride as reducing agent and the results substantiate that dendrimer encapsulated AgNPs can be an effective catalyst for the substituted nitro aromatic reduction reactions. Also the kinetics of different nitro compounds reductions was studied and presented.

  16. Interactions of Poly(amidoamine) Dendrimers with Human Serum Albumin: Binding Constants and Mechanisms

    Giri, Jyotsnendu; Diallo, Mamadou S.; Simpson, André J.; Liu, Yi; Goddard, William A., III; Kumar, Rajeev; Woods, Gwen C.

    2011-01-01

    The interactions of nanomaterials with plasma proteins have a significant impact on their in vivo transport and fate in biological fluids. This article discusses the binding of human serum albumin (HSA) to poly(amidoamine) [PAMAM] dendrimers. We use protein-coated silica particles to measure the HSA binding constants (K_b) of a homologous series of 19 PAMAM dendrimers in aqueous solutions at physiological pH (7.4) as a function of dendrimer generation, terminal group, and core chemistry. To g...

  17. Influence of Tm+3 concentration on the non-linear optical effects of the BiB3O6 : Tm3+ glass nanoparticle-doped polymer

    Majchrowski, A; Ebothe, J; Ozga, K; Kityk, I V; Reshak, A H; Lukasiewicz, T; Brik, M G

    2010-01-01

    It is shown that BiB 3 O 6 : Tm 3+ glass nanoparticles incorporated into polymethylmethacrylate (PMMA) and polycarbonate (PC) polymer matrices show good second-order susceptibilities under bicolour coherent laser treatment. It is found that only during incorporation into highly polarized PC matrices could one observe an enhancement of the second-order susceptibilities with increasing laser treated power densities. The main increase is observed for all samples at power densities equal to about 0.4 GW cm -2 . After passing this value there is a saturation of the output susceptibilities and even an abrupt decrease. The most striking feature is the achievement of second-order susceptibilities equal to about 5 pm V -1 for samples containing 4% nanoparticle (NP) content in the PC matrix. A further increase in the NP concentration to 6% leads to a decrease in susceptibility to 15%. In the case of PMMA matrices these changes do not exceed the background. The same situation is present for the pure BIBO and low-doped Tm materials. The effect is maximal for a low concentration of Tm-about 0.75%. In the case of bulk glasses the intensity dependences of the second-harmonic generation unambiguously show that the achieved maximal values of second-order susceptibilities do not exceed 3 pm V -1 for 0.5% Tm concentration.

  18. Ultra-small lipid-dendrimer hybrid nanoparticles as a promising strategy for antibiotic delivery: In vitro and in silico studies.

    Sonawane, Sandeep J; Kalhapure, Rahul S; Rambharose, Sanjeev; Mocktar, Chunderika; Vepuri, Suresh B; Soliman, Mahmoud; Govender, Thirumala

    2016-05-17

    The purpose of this study was to explore the preparation of a new lipid-dendrimer hybrid nanoparticle (LDHN) system to effectively deliver vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) infections. Spherical LDHNs with particle size, polydispersity index and zeta potential of 52.21±0.22 nm, 0.105±0.01, and -14.2±1.49 mV respectively were prepared by hot stirring and ultrasonication using Compritol 888 ATO, G4 PAMAM- succinamic acid dendrimer, and Kolliphor RH-40. Vancomycin encapsulation efficiency (%) in LDHNs was almost 4.5-fold greater than in lipid-polymer hybrid nanoparticles formulated using Eudragit RS 100. Differential scanning calorimetry and Fourier transform-infrared studies confirmed the formation of LDHNs. The interactions between the drug-dendrimer complex and lipid molecules using in silico modeling revealed the molecular mechanism behind the enhanced encapsulation and stability. Vancomycin was released from LDHNs over the period of 72 h with zero order kinetics and super case II transport mechanism. The minimum inhibitory concentration (MIC) against S. aureus and MRSA were 15.62 μg/ml and 7.81 μg/ml respectively. Formulation showed sustained activity with MIC of 62.5 μg/ml against S. aureus and 500 μg/ml against MRSA at the end of 72 and 54 h period respectively. The results suggest that the LDHN system can be an effective strategy to combat resistant infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. The effect of the triblock properties on the morphologies and photophysical properties of nanoparticle loaded with carboxylic dendrimer phthalocyanine

    Lv, Huafei; Chen, Zhe; Yu, Xinxin; Pan, Sujuan; Zhang, Tiantian; Xie, Shusen; Yang, Hongqin; Peng, Yiru

    2016-09-01

    Photodynamic therapy (PDT) is an emerging alternative treatment for various cancers and age-related macular degeneration. Phthalocyanines (Pcs) and their substituted derivatives are under intensive investigation as the second generation photosensitizers. A big challenge for the application of Pcs is poor solubility and limited accumulation in the tumor tissues, which severely reduced its PDT efficacy. Nano-delivery systems such as polymeric micelles are promising tools for increasing the solubility and improving delivery efficiency of Pcs for PDT application. In this paper, nanoparticles of amphiphilic triblock copolymer poly(L-lysine)-b-poly (ethylene glycol)-b-poly(L-lysine) were developed to encapsulate 1-2 generation carboxylic poly (benzyl aryl ether) dendrimer. The morphologies and photophysical properties of polymeric nanoparticles loaded with 1-2 generation dendritic phthalocyanines (G1-ZnPc(COOH)8/m and G2-ZnPc(COOH)16/m) were studied by AFM, UV/Vis and fluorescent spectroscopic method. The morphologies of self-assembled PLL-PEG-PLL aggregates exhibited concentration dependence. Its morphologies changed from cocoon-like to spheral. The diameters of G1-ZnPc(COOH)8/m and G2-ZnPc(COOH)16/m were in the range of 33-147 nm, increasing with the increase of the concentration of PLL-PEG-PLL. The morphologies of G2-ZnPc(COOH)16/m also changed from cocoon-like to sphere with the increase of the concentration of PLL-PEG-PLL. It was found that, the no obviously Q change was observed between the free phthalocyanines and nanoparticles. The fluorescence intensity of polymer nanoparticles were higher enhanced compared with free dendritic phthalocyanines. The dendrimer phthalocyanine loaded with poly(L-lysine)-b-poly (ethylene glycol)-b-poly(L-lysine) presented suitable physical stability, improved photophysical properties suggesting it may be considered as a promising formulation for PDT.

  20. Sulfur polymer cement concrete

    Weber, H.H.; McBee, W.C.

    1990-01-01

    Sulfur-based composite materials formulated using sulfur polymer cement (SPC) and mineral aggregates are described and compared with conventional portland cement based materials. Materials characteristics presented include mechanical strength, chemical resistance, impact resistance, moisture permeation, and linear shrinkage during placement and curing. Examples of preparation and placement of sulfur polymer cement concrete (SC) are described using commercial scale equipment. SC applications presented are focused into hostile chemical environments where severe portland cement concrete (PCC) failure has occurred

  1. Amperometric biosensor based on carbon nanotubes coated with polyaniline/dendrimer-encapsulated Pt nanoparticles for glucose detection

    Xu Lihuan; Zhu Yihua; Yang Xiaoling; Li Chunzhong

    2009-01-01

    A novel amperometric glucose biosensor based on the nanocomposites of multi-wall carbon nanotubes (CNT) coated with polyaniline (PANI) and dendrimer-encapsulated Pt nanoparticles (Pt-DENs) is prepared. CNT coated with protonated PANI is in situ synthesized and Pt-DENs is absorbed on PANI/CNT composite surface by self-assembly method. Then Glucose oxidase (GOx) is crosslink-immobilizated onto Pt-DENs/PANI/CNT composite film. The results show that the fabricated GOx/Pt-DENs/PANI/CNT electrode exhibits excellent response performance to glucose, such as low detection limit (0.5 μM), wide linear range (1 μM-12 mM), short response time (about 5 s), high sensitivity (42.0 μA mM -1 cm -2 ) and stability (83% remains after 3 weeks).

  2. Biodegradable Polymers

    Vroman, Isabelle; Tighzert, Lan

    2009-01-01

    Biodegradable materials are used in packaging, agriculture, medicine and other areas. In recent years there has been an increase in interest in biodegradable polymers. Two classes of biodegradable polymers can be distinguished: synthetic or natural polymers. There are polymers produced from feedstocks derived either from petroleum resources (non renewable resources) or from biological resources (renewable resources). In general natural polymers offer fewer advantages than synthetic polymers. ...

  3. SU-F-T-44: A Comparison of the Pre-Plan, Intra-Operative Plan, and Post-Implant Dosimetry for a Prostate Implant Case Using Prefabricated Linear Polymer-Encapsulated Pd-103

    Sheu, R; Powers, A; McGee, H; Stock, R; Lo, Y

    2016-01-01

    Purpose: To investigate the reproducibility and limitations of Pd-103 prostate brachytherapy using fixed length linear sources (CivaString). Methods: An LDR prostate brachytherapy case which was preplanned on MR images with prefabricated linear polymer-encapsulated Pd-103 sources (CivaString) was studied and compared with ultrasound based intra-operative planning and CT based post-implant dosimetry. We evaluated the following parameters among the three studies: prostate geometry (volume and cross sectional area), needle position and alignment deviations, and dosimetry parameters (D90). Results: The prostate volumes and axial cross sectional areas at center of prostate were measured as 41.8, 39.3 and 36.8 cc, and 14.9, 14.3, and 11.3 respectively on pre-plan MR, inter-op US, and post-implant CT studies. The deviation of prostate volumes and axial cross sectional areas measured on pre-planning MR and intra-operative US were within 5%. 17 out of 19 pre-planned needles were positioned within 5mm (the template grid size). One needle location was adjusted intra-operatively and another needle was removed due to proximity to urethra. The needle pathways were not always parallel to the trans-rectal probe due to the flexibility of CivaString. The angle of deviation was up to 10 degrees. Two pairs of needles were exchanged to better fit the length of prostate at the time of implant. This resulted in a prostate D90 of 153.8 Gy (124%) and 131.4 Gy (106.7%) for intra-op and PID respectively. Conclusion: Preplanning is a necessary part of implants performed with prefabricated linear polymer sources. However, as is often the case, there were real-time deviations from the pre-plan. Intra-op planning provides the ability conform to anatomy at the time of implant. Therefore, we propose to develop a systematic way to order extra strings of different length to provide the flexibility to perform intra-operative planning with fixed length strands.

  4. SU-F-T-44: A Comparison of the Pre-Plan, Intra-Operative Plan, and Post-Implant Dosimetry for a Prostate Implant Case Using Prefabricated Linear Polymer-Encapsulated Pd-103

    Sheu, R; Powers, A; McGee, H; Stock, R; Lo, Y [Mount Sinai Medical Center, New York, NY (United States)

    2016-06-15

    Purpose: To investigate the reproducibility and limitations of Pd-103 prostate brachytherapy using fixed length linear sources (CivaString). Methods: An LDR prostate brachytherapy case which was preplanned on MR images with prefabricated linear polymer-encapsulated Pd-103 sources (CivaString) was studied and compared with ultrasound based intra-operative planning and CT based post-implant dosimetry. We evaluated the following parameters among the three studies: prostate geometry (volume and cross sectional area), needle position and alignment deviations, and dosimetry parameters (D90). Results: The prostate volumes and axial cross sectional areas at center of prostate were measured as 41.8, 39.3 and 36.8 cc, and 14.9, 14.3, and 11.3 respectively on pre-plan MR, inter-op US, and post-implant CT studies. The deviation of prostate volumes and axial cross sectional areas measured on pre-planning MR and intra-operative US were within 5%. 17 out of 19 pre-planned needles were positioned within 5mm (the template grid size). One needle location was adjusted intra-operatively and another needle was removed due to proximity to urethra. The needle pathways were not always parallel to the trans-rectal probe due to the flexibility of CivaString. The angle of deviation was up to 10 degrees. Two pairs of needles were exchanged to better fit the length of prostate at the time of implant. This resulted in a prostate D90 of 153.8 Gy (124%) and 131.4 Gy (106.7%) for intra-op and PID respectively. Conclusion: Preplanning is a necessary part of implants performed with prefabricated linear polymer sources. However, as is often the case, there were real-time deviations from the pre-plan. Intra-op planning provides the ability conform to anatomy at the time of implant. Therefore, we propose to develop a systematic way to order extra strings of different length to provide the flexibility to perform intra-operative planning with fixed length strands.

  5. Study of the interactions of PAMAM-NH2 G4 dendrimer with selected natural amino acids in aqueous solutions

    Buczkowski, Adam; Palecz, Bartlomiej

    2014-01-01

    Highlights: • Calorimetric titration and dilution calorimetry show strong interactions between PAMAM-NH 2 G4 dendrimer and amino acids. • The more polar the amino acid side chain, the more exothermic the effects of the direct interactions with dendrimer. • Macromolecule of PAMAM-NH 2 G4 dendrimer can coordinate 20 to 40 molecules of amino acid. -- Abstract: The interactions of PAMAM-NH 2 G4 dendrimer with selected natural amino acids (Gly, Ala, Val, Leu, Ile, Phe, Ser, Thr, Met, Asn, Gln, Pro and Trp) in aqueous solutions were measured with the use of the techniques of calorimetric titration and dilution calorimetry. The results of calorimetric measurements show strong interactions between PAMAM-NH 2 G4 dendrimer and amino acids with polar substituents. A macromolecule of PAMAM-NH 2 G4 dendrimer can coordinate 20 to 40 molecules of amino acid

  6. Dendrimer-based Macromolecular MRI Contrast Agents: Characteristics and Application

    Hisataka Kobayashi

    2003-01-01

    Full Text Available Numerous macromolecular MRI contrast agents prepared employing relatively simple chemistry may be readily available that can provide sufficient enhancement for multiple applications. These agents operate using a ~100-fold lower concentration of gadolinium ions in comparison to the necessary concentration of iodine employed in CT imaging. Herein, we describe some of the general potential directions of macromolecular MRI contrast agents using our recently reported families of dendrimer-based agents as examples. Changes in molecular size altered the route of excretion. Smaller-sized contrast agents less than 60 kDa molecular weight were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Hydrophilic and larger-sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants formed with polypropylenimine diaminobutane dendrimer cores created liver contrast agents. Larger hydrophilic agents are useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents, which also might be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

  7. Synthetic Strategies towards Fullerene-Rich Dendrimer Assemblies

    Jean-François Nierengarten

    2012-02-01

    Full Text Available The sphere-shaped fullerene has attracted considerable interest not least due to the peculiar electronic properties of this carbon allotrope and the fascinating materials emanating from fullerene-derived structures. The rapid development and tremendous advances in organic chemistry allow nowadays the modification of C60 to a great extent by pure chemical means. It is therefore not surprising that the fullerene moiety has also been part of dendrimers. At the initial stage, fullerenes have been examined at the center of the dendritic structure mainly aimed at possible shielding effects as exerted by the dendritic environment and light-harvesting effects due to multiple chromophores located at the periphery of the dendrimer. In recent years, also many research efforts have been devoted towards fullerene-rich nanohybrids containing multiple C60 units in the branches and/or as surface functional groups. In this review, synthetic efforts towards the construction of dendritic fullerene-rich nanostructures have been compiled and will be summarized herein.

  8. Morphological and structural characterizations of dendrimer-mediated metallic Ti and Al thin film nanocomposites

    Curry, M. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Li, X. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Department of Metallurgical and Materials Science and Engineering, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Zhang, J. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Weaver, M.L. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Department of Metallurgical and Materials Science and Engineering, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Street, S.C. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States) and Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487-0209 (United States)]. E-mail: sstreet@bama.ua.edu

    2007-02-26

    Evidence is presented here for significant influence on the surface topography of Ti and Al films in the presence of poly(amidoamine) dendrimer monolayers [generations G(4-8)] on SiO {sub x}. X-ray photoelectron spectroscopy analysis clearly indicates formation of nitrides and carbides for Ti metal grown on dendrimer monolayers. In addition, obvious trends in measured correlation lengths and crystalline growth modes of Ti films indicate grain sizes tracking the intrinsic roughness of dendrimer monolayers. No formation of metal nitride is observed for Al depositions. Atomic force microscopy analyses show significant changes in rms vertical roughness and aggregation of as-deposited Ti or Al in presence of dendrimer monolayers.

  9. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M.

    2016-01-01

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

  10. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M.

    2016-05-01

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

  11. Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities.

    Ciepluch, Karol; Weber, Monika; Katir, Nadia; Caminade, Anne-Marie; El Kadib, Abdelkrim; Klajnert, Barbara; Majoral, Jean Pierre; Bryszewska, Maria

    2013-03-01

    The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is the first step in checking whether new compounds can be considered as drugs for treating neurodegenerative diseases. The effect of viologen-phosphorus dendrimers on AChE and BChE activities was studied. The results show that the effects on the cholinesterase activities depend on dendrimer type and size. Viologen dendrimers can interact with the enzymes in two ways: they can bind either to a peripheral site of the enzyme or to amino acids located near the active site, inhibiting catalysis by both cholinesterases. All tested non-toxic viologen-phosphorus dendrimers inhibited the activities of both cholinesterases, showing their potential as new drugs for treating neurodegenerative diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M., E-mail: smavilac@cityu.edu.hk [City University of Hong Kong, Department of Physics and Materials Science (Hong Kong, People’s Republic of China) (China)

    2016-05-15

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

  13. Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

    Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

    2015-09-08

    Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

  14. Aptamer-conjugated dendrimer-modified quantum dots for glioblastoma cells imaging

    Li Zhiming; Huang Peng; He Rong; Bao Chenchen; Cui Daxiang; Zhang Xiaomin; Ren Qiushi

    2009-01-01

    Targeted quantum dots have shown potential as a platform for development of cancer imaging. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In present work, polyamidoamine dendrimers were used to modify surface of quantum dots and improve their solubility in water solution. Then, dendrimer-modified quantum dots were conjugated with DNA aptamer, GBI-10, can recognize the extracellular matrix protein tenascin-C on the surface of human glioblastoma cells. The dendrimer-modified quantum dots exhibit water-soluble, high quantum yield, and good biocompatibility. Aptamer-conjugated quantum dots can specifically target U251 human glioblastoma cells. High-performance aptamer-conjugated dendrimers modified quantum dot-based nanoprobes have great potential in application such as cancer imaging.

  15. Synthesis of Dendrimer Containing Dialkylated-fluorene Unit as a Core Chromophore via Click Chemistry

    Han, Seung Choul; Lee, Jae Wook; Jin, Sung Ho

    2012-01-01

    The convergent synthetic strategy for the emissive dendrimers having the chromophore at core via the coppercatalyzed 1,3-dipolar cycloaddition reaction between alkyne and azide was described. 2,7-Diazido-9,9-dioctyl- 9H-fluorene, designed to serve as the core in dendrimer, was stitched with the alkyne-functionalized Frechettype and PAMAM dendrons by the click chemistry leading to the formation of the corresponding fluorescent dendrimers in high yields. The preliminary photoluminescence studies indicated that 2,7-diazido-9,9-dioctyl- 9H-fluorene showed no fluorescence due to the quenching effect from the electron-rich α-nitrogen of the azido group but the dendrimers fluoresced due to the elimination of the quenching through the formation of the triazole ring

  16. Kinetic and thermodynamic study of the transfer of anionic polyamidoamine dendrimers across two immiscible liquids

    Gonzalez-Fuentes, Miguel A.; Manriquez, J.; Antano-Lopez, R.; Godinez, Luis A.

    2011-01-01

    The kinetics and thermodynamics for the phase transfer of carboxyl-terminated polyamidoamine (PAMAM) dendrimers across the water/dichloroethane interface were analyzed by cyclic voltammetry and electrochemical impedance spectroscopy. A three phase junction was employed by inserting a cylindrical gold electrode through the liquid-liquid interface. The reversible redox species decamethylferrocene (DMFc) was used in the organic phase in order to promote dendrimer transfer. It was found that the electrochemical behaviour of DMFc at the gold/dichloroethane interface depends on the generation and concentration of the dendrimer species in the aqueous phase. In addition, it was observed that the electrochemically driven transfer of these macromolecules corresponds to a quasi-reversible process. The data obtained from thermodynamic studies indicate that dendrimers are transferred between the two phases under study by an entropy controlled process.

  17. Iodine-Containing Mass-Defect-Tuned Dendrimers for Use as Internal Mass Spectrometry Calibrants

    Giesen, Joseph A.; Diament, Benjamin J.; Grayson, Scott M.

    2018-03-01

    Calibrants based on synthetic dendrimers have been recently proposed as a versatile alternative to peptides and proteins for both MALDI and ESI mass spectrometry calibration. Because of their modular synthetic platform, dendrimer calibrants are particularly amenable to tailoring for specific applications. Utilizing this versatility, a set of dendrimers has been designed as an internal calibrant with a tailored mass defect to differentiate them from the majority of natural peptide analytes. This was achieved by incorporating a tris-iodinated aromatic core as an initiator for the dendrimer synthesis, thereby affording multiple calibration points ( m/z range 600-2300) with an optimized mass-defect offset relative to all peptides composed of the 20 most common proteinogenic amino acids. [Figure not available: see fulltext.

  18. Effect of methotrexate conjugated PAMAM dendrimers on the viability of MES-SA uterine cancer cells

    Samreen Khatri

    2014-01-01

    Full Text Available The aim of this work was to synthesize methotrexate (MTX-polyamidoamine (PAMAM dendritic nanoconjugates and to study their effect on cell viability in uterine sarcoma cells. The amide-bonded PAMAM dendrimer-MTX conjugates were prepared by conjugation between the amine-terminated G5 dendrimer and the carboxylic groups of the MTX using a dicyclohexylcarbodiimide coupling reaction. The formation of conjugates was evaluated by ultraviolet (UV and 1 H nuclear magnetic resonance ( 1 H NMR spectroscopy studies. The cell survival of MES-SA cells, a uterine sarcoma cell line, was evaluated in the presence of the dendrimer-MTX nanoconjugate, using appropriate controls. The UV and 1 H NMR study confirmed the formation of covalent bonds between the drug and the dendrimer. The cell viability study indicated that the nanoconjugates had significantly improved cell killing compared to the free MTX.

  19. Interactive transport of guanidinylated poly(propylene imine)-based dendrimers through liposomal and cellular membranes.

    Tsogas, Ioannis; Sideratou, Zili; Tsiourvas, Dimitris; Theodossiou, Theodossis A; Paleos, Constantinos M

    2007-10-15

    The ability of guanidinylated poly(propylene imine) dendrimers to translocate across lipid bilayers was assessed by employing either a model phosphate-bearing liposomal membrane system or A549 human lung carcinoma cells. Two dendrimer generations, differing in the number of surface guanidinium groups, were employed, while surface acetylation or the use of spacers affected the binding of the guanidinium group to the phosphate moiety and finally the transport efficiency. Following adhesion of dendrimers with liposomes, fusion or transport occurred. Transport through the liposomal bilayer was observed at low guanidinium/phosphate molar ratios, and was enhanced when the bilayer was in the liquid-crystalline phase. For effective transport through the liposomal membrane, an optimum balance between the binding strength and the degree of hydrophobicity of the guanidinylated dendrimer is required. In experiments performed in vitro with cells, efficient penetration and internalization in subcellular organelles and cytosol was observed.

  20. Phosphorus-Based Dendrimer ABP Treats Neuroinflammation by Promoting IL-10-Producing CD4(+) T Cells.

    Hayder, Myriam; Varilh, Marjorie; Turrin, Cédric-Olivier; Saoudi, Abdelhadi; Caminade, Anne-Marie; Poupot, Rémy; Liblau, Roland S

    2015-11-09

    Dendrimers are polyfunctional nano-objects of perfectly defined structure that can provide innovative alternatives for the treatment of chronic inflammatory diseases, including multiple sclerosis (MS). To investigate the efficiency of a recently described amino-bis(methylene phosphonate)-capped ABP dendrimer as a potential drug candidate for MS, we used the classical mouse model of MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). Our study provides evidence that the ABP dendrimer prevents the development of EAE and inhibits the progression of established disease with a comparable therapeutic benefit as the approved treatment Fingolimod. We also show that the ABP dendrimer redirects the pathogenic myelin-specific CD4(+) T cell response toward IL-10 production.

  1. Antibacterial action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles against Escherichia coli correlated with molecular chain conformation

    Wen, Yan [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); School of Science, Tianjin University of Commerce, Tianjin 300134 (China); Yao, Fanglian, E-mail: yaofanglian@tju.edu.cn [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Sun, Fang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Tan, Zhilei [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300222 (China); Tian, Liang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Xie, Lei; Song, Qingchao [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300222 (China)

    2015-03-01

    The action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles (CM-HTCC/PAMAM) against Escherichia coli (E. coli) was investigated via a combination of approaches including measurements of cell membrane integrity, outer membrane (OM) and inner membrane (IM) permeability, and scanning electron microscopy (SEM). CM-HTCC/PAMAM dendrimer nanoparticles likely acted in a sequent event-driven mechanism, beginning with the binding of positively charged groups from nanoparticle surface with negative cell surface, thereby causing the disorganization of cell membrane, and subsequent leakage of intracellular components which might ultimately lead to cell death. Moreover, the chain conformation of polymers was taken into account for a better understanding of the antibacterial action mode by means of viscosity and GPC measurements. High utilization ratio of positive charge and large specific surface area generated from a compacted conformation of CM-HTCC/PAMAM, significantly different from the extended conformation of HTCC, were proposed to be involved in the antibacterial action. - Highlights: • The nanoparticles exerted antibacterial activity in a sequent event-driven manner. • Electrostatic interaction and surface adsorption shared roles in antibacterial mode. • The two factors were controlled by the compacted conformation of nanoparticles.

  2. Antibacterial action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles against Escherichia coli correlated with molecular chain conformation

    Wen, Yan; Yao, Fanglian; Sun, Fang; Tan, Zhilei; Tian, Liang; Xie, Lei; Song, Qingchao

    2015-01-01

    The action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles (CM-HTCC/PAMAM) against Escherichia coli (E. coli) was investigated via a combination of approaches including measurements of cell membrane integrity, outer membrane (OM) and inner membrane (IM) permeability, and scanning electron microscopy (SEM). CM-HTCC/PAMAM dendrimer nanoparticles likely acted in a sequent event-driven mechanism, beginning with the binding of positively charged groups from nanoparticle surface with negative cell surface, thereby causing the disorganization of cell membrane, and subsequent leakage of intracellular components which might ultimately lead to cell death. Moreover, the chain conformation of polymers was taken into account for a better understanding of the antibacterial action mode by means of viscosity and GPC measurements. High utilization ratio of positive charge and large specific surface area generated from a compacted conformation of CM-HTCC/PAMAM, significantly different from the extended conformation of HTCC, were proposed to be involved in the antibacterial action. - Highlights: • The nanoparticles exerted antibacterial activity in a sequent event-driven manner. • Electrostatic interaction and surface adsorption shared roles in antibacterial mode. • The two factors were controlled by the compacted conformation of nanoparticles

  3. Adsorption of precious metals in water by dendrimer modified magnetic nanoparticles

    Yen, Chia-Hsin [Institute of Environmental Engineering, National Chiao Tung University, 300 Hsinchu, Taiwan (China); Lien, Hsing-Lung, E-mail: lien.sam@nuk.edu.tw [Department of Civil and Environmental Engineering, National University of Kaohsiung, 811 Kaohsiung, Taiwan (China); Chung, Jung-Shing [Department of Civil and Environmental Engineering, National University of Kaohsiung, 811 Kaohsiung, Taiwan (China); Yeh, Hund-Der [Institute of Environmental Engineering, National Chiao Tung University, 300 Hsinchu, Taiwan (China)

    2017-01-15

    Highlights: • A reusable magnetic nano-adsorbent is prepared for precious metal adsorption. • The nano-adsorbent (MNP-G3) is synthesized by magnetic nanoparticles and dendrimer. • Higher valent ions show higher adsorption capacity by MNP-G3 suggesting complexation involved. • The pseudo second-order model best describe the adsorption kinetics. • MNP-G3 modified by EDTA significantly improve its adsorption ability for Ag(I). - Abstract: Magnetic nanoparticles modified by third-generation dendrimers (MNP-G3) and MNP-G3 further modified by ethylenediaminetetraacetic acid (EDTA) (MNP-G3-EDTA) were conducted to investigate their ability for recovery of precious metals (Pd(IV), Au(III), Pd(II) and Ag(I)) in water. Experiments were carried out using batch reactors for the studies of adsorption kinetics, adsorption isotherms, competitive adsorption and regeneration. The pseudo second-order model is the best-fit model among others suggesting that the adsorption of precious metals by MNP-G3 in water is a chemisorption process. Three adsorption isotherms namely Langmuir, Freundlich and Dubinin-Radushkevich isotherm were examined and the results showed the similarities and consistency of both linear and nonlinear analyses. Pd(IV) and Au(III) with higher valence exhibited relatively better adsorption efficiency than Pd(II) and Ag(I) with lower valence suggesting that the adsorption of precious metals by MNP-G3 is a function of valence. In the presence of the competing ion Zn(II), the adsorption efficiency of MNP-G3 for all four precious metals was declined significantly. The use of MNP-G3-EDTA revealed an increase in the adsorption efficiency for all four precious metals. However, the low selectivity of MNP-G3 towards precious metals was not enhanced by the modification of EDTA onto the MNP-G3. The regeneration of metal-laden MNP-G3 can be readily performed by using 1.0% HCl solution as a desorbent solution.

  4. Fate and transformation products of amine-terminated PAMAM dendrimers under ozonation and irradiation

    Santiago-Morales, Javier; Rosal, Roberto; Hernando, María D.; Ulaszewska, Maria M.; García-Calvo, Eloy; Fernández-Alba, Amadeo R.

    2014-01-01

    Highlights: • We detected transformation products from dendrimer under ozonation and irradiation. • Retro-Michael fragmentation pathway with highly oxygenated structures. • High toxicity of G3 PAMAM dendrimer for green algae. • Reactive oxygen species were associated with the toxic damage. • Transformation mixtures could be more toxic than the parent dendrimer. -- Abstract: This article deals with the degradation of a third-generation (G3) poly(amidoamine) (PAMAM) dendrimer under ozonation and irradiation. The identification and quantification of G3 PAMAM dendrimer and its transformation products has been performed by liquid chromatography–electrospray ionization-hybrid quadrupole time-of-flight-mass spectrometry. The dendrimer was completely depleted by ozone in less than 1 min. The effect of ultraviolet irradiation was attributed to hydroxyl-mediated oxidation. The transformation products were attributed to the oxidation of amines, which resulted in highly oxidized structures with abundance of carboxylic acids, which started from the formation of amine oxide and the scission of the C-N bond of the amide group. We studied the toxicity of treated mixtures for six different organisms: the acute toxicity for the bacterium Vibrio fischeri and the microcrustacean Daphnia magna, the multigenerational growth inhibition of the alga Pseudokirchneriella subcapitata, and the seed germination phytotoxicity of Licopersicon esculentum, Lactuca sativa and Lolium perenne. Ozonation and irradiation originated transformation products are more toxic than the parent dendrimer. The toxicity of the dendrimer for the green alga was linked to a strong increase of intracellular reactive oxygen species with intense lipid peroxidation

  5. Fate and transformation products of amine-terminated PAMAM dendrimers under ozonation and irradiation

    Santiago-Morales, Javier [Department of Chemical Engineering, University of Alcalá, 28871 Alcalá de Henares, Madrid (Spain); Rosal, Roberto, E-mail: roberto.rosal@uah.es [Department of Chemical Engineering, University of Alcalá, 28871 Alcalá de Henares, Madrid (Spain); Advanced Study Institute of Madrid, IMDEA Agua, Parque Científico Tecnológico, 28805 Alcalá de Henares, Madrid (Spain); Hernando, María D. [Spanish National Institute for Agricultural and Food Research and Technology – INIA, Crta. de la Coruña, km 7.5, 28040 Madrid (Spain); Ulaszewska, Maria M. [Advanced Study Institute of Madrid, IMDEA Agua, Parque Científico Tecnológico, 28805 Alcalá de Henares, Madrid (Spain); García-Calvo, Eloy [Department of Chemical Engineering, University of Alcalá, 28871 Alcalá de Henares, Madrid (Spain); Advanced Study Institute of Madrid, IMDEA Agua, Parque Científico Tecnológico, 28805 Alcalá de Henares, Madrid (Spain); Fernández-Alba, Amadeo R. [Advanced Study Institute of Madrid, IMDEA Agua, Parque Científico Tecnológico, 28805 Alcalá de Henares, Madrid (Spain); Pesticide Residue Research Group, Department of Hydrogeology and Analytical Chemistry, University of Almería, 04120 Almería (Spain)

    2014-02-15

    Highlights: • We detected transformation products from dendrimer under ozonation and irradiation. • Retro-Michael fragmentation pathway with highly oxygenated structures. • High toxicity of G3 PAMAM dendrimer for green algae. • Reactive oxygen species were associated with the toxic damage. • Transformation mixtures could be more toxic than the parent dendrimer. -- Abstract: This article deals with the degradation of a third-generation (G3) poly(amidoamine) (PAMAM) dendrimer under ozonation and irradiation. The identification and quantification of G3 PAMAM dendrimer and its transformation products has been performed by liquid chromatography–electrospray ionization-hybrid quadrupole time-of-flight-mass spectrometry. The dendrimer was completely depleted by ozone in less than 1 min. The effect of ultraviolet irradiation was attributed to hydroxyl-mediated oxidation. The transformation products were attributed to the oxidation of amines, which resulted in highly oxidized structures with abundance of carboxylic acids, which started from the formation of amine oxide and the scission of the C-N bond of the amide group. We studied the toxicity of treated mixtures for six different organisms: the acute toxicity for the bacterium Vibrio fischeri and the microcrustacean Daphnia magna, the multigenerational growth inhibition of the alga Pseudokirchneriella subcapitata, and the seed germination phytotoxicity of Licopersicon esculentum, Lactuca sativa and Lolium perenne. Ozonation and irradiation originated transformation products are more toxic than the parent dendrimer. The toxicity of the dendrimer for the green alga was linked to a strong increase of intracellular reactive oxygen species with intense lipid peroxidation.

  6. Magnetic properties of dendrimer structures with different coordination numbers: A Monte Carlo study

    Masrour, R.; Jabar, A.

    2016-11-01

    We investigate the magnetic properties of Cayley trees of large molecules with dendrimer structure using Monte Carlo simulations. The thermal magnetization and magnetic susceptibility of a dendrimer structure are given with different coordination numbers, Z=3, 4, 5 and different generations g=3 and 2. The variation of magnetizations with the exchange interactions and crystal fields have been given of this system. The magnetic hysteresis cycles have been established.

  7. Epitaxially Grown Ultra-Flat Self-Assembling Monolayers with Dendrimers

    Takane Imaoka

    2018-02-01

    Full Text Available Mono-molecular films formed by physical adsorption and dendrimer self-assembly were prepared on various substrate surfaces. It was demonstrated that a uniform dendrimer-based monolayer on the subnanometer scale can be easily constructed via simple dip coating. Furthermore, it was shown that an epitaxially grown monolayer film reflecting the crystal structure of the substrate (highly ordered pyrolytic graphite (HOPG can also be formed by aligning specific conditions.

  8. Charge transport properties of carbazole dendrimers in organic field-effect transistors

    Mutkins, Karyn; Chen, Simon S. Y.; Aljada, Muhsen; Powell, Ben J.; Olsen, Seth; Burn, Paul L.; Meredith, Paul

    2011-10-01

    We report three generations of p-type dendrimer semiconductors comprised of spirobifluorene cores, carbazole branching units and fluorene surface groups for use in organic field-effect transistors (OFETs). The group of dendrimers are defined by their generation and noted as SBF-(Gx)2, where x is the generation. Top contact-bottom gate OFETs were fabricated by spin-coating the dendrimers onto an n-octyltrichlorosilane (OTS) passivated silicon dioxide surface. The dendrimer films were found to be amorphous. The highest mobility was measured for the first generation dendrimer (SBF-(G1)2), which had an average mobility of (6.6 +/- 0.2) × 10-5 cm2/V s and an ON/OFF ratio of 3.0 × 104. As the generation of the dendrimer was increased there was only a slight decrease in the measured mobility in spite of the significantly different molecular sizes of the dendrimers. The mobility of SBF-(G3)2, which had a hydrodynamic radius almost twice of SBF-(G1)2, still had an average mobility of (4.7 +/- 0.6) × 10-5 cm2/V s and an ON/OFF ratio of 2.7 × 103. Density functional theory calculations showed that the highest occupied molecular orbital was distributed over the core and carbazole units meaning that both intra- and intermolecular charge transfer could occur enabling the hole mobility to remain essentially constant even though the dendrimers would pack differently in the solid-state.

  9. Thin Films of Novel Linear-Dendritic Diblock Copolymers

    Iyer, Jyotsna; Hammond, Paula

    1998-03-01

    A series of diblock copolymers with one linear block and one dendrimeric block have been synthesized with the objective of forming ultrathin film nanoporous membranes. Polyethyleneoxide serves as the linear hydrophilic portion of the diblock copolymer. The hyperbranched dendrimeric block consists of polyamidoamine with functional end groups. Thin films of these materials made by spin casting and the Langmuir-Blodgett techniques are being studied. The effect of the polyethylene oxide block size and the number and chemical nature of the dendrimer end group on the nature and stability of the films formed willbe discussed.

  10. Targeting human liver cancer cells with lactobionic acid-G(4)-PAMAM-FITC sorafenib loaded dendrimers.

    Iacobazzi, Rosa Maria; Porcelli, Letizia; Lopedota, Angela Assunta; Laquintana, Valentino; Lopalco, Antonio; Cutrignelli, Annalisa; Altamura, Emiliano; Di Fonte, Roberta; Azzariti, Amalia; Franco, Massimo; Denora, Nunzio

    2017-08-07

    Reported here is the synthesis and biological evaluation of the asialoglycoprotein receptor (ASGP-R) targeted fourth generation poliamidoamine dendrimer (G(4)-PAMAM) loaded with sorafenib. The ASGP-R targeted dendrimer was obtained by conjugation of Lactobionic acid (La) to the G(4)-PAMAM dendrimer, followed by acetylation (Ac) of the free amino groups in order to reduce the non-specific interactions with the cell membrane. Moreover, by additionally grafting fluorescein (FITC), it was easy to characterize the internalization pathway and the intracellular fate of the targeted dendrimer Ac-La-G(4)-PAMAM-FITC. In vitro experiments performed on HepG-2 and HLE cell lines, allowed to study the ability of the dendrimers to affect the cell vitality. Confocal microscopy and cytofluorimetric analysis confirmed higher binding and uptake ability of the Ac-La-G(4)-PAMAM-FITC dendrimer in well differentiated and ASGP-R expressing human liver cancer cell line HepG-2 compared non-expressing HLE cells. Ac-La-G(4)-PAMAM-FITC dendrimer loaded with sorafenib was stable and showed sustained sorafenib release. As evidenced by the cytotoxicity studies, sorafenib included in the dendrimer maintained its effectiveness, and was able to produce a longer lasting effect over the time compared to molar equivalent doses of free sorafenib. This new targeted dendrimer appears to be a suitable carrier for the delivery of sorafenib to liver cancer cells expressing ASGP-R. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Engineering CNDP's of dendrimers containing phosphorous interior compositions to produce new emerging properties

    Caminade, Anne-Marie; Majoral, Jean-Pierre

    2018-03-01

    Phosphorus-containing dendrimers are defined as dendrimers having at least one phosphorus atom at each branching point. In this review, we will show how phosphorhydrazone dendrimers can be modified at will at the level of the core and of the branches, to afford specific properties, such as fluorescence to image biological events. Accelerated methods of synthesis of phosphorus (one step for one generation) will be also displayed, as well as the specific reactivity of P=N-P=S linkages obtained in most of these accelerated method of synthesis, which has led to particularly original dendritic architectures, such as dendrons included in dendrimers. Finally, we will display how modifications of the internal structure of a series of dendrimers having the same type and number of terminal functions can deeply modify their biological anti-inflammatory properties. Among the six critical nanoscale design parameters (CNDP), we will show how two of them, i.e., architecture and elemental composition, have been particularly engineered to modify phosphorus-containing dendrimers, in order to fulfill the desired properties.

  12. Molecular dynamics simulations of single siloxane dendrimers: Molecular structure and intramolecular mobility of terminal groups

    Kurbatov, A. O.; Balabaev, N. K.; Mazo, M. A.; Kramarenko, E. Yu.

    2018-01-01

    Molecular dynamics simulations of two types of isolated siloxane dendrimers of various generations (from the 2nd to the 8th) have been performed for temperatures ranging from 150 K to 600 K. The first type of dendrimer molecules has short spacers consisting of a single oxygen atom. In the dendrimers of the second type, spacers are longer and comprised of two oxygen atoms separated by a single silicon atom. A comparative analysis of molecular macroscopic parameters such as the gyration radius and the shape factor as well as atom distributions within dendrimer interior has been performed for varying generation number, temperature, and spacer length. It has been found that the short-spacer dendrimers of the 7th and 8th generations have a stressed central part with elongated bonds and deformed valence angles. Investigation of the time evolution of radial displacements of the terminal Si atoms has shown that a fraction of the Si groups have a reduced mobility. Therefore, rather long time trajectories (of the order of tens of nanoseconds) are required to study dendrimer intramolecular dynamics.

  13. Molecular Determinants of the Cellular Entry of Asymmetric Peptide Dendrimers and Role of Caveolae.

    Prarthana V Rewatkar

    Full Text Available Caveolae are flask-shaped plasma membrane subdomains abundant in most cell types that participate in endocytosis. Caveola formation and functions require membrane proteins of the caveolin family, and cytoplasmic proteins of the cavin family. Cationic peptide dendrimers are non-vesicular chemical carriers that can transport pharmacological agents or genetic material across the plasma membrane. We prepared a panel of cationic dendrimers and investigated whether they require caveolae to enter into cells. Cell-based studies were performed using wild type or caveola-deficient i.e. caveolin-1 or PTRF gene-disrupted cells. There was a statistically significant difference in entry of cationic dendrimers between wild type and caveola-deficient cells. We further unveiled differences between dendrimers with varying charge density and head groups. Our results show, using a molecular approach, that (i expression of caveola-forming proteins promotes cellular entry of cationic dendrimers and (ii dendrimer structure can be modified to promote endocytosis in caveola-forming cells.

  14. COMPUTER SIMULATION OF LOCAL MOBILITY IN DENDRIMERS WITH ASYMMETRIC BRANCHING BY BROWNIAN DYNAMICS METHOD

    O. V. Shavykin

    2016-09-01

    Full Text Available The Brownian dynamics method has been used to study the effect of the branching asymmetry on the local orientational mobility of segments and bonds in dendrimers in good solvent. “Coarse-grained” models of flexible dendrimers with different branching symmetry but with the same average segment length were considered. The frequency dependences of the rate of the spin-lattice relaxation nuclear magnetic resonance (NMR [1/T1H(H] for segments or bonds located at different distances from terminal monomers were calculated. After the exclusion of the contribution of the overall dendrimer rotation the position of the maxima of the frequency dependences [1/T1H(ωH] for different segments with the same length doesn’t depend on their location inside a dendrimer both for phantom models and for models with excluded volume interactions. This effect doesn’t depend also on the branching symmetry, but the position of the maximum [1/T1H(ωH] is determined by the segment length. For bonds inside segments the positions of the maximum [1/T1H(ωH] coincide for all models considered. Therefore, the obtained earlier conclusion about the weak influence of the excluded volume interactions on the local dynamics in the flexible symmetric dendrimers can be generalized for dendrimers with an asymmetric branching.

  15. Effect of increased surface hydrophobicity via drug conjugation on the clearance of inhaled PEGylated polylysine dendrimers.

    Haque, Shadabul; McLeod, Victoria M; Jones, Seth; Fung, Sandy; Whittaker, Michael; McIntosh, Michelle; Pouton, Colin; Owen, David J; Porter, Christopher J H; Kaminskas, Lisa M

    2017-10-01

    PEGylated polylysine dendrimers are attractive and well tolerated inhalable drug delivery platforms that have the potential to control the release, absorption kinetics and lung retention time of conjugated drugs. The clinical application of these systems though, would likely require partial substitution of surface PEG groups with drug molecules that are anticipated to alter their lung clearance kinetics and clearance pathways. In the current study, we therefore evaluated the impact of increased surface hydrophobicity via substitution of 50% surface PEG groups with a model hydrophobic drug (α-carboxyl OtButylated methotrexate) on the lung clearance of a Generation 5 PEGylated polylysine dendrimer in rats. PEG substitution with OtBu-methotrexate accelerated lung clearance of the dendrimer by increasing polylysine scaffold catabolism, improving systemic absorption of the intact dendrimer and low molecular weight products of scaffold catabolism, and enhancing mucociliary clearance. These results suggest that the conjugation of hydrophobic drug on the surface of a PEGylated dendrimer is likely to accelerate lung clearance when compared to a fully PEGylated dendrimer. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  16. A combinatorial approach of inclusion complexation and dendrimer synthesization for effective targeting EGFR-TK.

    Shende, Pravin; Patil, Sampada; Gaud, R S

    2017-07-01

    The aim of the present study was to use a combinatorial approach of inclusion complexation and dendrimer synthesization of gefitinib using solvent-free technique for targeting EGFR-TK to treat Non-Small-Cell Lung Cancer (NSCLC). The inclusion complex of gefitinib with β-cyclodextrin was prepared by trituration method. This complex encapsulated G4 PAMAM dendrimers were synthesized by Michael addition and amidation reactions using green chemistry and then PEGylated by conjugation reaction. FTIR and DSC confirmed the formation of inclusion complex of gefitinib and β-cyclodextrin and PEGylation of G4 PAMAM dendrimers. Gefitinib showed higher solubility, encapsulation efficiency and controlled release profile from PEGylated dendrimers compared to inclusion complex. The PEGylated dendrimers of inclusion complex of gefitinib were found to reduce hemolytic toxicity and lesser GI 50 value on Human lung cancer cell line A-549 by effective targeting EGFR-TK. A combinatorial approach of inclusion complexation and dendrimer synthesization is one of the alternative advanced approaches to treat NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Supramolecular assembly of a series of chiral dendrimers in interfacial films

    Yuan Jing; Deng Guojun; Fan Qinghua; Liu Minghua

    2004-01-01

    Supramolecular assembly and interfacial properties of a series of novel binaphthyl containing dendrimers from generation 1 through generation 4 have been investigated at the air/water interface and in solid substrates. Due to the lack of either long alkyl chains or strong hydrophilic groups, the dendrimer molecules tend to aggregate together to form stable two-dimensional ultrathin films, as verified by π-A and A-t measurements. Atomic force microscope (AFM) measurements of the transferred one-layer ultrathin films indicate that all the dendrimers show disk-like morphologies, which could be varied in particle size upon changing the surface pressure. The height profiles reveal that the height of the disks is between that of a monolayer and a bilayer, indicating that they are formed due to the aggregation of dendrimers with a distortion and/or partial overlapping. Circular dichroism (CD) spectra of the transferred multilayer films show Cotton effects due to the exciton couplet of the aromatic moieties adjacent to the bis(diphenylphosphino)-binaphthyl moiety, which is an active catalytic site for the dendrimer. With the increment of the generation, the intensity of the Cotton effects increased, suggesting that the optical active site of the dendrimer can be controlled by the outside wedge

  18. Dendrimer Nanoscaffolds for Potential Theranostics of Prostate Cancer with a Focus on Radiochemistry

    Lo, Su-Tang; Kumar, Amit; Hsieh, Jer-Tsong; Sun, Xiankai

    2013-01-01

    Dendrimers are a class of structurally defined macromolecules featured with a central core, a low-density interior formed by repetitive branching units, and a high-density exterior terminated with surface functional groups. In contrast to their polymeric counterparts, dendrimers are nano-sized and symmetrically shaped, which can be reproducibly synthesized in a large scale with monodispersity. These unique features have made dendrimers of increasing interest for drug delivery and other biomedical applications as a nanoscaffold system. Intended to address the potential use of dendrimers for the development of theranostic agents, which combines therapeutics and diagnostics in a single entity for personalized medicine, this review focuses on the reported methodologies of using dendrimer nanoscaffolds for targeted imaging and therapy of prostate cancer. Of particular interest, relevant chemistry strategies are discussed due to their important roles in the design and synthesis of diagnostic and therapeutic dendrimer-based nanoconjugates and potential theranostic agents, targeted or non-targeted. Given the developing status of nanoscaffolded theranostics, major challenges and potential hurdles are discussed along with the examples representing current advances. PMID:23294202

  19. Precise localization of metal nanoparticles in dendrimer nanosnakes or inner periphery and consequences in catalysis

    Liu, Xiang; Gregurec, Danijela; Irigoyen, Joseba; Martinez, Angel; Moya, Sergio; Ciganda, Roberto; Hermange, Philippe; Ruiz, Jaime; Astruc, Didier

    2016-10-01

    Understanding the relationship between the location of nanoparticles (NPs) in an organic matrix and their catalytic performances is essential for catalyst design. Here we show that catalytic activities of Au, Ag and CuNPs stabilized by dendrimers using coordination to intradendritic triazoles, galvanic replacement or stabilization outside dendrimers strongly depends on their location. AgNPs are found at the inner click dendrimer periphery, whereas CuNPs and AuNPs are encapsulated in click dendrimer nanosnakes. AuNPs and AgNPs formed by galvanic replacement are larger than precursors and only partly encapsulated. AuNPs are all the better 4-nitrophenol reduction catalysts as they are less sterically inhibited by the dendrimer interior, whereas on the contrary CuNPs are all the better alkyne azide cycloaddition catalysts as they are better protected from aerobic oxidation inside dendrimers. This work highlights the role of the location in macromolecules on the catalytic efficiency of metal nanoparticles and rationalizes optimization in catalyst engineering.

  20. Molecular Determinants of the Cellular Entry of Asymmetric Peptide Dendrimers and Role of Caveolae.

    Rewatkar, Prarthana V; Parekh, Harendra S; Parat, Marie-Odile

    2016-01-01

    Caveolae are flask-shaped plasma membrane subdomains abundant in most cell types that participate in endocytosis. Caveola formation and functions require membrane proteins of the caveolin family, and cytoplasmic proteins of the cavin family. Cationic peptide dendrimers are non-vesicular chemical carriers that can transport pharmacological agents or genetic material across the plasma membrane. We prepared a panel of cationic dendrimers and investigated whether they require caveolae to enter into cells. Cell-based studies were performed using wild type or caveola-deficient i.e. caveolin-1 or PTRF gene-disrupted cells. There was a statistically significant difference in entry of cationic dendrimers between wild type and caveola-deficient cells. We further unveiled differences between dendrimers with varying charge density and head groups. Our results show, using a molecular approach, that (i) expression of caveola-forming proteins promotes cellular entry of cationic dendrimers and (ii) dendrimer structure can be modified to promote endocytosis in caveola-forming cells.