A star-shaped polythiophene dendrimer coating for solid-phase microextraction of triazole agrochemicals.

Science.gov (United States)

Abolghasemi, Mir Mahdi; Habibiyan, Rahim; Jaymand, Mehdi; Piryaei, Marzieh

2018-02-14

A nanostructured star-shaped polythiophene dendrimer was prepared and used as a fiber coating for headspace solid phase microextraction of selected triazolic pesticides (tebuconazole, hexaconazole, penconazole, diniconazole, difenoconazole, triticonazole) from water samples. The dendrimer with its large surface area was characterized by thermogravimetric analysis, UV-Vis spectroscopy and field emission scanning electron microscopy. It was placed on a stainless steel wire for use in SPME. The experimental conditions for fiber coating, extraction, stirring rate, ionic strength, pH value, desorption temperature and time were optimized. Following thermal desorption, the pesticides were quantified by GC-MS. Under optimum conditions, the repeatability (RSD) for one fiber (for n = 3) ranges from 4.3 to 5.6%. The detection limits are between 8 and 12 pg mL -1 . The method is fast, inexpensive (in terms of equipment), and the fiber has high thermal stability. Graphical abstract Schematic presentation of a nanostructured star-shaped polythiophene dendrimer for use in headspace solid phase microextraction of the triazolic pesticides (tebuconazole, hexaconazole, penconazole, diniconazole, difenoconazole, triticonazole). They were then quantified by gas chromatography-mass spectrometry.

Research progress on synthesis and characteristic about dendrimers

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Dendrimer-protein interactions versus dendrimer-based nanomedicine.

Science.gov (United States)

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.

[Dendrimers in biomedical sciences and nanotechnology].

Science.gov (United States)

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.

Synthesis of Dendrimer Containing Carbazole Unit as a Core Chromophore

International Nuclear Information System (INIS)

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

Electrochemical Interrogation of G3-Poly(propylene thiophenoimine Dendritic Star Polymer in Phenanthrene Sensing

Directory of Open Access Journals (Sweden)

Hlamulo R. Makelane

2015-09-01

Full Text Available A novel dendritic star-copolymer, generation 3 poly(propylene thiophenoimine (G3PPT-co-poly(3-hexylthiophene (P3HT star co-polymer on gold electrode (i.e., Au|G3PPT-co-P3HT was used as a sensor system for the determination of phenanthrene (PHE. The G3PPT-co-P3HT star co-polymer was synthesized via in situ electrochemical co-polymerization of generation 3 poly (propylene thiophenoimine and poly (3-hexylthiophene on gold electrode. 1HNMR spectroscopy was used to determine the regioregularity of the polymer composites, whereas Fourier transform infrared spectroscopy and scanning electron microscopy were used to study their structural and morphological properties. Au|G3PPT-co-P3HT in the absence of PHE, exhibited reversible electrochemistry attributable to the oligo (thiophene ‘pendants’ of the dendrimer. PHE produced an increase in the voltammetric signals (anodic currents due to its oxidation on the dendritic material to produce catalytic current, thereby suggesting the suitability of the Au|G3PPT-co-P3HT electrode as a PHE sensor. The electrocatalysis of PHE was made possible by the rigid and planar oligo-P3HT species (formed upon the oxidation of the oligo (thiophene pendants of the star-copolymer, which allowed the efficient capture (binding and detection (electrocatalytic oxidation of PHE molecules.

Star-Branched Polymers (Star Polymers)

KAUST Repository

Hirao, Akira; Hayashi, Mayumi; Ito, Shotaro; Goseki, Raita; Higashihara, Tomoya; Hadjichristidis, Nikolaos

2015-01-01

The synthesis of well-defined regular and asymmetric mixed arm (hereinafter miktoarm) star-branched polymers by the living anionic polymerization is reviewed in this chapter. In particular, much attention is being devoted to the synthetic

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

Science.gov (United States)

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

Dendrimers for Drug Delivery

Directory of Open Access Journals (Sweden)

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.

Electronic transport study in PAMAM dendrimers

International Nuclear Information System (INIS)

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)

Complex macromolecular architectures: synthesis, characterization, and self-assembly

National Research Council Canada - National Science Library

Hadjichristidis, Nikos

2011-01-01

...)s and gluco-polymers, star-branched and dendrimer-like hyperbranched polymers, cyclic polymers, dendrigraft polymers, rod-coil and helix-coil block copolymers are introduced chapter by chapter in the book...

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

Science.gov (United States)

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.

Dendrimers: new hope for cancer

International Nuclear Information System (INIS)

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

Dendrimers bind antioxidant polyphenols and cisplatin drug.

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Dendrimers for siRNA Delivery

Directory of Open Access Journals (Sweden)

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.

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

OpenAIRE

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...

Collapse of Telechelic Star Polymers to Watermelon Structures

Science.gov (United States)

Verso, Federica Lo; Likos, Christos N.; Mayer, Christian; Löwen, Hartmut

2006-05-01

Conformational properties of star-shaped polymer aggregates that carry attractive end groups, called telechelic star polymers, are investigated by simulation and analytical variational theory. We focus on the case of low telechelic star polymer functionalities, f≤5, a condition which allows aggregation of all attractive monomers on one site. We establish the functionality- and polymerization-number dependence of the transition temperature from the “star burst” to the “watermelon” macroparticle structure. Extensions to telechelic stars featuring partially collapsed configurations are also discussed.

Redox-Active Star Molecules Incorporating the 4-Benzoylpyridinium Cation - Implications for the Charge Transfer Along Branches vs. Across the Perimeter in Dendrimer

Science.gov (United States)

Leventis, Nicholas; Yang, Jinua; Fabrizio,Even F.; Rawashdeh, Abdel-Monem M.; Oh, Woon Su; Sotiriou-Leventis, Chariklia

2004-01-01

Dendrimers are self-repeating globular branched star molecules, whose fractal structure continues to fascinate, challenge, and inspire. Functional dendrimers may incorporate redox centers, and potential applications include antennae molecules for light harvesting, sensors, mediators, and artificial biomolecules. We report the synthesis and redox properties of four star systems incorporating the 4-benzoyl-N-alkylpyridinium cation; the redox potential varies along the branches but remains constant at fixed radii. Bulk electrolysis shows that at a semi-infinite time scale all redox centers are electrochemically accessible. However, voltammetric analysis (cyclic voltammetry and differential pulse voltammetry) shows that on1y two of the three redox-active centers in the perimeter are electrochemically accessible during potential sweeps as slow as 20 mV/s and as fast as 10 V/s. On the contrary, both redox centers along branches are accessible electrochemically within the same time frame. These results are explained in terms of slow through-space charge transfer and the globular 3-D folding of the molecules and are discussed in terms of their implications on the design of efficient redox functional dendrimers.

Ligand-Receptor Interaction-Mediated Transmembrane Transport of Dendrimer-like Soft Nanoparticles: Mechanisms and Complicated Diffusive Dynamics.

Science.gov (United States)

Liang, Junshi; Chen, Pengyu; Dong, Bojun; Huang, Zihan; Zhao, Kongyin; Yan, Li-Tang

2016-05-09

Nearly all nanomedical applications of dendrimer-like soft nanoparticles rely on the functionality of attached ligands. Understanding how the ligands interact with the receptors in cell membrane and its further effect on the cellular uptake of dendrimer-like soft nanoparticles is thereby a key issue for their better application in nanomedicine. However, the essential mechanism and detailed kinetics for the ligand-receptor interaction-mediated transmembrane transport of such unconventional nanoparticles remain poorly elucidated. Here, using coarse-grained simulations, we present the very first study of molecular mechanism and kinetics behaviors for the transmembrane transport of dendrimer-like soft nanoparticles conjugated with ligands. A phase diagram of interaction states is constructed through examining ligand densities and membrane tensions that allows us to identify novel endocytosis mechanisms featured by the direct wrapping and the penetration-extraction vesiculation. The results provide an in-depth insight into the diffusivity of receptors and dendrimer in the membrane plane and demonstrate how the ligand density influences receptor diffusion and uptake kinetics. It is interesting to find that the ligand-conjugated dendrimers present superdiffusive behaviors on a membrane, which is revealed to be driven by the random fluctuation dynamics of the membrane. The findings facilitate our understanding of some recent experimental observations and could establish fundamental principles for the future development of such important nanomaterials for widespread nanomedical applications.

On Topological Indices of Certain Dendrimer Structures

Science.gov (United States)

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.

CHAPTER 1. Miktoarm Star (µ-Star) Polymers: A Successful Story

KAUST Repository

Iatrou, Hermis; Avgeropoulos, Apostolos; Sakellariou, Georgios; Pitsikalis, Marinos; Hadjichristidis, Nikolaos

2017-01-01

The term miktoarm stars (coming from the Greek word μιτσ meaning mixed) was adopted in 1992 by our group for star polymers with either chemical (e.g., AB), molecular weight (e.g., AA′), topological (e.g., (AB)-junction-(BA)), or functional group (e.g., AA) asymmetry. The first μ-stars synthesized by anionic polymerization, on the one hand, guided polymer chemists working with other types of polymerization techniques towards this direction and, on the other hand, helped polymer physicists to carry out experiments and develop theories on the influence of the architecture on the morphology of block copolymers. Synthetic strategies based on anionic polymerization, as well as a few examples showing the influence of the miktoarm structure on the morphology of block copolymers, are reviewed in this chapter.

CHAPTER 1. Miktoarm Star (µ-Star) Polymers: A Successful Story

KAUST Repository

Iatrou, Hermis

2017-04-13

The term miktoarm stars (coming from the Greek word μιτσ meaning mixed) was adopted in 1992 by our group for star polymers with either chemical (e.g., AB), molecular weight (e.g., AA′), topological (e.g., (AB)-junction-(BA)), or functional group (e.g., AA) asymmetry. The first μ-stars synthesized by anionic polymerization, on the one hand, guided polymer chemists working with other types of polymerization techniques towards this direction and, on the other hand, helped polymer physicists to carry out experiments and develop theories on the influence of the architecture on the morphology of block copolymers. Synthetic strategies based on anionic polymerization, as well as a few examples showing the influence of the miktoarm structure on the morphology of block copolymers, are reviewed in this chapter.

Entropy-induced separation of star polymers in porous media

International Nuclear Information System (INIS)

Blavats'ka, V.; Ferber, C. von; Holovatch, Yu.

2006-01-01

We present a quantitative picture of the separation of star polymers in a solution where part of the volume is influenced by a porous medium. To this end, we study the impact of long-range-correlated quenched disorder on the entropy and scaling properties of f-arm star polymers in a good solvent. We assume that the disorder is correlated on the polymer length scale with a power-law decay of the pair correlation function g(r)∼r -a . Applying the field-theoretical renormalization group approach we show in a double expansion in ε=4-d and δ=4-a that there is a range of correlation strengths δ for which the disorder changes the scaling behavior of star polymers. In a second approach we calculate for fixed space dimension d=3 and different values of the correlation parameter a the corresponding scaling exponents γ f that govern entropic effects. We find that γ f -1, the deviation of γ f from its mean field value is amplified by the disorder once we increase δ beyond a threshold. The consequences for a solution of diluted chain and star polymers of equal molecular weight inside a porous medium are that star polymers exert a higher osmotic pressure than chain polymers and in general higher branched star polymers are expelled more strongly from the correlated porous medium. Surprisingly, polymer chains will prefer a stronger correlated medium to a less or uncorrelated medium of the same density while the opposite is the case for star polymers

Nano-Star-Shaped Polymers for Drug Delivery Applications.

Science.gov (United States)

Yang, Da-Peng; Oo, Ma Nwe Nwe Linn; Deen, Gulam Roshan; Li, Zibiao; Loh, Xian Jun

2017-11-01

With the advancement of polymer engineering, complex star-shaped polymer architectures can be synthesized with ease, bringing about a host of unique properties and applications. The polymer arms can be functionalized with different chemical groups to fine-tune the response behavior or be endowed with targeting ligands or stimuli responsive moieties to control its physicochemical behavior and self-organization in solution. Rheological properties of these solutions can be modulated, which also facilitates the control of the diffusion of the drug from these star-based nanocarriers. However, these star-shaped polymers designed for drug delivery are still in a very early stage of development. Due to the sheer diversity of macromolecules that can take on the star architectures and the various combinations of functional groups that can be cross-linked together, there remain many structure-property relationships which have yet to be fully established. This review aims to provide an introductory perspective on the basic synthetic methods of star-shaped polymers, the properties which can be controlled by the unique architecture, and also recent advances in drug delivery applications related to these star candidates. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymer architecture and drug delivery.

Science.gov (United States)

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.

Templating Organosilicate Vitrification Using Unimolecular Self Organizing Polymers: Evolution of Morphology and Nanoporosity Development with Network Formation

International Nuclear Information System (INIS)

Kim, H.-C.

2004-01-01

Star-shaped polymers with a compatibilizing outer corona were dispersed into a thermosetting organosilicate matrix and used to create a nanoporous material. These environmentally responsive copolymers create nano-sized domains through a matrix-mediated collapse of the interior core of the core-corona polymeric structure. This approach relies on the outer corona of the star to compatibilize the insoluble core with the thermosetting resin and prevent aggregation such that these individual molecules template the crosslinking of the matrix and ultimately generate a single hole. The organic polymer was selectively thermalized leaving behind its latent image in the matrix with a pore size that reflected the size of the polymer molecule, and provided the expected reduction in dielectric constant. The morphology development as a function of arm number, molecular weight and volume fraction in mixtures with organosilicates as a function of cure/network conversion was investigated by SAXS, SANS, DMA, TEM and FE-SEM measurements. Amphiphilic star-shaped polymers of various block lengths and arm number, prepared by tandem controlled ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) from dendritic initiators, were further tailored to facilitate contrast enhancement for various measurements by the incorporation of either ferrocenyl units or deuterated monomers. The pore sizes achieved by the star and dendrimer-like star macromolecular architectures range from ∼7 to 40nm, depending on the molecular weight and architecture

Universal size properties of a star-ring polymer structure in disordered environments

Science.gov (United States)

Haydukivska, K.; Blavatska, V.

2018-03-01

We consider the complex polymer system, consisting of a ring polymer connected to the f1-branched starlike structure, in a good solvent in the presence of structural inhomogeneities. In particular cases f1=1 and f1=2 , such a system restores the synthesized tadpole-shaped polystyrenes [Doi et al., Macromolecules 46, 1075 (2013), 10.1021/ma302511j]. We assume that structural defects are correlated at large distances x according to a power law x-a. Applying the direct polymer renormalization approach, we evaluate the universal size characteristics such as the ratio of the radii of gyration of star-ring and star topologies, and compare the effective sizes of single arms in complex structures and isolated polymers of the same total molecular weight. The nontrivial impact of disorder on these quantities is analyzed.

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

Science.gov (United States)

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.

Small cell foams and blends and a process for their preparation

Science.gov (United States)

Hedstrand, D.M.; Tomalia, D.A.

1995-02-07

Dense star polymers or dendrimers, modified by capping with a hydrophobic group capable of providing a hydrophobic outer shell, act as molecular nucleating agents. These modified dense star polymers or dendrimers are particularly effective for the production of small cell foams.

RAFT Synthesis and Self-Assembly of Free-Base Porphyrin Cored Star Polymers

Directory of Open Access Journals (Sweden)

Lin Wu

2011-01-01

Full Text Available Reversible addition fragmentation chain transfer (RAFT synthesis and self-assembly of free-base porphyrin cored star polymers are reported. The polymerization, in the presence of a free-base porphyrin cored chain transfer agent (CTA-FBP, produced porphyrin star polymers with controlled molecular weights and narrow polydispersities for a number of monomers including N, N-dimethylacrylamide (DMA and styrene (St. Well-defined amphiphilic star block copolymers, P-(PS-PDMA4 and P-(PDMA-PS4 (P: porphyrin, were also prepared and used for self-assembly studies. In methanol, a selective solvent for PDMA, spherical micelles were observed for both block copolymers as characterized by TEM. UV-vis studies suggested star-like micelles were formed from P-(PS-PDMA4, while P-(PDMA-PS4 aggregated into flower-like micelles. Spectrophotometric titrations indicated that the optical response of these two micelles to external ions was a function of micellar structures. These structure-related properties will be used for micelle studies and functional material development in the future.

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

OpenAIRE

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...

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

International Nuclear Information System (INIS)

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).

Polystyrene star-shaped polymers made by the new In-Inmethod

International Nuclear Information System (INIS)

Fazeli, N.; Afshar Toromi, F.

2002-01-01

Three main methods are usually used for the synthesis of star-shaped polymers, where each one has its own advantages and disadvantages. Among these techniques, i n-out m ethod is the best one to produce hetero arm star polymers with narrow molecular weight distribution and long arms with active sites at the end of the second-generation arms. This method, however, has some difficulties during the synthesis of hetero-arm star polymers with styrene or dienes as the second monomers. The reason is that in the o ut s tep, the carbanions of the growing chain attack the existing double bonds of the other cores and produce an irreversible gel. The new i n-in m ethod mentioned in this paper, is used to synthesize double-star polystyrene polymers with relatively narrow molecular weight distribution and without occurrence of any gelation during the process. With the monomers, which are able to attack the existing double bonds of the cores of the star polymers, it is also possible to produce-hetero-arm star polymers using this new method

Fluorescent quantum dot hydrophilization with PAMAM dendrimer

Science.gov (United States)

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.

Fluorescent quantum dot hydrophilization with PAMAM dendrimer

Energy Technology Data Exchange (ETDEWEB)

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.

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

DEFF Research Database (Denmark)

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...

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

Science.gov (United States)

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.

Dendrimer sensors probed with neutron reflectometry

International Nuclear Information System (INIS)

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.

Synthesis and Properties of Star HPMA Copolymer Nanocarriers Synthesised by RAFT Polymerisation Designed for Selective Anticancer Drug Delivery and Imaging.

Science.gov (United States)

Chytil, Petr; Koziolová, Eva; Janoušková, Olga; Kostka, Libor; Ulbrich, Karel; Etrych, Tomáš

2015-06-01

High-molecular-weight star polymer drug nanocarriers intended for the treatment and/or visualisation of solid tumours were synthesised, and their physico-chemical and preliminary in vitro biological properties were determined. The water-soluble star polymer carriers were prepared by the grafting of poly(amido amine) (PAMAM) dendrimers by hetero-telechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, synthesised by the controlled radical Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation. The well-defined star copolymers with Mw values ranging from 2 · 10(5) to 6 · 10(5) showing a low dispersity (approximately 1.2) were prepared in a high yield. A model anticancer drug, doxorubicin, was bound to the star polymer through a hydrazone bond, enabling the pH-controlled drug release in the target tumour tissue. The activated polymer arm ends of the star copolymer carrier enable a one-point attachment for the targeting ligands and/or a labelling moiety. In this study, the model TAMRA fluorescent dye was used to prove the feasibility of the polymer carrier visualisation by optical imaging in vitro. The tailor-made structure of the star polymer carriers should facilitate the synthesis of targeted polymer-drug conjugates, even polymer theranostics, for simultaneous tumour drug delivery and imaging. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of the interaction parameter and topological scaling features of symmetric star polymers in dilute solution

KAUST Repository

Rai, Durgesh K.; Beaucage, Gregory; Ratkanthwar, Kedar; Beaucage, Peter; Ramachandran, Ramnath; Hadjichristidis, Nikolaos

2015-01-01

Star polymers provide model architectures to understand the dynamic and rheological effects of chain confinement for a range of complex topological structures like branched polymers, colloids, and micelles. It is important to describe the structure of such macromolecular topologies using small-angle neutron and x-ray scattering to facilitate understanding of their structure-property relationships. Modeling of scattering from linear, Gaussian polymers, such as in the melt, has applied the random phase approximation using the Debye polymer scattering function. The Flory-Huggins interaction parameter can be obtained using neutron scattering by this method. Gaussian scaling no longer applies for more complicated chain topologies or when chains are in good solvents. For symmetric star polymers, chain scaling can differ from ν=0.5(df=2) due to excluded volume, steric interaction between arms, and enhanced density due to branching. Further, correlation between arms in a symmetric star leads to an interference term in the scattering function first described by Benoit for Gaussian chains. In this work, a scattering function is derived which accounts for interarm correlations in symmetric star polymers as well as the polymer-solvent interaction parameter for chains of arbitrary scaling dimension using a hybrid Unified scattering function. The approach is demonstrated for linear, four-arm and eight-arm polyisoprene stars in deuterated p-xylene.

Determination of the interaction parameter and topological scaling features of symmetric star polymers in dilute solution

KAUST Repository

Rai, Durgesh K.

2015-07-15

Star polymers provide model architectures to understand the dynamic and rheological effects of chain confinement for a range of complex topological structures like branched polymers, colloids, and micelles. It is important to describe the structure of such macromolecular topologies using small-angle neutron and x-ray scattering to facilitate understanding of their structure-property relationships. Modeling of scattering from linear, Gaussian polymers, such as in the melt, has applied the random phase approximation using the Debye polymer scattering function. The Flory-Huggins interaction parameter can be obtained using neutron scattering by this method. Gaussian scaling no longer applies for more complicated chain topologies or when chains are in good solvents. For symmetric star polymers, chain scaling can differ from ν=0.5(df=2) due to excluded volume, steric interaction between arms, and enhanced density due to branching. Further, correlation between arms in a symmetric star leads to an interference term in the scattering function first described by Benoit for Gaussian chains. In this work, a scattering function is derived which accounts for interarm correlations in symmetric star polymers as well as the polymer-solvent interaction parameter for chains of arbitrary scaling dimension using a hybrid Unified scattering function. The approach is demonstrated for linear, four-arm and eight-arm polyisoprene stars in deuterated p-xylene.

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

OpenAIRE

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...

Synthesis of cationic star polymers by simplified electrochemically mediated ATRP

Directory of Open Access Journals (Sweden)

P. Chmielarz

2016-10-01

Full Text Available Cyclodextrin-based cationic star polymers were synthesized using β-cyclodextrin (β-CD core, and 2-(dimethylamino ethyl methacrylate (DMAEMA as hydrophilic arms. Star-shaped polymers were prepared via a simplified electrochemically mediated ATRP (seATRP under potentiostatic and galvanostatic conditions. The polymerization results showed molecular weight (MW evolution close to theoretical values, and maintained narrow molecular weight distribution (MWD of obtained stars. The rate of the polymerizations was controlled by applying more positive potential values thereby suppressing star-star coupling reactions. Successful chain extension of the ω-functional arms with a hydrophobic n-butyl acrylate (BA formed star block copolymers and confirmed the living nature of the β-CD-PDMAEMA star polymers prepared by seATRP. Novelty of this work is that the β-CD-PDMAEMA-b-PBA cationic star block copolymers were synthesized for the first time via seATRP procedure, utilizing only 40 ppm of catalyst complex. The results from 1H NMR spectral studies support the formation of cationic star (copolymers.

Universal shape characteristics for the mesoscopic star-shaped polymer via dissipative particle dynamics simulations

Science.gov (United States)

Kalyuzhnyi, O.; Ilnytskyi, J. M.; Holovatch, Yu; von Ferber, C.

2018-05-01

In this paper we study the shape characteristics of star-like polymers in various solvent quality using a mesoscopic level of modeling. The dissipative particle dynamics simulations are performed for the homogeneous and four different heterogeneous star polymers with the same molecular weight. We analyse the gyration radius and asphericity at the poor, good and θ-solvent regimes. Detailed explanation based on interplay between enthalpic and entropic contributions to the free energy and analyses on of the asphericity of individual branches are provided to explain the increase of the apsphericity in θ-solvent regime.

Bifunctional Phosphorus Dendrimers and Their Properties.

Science.gov (United States)

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.

Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

Directory of Open Access Journals (Sweden)

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.

A soluble star-shaped silsesquioxane-cored polymer-towards novel stabilization of pH-dependent high internal phase emulsions.

Science.gov (United States)

Xing, Yuxiu; Peng, Jun; Xu, Kai; Gao, Shuxi; Gui, Xuefeng; Liang, Shengyuan; Sun, Longfeng; Chen, Mingcai

2017-08-30

A well-defined pH-responsive star-shaped polymer containing poly(N,N-dimethylaminoethyl methacrylate) (PDMA) arms and a cage-like methacryloxypropyl silsesquioxane (CMSQ-T 10 ) core was used as an interfacial stabilizer for emulsions consisting of m-xylene and water. We explored the properties of the CMSQ/PDMA star-shaped polymer using the characteristic results of nuclear magnetic resonance (NMR) spectroscopy, size exclusion chromatography (SEC), dynamic light scattering (DLS), and zeta potential and conductivity measurements. The interfacial tension results showed that the CMSQ/PDMA star-shaped polymer reduced the interfacial tension between water and oil in a pH-dependent manner. Gelled high internal phase emulsions (HIPEs) including o/w and w/o types were formed in the pH ranges of 1.2-5.8 and 9.1-12.3 with the CMSQ/PDMA star-shaped polymer as a stabilizer, when the oil fractions were 80-90 vol% and 10-20 vol%, respectively. The soluble star-shaped polymer aggregated spontaneously to form a microgel that adsorbed to the two immiscible phases. Images of the fluorescently labeled polymers demonstrated that there was a star-shaped polymer in the continuous phase, and the non-Pickering stabilization based on the percolating network of the star-shaped polymer also contributed to the stabilization of the HIPE. This pH-dependent HIPE was prepared with a novel stabilization mechanism consisting of microgel adsorption and non-Pickering stabilization. Moreover, the preparation of HIPEs provided the possibility of their application in porous materials and responsive materials.

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

Tailoring the dendrimer core for efficient gene delivery.

Science.gov (United States)

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

Utilization of star-shaped polymer architecture in the creation of high-density polymer brush coatings for the prevention of platelet and bacteria adhesion

Science.gov (United States)

Totani, Masayasu; Terada, Kayo; Terashima, Takaya; Kim, Ill Yong; Ohtsuki, Chikara; Xi, Chuanwu; Tanihara, Masao

2014-01-01

We demonstrate utilization of star-shaped polymers as high-density polymer brush coatings and their effectiveness to inhibit the adhesion of platelets and bacteria. Star polymers consisting of poly(2-hydroxyethyl methacrylate) (PHEMA) and/or poly(methyl methacrylate) (PMMA), were synthesized using living radical polymerization with a ruthenium catalyst. The polymer coatings were prepared by simple drop casting of the polymer solution onto poly(ethylene terephthalate) (PET) surfaces and then dried. Among the star polymers prepared in this study, the PHEMA star polymer (star-PHEMA) and the PHEMA/PMMA (mol. ratio of 71/29) heteroarm star polymer (star-H71M29) coatings showed the highest percentage of inhibition against platelet adhesion (78–88% relative to noncoated PET surface) and Escherichia coli (94–97%). These coatings also showed anti-adhesion activity against platelets after incubation in Dulbecco's phosphate buffered saline or surfactant solution for 7 days. In addition, the PMMA component of the star polymers increased the scratch resistance of the coating. These results indicate that the star-polymer architecture provides high polymer chain density on PET surfaces to prevent adhesion of platelets and bacteria, as well as coating stability and physical durability to prevent exposure of bare PET surfaces. The star polymers provide a simple and effective approach to preparing anti-adhesion polymer coatings on biomedical materials against the adhesion of platelets and bacteria. PMID:25485105

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

Science.gov (United States)

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.

Effect of oligonucleic acid (ONA) backbone features on assembly of ONA-star polymer conjugates: a coarse-grained molecular simulation study.

Science.gov (United States)

Condon, Joshua E; Jayaraman, Arthi

2017-10-04

Understanding the impact of incorporating new physical and chemical features in oligomeric DNA mimics, termed generally as "oligonucleic acids" (ONAs), on their structure and thermodynamics will be beneficial in designing novel materials for a variety of applications. In this work, we conduct coarse-grained molecular simulations of ONA-star polymer conjugates with varying ONA backbone flexibility, ONA backbone charge, and number of arms in the star polymer at a constant ONA strand volume fraction to elucidate the effect of these design parameters on the thermodynamics and assembly of multi-arm ONA-star polymer conjugates. We quantify the thermo-reversible behavior of the ONA-star polymer conjugates by quantifying the hybridization of the ONA strands in the system as a function of temperature (i.e. melting curve). Additionally, we characterize the assembly of the ONA-star polymer conjugates by tracking cluster formation and percolation as a function of temperature, as well as cluster size distribution at temperatures near the assembly transition region. The key results are as follows. The melting temperature (T m ) of the ONA strands decreases upon going from a neutral to a charged ONA backbone and upon increasing flexibility of the ONA backbone. Similar behavior is seen for the assembly transition temperature (T a ) with varying ONA backbone charge and flexibility. While the number of arms in the ONA-star polymer conjugate has a negligible effect on the ONA T m in these systems, as the number of ONA-star polymer arms increase, the assembly temperature T a increases and local ordering in the assembled state improves. By understanding how factors like ONA backbone charge, backbone flexibility, and ONA-star polymer conjugate architecture impact the behavior of ONA-star polymer conjugate systems, we can better inform how the selection of ONA chemistry will influence resulting ONA-star polymer assembly.

SANS structural characterization of fullerenol-derived star polymers in solutions

CERN Document Server

Jeng, U S; Wang, L Y; Chiang, L Y; Ho, D L; Han, C C

2002-01-01

We have studied the chain conformations of fullerenol-derived star polymers in two organic solvents using small-angle neutron scattering (SANS). The SANS results indicate that the six poly(urethane-ether) arms, chemically bonded on the fullerenol of the C sub 6 sub 0 -based star polymer, have a Gaussian chain conformation in toluene. However, these arms exhibit a pronounced excluded-volume effect in dimethylformamide solutions. We use a scattering model, with the polydispersity of the polymer taken into account, and a fractal model to extract the radius of gyration R sub g values and the persistence lengths of the C sub 6 sub 0 -star polymers in these two organic solutions. (orig.)

Synthesis and characterisation of star polymer/silicon carbide nanocomposites

International Nuclear Information System (INIS)

Majewski, Peter; Choudhury, Namita Roy; Spori, Doris; Wohlfahrt, Ellen; Wohlschloegel, Markus

2006-01-01

A new type of composite material's preparation and property are reported in this paper. The composite was formed by solution blending a styrene ethylene butylenes (SEBS) star polymer with silicon carbide at various compositions. The composites were characterised using spectroscopic, microscopic and thermal techniques. Photo-acoustic Fourier transform infrared spectroscopy (PA-FT-IR) and transmission electron microscopy (TEM) results show that the SiC resides uniformly in the organic network. Thermogravimetric analysis (TGA) of the hybrid shows that the thermal stability of the composite is higher than that of the star polymer. The maximum decomposition temperature increases by 73 deg. C. Dynamic mechanical analysis (DMA) of the hybrid shows that the storage modulus of the star polymer increases after the composite formation, indicating the existence of thermodynamically stable SiC nanoparticles mostly in the micro-phase separated multiarm structure of the polymer

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

Science.gov (United States)

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.

Star polymer-based unimolecular micelles and their application in bio-imaging and diagnosis.

Science.gov (United States)

Jin, Xin; Sun, Pei; Tong, Gangsheng; Zhu, Xinyuan

2018-02-03

As a novel kind of polymer with covalently linked core-shell structure, star polymers behave in nanostructure in aqueous medium at all concentration range, as unimolecular micelles at high dilution condition and multi-micelle aggregates in other situations. The unique morphologies endow star polymers with excellent stability and functions, making them a promising platform for bio-application. A variety of functions including imaging and therapeutics can be achieved through rational structure design of star polymers, and the existence of plentiful end-groups on shell offers the opportunity for further modification. In the last decades, star polymers have become an attracting platform on fabrication of novel nano-systems for bio-imaging and diagnosis. Focusing on the specific topology and physicochemical properties of star polymers, we have reviewed recent development of star polymer-based unimolecular micelles and their bio-application in imaging and diagnosis. The main content of this review summarizes the synthesis of integrated architecture of star polymers and their self-assembly behavior in aqueous medium, focusing especially on the recent advances on their bio-imaging application and diagnosis use. Finally, we conclude with remarks and give some outlooks for further exploration in this field. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tecto-dendrimers: a study of covalently bound nanospheres

Energy Technology Data Exchange (ETDEWEB)

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.

Dynamic Properties of Star-Branched Polymer Brushes

International Nuclear Information System (INIS)

Sikorski, A.; Romiszowski, P.

2004-01-01

We studied a simplified model of a polymer brush. It consisted of star-branched chains, which were restricted to a simple cubic lattice. Each star-branched macromolecule consisted of three linear arms of equal length emanating from a common origin (the branching point). The chains were grafted to an impenetrable surface, i.e. they were terminally attached to the surface with one arm. The number of chains was varied from low to high grafting density. The model system was studied at good solvent conditions because the excluded volume effect was the only potential of interaction included in the model. The properties of this model system were studied by means of Monte Carlo simulation. The sampling algorithm was based on local changes of chain conformations. The dynamic properties of the polymer brush were studied and correlated with its structure. The differences in relaxation times of particular star arms were shown. The short-time mobility of polymer layers was analyzed. The lateral self-diffusion of chains was also studied and discussed. (author)

Disorder effects on the static scattering function of star branched polymers

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V. Blavatska

2012-10-01

Full Text Available We present an analysis of the impact of structural disorder on the static scattering function of f-armed star branched polymers in d dimensions. To this end, we consider the model of a star polymer immersed in a good solvent in the presence of structural defects, correlated at large distances r according to a power law ~r-a. In particular, we are interested in the ratio g(f of the radii of gyration of star and linear polymers of the same molecular weight, which is a universal experimentally measurable quantity. We apply a direct polymer renormalization approach and evaluate the results within the double ϵ = 4 - d, δ = 4 - a-expansion. We find an increase of g(f with an increasing δ. Therefore, an increase of disorder correlations leads to an increase of the size measure of a star relative to linear polymers of the same molecular weight.

A supramolecular miktoarm star polymer based on porphyrin metal complexation in water.

Science.gov (United States)

Hou, Zhanyao; Dehaen, Wim; Lyskawa, Joël; Woisel, Patrice; Hoogenboom, Richard

2017-07-25

A novel supramolecular miktoarm star polymer was successfully constructed in water from a pyridine end-decorated polymer (Py-PmDEGA) and a metalloporphyrin based star polymer (ZnTPP-(PEG) 4 ) via metal-ligand coordination. The Py-PmDEGA moiety was prepared via a combination of reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequent aminolysis and Michael addition reactions to introduce the pyridine end-group. The ZnTPP(PEG) 4 star-polymer was synthesized by the reaction between tetrakis(p-hydroxyphenyl)porphyrin and toluenesulfonyl-PEG, followed by insertion of a zinc ion into the porphyrin core. The formation of a well-defined supramolecular AB 4 -type miktoarm star polymer was unambiguously demonstrated via UV-Vis spectroscopic titration, isothermal titration calorimetry (ITC) and diffusion ordered NMR spectroscopy (DOSY).

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

KAUST Repository

Wang, Shuaipeng; Song, Xiaowan; Feng, Xiaoshuang; Chen, Peng; Qian, Jiasheng; Xia, Ru; Miao, Jibin

2014-01-01

. 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

Uniform Distance Scaling Behavior of Planet-Satellite Nanostructures Made by Star Polymers.

Science.gov (United States)

Rossner, Christian; Tang, Qiyun; Glatter, Otto; Müller, Marcus; Vana, Philipp

2017-02-28

Planet-satellite nanostructures from RAFT star polymers and larger (planet) as well as smaller (satellite) gold nanoparticles are analyzed in experiments and computer simulations regarding the influence of arm number of star polymers. A uniform scaling behavior of planet-satellite distances as a function of arm length was found both in the dried state (via transmission electron microscopy) after casting the nanostructures on surfaces and in the colloidally dispersed state (via simulations and small-angle X-ray scattering) when 2-, 3-, and 6-arm star polymers were employed. This indicates that the planet-satellite distances are mainly determined by the arm length of star polymers. The observed discrepancy between TEM and simulated distances can be attributed to the difference of polymer configurations in dried and dispersed state. Our results also show that these distances are controlled by the density of star polymers end groups, and the number of grabbed satellite particles is determined by the magnitude of the corresponding density. These findings demonstrate the feasibility to precisely control the planet-satellite structures at the nanoscale.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Developmental toxicity of low generation PAMAM dendrimers in zebrafish

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

Self-Assembly of Telechelic Tyrosine End-Capped PEO Star Polymers in Aqueous Solution.

Science.gov (United States)

Edwards-Gayle, Charlotte J C; Greco, Francesca; Hamley, Ian W; Rambo, Robert P; Reza, Mehedi; Ruokolainen, Janne; Skoulas, Dimitrios; Iatrou, Hermis

2018-01-08

We investigate the self-assembly of two telechelic star polymer-peptide conjugates based on poly(ethylene oxide) (PEO) four-arm star polymers capped with oligotyrosine. The conjugates were prepared via N-carboxy anhydride-mediated ring-opening polymerization from PEO star polymer macroinitiators. Self-assembly occurs above a critical aggregation concentration determined via fluorescence probe assays. Peptide conformation was examined using circular dichroism spectroscopy. The structure of self-assembled aggregates was probed using small-angle X-ray scattering and cryogenic transmission electron microscopy. In contrast to previous studies on linear telechelic PEO-oligotyrosine conjugates that show self-assembly into β-sheet fibrils, the star architecture suppresses fibril formation and micelles are generally observed instead, a small population of fibrils only being observed upon pH adjustment. Hydrogelation is also suppressed by the polymer star architecture. These peptide-functionalized star polymer solutions are cytocompatible at sufficiently low concentration. These systems present tyrosine at high density and may be useful in the development of future enzyme or pH-responsive biomaterials.

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

Science.gov (United States)

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.

STAR POLYMERS IN GOOD SOLVENTS FROM DILUTE TO CONCENTRATED REGIMES: CROSSOVER APPROACH

Directory of Open Access Journals (Sweden)

S.B.Kiselev

2002-01-01

Full Text Available An introduction is given to the crossover theory of the conformational and thermodynamic properties of star polymers in good solvents. The crossover theory is tested against Monte Carlo simulation data for the structure and thermodynamics of model star polymers. In good solvent conditions, star polymers approach a "universal" limit as N → ∞, however, there are two types of approach towards this limit. In the dilute regime, a critical degree of polymerization N* is found to play a similar role as the Ginzburg number in the crossover theory for critical phenomena in simple fluids. A rescaled penetration function is found to control the free energy of star polymer solutions in the dilute and semidilute regions. This equation of state captures the scaling behaviour of polymer solutions in the dilute/semidilute regimes and also performs well in the concentrated regimes, where the details of the monomer-monomer interactions become important.

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

Science.gov (United States)

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

An intrinsically fluorescent dendrimer as a nanoprobe of cell transport.

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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.

Multiscale simulations of star polymer melts

NARCIS (Netherlands)

Liu, L.

2014-01-01

Depending on the architecture, polymers are observed to show different dynamical and rheological properties. The results obtained from this work will not only contribute to a fundamental understanding of the character of star polymeric systems, but also possibly help to design industrial

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

Directory of Open Access Journals (Sweden)

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.

A review on comparative study of PPI and PAMAM dendrimers

International Nuclear Information System (INIS)

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.

A review on comparative study of PPI and PAMAM dendrimers

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

Investigation of star polymer nanoshells for use in diagnostic imaging and photothermal cancer therapy applications

Science.gov (United States)

Gomez, Lizabeth

Gold nanoshells can be designed to possess high light scattering and strong absorption of near-infrared light. Thus, they have the potential to be used in biological applications as contrast agents for diagnostic imaging as well as for thermal ablation of tumor cells in future cancer treatments. In this study, gold nanoshells with dye-loaded star polymer cores were investigated. Uniform near-infrared gold nanoshells with 100 nm diameters were successfully generated using different batches of star polymer templates and were characterized by UV-visible spectroscopy and scanning electron microscopy. The star polymers used were block copolymer structures with a hydrophobic polystyrene (PS) core and a hydrophilic poly(N,N-dimethylaminoethylmethracrylate) (DMAEMA) outer shell. Within this work, a general procedure was established in order to achieve a desired gold nanoshell size regardless of the star polymer batch used, since the synthesis process conditions can cause star polymers to vary in size as well in the number and length of amino-functionalized arms. Control of the gold nanoshell diameter was optimized after an in-depth analysis of the synthesis parameters that affected the formation and final size of the dye-loaded star polymer gold nanoshells. The main parameters examined were pH of the gold seeds used to nucleate the templates and the ratio of star polymer to gold hydroxide used during the growth of the outer gold shell.

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.

Science.gov (United States)

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.

From dendrimers to fractal polymers and beyond

Directory of Open Access Journals (Sweden)

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.

Controlled doping by self-assembled dendrimer-like macromolecules

Science.gov (United States)

Wu, Haigang; Guan, Bin; Sun, Yingri; Zhu, Yiping; Dan, Yaping

2017-02-01

Doping via self-assembled macromolecules might offer a solution for developing single atom electronics by precisely placing individual dopants at arbitrary location to meet the requirement for circuit design. Here we synthesize dendrimer-like polyglycerol macromolecules with each carrying one phosphorus atom in the core. The macromolecules are immobilized by the coupling reagent onto silicon surfaces that are pre-modified with a monolayer of undecylenic acid. Nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) are employed to characterize the synthesized macromolecules and the modified silicon surfaces, respectively. After rapid thermal annealing, the phosphorus atoms carried by the macromolecules diffuse into the silicon substrate, forming dopants at a concentration of 1017 cm-3. Low-temperature Hall effect measurements reveal that the ionization process is rather complicated. Unlike the widely reported simple ionization of phosphorus dopants, nitrogen and carbon are also involved in the electronic activities in the monolayer doped silicon.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Recent Advances in Click Chemistry Applied to Dendrimer Synthesis

Directory of Open Access Journals (Sweden)

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.

Osmotic pressure and virial coefficients of star and comb polymer solutions: dissipative particle dynamics.

Science.gov (United States)

Wang, Tzu-Yu; Fang, Che-Ming; Sheng, Yu-Jane; Tsao, Heng-Kwong

2009-03-28

The effects of macromolecular architecture on the osmotic pressure pi and virial coefficients (B(2) and B(3)) of star and comb polymers in good solvents are studied by dissipative particle dynamics simulations for both dilute and semiconcentrated regimes. The dependence of the osmotic pressure on polymer concentration is directly calculated by considering two reservoirs separated by a semipermeable, fictitious membrane. Our simulation results show that the ratios A(n+1) identical with B(n+1)/R(g)(3n) are essentially constant and A(2) and A(3) are arm number (f) dependent, where R(g) is zero-density radius of gyration. The value of dimensionless virial ratio g = A(3)/A(2)(2) increases with arm number of stars whereas it is essentially arm number independent for comb polymers. In semiconcentrated regime the scaling relation between osmotic pressure and volume fraction, pi proportional to phi(lambda), still holds for both star and comb polymers. For comb polymers, the exponent lambda is close to lambda(*) (approximately = 2.73 for linear chains) and is independent of the arm number. However, for star polymers, the exponent lambda deviates from lambda(*) and actually grows with increasing the arm number. This may be attributed to the significant ternary interactions near the star core in the many-arm systems.

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

NARCIS (Netherlands)

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

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

International Nuclear Information System (INIS)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

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

OpenAIRE

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...

Molecular weight (hydrodynamic volume) dictates the systemic pharmacokinetics and tumour disposition of PolyPEG star polymers.

Science.gov (United States)

Khor, Song Yang; Hu, Jinming; McLeod, Victoria M; Quinn, John F; Williamson, Mark; Porter, Christopher J H; Whittaker, Michael R; Kaminskas, Lisa M; Davis, Thomas P

2015-11-01

Herein we report for the first time the biological fate of poly[(oligoethylene glycol) acrylate] (POEGA) star polymers synthesised via a versatile arm-first reversible addition-fragmentation chain transfer (RAFT) polymerisation approach. The biopharmaceutical behaviour of three different molecular weight (49, 64 and 94kDa) POEGA stars was evaluated in rats and nude mice bearing human MDA MB-231 tumours after intravenous administration. The 94kDa star polymer exhibited a longer plasma exposure time than the 49kDa or 64kDa star polymer; an observation attributable to differences in the rates of both polymer biodegradation and urinary excretion. Tumour biodistribution also correlated with molecular weight and was greatest for the longest circulating 94kDa star. Different patterns of liver and spleen biodistribution were observed between mice and rats for the different sized polymers. The polymers were also well-tolerated in vivo and in vitro at therapeutic concentrations. Advances in nanotechnology has enabled scientists to produce nanoparticle as drug carriers in cancer therapeutics. In this article, the authors studied the biological fate of poly[(oligoethylene glycol) acrylate] (POEGA) star polymers of different size, after intravenous injections. This would allow the subsequent comparison to other drug delivery systems for better drug delivery. Copyright © 2015 Elsevier Inc. All rights reserved.

Three Arm Star Homo- And Co-Polymers Via Atom Transfer Radical Polymerization

International Nuclear Information System (INIS)

Amin, A.; Sobh, R.A.; Ayoub, M.M.H.

2005-01-01

Star homo and co-polymers of some vinyl monomers such as methylmethacrylate, butylmethacrylate and styrene (MMA, BMA, St.) were prepared using N, N, N', N' tetramethylethylenediamine ligand/ CuBr catalytic system via atom transfer radical polymerization (ATRP). Three armed benzene based core was successfully used as initiator. Low polydispersities and regular molecular weight values were obtained in most cases especially at low conversions. MMA and BuMA showed comparable behavior where controlled and true ATRP was observed even at the high conversions. However, styrene monomer recorded irregular high polydispersities at high conversions in spite of the relatively low molecular weight values. 1HNMR confirmed the structures of the resulting polymers. Transmission Electron microscope (TEM) proved the nano-structure of the star polymers. The thermal behavior of the MMA star homo and copolymers was studied. The effect of the star shape on the thermal behavior was very clear with respect to the linear ones

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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)

Supramolecular coordination polymer formed from artificial light-harvesting dendrimer.

Science.gov (United States)

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

A New All-Solid-State Hyperbranched Star Polymer Electrolyte for Lithium Ion Batteries: Synthesis and Electrochemical Properties

International Nuclear Information System (INIS)

Wang, Ailian; Xu, Hao; Zhou, Qian; Liu, Xu; Li, Zhengyao; Gao, Rui; Wu, Na; Guo, Yuguo; Li, Huayi; Zhang, Liaoyun

2016-01-01

Highlights: • A new hyperbranched multi-arm star polymer was successfully synthesized. • The star polymer electrolyte has good thermal stability and forming-film property. • The ion conductivity electrolyte can reach 8.3 × 10"−"5 S cm"−"1 at room temperature. • The star polymer electrolyte has wide electrochemical windows of 4.7 V. - Abstract: A new hyperbranched multi-arm star polymer with hyperbranched polystyrene (HBPS) as core and polymethyl methacrylate-block-poly(ethylene glycol) methyl ether methacrylate(PMMA-b-PPEGMA) as arms was firstly synthesized by atom transfer radical polymerization. The obtained hyperbranched multi-arm star polymer (HBPS-(PMMA-b-PPEGMA)_x) exhibited good thermal stability with a thermal decomposition temperature of 372 °C. The transparent, free-standing, flexible polymer electrolyte film of the blending of HBPS-(PMMA-b-PPEGMA)_x and lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) was successfully fabricated by a solution casting method. The ionic conductivity of the hyperbranched star polymer electrolyte with a molar ratio of [EO]/[Li] of 30 could reach 8.3 × 10"−"5 S cm"−"1 at 30 °C (with the content of PPEGMA of 83.7%), and 2.0 × 10"−"4 S cm"−"1 at 80 °C (with the content of PPEGMA of 51.6%). The effect of the concentration of lithium salts on ionic conductivity was also investigated. The obtained all-solid-state polymer electrolyte possessed a wide electrochemical stability window of 4.7 V (vs. Li"+/Li), and a lithium-ion transference number (t_L_i"+) up to 0.31. The interfacial impedance of the fabricated LiÔöépolymer electrolyteÔöéLi symmetric cell based on hyperbranched star multi-arm polymer electrolyte exhibited good interfacial compatibility between all-solid-state polymer electrolyte and electrodes. The excellent properties of the hyperbranched star polymer electrolyte made it attractive as solid-state polymer electrolyte for lithium-ion batteries.

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

NARCIS (Netherlands)

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

Biphasic interactions between a cationic dendrimer and actin.

Science.gov (United States)

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.

Arm retraction dynamics of entangled star polymers: A forward flux sampling method study

Science.gov (United States)

Zhu, Jian; Likhtman, Alexei E.; Wang, Zuowei

2017-07-01

The study of dynamics and rheology of well-entangled branched polymers remains a challenge for computer simulations due to the exponentially growing terminal relaxation times of these polymers with increasing molecular weights. We present an efficient simulation algorithm for studying the arm retraction dynamics of entangled star polymers by combining the coarse-grained slip-spring (SS) model with the forward flux sampling (FFS) method. This algorithm is first applied to simulate symmetric star polymers in the absence of constraint release (CR). The reaction coordinate for the FFS method is determined by finding good agreement of the simulation results on the terminal relaxation times of mildly entangled stars with those obtained from direct shooting SS model simulations with the relative difference between them less than 5%. The FFS simulations are then carried out for strongly entangled stars with arm lengths up to 16 entanglements that are far beyond the accessibility of brute force simulations in the non-CR condition. Apart from the terminal relaxation times, the same method can also be applied to generate the relaxation spectra of all entanglements along the arms which are desired for the development of quantitative theories of entangled branched polymers. Furthermore, we propose a numerical route to construct the experimentally measurable relaxation correlation functions by effectively linking the data stored at each interface during the FFS runs. The obtained star arm end-to-end vector relaxation functions Φ (t ) and the stress relaxation function G(t) are found to be in reasonably good agreement with standard SS simulation results in the terminal regime. Finally, we demonstrate that this simulation method can be conveniently extended to study the arm-retraction problem in entangled star polymer melts with CR by modifying the definition of the reaction coordinate, while the computational efficiency will depend on the particular slip-spring or slip

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

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

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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.

White polymer light-emitting diodes based on star-shaped polymers with an orange dendritic phosphorescent core.

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Zhu, Minrong; Li, Yanhu; Cao, Xiaosong; Jiang, Bei; Wu, Hongbin; Qin, Jingui; Cao, Yong; Yang, Chuluo

2014-12-01

A series of new star-shaped polymers with a triphenylamine-based iridium(III) dendritic complex as the orange-emitting core and poly(9,9-dihexylfluorene) (PFH) chains as the blue-emitting arms is developed towards white polymer light-emitting diodes (WPLEDs). By fine-tuning the content of the orange phosphor, partial energy transfer and charge trapping from the blue backbone to the orange core is realized to achieve white light emission. Single-layer WPLEDs with the configuration of ITO (indium-tin oxide)/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/polymer/CsF/Al exhibit a maximum current efficiency of 1.69 cd A(-1) and CIE coordinates of (0.35, 0.33), which is very close to the pure white-light point of (0.33, 0.33). To the best of our knowledge, this is the first report on star-shaped white-emitting single polymers that simultaneously consist of fluorescent and phosphorescent species. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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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

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

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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

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

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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.

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

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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.

Polyphenylene dendrimers

International Nuclear Information System (INIS)

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

Structure-skin permeability relationship of dendrimers.

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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)

Preclinical studies of dendrimer prodrugs.

Science.gov (United States)

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.'

Optical absorption in dendrimers

International Nuclear Information System (INIS)

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

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

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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.

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

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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.

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

DEFF Research Database (Denmark)

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...

Palladium N-Heterocyclic Carbene Precatalyst Site Isolated in the Core of a Star Polymer

KAUST Repository

Bukhriakov, Konstantin; Mugemana, Clement; Vu, Khanh B.; Rodionov, Valentin

2015-01-01

An approach for supporting a Pd-NHC complex on a soluble star polymer with nanoscale dimensions is described. The resulting star polymer catalyst exhibits excellent activity in cross-coupling reactions, is stable in air and moisture, and is easily recoverable and recyclable. These properties are distinct and unattainable with the small-molecule version of the same catalyst. © 2015 American Chemical Society.

Palladium N-Heterocyclic Carbene Precatalyst Site Isolated in the Core of a Star Polymer

KAUST Repository

Bukhriakov, Konstantin

2015-10-02

An approach for supporting a Pd-NHC complex on a soluble star polymer with nanoscale dimensions is described. The resulting star polymer catalyst exhibits excellent activity in cross-coupling reactions, is stable in air and moisture, and is easily recoverable and recyclable. These properties are distinct and unattainable with the small-molecule version of the same catalyst. © 2015 American Chemical Society.

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

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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.

Viscoelasticity, nonlinear shear start-up, and relaxation of entangled star polymers

KAUST Repository

Snijkers, Frank

2013-07-23

We report on a detailed rheological investigation of well-defined symmetric entangled polymer stars of low functionality with varying number of arms, molar mass of the arms, and solvent content. Emphasis is placed on the response of the stars in simple shear, during start-up, and for relaxation upon flow cessation. To reduce experimental artifacts associated with edge fracture (primarily) and wall slip, we employ a homemade cone-partitioned plate fixture which was successfully implemented in recent studies. Reliable data for these highly entangled stars could be obtained for Weissenberg numbers below 300. The appearance of a stress overshoot during start-up with a corresponding strain approaching a value of 2 suggests that in the investigated shear regime the stars orient but do not stretch. This is corroborated by the fact that the empirical Cox-Merx rule appears to be validated, within experimental error. On the other hand, the (shear) rate dependent steady shear viscosity data exhibit a slope smaller than the convective constraint release slope of -1 (for linear polymers) for the investigated range of rates. The broadness of the stress overshoot reflects the broad linear relaxation spectrum of the stars. The initial stress relaxation rate, reflecting the initial loss of entanglements due to the action of convective constraint release in steady shear flow, increases with Weissenberg number. More importantly, when compared against the relevant rates for comb polymers with relatively short arms, the latter are slower at larger Weissenberg numbers. At long times, the relaxation data are consistent with the linear viscoelastic data on these systems. © 2013 American Chemical Society.

Structure of Carbon Nanotube-dendrimer composite

OpenAIRE

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,...

Star-shaped Polymers through Simple Wavelength-Selective Free-Radical Photopolymerization.

Science.gov (United States)

Eibel, Anna; Fast, David E; Sattelkow, Jürgen; Zalibera, Michal; Wang, Jieping; Huber, Alex; Müller, Georgina; Neshchadin, Dmytro; Dietliker, Kurt; Plank, Harald; Grützmacher, Hansjörg; Gescheidt, Georg

2017-11-06

Star-shaped polymers represent highly desired materials in nanotechnology and life sciences, including biomedical applications (e.g., diagnostic imaging, tissue engineering, and targeted drug delivery). Herein, we report a straightforward synthesis of wavelength-selective multifunctional photoinitiators (PIs) that contain a bisacylphosphane oxide (BAPO) group and an α-hydroxy ketone moiety within one molecule. By using three different wavelengths, these photoactive groups can be selectively addressed and activated, thereby allowing the synthesis of ABC-type miktoarm star polymers through a simple, highly selective, and robust free-radical polymerization method. The photochemistry of these new initiators and the feasibility of this concept were investigated in unprecedented detail by using various spectroscopic techniques. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optically nonlinear energy transfer in light-harvesting dendrimers

OpenAIRE

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...

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

Dendrimer Prodrugs

Directory of Open Access Journals (Sweden)

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.

Computer simulations of dendrimer-polyelectrolyte complexes.

Science.gov (United States)

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.

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

Science.gov (United States)

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

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

Science.gov (United States)

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 ...

Core Cross-linked Star Polymers for Temperature/pH Controlled Delivery of 5-Fluorouracil

Directory of Open Access Journals (Sweden)

Elizabeth Sánchez-Bustos

2016-01-01

Full Text Available RAFT polymerization with cross-linking was used to prepare core cross-linked star polymers bearing temperature sensitive arms. The arms consisted of a diblock copolymer containing N-isopropylacrylamide (NIPAAm and 4-methacryloyloxy benzoic acid (4MBA in the temperature sensitive block and poly(hexyl acrylate forming the second hydrophobic block, while ethyleneglycol dimethacrylate was used to form the core. The acid comonomer provides pH sensitivity to the arms and also increases the transition temperature of polyNIPAAm to values in the range of 40 to 46°C. Light scattering and atomic force microscopy studies suggest that loose core star polymers were obtained. The star polymers were loaded with 5-fluorouracil (5-FU, an anticancer agent, in values of up to 30 w/w%. In vitro release experiments were performed at different temperatures and pH values, as well as with heating and cooling temperature cycles. Faster drug release was obtained at 42°C or pH 6, compared to normal physiological conditions (37°C, pH 7.4. The drug carriers prepared acted as nanopumps changing the release kinetics of 5-FU when temperatures cycles were applied, in contrast with release rates at a constant temperature. The prepared core cross-linked star polymers represent advanced drug delivery vehicles optimized for 5-FU with potential application in cancer treatment.

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

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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.

Probing the binding of cationic lipids with dendrimers.

Science.gov (United States)

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.

Glycopeptide dendrimers. Part I

Czech Academy of Sciences Publication Activity Database

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

Integral equation theory study on the phase separation in star polymer nanocomposite melts.

Science.gov (United States)

Zhao, Lei; Li, Yi-Gui; Zhong, Chongli

2007-10-21

The polymer reference interaction site model theory is used to investigate phase separation in star polymer nanocomposite melts. Two kinds of spinodal curves were obtained: classic fluid phase boundary for relatively low nanoparticle-monomer attraction strength and network phase boundary for relatively high nanoparticle-monomer attraction strength. The network phase boundaries are much more sensitive with nanoparticle-monomer attraction strength than the fluid phase boundaries. The interference among the arm number, arm length, and nanoparticle-monomer attraction strength was systematically investigated. When the arm lengths are short, the network phase boundary shows a marked shift toward less miscibility with increasing arm number. When the arm lengths are long enough, the network phase boundaries show opposite trends. There exists a crossover arm number value for star polymer nanocomposite melts, below which the network phase separation is consistent with that of chain polymer nanocomposite melts. However, the network phase separation shows qualitatively different behaviors when the arm number is larger than this value.

DNA assisted self-assembly of PAMAM dendrimers.

Science.gov (United States)

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.

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

Science.gov (United States)

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

Effect of increased surface hydrophobicity via drug conjugation on the clearance of inhaled PEGylated polylysine dendrimers.

Science.gov (United States)

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.

Positron annihilation study of polyphenylene dendrimers

International Nuclear Information System (INIS)

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

Quantification of interaction and topological parameters of polyisoprene star polymers under good solvent conditions

KAUST Repository

Rai, Durgesh K.

2016-05-05

Mass fractal scaling, reflected in the mass fractal dimension df, is independently impacted by topology, reflected in the connectivity dimension c, and by tortuosity, reflected in the minimum dimension dmin. The mass fractal dimension is related to these other dimensions by df=cdmin. Branched fractal structures have a higher mass fractal dimension compared to linear structures due to a higher c, and extended structures have a lower dimension compared to convoluted self-avoiding and Gaussian walks due to a lower dmin. It is found, in this work, that macromolecules in thermodynamic equilibrium display a fixed mass fractal dimension df under good solvent conditions, regardless of chain topology. These equilibrium structures accommodate changes in chain topology such as branching c by a decrease in chain tortuosity dmin. Symmetric star polymers are used to understand the structure of complex macromolecular topologies. A recently published hybrid Unified scattering function accounts for interarm correlations in symmetric star polymers along with polymer-solvent interaction for chains of arbitrary scaling dimension. Dilute solutions of linear, three-arm and six-arm polyisoprene stars are studied under good solvent conditions in deuterated p-xylene. Reduced chain tortuosity can be viewed as steric straightening of the arms. Steric effects for star topologies are quantified, and it is found that steric straightening of arms is more significant for lower-molecular-weight arms. The observation of constant df is explained through a modification of Flory-Krigbaum theory for branched polymers.

Regional Morphology and Transport of PAMAM Dendrimers Across Isolated Rat Intestinal Tissue.

Science.gov (United States)

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.

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

NARCIS (Netherlands)

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

Fe3O4 nanoparticles modified by CD-containing star polymer for MRI and drug delivery.

Science.gov (United States)

Cha, Ruitao; Li, Juanjuan; Liu, Yang; Zhang, Yifan; Xie, Qian; Zhang, Mingming

2017-10-01

Fe 3 O 4 nanoparticles with ultrasmall sizes show good T 1 or T 1 +T 2 contrast abilities, and have attracted considerable interest in the field of magnetic resonance imaging (MRI) contrast agents. For effective biomedical applications, the colloidal stability and biocompatibility of the Fe 3 O 4 nanoparticles need to be improved without reducing MRI relaxivity. In this paper, star polymers were used as coating materials to modify Fe 3 O 4 nanoparticles in view of their dense molecular architecture with moderate flexibility. The star polymer was composed of a β-cyclodextrin (β-CD) core and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) arms. Meanwhile, reduced glutathione (GSH), as a model drug, was also associated with the star polymer. Thus, a new platform for simultaneous diagnosis and treatment was achieved. Compared to the Fe 3 O 4 nanoparticles coated with linear polymers, the Fe 3 O 4 nanoparticles coated with star polymers (Fe 3 O 4 @GCP) possessed higher GSH association capacity and better stability in serum-containing solution. GSH could be released from Fe 3 O 4 @GCP nanoparticles in response to pH value of the solution. Since the sulfhydryl group on GSH is able to combine free radicals, Fe 3 O 4 @GCP nanoparticles exhibited less cytotoxicity compared to the Fe 3 O 4 nanoparticles without including GSH. Furthermore, the nanoparticles could also serve as good T 1 MRI contrast agent, and the MRI relaxivity of Fe 3 O 4 @GCP nanoparticles did not decrease after coated with the star polymer. These results indicate that the precisely designed Fe 3 O 4 @GCP nanoparticles could be used as a versatile promising theranostic nano-platform. Copyright © 2017 Elsevier B.V. All rights reserved.

Optical absorption in compact and extended dendrimers

International Nuclear Information System (INIS)

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

Preparation of a Mini-Library of Thermo-Responsive Star (NVCL/NVP-VAc Polymers with Tailored Properties Using a Hexafunctional Xanthate RAFT Agent

Directory of Open Access Journals (Sweden)

Norma Aidé Cortez-Lemus

2017-12-01

Full Text Available A mini-library of star-shaped thermoresponsive polymers having six arms was prepared using a hexafunctional xanthate by reversible addition–fragmentation chain transfer (RAFT polymerization. Star polymers with homopolymeric arms of poly(N-vinylcaprolactam (PNVCL, copolymeric arms of poly(N-vinylcaprolactam-co-N-vinylpyrrolidone (PNVCL-co-PNVP and also arms of block copolymers of PNVCL-b-PVAc, (PNVCL-co-PNVP-b-PVAc, and combinations of them changing the order of the block was achieved exploiting the R-RAFT synthetic methodology (or R-group approach, wherein the thiocarbonyl group is transferred to the polymeric chain end. Taking advantage of the RAFT benefits, the molecular weight of the star polymers was controlled (Mn = 11,880–153,400 g/mol to yield star polymers of different sizes and lower critical solution temperature (LCST values. Removing the xanthate group of the star polymers allowed for the introduction of specific functional groups at the ends of the star arms and resulted in an increase of the LCST values. Star PNVCL-b-PVAc diblock copolymers with PVAc contents of 5–26 mol % were prepared; the hydrophobic segment (PVAc is located at the end of the star arms. Interestingly, when the PVAc content was 5–7 mol %, the hydrodynamic diameter (Dh value of the aggregates formed in water was almost the same sa the Dh of the corresponding PNVCL star homopolymers. It is proposed that these star block copolymers self-assemble into single flowerlike micelles, showing great stability in aqueous solution. Star block copolymers with the PVAc hydrophobic block in the core of the star, such as PVAc-b-(PNVCL-co-PNVP, form micellar aggregates in aqueous solution with Dh values in the range from ~115 to 245 nm while maintaining a thermoresponsive behavior. Micellar aggregates of selected star polymers were used to encapsulate methotrexate (MTX showing their potential in the temperature controlled release of this antineoplasic drug. The importance

Photocrosslinkable Star Polymers via RAFT-Copolymerizations with N-Ethylacrylate-3,4-dimethylmaleimide

Directory of Open Access Journals (Sweden)

Philipp Vana

2013-06-01

Full Text Available This paper describes the Z-RAFT-star copolymerization of n-butyl acrylate (BA and N-isopropyl acrylamide (NIPAm, respectively, with N-ethylacrylate-3,4-dimethylmaleimide (1.1, a monomer carrying a UV-reactive unit that undergoes photocrosslinking. Addition of 1.1 slows down the polymerization rate both for BA and for NIPAm polymerization. Double star formation due to radical attack to the 3,4-dimethylmaleimide moiety was found in the case of BA. Dead polymer formation, presumably due to aminolysis as side-reaction, was pronounced in the NIPAm system. These two effects broadened the molar mass distributions, but did not impede the formation of functional star polymers. The composition of the copolymers as well as the reactivity ratios for the applied comonomers were determined via NMR spectroscopy (BA-co-1.1 r1.1 = 2.24 rBA = 0.95; NIPAm-co-1.1 r1.1 = 0.96 rNIPAm = 0.05. In both cases, the comonomer is consumed preferably in the beginning of the polymerization, thus forming gradient copolymer stars with the UV-reactive units being located in the outer sphere.

DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

DEFF Research Database (Denmark)

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...

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

Supramolecular assembly of a series of chiral dendrimers in interfacial films

International Nuclear Information System (INIS)

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

Interaction between viologen-phosphorus dendrimers and α-synuclein

International Nuclear Information System (INIS)

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.

Polymer liquids fracture like solids

DEFF Research Database (Denmark)

Huang, Qian; Hassager, Ole

2017-01-01

While fracture in brittle solids has been studied for centuries until today, there are few studies on fracture in polymer liquids. Recent developments in experimental techniques, especially the combination of controlled filament stretching rheometry and high speed imaging, have opened new windows...... into the detailed study of fracture processes for polymer liquids. High speed imaging shows that polymer liquids fracture like solids with initiation and propagation of an edge fracture. However, remarkable features such as highly reproducible critical stress, independent appearance of multiple fractures...

Self and collective dynamics of ordered star polymer solutions

CERN Document Server

Stellbrink, J; Monkenbusch, M; Richter, D; Ehlers, G; Schleger, P

2002-01-01

We investigated the dynamics of 18-arm polyisoprene star polymer solutions well above their overlap concentration c sup *. Combining neutron spin echo spectroscopy (NSE) and selective H/D labelling, we were able to separate inter- (collective) and intra-star (self) dynamics. Only at low Q-vectors do self and collective dynamics become discernible. Here, collective dynamics are found to be consistent with a colloidal approach resulting from star-star interactions. The collective short time diffusion coefficient D sub e sub f sub f is well described by the term D sub 0 /S(Q), with D sub 0 the diffusion coefficient at infinite dilution. At Q sub m , the peak position in the structure factor S(Q), no difference is observable between collective and self dynamics. For covering the slowed-down dynamics at Q sub m the time range of NSE was extended for the first time up to 350 ns using long wavelengths, lambda=19 A, at IN15 (ILL, Grenoble). We found that S(Q,t)/S(Q,0) relaxes into a concentration-dependent plateau. T...

Is life most likely around Sun-like stars?

Science.gov (United States)

Lingam, Manasvi; Loeb, Abraham

2018-05-01

We consider the habitability of Earth-analogs around stars of different masses, which is regulated by the stellar lifetime, stellar wind-induced atmospheric erosion, and biologically active ultraviolet (UV) irradiance. By estimating the timescales associated with each of these processes, we show that they collectively impose limits on the habitability of Earth-analogs. We conclude that planets orbiting most M-dwarfs are not likely to host life, and that the highest probability of complex biospheres is for planets around K- and G-type stars. Our analysis suggests that the current existence of life near the Sun is slightly unusual, but not significantly anomalous.

M-Polynomial and Related Topological Indices of Nanostar Dendrimers

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Core Cross-Linked Multiarm Star Polymers with Aggregation-Induced Emission and Temperature Responsive Fluorescence Characteristics

KAUST Repository

Zhang, Zhen

2017-05-19

Aggregation-induced emission (AIE) active core cross-linked multiarm star polymers, carrying polystyrene (PS), polyethylene (PE), or polyethylene-b-polycaprolactone (PE-b-PCL) arms, have been synthesized through an “arm-first” strategy, by atom transfer radical copolymerization (ATRP) of a double styrene-functionalized tetraphenylethene (TPE-2St) used as a cross-linker with linear arm precursors possessing terminal ATRP initiating moieties. Polyethylene macroinitiator (PE–Br) was prepared via the polyhomologation of dimethylsulfoxonium methylide with triethylborane followed by oxidation/hydrolysis and esterification of the produced PE–OH with 2-bromoisobutyryl bromide; polyethylene-block-poly(ε-caprolactone) diblock macroinitiator was derived by combining polyhomologation with ring-opening polymerization (ROP). All synthesized star polymers showed AIE-behavior either in solution or in bulk. At high concentration in good solvents (e.g., THF, or toluene) they exhibited low photoluminescence (PL) intensity due to the inner filter effect. In sharp contrast to the small molecule TPE-2St, the star polymers were highly emissive in dilute THF solutions. This can be attributed to the cross-linked structure of poly(TPE-2St) core which restricts the intramolecular rotation and thus induces emission. In addition, the PL intensity of PE star polymers in THF(solvent)/n-hexane(nonsolvent) mixtures, due to their nearly spherical shape, increased when the temperature decreased from 55 to 5 °C with a linear response in the range 40–5 °C.

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

Science.gov (United States)

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.

Dendrimers in drug research

DEFF Research Database (Denmark)

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...

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Host-guest chemistry of dendrimer-drug complexes. 2. Effects of molecular properties of guests and surface functionalities of dendrimers.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Interactions of PAMAM dendrimers with SDS at the solid-liquid interface.

Science.gov (United States)

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

2013-05-14

This work addresses structural and nonequilibrium effects of the interactions between well-defined cationic poly(amidoamine) PAMAM dendrimers of generations 4 and 8 and the anionic surfactant sodium dodecyl sulfate (SDS) at the hydrophilic silica-water interface. Neutron reflectometry and quartz crystal microbalance with dissipation monitoring were used to reveal the adsorption from premixed dendrimer/surfactant solutions as well as sequential addition of the surfactant to preadsorbed layers of dendrimers. PAMAM dendrimers of both generations adsorb to hydrophilic silica as a compact monolayer, and the adsorption is irreversible upon rinsing with salt solution. SDS adsorbs on the dendrimer layer and at low bulk concentrations causes the expansion of the dendrimer layers on the surface. When the bulk concentration of SDS is increased, the surfactant layer consists of aggregates or bilayer-like structures. The adsorption of surfactant is reversible upon rinsing, but slight changes of the structure of the preadsorbed PAMAM monolayer were observed. The adsorption from premixed solutions close to charge neutrality results in thick multilayers, but the surface excess is lower when the bulk complexes have a net negative charge. A critical examination of the pathway of adsorption for the interactions of SDS with preadsorbed PAMAM monolayers and premixed PAMAM/SDS solutions with hydrophilic silica revealed that nonequilibrium effects are important only in the latter case, and the application of a thermodynamic model to such experimental data would be inappropriate.

Phosphorus dendrimers for nanomedicine.

Science.gov (United States)

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.

Star Polymers Reduce Islet Amyloid Polypeptide Toxicity via Accelerated Amyloid Aggregation.

Science.gov (United States)

Pilkington, Emily H; Lai, May; Ge, Xinwei; Stanley, William J; Wang, Bo; Wang, Miaoyi; Kakinen, Aleksandr; Sani, Marc-Antonie; Whittaker, Michael R; Gurzov, Esteban N; Ding, Feng; Quinn, John F; Davis, Thomas P; Ke, Pu Chun

2017-12-11

Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy against amyloidogenesis is to minimize the populations of toxic oligomers and protofibrils by inhibiting protein aggregation with small molecules or nanoparticles. However, melanin synthesis in nature is realized by accelerated protein fibrillation to circumvent accumulation of toxic intermediates. Accordingly, we designed and demonstrated the use of star-shaped poly(2-hydroxyethyl acrylate) (PHEA) nanostructures for promoting aggregation while ameliorating the toxicity of human islet amyloid polypeptide (IAPP), the peptide involved in glycemic control and the pathology of type 2 diabetes. The binding of PHEA elevated the β-sheet content in IAPP aggregates while rendering a new morphology of "stelliform" amyloids originating from the polymers. Atomistic molecular dynamics simulations revealed that the PHEA arms served as rodlike scaffolds for IAPP binding and subsequently accelerated IAPP aggregation by increased local peptide concentration. The tertiary structure of the star nanoparticles was found to be essential for driving the specific interactions required to impel the accelerated IAPP aggregation. This study sheds new light on the structure-toxicity relationship of IAPP and points to the potential of exploiting star polymers as a new class of therapeutic agents against amyloidogenesis.

Single-molecule imaging reveals topological isomer-dependent diffusion by 4-armed star and dicyclic 8-shaped polymers

KAUST Repository

Habuchi, Satoshi

2015-04-21

Diffusion dynamics of topological isomers of polymer molecules was investigated at the single-molecule level in a melt state by employing the fluorophore-incorporated 4-armed star and the corresponding doubly-cyclized, 8-shaped poly(THF) chains. While the single-molecule fluorescence imaging experiment revealed that the diffusion of the 4-armed star polymer was described by a single Gaussian distribution, the diffusion of the 8-shaped polymer exhibited a double Gaussian distribution behaviour. We reasoned that the two 8-shaped polymeric isomers have distinct diffusion modes in the melt state, although ensemble-averaged experimental methods cannot detect differences in overall conformational state of the isomers. The single-molecule experiments suggested that one of the 8-shaped polymeric isomer, having the horizontally oriented form, causes an efficient threading with the linear matrix chains which leads to the slower diffusion compared with the corresponding 4-armed star polymer, while the other 8-shaped polymeric isomer, having the vertically oriented form, displayed faster diffusion by the suppression of effective threading with the linear matrix chains due to its contracted chain conformation.

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

Science.gov (United States)

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.

Anticancer copper(II) phosphorus dendrimers are potent proapoptotic Bax activators.

Science.gov (United States)

Mignani, Serge; El Brahmi, Nabil; Eloy, Laure; Poupon, Joel; Nicolas, Valérie; Steinmetz, Anke; El Kazzouli, Said; Bousmina, Mosto M; Blanchard-Desce, Mireille; Caminade, Anne-Marie; Majoral, Jean-Pierre; Cresteil, Thierry

2017-05-26

A multivalent phosphorus dendrimer 1G 3 and its corresponding Cu-complex, 1G 3 -Cu have been recently identified as agents retaining high antiproliferative potency. This antiproliferative capacity was preserved in cell lines overexpressing the efflux pump ABC B1, whereas cross-resistance was observed in ovarian cancer cell lines resistant to cisplatin. Theoretical 3D models were constructed: the dendrimers appear as irregularly shaped disk-like nano-objects of about 22 Å thickness and 49 Å diameter, which accumulated in cells after penetration by endocytosis. To get insight in their mode of action, cell death pathways have been examined in human cancer cell lines: early apoptosis was followed by secondary necrosis after multivalent phosphorus dendrimers exposure. The multivalent plain phosphorus dendrimer 1G 3 moderately activated caspase-3 activity, in contrast with the multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu which strikingly reduced the caspase-3 content and activity. This decrease of caspase activity is not related to the presence of copper, since inorganic copper has no or little effect on caspase-3. Conversely the potent apoptosis activation could be related to a noticeable translocation of Bax to the mitochondria, resulting in the release of AIF into the cytosol, its translocation to the nucleus and a severe DNA fragmentation, without alteration of the cell cycle. The multivalent Cu-conjugated phosphorus dendrimer is more efficient than its non-complexed analog to activate this pathway in close relationship with the higher antiproliferative potency. Therefore, this multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu can be considered as a new and promising first-in-class antiproliferative agent with a distinctive mode of action, inducing apoptosis tumor cell death through Bax activation pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

Science.gov (United States)

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

Pharmaceutical and biomedical potential of surface engineered dendrimers.

Science.gov (United States)

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

Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications.

Science.gov (United States)

Kannan, R M; Nance, E; Kannan, S; Tomalia, D A

2014-12-01

Dendrimers are discrete nanostructures/nanoparticles with 'onion skin-like' branched layers. Beginning with a core, these nanostructures grow in concentric layers to produce stepwise increases in size that are similar to the dimensions of many in vivo globular proteins. These branched tree-like concentric layers are referred to as 'generations'. The outer generation of each dendrimer presents a precise number of functional groups that may act as a monodispersed platform for engineering favourable nanoparticle-drug and nanoparticle-tissue interactions. These features have attracted significant attention in medicine as nanocarriers for traditional small drugs, proteins, DNA/RNA and in some instances as intrinsically active nanoscale drugs. Dendrimer-based drugs, as well as diagnostic and imaging agents, are emerging as promising candidates for many nanomedicine applications. First, we will provide a brief survey of recent nanomedicines that are either approved or in the clinical approval process. This will be followed by an introduction to a new 'nanoperiodic' concept which proposes nanoparticle structure control and the engineering of 'critical nanoscale design parameters' (CNDPs) as a strategy for optimizing pharmocokinetics, pharmocodynamics and site-specific targeting of disease. This paradigm has led to the emergence of CNDP-directed nanoperiodic property patterns relating nanoparticle behaviour to critical in vivo clinical translation issues such as cellular uptake, transport, elimination, biodistribution, accumulation and nanotoxicology. With a focus on dendrimers, these CNDP-directed nanoperiodic patterns are used as a strategy for designing and optimizing nanoparticles for a variety of drug delivery and imaging applications, including a recent dendrimer-based theranostic nanodevice for imaging and treating cancer. Several emerging preclinical dendrimer-based nanotherapy concepts related to inflammation, neuro-inflammatory disorders, oncology and infectious

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

Science.gov (United States)

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

Optically nonlinear energy transfer in light-harvesting dendrimers

Science.gov (United States)

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.

Viologen-Phosphorus Dendrimers Inhibit α-Synuclein Fibrillation.

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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.

Poly(amido amine) dendrimers in oral delivery.

Science.gov (United States)

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.

The effects of pH, salt and bond stiffness on charged dendrimers

International Nuclear Information System (INIS)

Huissmann, Sebastian; Wynveen, Aaron; Likos, Christos N; Blaak, Ronald

2010-01-01

We have performed molecular dynamics simulations of charged dendrimers with various charge distributions, and including both rigid and soft bonds between the monomers. Whereas the rigid bonds result in a shell-like structure, the soft bonds lead to a larger dendrimer size and a more homogeneous monomer distribution. The measured density profiles of counter-ions and co-ions are compared with those stemming from Poisson-Boltzmann theory. The latter is in very good agreement with simulations for the soft-bond model, whereas for rigid bonds, significant discrepancies arise caused by the fact that Poisson-Boltzmann theory neglects finite-size ion effects. The addition of monovalent salt has no significant influence on the behavior of the dendrimers. (fast track communication)

Differential Rotation in Sun-like Stars from Surface Variability and Asteroseismology

Science.gov (United States)

Nielsen, Martin Bo

2017-03-01

The Sun and other stars are known to oscillate. Through the study of small perturbations to the frequencies of these oscillations the rotation of the deep interior can be inferred. However, thus far the internal rotation of other Sun-like stars is unknown. The NASA Kepler mission has observed a multitude of Sun-like stars over a period of four years. This has provided high-quality photometric data that can be used to study the rotation of stars with two different techniques: asteroseismology and surface activity. Asteroseismology provides a means of measuring rotation in the stellar interior, while photometric variability from magnetically active regions are sensitive to rotation at the stellar surface. The combination of these two methods can be used to constrain the radial differential rotation in Sun-like stars. First, we developed an automated method for measuring the rotation of stars using surface variability. This method was initially applied to the entire Kepler catalog, out of which we detected signatures of rotation in 12,000 stars across the main sequence, providing robust estimates of the surface rotation rates and the associated errors. Second, we performed an asteroseismic analysis of six Sun-like stars, where we were able to measure the rotational splitting as a function of frequency in the p-mode envelope. This was done by dividing the oscillation spectrum into individual segments, and fitting a model independently to each segment. We found that the measured splittings were all consistent with a constant value, indicating little differential rotation. Third, we compared the asteroseismic rotation rates of five Sun-like stars to their surface rotation rates. We found that the values were in good agreement, again indicating little differential rotation between the regions where the two methods are most sensitive. Finally, we discuss how the surface rotation rates may be used as a prior on the seismic envelope rotation rate in a double-zone model

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

Science.gov (United States)

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.

Perspective: Dendrimer drugs for infection and inflammation.

Science.gov (United States)

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.

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

KAUST Repository

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.

Structural Studies of Three-Arm Star Block Copolymers Exposed to Extreme Stretch Suggests a Persistent Polymer Tube

Science.gov (United States)

Mortensen, Kell; Borger, Anine L.; Kirkensgaard, Jacob J. K.; Garvey, Christopher J.; Almdal, Kristoffer; Dorokhin, Andriy; Huang, Qian; Hassager, Ole

2018-05-01

We present structural small-angle neutron scattering studies of a three-armed polystyrene star polymer with short deuterated segments at the end of each arm. We show that the form factor of the three-armed star molecules in the relaxed state agrees with that of the random phase approximation of Gaussian chains. Upon exposure to large extensional flow conditions, the star polymers change conformation resulting in a highly stretched structure that mimics a fully extended three-armed tube model. All three arms are parallel to the flow, one arm being either in positive or negative stretching direction, while the two other arms are oriented parallel, right next to each other in the direction opposite to the first arm.

Preparation of Cu Nanoclusters within Dendrimer Templates

National Research Council Canada - National Science Library

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+).

Biological properties of water-soluble phosphorhydrazone dendrimers

Directory of Open Access Journals (Sweden)

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.

Noncovalent synthesis of protein dendrimers

NARCIS (Netherlands)

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

A blue-emitting CdS/dendrimer nanocomposite

International Nuclear Information System (INIS)

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.)

Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl-propanoic acid (bis-HMPA containing peripheral amino acid residues for gene transfection

Directory of Open Access Journals (Sweden)

Silvana Alfei

2017-08-01

Full Text Available Dendrimers, the emerging man made, highly branched, star-shaped macromolecules with nanometer-scale dimensions are well known for their well defined and high controlled architecture, their versatility and high functionality and are of eminent interest in nanomedical applications such as drug delivery, gene transfection, and imaging. In this paper, versatile protocols for the synthesis of polyester-based, hydrolysable, polycationic dendrimers have been setup. A fourth generation dendrimer equipped with 48 peripheral hydroxyl groups was prepared from 2,2-bis(hydroxymethylpropanoic acid and was used for grafting BOC-amino acids or as “hypercores” on which dendrons functionalized with BOC-amino acids were attached. A library of 15 polycationic homo- and hetero-dendrimers in the form of hydrochloride was obtained. Their structures and composition were confirmed by NMR analysis and by experimental molecular weight computed by volumetric titration. Their buffer capacity and results obtained from cytotoxicity assays and tests of binding with both pDNA and siRNA were very satisfactory.

The structure of carbosilane dendrimers of higher generations

International Nuclear Information System (INIS)

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

Role of PAMAM-OH dendrimers against the fibrillation pathway of biomolecules.

Science.gov (United States)

Sekar, Gajalakshmi; Florance, Ida; Sivakumar, A; Mukherjee, Amitava; Chandrasekaran, Natarajan

2016-12-01

The binding behavior of nanoparticle with proteins determines its biocompatibility. This study reports the interaction of ten different biomolecules (proteins-BSA, HSA, haemoglobin, gamma globulin, transferrin and enzymes-hog and bacillus amylase, lysozyme from chicken and human and laccases from Tramates versicolor) with a surface group hydroxylated Poly AMido AMide dendrimer (PAMAM) of generation 5. The study has utilized various spectroscopic methods like UV-vis spectroscopy, Fluorescence emission, Synchronous, 3-D spectroscopy and Circular Dichroism to detect the binding induced structural changes in biomolecules that occur upon interaction with mounting concentration of the dendrimers. Aggregation of proteins results in the formation of amyloid fibrils causing several human diseases. In this study, fibrillar samples of all ten biomolecules formed in the absence and the presence of dendrimers were investigated with Congo Red absorbance and ThT Assay to detect fibril formation, Trp Emission and 3-D scan to evaluate the effect of fibrillation on aromatic environment of biomolecules, and CD spectroscopy to measure the conformational changes in a quantitative manner. These assays have generated useful information on the role of dendrimers in amyloid fibril formation of biomolecules. The outcomes of the study remain valuable in evaluating the biological safety of PAMAM-OH dendrimers for their biomedical application in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural studies of three-arm star block copolymers exposed to extreme stretch suggests persistent polymer tube

DEFF Research Database (Denmark)

Garvey, Christopher J.; Almdal, Kristoffer; Dorokhin, Andriy

2018-01-01

We present structural SANS-studies of a three-armed polystyrene star polymer with short deuterated segments at the end of each arm. We show that the form factor of the three-armed star molecules in the relaxed state agrees with that of the random phase approximation of Gaussian chains. Upon...

Paramagnetic NMR investigation of dendrimer-based host-guest interactions.

Directory of Open Access Journals (Sweden)

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.

Dendrimer-based dynamic combinatorial libraries

NARCIS (Netherlands)

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

Fluorescent properties of novel dendrimer dyes based on thiazole orange

International Nuclear Information System (INIS)

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.

The effects of surfactant on the structure of ZnCr2O4 dendrimer like nanostructures used in degradation of Eriochrome Black T

Science.gov (United States)

Sabet, Mohammad; Jahangiri, Hasan

2018-01-01

In this experimental work, we synthesized ZnCr2O4 nano dendrimer-like structures via a simple hydrothermal method. Different parameters such as the reaction time and temperature and the surfactant kind were changed to obtain different particle sizes and morphologies. Scanning electron microscopy was utilized to obtain the products morphologies. The results showed the product is mainly composed of dendrimer-like structures. Also, it was found the mentioned parameters had significant effects on the product sizes and morphologies. Furthermore, it was found key parameters that determine the morphology of the product is surfactant type and each surfactant creates a unique morphology. The crystallinity and crystallite size were studied by x-ray diffraction pattern. Also, the composition of the product was determined by energy dispersive x-ray analysis. Diffuse reflectance spectroscopy (DRS) was used to the investigation of the optical properties of the product. The results obtained from DRS spectra showed the product has about 3.3 eV band gap. The photocatalytic activity of the product showed that ZnCr2O4 has a significant photocatalytic activity and it can decompose Eriochrome Black T about 91% under ultra violet radiation.

Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Prevalence of Earth-size planets orbiting Sun-like stars.

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Petigura, Erik A; Howard, Andrew W; Marcy, Geoffrey W

2013-11-26

Determining whether Earth-like planets are common or rare looms as a touchstone in the question of life in the universe. We searched for Earth-size planets that cross in front of their host stars by examining the brightness measurements of 42,000 stars from National Aeronautics and Space Administration's Kepler mission. We found 603 planets, including 10 that are Earth size ( ) and receive comparable levels of stellar energy to that of Earth (1 - 2 R[Symbol: see text] ). We account for Kepler's imperfect detectability of such planets by injecting synthetic planet-caused dimmings into the Kepler brightness measurements and recording the fraction detected. We find that 11 ± 4% of Sun-like stars harbor an Earth-size planet receiving between one and four times the stellar intensity as Earth. We also find that the occurrence of Earth-size planets is constant with increasing orbital period (P), within equal intervals of logP up to ~200 d. Extrapolating, one finds 5.7(-2.2)(+1.7)% of Sun-like stars harbor an Earth-size planet with orbital periods of 200-400 d.

Light-emitting dendrimer film morphology: A neutron reflectivity study

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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.

Nanoscale effects in dendrimer-mediated targeting of neuroinflammation.

Science.gov (United States)

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.

Transepithelial and endothelial transport of poly (amidoamine) dendrimers.

Science.gov (United States)

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.

Practical computational toolkits for dendrimers and dendrons structure design

Science.gov (United States)

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.

Some new aspects of dendrimer applications

International Nuclear Information System (INIS)

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

Aqueous synthesis of ZnTe/dendrimer nanocomposites and their antimicrobial activity: implications in therapeutics

Science.gov (United States)

Ghosh, S.; Ghosh, D.; Bag, P. K.; Bhattacharya, S. C.; Saha, A.

2011-03-01

The present strategy proposes a simple and single step aqueous route for synthesizing stable, fluorescent ZnTe/dendrimer nanocomposites with varying dendrimer terminal groups. In these hybrid materials, the fluorescence of the semiconductor combines with the biomimetic properties of the dendrimer making them suitable for various biomedical applications. The ZnTe nanocomposites thus obtained demonstrate bactericidal activity against enteropathogenic bacteria without having toxic effects on the human erythrocytes. The average size of the ZnTe nanoparticles within the dendrimer matrix was in the range of 2.9-6.0 nm, and they have a good degree of crystallinity with a hexagonal crystal phase. The antibacterial activities of the ZnTe/dendrimer nanocomposites (ZnTe DNCs) as well other semiconductor nanocomposites were evaluated against enteropathogenic bacteria including multi-drug resistant Vibrio cholerae serogroup O1 and enterotoxigenic Escherichia coli (ETEC). ZnTe DNCs had significant antibacterial activity against strains of V. cholerae and ETEC with minimum inhibitory concentrations ranging from 64 to 512 μg ml-1 and minimum bactericidal concentrations ranging from 128 to 1000 μg ml-1. Thus, the observed results suggest that these water-soluble active nanocomposites have potential for the treatment of enteric diseases like diarrhoea and cholera.The present strategy proposes a simple and single step aqueous route for synthesizing stable, fluorescent ZnTe/dendrimer nanocomposites with varying dendrimer terminal groups. In these hybrid materials, the fluorescence of the semiconductor combines with the biomimetic properties of the dendrimer making them suitable for various biomedical applications. The ZnTe nanocomposites thus obtained demonstrate bactericidal activity against enteropathogenic bacteria without having toxic effects on the human erythrocytes. The average size of the ZnTe nanoparticles within the dendrimer matrix was in the range of 2.9-6.0 nm, and they

Evaluation of Nanocarrier Targeted Drug Delivery of Capecitabine-PAMAM Dendrimer Complex in a Mice Colorectal Cancer Model

Directory of Open Access Journals (Sweden)

Fatemeh Nabavizadeh

2016-09-01

Full Text Available Capecitabine, an effective anticancer drug in colorectal cancer chemotherapy, may create adverse side effects on healthy tissues. In the present study, we first induced colon adenocarcinoma with azoxymethane, a carcinogen agent, and then investigated the potentiality of polyamidoamine (PAMAM dendrimer to improve capecitabine therapeutic index and decrease its adverse side effects on healthy tissues like liver and bone marrow. Other variables such as nanoparticle concentrations have also been investigated. Drug loading concentration (DLC and encapsulation efficiency (EE were calculated for capecitabine/dendrimer complex. Experimental results showed an increase in DLC percentage resulted from elevated capecitabine/dendrimer ratio. Capecitabine/dendrimer complex could reduce tumor size and adverse side effects in comparison with free capecitabine form.

Accelerated Combinatorial High Throughput Star Polymer Synthesis via a Rapid One-Pot Sequential Aqueous RAFT (rosa-RAFT) Polymerization Scheme.

Science.gov (United States)

Cosson, Steffen; Danial, Maarten; Saint-Amans, Julien Rosselgong; Cooper-White, Justin J

2017-04-01

Advanced polymerization methodologies, such as reversible addition-fragmentation transfer (RAFT), allow unprecedented control over star polymer composition, topology, and functionality. However, using RAFT to produce high throughput (HTP) combinatorial star polymer libraries remains, to date, impracticable due to several technical limitations. Herein, the methodology "rapid one-pot sequential aqueous RAFT" or "rosa-RAFT," in which well-defined homo-, copolymer, and mikto-arm star polymers can be prepared in very low to medium reaction volumes (50 µL to 2 mL) via an "arm-first" approach in air within minutes, is reported. Due to the high conversion of a variety of acrylamide/acrylate monomers achieved during each successive short reaction step (each taking 3 min), the requirement for intermediary purification is avoided, drastically facilitating and accelerating the star synthesis process. The presented methodology enables RAFT to be applied to HTP polymeric bio/nanomaterials discovery pipelines, in which hundreds of complex polymeric formulations can be rapidly produced, screened, and scaled up for assessment in a wide range of applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A polyamidoamine dendrimer-streptavidin supramolecular architecture for biosensor development.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Investigation of Dendrimer-Membrane Interactions

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Seismology of rapidly rotating and solar-like stars

Science.gov (United States)

Reese, Daniel Roy

2018-05-01

A great deal of progress has been made in stellar physics thanks to asteroseismology, the study of pulsating stars. Indeed, asteroseismology is currently the only way to probe the internal structure of stars. The work presented here focuses on some of the theoretical aspects of this domain and addresses two broad categories of stars, namely solar-like pulsators (including red giants), and rapidly rotating pulsating stars. The work on solar-like pulsators focuses on setting up methods for efficiently characterising a large number of stars, in preparation for space missions like TESS and PLATO 2.0. In particular, the AIMS code applies an MCMC algorithm to find stellar properties and a sample of stellar models which fit a set of seismic and classic observational constraints. In order to reduce computation time, this code interpolates within a precalculated grid of models, using a Delaunay tessellation which allows a greater flexibility on the construction of the grid. Using interpolated models based on the outputs from this code or models from other forward modelling codes, it is possible to obtain refined estimates of various stellar properties such as the mean density thanks to inversion methods put together by me and G. Buldgen, my former PhD student. Finally, I show how inversion-type methods can also be used to test more qualitative information such as whether a decreasing rotation profile is compatible with a set of observed rotational splittings and a given reference model. In contrast to solar-like pulsators, the pulsation modes of rapidly rotating stars remain much more difficult to interpret due to the complexity of the numerical calculations needed to calculate such modes, the lack of simple frequency patterns, and the fact that it is difficult to predict mode amplitudes. The work described here therefore focuses on addressing the above difficulties one at a time in the hopes that it will one day be possible to carry out detailed asteroseismology in these

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

Science.gov (United States)

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.

Glycopeptide dendrimers. Part II

Czech Academy of Sciences Publication Activity Database

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

Review Dendrimer : Definisi, Sintesis, Aplikasi Dan Prospektif

OpenAIRE

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...

Gene Transfer in Eukaryotic Cells Using Activated Dendrimers

Science.gov (United States)

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.

Preliminary biological evaluation of a urea-functionalized dendrimer

International Nuclear Information System (INIS)

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.)

Oligothia dendrimers for the formation of gold nanoparticles

NARCIS (Netherlands)

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

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

Science.gov (United States)

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.

Energy transfer dynamics in Light-Harvesting Dendrimers

Science.gov (United States)

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.

Preparation of pH-sensitive amphiphilic block star polymers, their self-assembling characteristics and release behavior on encapsulated molecules

KAUST Repository

Song, Xiaowan; Cao, Ming; Chen, Peng; Xia, Ru; Zheng, Zhengzhi; Miao, Jibin; Yang, Bin; Su, Lifen; Qian, Jiasheng; Feng, Xiaoshuang

2016-01-01

Poly(ethylene glycol) (PEG), a polymer with excellent biocompatibility, was widely used to form nanoparticles for drug delivery applications. In this paper, based on PEG, a series of pH-sensitive amphiphilic block star polymers of poly

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

Directory of Open Access Journals (Sweden)

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

pH controlled gating of toxic protein pores by dendrimers

Science.gov (United States)

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

Exciton Transport Simulations in Phenyl Cored Thiophene Dendrimers

Science.gov (United States)

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.

Tailoring silver nanoparticle construction using dendrimer templated silica networks

International Nuclear Information System (INIS)

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

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

Directory of Open Access Journals (Sweden)

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

Intramolecular evolution from a locally excited state to an excimer-like state in a multichromophoric dendrimer evidenced by a femtosecond fluorescence upconversion study

NARCIS (Netherlands)

Karni, Y.; Jordens, S.; Belder, G. De; Schweitzer, G.; Hofkens, J.; Gensch, T.; Maus, M.; Schryver, F.C. De; Herrmann, A.; Müllen, K.

1999-01-01

A time-resolved fluorescence upconversion study on a polyphenylene dendrimer with eight peryleneimide chromophores on the surface and on a monochromophoric model compound is reported. The time-dependent fluorescence spectra of the dendrimer show that the initial excitation is into a locally excited

Core Cross-Linked Multiarm Star Polymers with Aggregation-Induced Emission and Temperature Responsive Fluorescence Characteristics

KAUST Repository

Zhang, Zhen; Bilalis, Panagiotis; Zhang, Hefeng; Gnanou, Yves; Hadjichristidis, Nikolaos

2017-01-01

Aggregation-induced emission (AIE) active core cross-linked multiarm star polymers, carrying polystyrene (PS), polyethylene (PE), or polyethylene-b-polycaprolactone (PE-b-PCL) arms, have been synthesized through an “arm-first” strategy, by atom

Antibacterial action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles against Escherichia coli correlated with molecular chain conformation

Energy Technology Data Exchange (ETDEWEB)

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.

Antibacterial action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles against Escherichia coli correlated with molecular chain conformation

International Nuclear Information System (INIS)

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

Synthesis and Rheological Properties of an Associative Star Polymer in Aqueous Solutions

DEFF Research Database (Denmark)

Hietala, Sami; Mononen, Pekka; Strandman, Satu

2007-01-01

synthesised by atom transfer radical. polymerization (ATRP) was found to fonn hydrogels at room temperature at polymer concentrations. Cp, over 22 gIL due to the interpolymer drophobic association of the PS blocks. Increasing Cp leads to stronger elastic networks at room temperature that show a gel......Rheological properties of aqueous solutions and hydrogels fonned by an amphiphiIic star block copolymer poly(acrylic acid)-blockpolystyrene (PAAS4-b-PS6)4. were investigated as a function of the polymer concentration (Cp), temperature, and added saIt concentration. The water-soluble polymer......-to-solution transition with increasing temperature. Increase of ionic strength decreases the moduli compared with the pure hydrogel but did not affect the gel-sol transition temperature significantly. Small-angle X-ray experiments showed two distinct scattering correlation peaks for samples above the gelling Cp, which...

Charge transport in highly efficient iridium cored electrophosphorescent dendrimers

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

DEFF Research Database (Denmark)

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....

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

DEFF Research Database (Denmark)

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....

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

International Nuclear Information System (INIS)

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

Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii

International Nuclear Information System (INIS)

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.

MLKL forms disulfide bond-dependent amyloid-like polymers to induce necroptosis.

Science.gov (United States)

Liu, Shuzhen; Liu, Hua; Johnston, Andrea; Hanna-Addams, Sarah; Reynoso, Eduardo; Xiang, Yougui; Wang, Zhigao

2017-09-05

Mixed-lineage kinase domain-like protein (MLKL) is essential for TNF-α-induced necroptosis. How MLKL promotes cell death is still under debate. Here we report that MLKL forms SDS-resistant, disulfide bond-dependent polymers during necroptosis in both human and mouse cells. MLKL polymers are independent of receptor-interacting protein kinase 1 and 3 (RIPK1/RIPK3) fibers. Large MLKL polymers are more than 2 million Da and are resistant to proteinase K digestion. MLKL polymers are fibers 5 nm in diameter under electron microscopy. Furthermore, the recombinant N-terminal domain of MLKL forms amyloid-like fibers and binds Congo red dye. MLKL mutants that cannot form polymers also fail to induce necroptosis efficiently. Finally, the compound necrosulfonamide conjugates cysteine 86 of human MLKL and blocks MLKL polymer formation and subsequent cell death. These results demonstrate that disulfide bond-dependent, amyloid-like MLKL polymers are necessary and sufficient to induce necroptosis.

THE OCCURRENCE RATE OF EARTH ANALOG PLANETS ORBITING SUN-LIKE STARS

International Nuclear Information System (INIS)

Catanzarite, Joseph; Shao, Michael

2011-01-01

Kepler is a space telescope that searches Sun-like stars for planets. Its major goal is to determine η Earth , the fraction of Sun-like stars that have planets like Earth. When a planet 'transits' or moves in front of a star, Kepler can measure the concomitant dimming of the starlight. From analysis of the first four months of those measurements for over 150,000 stars, Kepler's Science Team has determined sizes, surface temperatures, orbit sizes, and periods for over a thousand new planet candidates. In this paper, we characterize the period probability distribution function of the super-Earth and Neptune planet candidates with periods up to 132 days, and find three distinct period regimes. For candidates with periods below 3 days, the density increases sharply with increasing period; for periods between 3 and 30 days, the density rises more gradually with increasing period, and for periods longer than 30 days, the density drops gradually with increasing period. We estimate that 1%-3% of stars like the Sun are expected to have Earth analog planets, based on the Kepler data release of 2011 February. This estimate of η Earth is based on extrapolation from a fiducial subsample of the Kepler planet candidates that we chose to be nominally 'complete' (i.e., no missed detections) to the realm of the Earth-like planets, by means of simple power-law models. The accuracy of the extrapolation will improve as more data from the Kepler mission are folded in. Accurate knowledge of η Earth is essential for the planning of future missions that will image and take spectra of Earth-like planets. Our result that Earths are relatively scarce means that a substantial effort will be needed to identify suitable target stars prior to these future missions.

Optical absorption and energy transfer processes in dendrimers

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

Molecular dynamics simulation of coarse-grained poly(L-lysine) dendrimers.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

Transport of dendrimer nanocarriers through epithelial cells via the transcellular route.

Science.gov (United States)

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.

Synthesis and study of conjugated polymers containing Di- or Triphenylamine

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

Directory of Open Access Journals (Sweden)

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

Self-assembly behavior of a linear-star supramolecular amphiphile based on host-guest complexation.

Science.gov (United States)

Wang, Juan; Wang, Xing; Yang, Fei; Shen, Hong; You, Yezi; Wu, Decheng

2014-11-04

A star polymer, β-cyclodextrin-poly(l-lactide) (β-CD-PLLA), and a linear polymer, azobenzene-poly(ethylene glycol) (Azo-PEG), could self-assemble into a supramolecular amphiphilic copolymer (β-CD-PLLA@Azo-PEG) based on the host-guest interaction between β-CD and azobenzene moieties. This linear-star supramolecular amphiphilic copolymer further self-assembled into a variety of morphologies, including sphere-like micelle, carambola-like micelle, naan-like micelle, shuttle-like lamellae, tube-like fiber, and random curled-up lamellae, by tuning the length of hydrophilic or hydrophobic chains. The variation of morphology was closely related to the topological structure and block ratio of the supramolecular amphiphiles. These self-assembly structures could disassemble upon an ultraviolet (UV) light irradiation.

Biodegradable star HPMA polymer-drug conjugates: biodegradability, distribution and anti-tumor efficacy

Czech Academy of Sciences Publication Activity Database

Etrych, Tomáš; Kovář, Lubomír; Strohalm, Jiří; Chytil, Petr; Říhová, Blanka; Ulbrich, Karel

2011-01-01

Roč. 154, č. 3 (2011), s. 241-248 ISSN 0168-3659 R&D Projects: GA AV ČR IAA400500806; GA AV ČR IAAX00500803; GA ČR GAP301/11/0325 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : star polymer * HPMA copolymers * drug release Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.732, year: 2011

Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii

Energy Technology Data Exchange (ETDEWEB)

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.

Dendrimers as Potential Therapeutic Tools in HIV Inhibition

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

Analysis of the Herschel DEBRIS Sun-like star sample

Science.gov (United States)

Sibthorpe, B.; Kennedy, G. M.; Wyatt, M. C.; Lestrade, J.-F.; Greaves, J. S.; Matthews, B. C.; Duchêne, G.

2018-04-01

This paper presents a study of circumstellar debris around Sun-like stars using data from the Herschel DEBRIS Key Programme. DEBRIS is an unbiased survey comprising the nearest ˜90 stars of each spectral type A-M. Analysis of the 275 F-K stars shows that excess emission from a debris disc was detected around 47 stars, giving a detection rate of 17.1^{+2.6}_{-2.3} per cent, with lower rates for later spectral types. For each target a blackbody spectrum was fitted to the dust emission to determine its fractional luminosity and temperature. The derived underlying distribution of fractional luminosity versus blackbody radius in the population showed that most detected discs are concentrated at f ˜ 10-5 and at temperatures corresponding to blackbody radii 7-40 au, which scales to ˜40 au for realistic dust properties (similar to the current Kuiper belt). Two outlying populations are also evident; five stars have exceptionally bright emission ( f > 5 × 10-5), and one has unusually hot dust <4 au. The excess emission distributions at all wavelengths were fitted with a steady-state evolution model, showing that these are compatible with all stars being born with a narrow belt that then undergoes collisional grinding. However, the model cannot explain the hot dust systems - likely originating in transient events - and bright emission systems - arising potentially from atypically massive discs or recent stirring. The emission from the present-day Kuiper belt is predicted to be close to the median of the population, suggesting that half of stars have either depleted their Kuiper belts (similar to the Solar system) or had a lower planetesimal formation efficiency.

Formation of Neutral Disk-Like Zone Around the Active Hot Stars in Symbiotic Binaries

Directory of Open Access Journals (Sweden)

Cariková Z.

2012-06-01

Full Text Available In this contribution we present the ionization structure in the enhanced wind from the hot star in symbiotic binaries during active phases. Rotation of the hot star leads to the compression of the outflowing material towards its equatorial plane. As a result, a neutral disk-like zone around the active hot star near the orbital plane is created. We modeled the compression of the wind and calculated the neutral disk-like zone in the enhanced wind from the hot star using the equation of the photoionization equilibrium. the presence of such neutral disk-like zones was also suggested on the basis of the modeling the spectral energy distribution of symbiotic binaries. We confront the calculated ionization structures in the enhanced wind from the hot star with the observations. the calculated column density of the neutral hydrogen atoms in the neutral disk-like zone and the emission measure of the ionized part of the wind from the hot star are in a good agreement with the quantities derived from observations during active phases. the presence of such neutral disk-like zones is transient, being connected with the active phases of symbiotic binaries. During quiescent phases, such neutral disk-like zones cannot be created because of insufficient mass-loss rate from the hot star.

Understanding the Structure-Function Relationships of Dendrimers in Environmental and Biomedical Applications

Science.gov (United States)

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

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Bodewein, Lambert [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany); Institute of Environmental Research (Biology V), RWTH Aachen University (Germany); Schmelter, Frank; Di Fiore, Stefano [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Molecular Biology Division, Aachen (Germany); Hollert, Henner [Institute of Environmental Research (Biology V), RWTH Aachen University (Germany); Fischer, Rainer [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany); Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Molecular Biology Division, Aachen (Germany); Fenske, Martina, E-mail: martina.fenske@ime.fraunhofer.de [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany)

2016-08-15

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos. �

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

International Nuclear Information System (INIS)

Bodewein, Lambert; Schmelter, Frank; Di Fiore, Stefano; Hollert, Henner; Fischer, Rainer; Fenske, Martina

2016-01-01

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos. �

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Formation of Silver and Gold Dendrimer Nanocomposites

International Nuclear Information System (INIS)

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

Well-defined 4-arm stars with hydroxy-terminated polyethylene, polyethylene-b-polycaprolactone and polyethylene-b-(polymethyl methacrylate) 2 arms

KAUST Repository

Zhang, Zhen

2016-07-20

Bis-boron-thexyl-silaboracycle was prepared by hydroboration of 1,4-bis(methyldivinylsilyl)butane with thexylborane and used to initiate the polyhomologation of dimethylsulfoxonium methylide to afford well-defined hydroxy-terminated 4-arm polyethylene (PE) stars. The synthesized PE stars were transformed to (PE-b-PCL)4 starblock copolymers via the ring-opening polymerization of ϵ-caprolactone (CL) initiated by the hydroxyl end groups of (PE-OH)4 in the presence of P2-tBu phosphazene base. Esterification of the hydroxyl groups of the OH-terminated PE star with 2,2-dichloroacetyl chloride led to (PE-Cl2)4 which was used as initiator (eight initiating atom transfer radical polymerization, ATRP, sites) for the synthesis of (PE-b-PMMA2)4 dendrimer-like stars by the ATRP of methyl methacrylate (MMA). All intermediates and final products were characterized by high temperature gel permeation chromatography and proton nuclear magnetic resonance spectroscopy. © 2016 The Royal Society of Chemistry.

Investigations on dendrimer space reveal solid and liquid tumor growth-inhibition by original phosphorus-based dendrimers and the corresponding monomers and dendrons with ethacrynic acid motifs.

Science.gov (United States)

El Brahmi, Nabil; Mignani, Serge M; Caron, Joachim; El Kazzouli, Saïd; Bousmina, Mosto M; Caminade, Anne-Marie; Cresteil, Thierry; Majoral, Jean-Pierre

2015-03-07

The well-known reactive diuretic ethacrynic acid (EA, Edecrin), with low antiproliferative activities, was chemically modified and grafted onto phosphorus dendrimers and the corresponding simple branched phosphorus dendron-like derivatives affording novel nanodevices showing moderate to strong antiproliferative activities against liquid and solid tumor cell lines, respectively.

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

Science.gov (United States)

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.

Demonstrating the Likely Neutron Star Nature of Five M31 Globular Cluster Sources with Swift-NuSTAR Spectroscopy

Science.gov (United States)

Maccarone, Thomas J.; Yukita, Mihoko; Hornschemeier, Ann; Lehmer, Bret D.; Antoniou, Vallia; Ptak, Andrew; Wik, Daniel R.; Zezas, Andreas; Boyd, Padi; Kennea, Jamie;

In Silico Characterization of the Binding Affinity of Dendrimers to Penicillin-Binding Proteins (PBPs): Can PBPs be Potential Targets for Antibacterial Dendrimers?

Science.gov (United States)

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.

Star polymer-drug conjugates with pH-controlled drug release and carrier degradation

Czech Academy of Sciences Publication Activity Database

Kostková, Hana; Schindler, Lucie; Kotrchová, Lenka; Kovář, Marek; Šírová, Milada; Kostka, Libor; Etrych, Tomáš

2017-01-01

Roč. 2017, 3 January (2017), s. 1-10, č. článku 8675435. ISSN 1687-4110 R&D Projects: GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 ; RVO:61388971 Keywords : star conjugate * HPMA copolymer * doxorubicin Subject RIV: CD - Macromolecular Chemistry; EE - Microbiology, Virology (MBU-M) OBOR OECD: Polymer science; Microbiology (MBU-M) Impact factor: 1.871, year: 2016

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

Science.gov (United States)

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.

Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement.

Science.gov (United States)

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.

Nature of the effective interaction between dendrimers

International Nuclear Information System (INIS)

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

Nature of the effective interaction between dendrimers

Energy Technology Data Exchange (ETDEWEB)

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.

Epoxy/anhydride thermosets modified with end-capped star polymers with poly(ethyleneimine cores of different molecular weight and poly(ε–caprolactone arms

Directory of Open Access Journals (Sweden)

C. Acebo

2015-09-01

Full Text Available Multiarm star polymers, with a hyperbranched poly(ethyleneimine (PEI core and poly(ε-caprolactone (PCL arms end-capped with acetyl groups were synthesized by ring-opening polymerization of ε-caprolactone from PEI cores of different molecular weight. These star polymers were used as toughening agents for epoxy/anhydride thermosets. The curing process was studied by calorimetry, thermomechanical analysis and infrared spectroscopy. The final properties of the resulting materials were determined by thermal and mechanical tests. The addition of the star polymers led to an improvement up to 130% on impact strength and a reduction in the thermal stresses up to 55%. The structure and molecular weight of the modifier used affected the morphology of the resulting materials. Electron microscopy showed phase-separated morphologies with nano-sized fine particles well adhered to the epoxy/anhydride matrix when the higher molecular weight modifier was used.

Phase behaviour of rod-like colloid + flexible polymer mixtures

NARCIS (Netherlands)

Lekkerkerker, H.N.W.; Stroobants, A.

The effect of non-adsorbing, flexible polymer on the isotropic-nematic transition in dispersions of rod-like colloids is investigated. A widening of the biphasic gap is observed, in combination with a marked polymer partitioning between the coexisting phases. Under certain conditions, areas of

Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review

Science.gov (United States)

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

Inhibition of the norepinephrine transporter by χ-conotoxin dendrimers.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Study of Dendrimers by Topological Indices

Directory of Open Access Journals (Sweden)

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.

Scaling Behavior of Dendritic Nanoparticle Mobility in Semidilute Polymer Solutions

NARCIS (Netherlands)

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 =

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

International Nuclear Information System (INIS)

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.

Retired A Stars and Their Companions. III. Comparing the Mass-Period Distributions of Planets Around A-Type Stars and Sun-Like Stars

Science.gov (United States)

Bowler, Brendan P.; Johnson, John Asher; Marcy, Geoffrey W.; Henry, Gregory W.; Peek, Kathryn M. G.; Fischer, Debra A.; Clubb, Kelsey I.; Liu, Michael C.; Reffert, Sabine; Schwab, Christian; Lowe, Thomas B.

2010-01-01

We present an analysis of ~5 years of Lick Observatory radial velocity measurements targeting a uniform sample of 31 intermediate-mass (IM) subgiants (1.5 lsim M */M sunlsim 2.0) with the goal of measuring the occurrence rate of Jovian planets around (evolved) A-type stars and comparing the distributions of their orbital and physical characteristics to those of planets around Sun-like stars. We provide updated orbital solutions incorporating new radial velocity measurements for five known planet-hosting stars in our sample; uncertainties in the fitted parameters are assessed using a Markov-Chain Monte Carlo method. The frequency of Jovian planets interior to 3 AU is 26+9 -8%, which is significantly higher than the 5%-10% frequency observed around solar-mass stars. The median detection threshold for our sample includes minimum masses down to {0.2, 0.3, 0.5, 0.6, 1.3} M Jup within {0.1, 0.3, 0.6, 1.0, 3.0} AU. To compare the properties of planets around IM stars to those around solar-mass stars we synthesize a population of planets based on the parametric relationship dN vprop M α P β dlnMdlnP, the observed planet frequency, and the detection limits we derived. We find that the values of α and β for planets around solar-type stars from Cumming et al. fail to reproduce the observed properties of planets in our sample at the 4σ level, even when accounting for the different planet occurrence rates. Thus, the properties of planets around A stars are markedly different than those around Sun-like stars, suggesting that only a small (~50%) increase in stellar mass has a large influence on the formation and orbital evolution of planets. Based on observations obtained at the Lick Observatory, which is operated by the University of California.

Cationic PAMAM dendrimers as pore-blocking binary toxin inhibitors.

Science.gov (United States)

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.

Phosphorus Dendrimers as Carriers of siRNA—Characterisation of Dendriplexes

Directory of Open Access Journals (Sweden)

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.

Structural properties of dendrimer-colloid mixtures

International Nuclear Information System (INIS)

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)

Natural and Synthetic Polymers as Inhibitors of Drug Efflux Pumps

Science.gov (United States)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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).

Chemical abundances of primary stars in the Sirius-like binary systems

Science.gov (United States)

Kong, X. M.; Zhao, G.; Zhao, J. K.; Shi, J. R.; Kumar, Y. Bharat; Wang, L.; Zhang, J. B.; Wang, Y.; Zhou, Y. T.

2018-05-01

Study of primary stars lying in Sirius-like systems with various masses of white dwarf (WD) companions and orbital separations is one of the key aspects to understand the origin and nature of barium (Ba) stars. In this paper, based on high-resolution and high-S/N spectra, we present systematic analysis of photospheric abundances for 18 FGK primary stars of Sirius-like systems including six giants and 12 dwarfs. Atmospheric parameters, stellar masses, and abundances of 24 elements (C, Na, Mg, Al, Si, S, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Sr, Y, Zr, Ba, La, Ce, and Nd) are determined homogeneously. The abundance patterns in these sample stars show that most of the elements in our sample follow the behaviour of field stars with similar metallicity. As expected, s-process elements in four known Ba giants show overabundance. A weak correlation was found between anomalies of s-process elemental abundance and orbital separation, suggesting that the orbital separation of the binaries could not be the main constraint to differentiate strong Ba stars from mild Ba stars. Our study shows that the large mass (>0.51 M⊙) of a WD companion in a binary system is not a sufficient condition to form a Ba star, even if the separation between the two components is small. Although not sufficient, it seems to be a necessary condition since Ba stars with lower mass WDs in the observed sample were not found. Our results support that [s/Fe] and [hs/ls] ratios of Ba stars are anti-correlated with the metallicity. However, the different levels of s-process overabundance among Ba stars may not be dominated mainly by the metallicity.

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

International Nuclear Information System (INIS)

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

Peptide dendrimers

Czech Academy of Sciences Publication Activity Database

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

Mono(pyridine-N-oxide) DOTA analog and its G1/G4-PAMAM dendrimer conjugates labeled with 177Lu: Radiolabeling and biodistribution studies

International Nuclear Information System (INIS)

Laznickova, A.; Biricova, V.; Laznicek, M.; Hermann, P.

2014-01-01

177 Lu radiolabeling of the first (G1-) or fourth (G4-) generation polyaminoamide (PAMAM) dendrimer conjugates with DOTA-like bifunctional chelator with one methylenepyridine-N-oxide pendant arm (DO3A-py NO-C ) stability of the radiolabeled species and their pharmacokinetic characteristics were evaluated in preclinical experiments. The results showed that the G1- and G4-dendrimer conjugates, modified in average with 7.5 or 57 DO3A-py NO-C chelating units, respectively, can also be labeled with 177 Lu with a high specific activity and radiochemical purity even at 37 °C. The radiolabeled species were stable for at least 24 h. Distribution profile of G1-dendrimer conjugate in organs and tissues of rats was more favorable than that of G4 one. On the other hand, the later dendrimer conjugate bears a substantially higher number of metal chelators per molecule enabling binding of a considerably larger number of radiometals. Our results indicate that an employment of dendrimer-chelate conjugates with bound radiometals might represent a prospective way for radiolabeling of biologically active target-specific macromolecules to obtain markedly high specific activity. - Highlights: • Chelation of DOTA-like ligands suitable for biomacromolecules modification. • Radiolabeling of modified PAMAM-dendrimers with 177 Lu. • Determination of stability of the labeled conjugates. • Pharmacokinetic characteristics evaluated in preclinical experiments

Force-induced desorption of 3-star polymers: a self-avoiding walk model

Science.gov (United States)

Janse van Rensburg, E. J.; Whittington, S. G.

2018-05-01

We consider a simple cubic lattice self-avoiding walk model of 3-star polymers adsorbed at a surface and then desorbed by pulling with an externally applied force. We determine rigorously the free energy of the model in terms of properties of a self-avoiding walk, and show that the phase diagram includes four phases, namely a ballistic phase where the extension normal to the surface is linear in the length, an adsorbed phase and a mixed phase, in addition to the free phase where the model is neither adsorbed nor ballistic. In the adsorbed phase all three branches or arms of the star are adsorbed at the surface. In the ballistic phase two arms of the star are pulled into a ballistic phase, while the remaining arm is in a free phase. In the mixed phase two arms in the star are adsorbed while the third arm is ballistic. The phase boundaries separating the ballistic and mixed phases, and the adsorbed and mixed phases, are both first order phase transitions. The presence of the mixed phase is interesting because it does not occur for pulled, adsorbed self-avoiding walks. In an atomic force microscopy experiment it would appear as an additional phase transition as a function of force.

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

Science.gov (United States)

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.

Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

International Nuclear Information System (INIS)

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)

Dendrimer-magnetic nanostructure: a Monte Carlo simulation

Science.gov (United States)

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.

Single-molecule imaging reveals topological isomer-dependent diffusion by 4-armed star and dicyclic 8-shaped polymers

KAUST Repository

Habuchi, Satoshi; Fujiwara, Susumu; Yamamoto, Takuya; Tezuka, Yasuyuki

2015-01-01

Diffusion dynamics of topological isomers of polymer molecules was investigated at the single-molecule level in a melt state by employing the fluorophore-incorporated 4-armed star and the corresponding doubly-cyclized, 8-shaped poly(THF) chains

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

KAUST Repository

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

Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.

Science.gov (United States)

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.

Dendrimers in Medicine

DEFF Research Database (Denmark)

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 ...

Electrostatic Swelling and Conformational Variation Observed in High-Generation Polyelectrolyte Dendrimers

International Nuclear Information System (INIS)

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.

Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

Directory of Open Access Journals (Sweden)

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.

Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

Energy Technology Data Exchange (ETDEWEB)

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)

Exploiting the Physicochemical Properties of Dendritic Polymers for Environmental and Biological Applications

Energy Technology Data Exchange (ETDEWEB)

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.

The effect of dendrimer charge inversion in complexes with linear polyelectrolytes

NARCIS (Netherlands)

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

Facile Preparation of Hybrid Zinc Porphyrin Dendrimer Using Coordination Complex

Energy Technology Data Exchange (ETDEWEB)

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.

Micelle-like nanoassemblies based on polymer-drug conjugates as an emerging platform for drug delivery.

Science.gov (United States)

Liu, Zhihong; Wang, Yutao; Zhang, Na

2012-07-01

During the past decades, polymer-drug conjugates are one of the hottest topics in novel drug development fields. Amphiphilic polymer-drug conjugates in aqueous solution could form micelles or micelle-like nanoassemblies. Compared with polymer-drug conjugates and the micelles into which drugs are physically entrapped, micelles or micelle-like nanoassemblies based on polymer-drug conjugates bring several additional advantages, including increased drug-loading capacity, enhanced intracellular uptake, reduced systemic toxicity, and improved therapeutic efficacy. This review focuses on recent progress achieved in the research field of micelles or micelle-like nanoassemblies based on polymer-drug conjugates. Firstly, properties of polymers, drugs, and linkers which could be used to build polymer-drug conjugate micelles or micelle-like nanoassemblies are summarized. Then, the characterization methods are described. Finally, the drug-targeting mechanisms are discussed. Micelles or micelle-like nanoassemblies based on polymer-drug conjugates as an emerging platform have the potential to achieve medical treatments with enhanced therapeutic effect. The application of micelles or micelle-like nanoassemblies based on polymer-drug conjugates may give new life to old active compounds abandoned due to their low solubility problems. For clinical application, there is a need to further optimize the properties of the polymer, drug, and linker.

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

Science.gov (United States)

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

Fast Rotating solar-like stars using asteroseismic datasets

DEFF Research Database (Denmark)

A. García, R.; Ceillier, T.; Campante, T.

2011-01-01

The NASA Kepler mission is providing an unprecedented set of asteroseismic data. In particular, short-cadence lightcurves (~60s samplings), allow us to study solar-like stars covering a wide range of masses, spectral types and evolutionary stages. Oscillations have been observed in around 600 out...

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

OpenAIRE

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...

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

OpenAIRE

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...

Simulation of bulk phases formed by polyphilic liquid crystal dendrimers

Directory of Open Access Journals (Sweden)

J.M. Ilnytskyi

2010-01-01

Full Text Available A coarse-grained simulation model for a third generation liquid crystalline dendrimer (LCDr is presented. It allows, for the first time, for a successful molecular simulation study of a relation between the shape of a polyphilic macromolecular mesogen and the symmetry of a macroscopic phase. The model dendrimer consists of a soft central sphere and 32 grafted chains each terminated by a mesogen group. The mesogenic pair interactions are modelled by the recently proposed soft core spherocylinder model of Lintuvuori and Wilson [J. Chem. Phys, 128, 044906, (2008]. Coarse-grained (CG molecular dynamics (MD simulations are performed on a melt of 100 molecules in the anisotropic-isobaric ensemble. The model LCDr shows conformational bistability, with both rod-like and disc-like conformations stable at lower temperatures. Each conformation can be induced by an external aligning field of appropriate symmetry that acts on the mesogens (uniaxial for rod-like and planar for disc-like, leading to formation of a monodomain smectic A (SmA or a columnar (Col phase, respectively. Both phases are stable for approximately the same temperature range and both exhibit a sharp transition to an isotropic cubic-like phase upon heating. We observe a very strong coupling between the conformation of the LCDr and the symmetry of a bulk phase, as suggested previously by theory. The study reveals rich potential in terms of the application of this form of CG modelling to the study of molecular self-assembly of liquid crystalline macromolecules.

Thermodynamic properties of a liquid crystal carbosilane dendrimer

Science.gov (United States)

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.

Charge transport properties of carbazole dendrimers in organic field-effect transistors

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Prevalence of Earth-size planets orbiting Sun-like stars

OpenAIRE

Petigura, Erik A.; Howard, Andrew W.; Marcy, Geoffrey W.

2013-01-01

Determining whether Earth-like planets are common or rare looms as a touchstone in the question of life in the universe. We searched for Earth-size planets that cross in front of their host stars by examining the brightness measurements of 42,000 stars from National Aeronautics and Space Administration's Kepler mission. We found 603 planets, including 10 that are Earth size (1-2 Earth-radii) and receive comparable levels of stellar energy to that of Earth (within a factor of four). We account...

Structural analysis of binding functionality of folic acid-PEG dendrimers against folate receptor.

Science.gov (United States)

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.

Synergistic effect of amino acids modified on dendrimer surface in gene delivery.

Science.gov (United States)

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.

Effect of generation on the electronic properties of light-emitting dendrimers

Science.gov (United States)

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.

Molecular dynamic analysis of the structure of dendrimers

Energy Technology Data Exchange (ETDEWEB)

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.

Molecular dynamic analysis of the structure of dendrimers

International Nuclear Information System (INIS)

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

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

OpenAIRE

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...

Effect of solvent-controlled aggregation on the intrinsic emission properties of PAMAM dendrimers

International Nuclear Information System (INIS)

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

The use of dendrimers as high-performance shells for round-trip energy transfer: efficient trans-cis photoisomerization from an excited triplet state produced within a dendrimer shell.

Science.gov (United States)

Miura, Yousuke; Momotake, Atsuya; Takeuchi, Keiichirou; Arai, Tatsuo

2011-01-01

A series of stilbene-cored poly(benzyl ether) dendrimers with benzophenone peripheries were synthesized and their photophysical and photochemical properties were studied. Fluorescence studies revealed that singlet-singlet energy transfer (SSET) from the stilbene core to the benzophenone units took place efficiently in dendrimers of all generations. Similarly, phosphorescence and time-resolved spectroscopic measurements indicated efficient triplet-triplet energy transfer (TTET) from the benzophenone periphery to the stilbene core. Upon excitation at 310 nm, the stilbene core isomerizes via an energy round trip within the dendrimer shell. The quantum yields for the energy round trip (Φ(ERT)), defined as the product of the quantum yields of SSET, intersystem crossing, and TTET (Φ(ERT) = Φ(SS)Φ(isc)Φ(TT)), were extremely high for all generations--99%, 95% and 94% for G1, G2, and G3, respectively--which means that the excitation energy of the dendrimer core was transferred to the dendrimer periphery and back to the core almost quantitatively. The quantum yield for photoisomerization of G1-G3 via an energy round trip was higher than for other stilbene-cored dendrimers, which mainly isomerize from the excited singlet state. Photostability in the dendrimers was also demonstrated and discussed.

Synthesis and Characterization of Poly(Amidoamine Dendrimers Encapsulatd 198Au Nanoparticles

Directory of Open Access Journals (Sweden)

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.

Continuous-time quantum walks on multilayer dendrimer networks

Science.gov (United States)

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.

DETECTABILITY OF EARTH-LIKE PLANETS IN CIRCUMSTELLAR HABITABLE ZONES OF BINARY STAR SYSTEMS WITH SUN-LIKE COMPONENTS

International Nuclear Information System (INIS)

Eggl, Siegfried; Pilat-Lohinger, Elke; Haghighipour, Nader

2013-01-01

Given the considerable percentage of stars that are members of binaries or stellar multiples in the solar neighborhood, it is expected that many of these binaries host planets, possibly even habitable ones. The discovery of a terrestrial planet in the α Centauri system supports this notion. Due to the potentially strong gravitational interaction that an Earth-like planet may experience in such systems, classical approaches to determining habitable zones (HZ), especially in close S-type binary systems, can be rather inaccurate. Recent progress in this field, however, allows us to identify regions around the star permitting permanent habitability. While the discovery of α Cen Bb has shown that terrestrial planets can be detected in solar-type binary stars using current observational facilities, it remains to be shown whether this is also the case for Earth analogs in HZs. We provide analytical expressions for the maximum and rms values of radial velocity and astrometric signals, as well as transit probabilities of terrestrial planets in such systems, showing that the dynamical interaction of the second star with the planet may indeed facilitate the planets' detection. As an example, we discuss the detectability of additional Earth-like planets in the averaged, extended, and permanent HZs around both stars of the α Centauri system.

DETECTABILITY OF EARTH-LIKE PLANETS IN CIRCUMSTELLAR HABITABLE ZONES OF BINARY STAR SYSTEMS WITH SUN-LIKE COMPONENTS

Energy Technology Data Exchange (ETDEWEB)

Eggl, Siegfried; Pilat-Lohinger, Elke [University of Vienna, Institute for Astrophysics, Tuerkenschanzstr. 17, A-1180 Vienna (Austria); Haghighipour, Nader, E-mail: siegfried.eggl@univie.ac.at [Institute for Astronomy and NASA Astrobiology Institute, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States)

2013-02-20

Given the considerable percentage of stars that are members of binaries or stellar multiples in the solar neighborhood, it is expected that many of these binaries host planets, possibly even habitable ones. The discovery of a terrestrial planet in the {alpha} Centauri system supports this notion. Due to the potentially strong gravitational interaction that an Earth-like planet may experience in such systems, classical approaches to determining habitable zones (HZ), especially in close S-type binary systems, can be rather inaccurate. Recent progress in this field, however, allows us to identify regions around the star permitting permanent habitability. While the discovery of {alpha} Cen Bb has shown that terrestrial planets can be detected in solar-type binary stars using current observational facilities, it remains to be shown whether this is also the case for Earth analogs in HZs. We provide analytical expressions for the maximum and rms values of radial velocity and astrometric signals, as well as transit probabilities of terrestrial planets in such systems, showing that the dynamical interaction of the second star with the planet may indeed facilitate the planets' detection. As an example, we discuss the detectability of additional Earth-like planets in the averaged, extended, and permanent HZs around both stars of the {alpha} Centauri system.

Aptamer-conjugated dendrimer-modified quantum dots for glioblastoma cells imaging

International Nuclear Information System (INIS)

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.

Structure of DNA-Functionalized Dendrimer Nanoparticles

OpenAIRE

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...

Uses of Dendrimers for DNA Microarrays

Directory of Open Access Journals (Sweden)

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.

Polymer research by neutron scattering

International Nuclear Information System (INIS)

Richter, D.

1993-01-01

Polymer physics aims on an understanding of the macroscopic behavior of polymer systems on the basis of their molecular structure and dynamics. For this purpose neutrons serve as a unique probe, allowing a simultaneous investigation of polymer structure and dynamics on a molecular scale. Furthermore, hydrogen deuterium exchange facilitates molecular labeling and offers the possibility to observe selected chains or chain parts in dense systems. Neutron small angle scattering reveals information on the conformation and possible aggregation of polymer chains. Data on linear and star like molecules are shown as examples. High resolution neutron spin-echospectroscopy observes the molecular dynamics of long chain molecules. Results on the large scale motion of chins in polymer melts are presented. finally, experiments on chain relaxation close to the glass transition are displayed. Three distinctly different relaxation processes are revealed. (author)

Tautomeric forms of PPI dendrimers functionalized with 4-(4′-ethoxybenzoyloxy)salicylaldehyde chromophores

International Nuclear Information System (INIS)

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.

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

Science.gov (United States)

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.

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.

Science.gov (United States)

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.

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

Science.gov (United States)

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.

Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

Science.gov (United States)

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.

Development of TREN dendrimers over mesoporous SBA-15 for CO2 adsorption

International Nuclear Information System (INIS)

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.

Quantitative assessment of surface functionality effects on microglial uptake and retention of PAMAM dendrimers

Science.gov (United States)

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.

Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications.

Science.gov (United States)

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.

Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities.

Science.gov (United States)

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.

Interaction of phosphorus dendrimers with HIV peptides—Fluorescence studies of nano-complexes formation

Energy Technology Data Exchange (ETDEWEB)

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.

Interaction of phosphorus dendrimers with HIV peptides—Fluorescence studies of nano-complexes formation

International Nuclear Information System (INIS)

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

Exploration of the brown dwarf regime around solar-like stars by CoRoT

OpenAIRE

Csizmadia, Szilárd

2016-01-01

Aims. A summary of the CoRoT brown dwarf investigations are presented. Methods. Transiting brown dwarfs around solar like stars were studied by using the photometric time-series of CoRoT, and ground based radial velocity measurements. Results. CoRoT detected three transiting brown dwarfs around F and G dwarf stars. The occurence rate of brown dwarfs was found to be 0.20 +/- 0.15% around solar-like stars which is compatible with the value obtained by Kepler-data.

Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

Energy Technology Data Exchange (ETDEWEB)

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.

Methotrexate loaded polyether-copolyester dendrimers for the treatment of gliomas: enhanced efficacy and intratumoral transport capability.

Science.gov (United States)

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.

THE MASS-DEPENDENCE OF ANGULAR MOMENTUM EVOLUTION IN SUN-LIKE STARS

International Nuclear Information System (INIS)

Matt, Sean P.; Baraffe, Isabelle; Chabrier, Gilles; Brun, A. Sacha; Bouvier, Jérôme

2015-01-01

To better understand the observed distributions of the rotation rate and magnetic activity of Sun-like and low-mass stars, we derive a physically motivated scaling for the dependence of the stellar wind torque on the Rossby number. The torque also contains an empirically derived scaling with stellar mass (and radius), which provides new insight into the mass-dependence of stellar magnetic and wind properties. We demonstrate that this new formulation explains why the lowest mass stars are observed to maintain rapid rotation for much longer than solar-mass stars, and simultaneously why older populations exhibit a sequence of slowly rotating stars, in which the low-mass stars rotate more slowly than solar-mass stars. The model also reproduces some previously unexplained features in the period-mass diagram for the Kepler field, notably: the particular shape of the ''upper envelope'' of the distribution, suggesting that ∼95% of Kepler field stars with measured rotation periods are younger than ∼4 Gyr; and the shape of the ''lower envelope'', corresponding to the location where stars transition between magnetically saturated and unsaturated regimes

Multifunctional Dendrimer-templated Antibody Presentation on Biosensor Surfaces for Improved Biomarker Detection.

Science.gov (United States)

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.

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

Directory of Open Access Journals (Sweden)

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

Poly(Propylene Imine Dendrimers and Amoxicillin as Dual-Action Antibacterial Agents

Directory of Open Access Journals (Sweden)

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.

In vitro evaluation of dendrimer prodrugs for oral drug delivery.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

National Research Council Canada - National Science Library

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...

Preparation of pH-sensitive amphiphilic block star polymers, their self-assembling characteristics and release behavior on encapsulated molecules

KAUST Repository

Song, Xiaowan

2016-05-28

Poly(ethylene glycol) (PEG), a polymer with excellent biocompatibility, was widely used to form nanoparticles for drug delivery applications. In this paper, based on PEG, a series of pH-sensitive amphiphilic block star polymers of poly(ethylene glycol)-block-poly(ethoxy ethyl glycidyl ether) (PEG-b-PEEGE) with different hydrophobic length were synthesized by living anionic ring-opening polymerization method. The products were characterized using 1H NMR and gel permeation chromatography. These copolymers could self-assemble in aqueous solution to form micellar structure with controlled morphologies. Transmission electron microscopy showed that the nanoparticles are spherical or rodlike with different hydrophilic mass fractions. The pH response of polymeric aggregates from PEG-b-PEEGE was detected by fluorescence probe technique at different pH. A pH-dependent release behavior was observed and pH-responsiveness of PEG-b-PEEGE was affected by the hydrophobic block length. These results demonstrated that star-shaped polymers (PEG-b-PEEGE) are attractive candidates as anticancer drug delivery carriers. © 2016 Springer-Verlag Berlin Heidelberg

Energy transfer to xanthene dyes in dansylated POPAM dendrimers

Science.gov (United States)

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.

Assess the Intra-molecular Cavity in PAMAM Dendrimers by Small Angle Neutron Scattering

International Nuclear Information System (INIS)

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

Transepithelial transport of PAMAM dendrimers across isolated rat jejunal mucosae in ussing chambers.

Science.gov (United States)

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.

Dendrimer and an active substance occluded in the dendrimer : a process for the preparation thereof and a process for releasing the active substance

NARCIS (Netherlands)

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

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

International Nuclear Information System (INIS)

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

Development of a Topical Resveratrol Formulation for Commercial Applications Using Dendrimer Nanotechnology.

Science.gov (United States)

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.

Dendrimer advances for the central nervous system delivery of therapeutics.

Science.gov (United States)

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.

Composition consisting of a dendrimer and an active substance

NARCIS (Netherlands)

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

Physicochemical and biological properties of self-assembled antisense/poly(amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio

OpenAIRE

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...

Stabilization of Lipid Membranes With Dendritic Polymers

Science.gov (United States)

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

A statistical analysis of IUE spectra of dwarf novae and nova-like stars

Science.gov (United States)

Ladous, Constanze

1990-01-01

First results of a statistical analysis of the IUE International Ultraviolet Explorer archive on dwarf novae and nova like stars are presented. The archive contains approximately 2000 low resolution spectra of somewhat over 100 dwarf novae and nova like stars. Many of these were looked at individually, but so far the collective information content of this set of data has not been explored. The first results of work are reported.

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

Directory of Open Access Journals (Sweden)

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

55 CANCRI: A COPLANAR PLANETARY SYSTEM THAT IS LIKELY MISALIGNED WITH ITS STAR

International Nuclear Information System (INIS)

Kaib, Nathan A.; Duncan, Martin J.; Raymond, Sean N.

2011-01-01

Although the 55 Cnc system contains multiple, closely packed planets that are presumably in a coplanar configuration, we use numerical simulations to demonstrate that they are likely to be highly inclined to their parent star's spin axis. Due to perturbations from its distant binary companion, this planetary system precesses like a rigid body about its parent star. Consequently, the parent star's spin axis and the planetary orbit normal likely diverged long ago. Because only the projected separation of the binary is known, we study this effect statistically, assuming an isotropic distribution for wide binary orbits. We find that the most likely projected spin-orbit angle is ∼50°, with a ∼30% chance of a retrograde configuration. Transit observations of the innermost planet—55 Cnc e—may be used to verify these findings via the Rossiter-McLaughlin effect. 55 Cancri may thus represent a new class of planetary systems with well-ordered, coplanar orbits that are inclined with respect to the stellar equator.

Biodegradable star HPMA polymer conjugates of doxorubicin for passive tumor targeting

Czech Academy of Sciences Publication Activity Database

Etrych, Tomáš; Strohalm, Jiří; Chytil, Petr; Černoch, Peter; Starovoytova, Larisa; Pechar, Michal; Ulbrich, Karel

2011-01-01

Roč. 42, č. 5 (2011), s. 527-539 ISSN 0928-0987 R&D Projects: GA AV ČR IAA400500806; GA AV ČR IAAX00500803; GA ČR GA203/08/0543 Institutional research plan: CEZ:AV0Z40500505 Keywords : dendrimer * HPMA copolymers * doxorubicin Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.212, year: 2011

Tuning the Solubility of Copper Complex in Atom Transfer Radical Self-Condensing Vinyl Polymerizations to Control Polymer Topology via One-Pot to the Synthesis of Hyperbranched Core Star Polymers

Directory of Open Access Journals (Sweden)

Zong-Cheng Chen

2014-09-01

Full Text Available In this paper, we propose a simple one-pot methodology for proceeding from atom transfer reaction-induced conventional free radical polymerization (AT-FRP to atom transfer self-condensing vinyl polymerization (AT-SCVP through manipulation of the catalyst phase homogeneity (i.e., CuBr/2,2'-bipyridine (CuBr/Bpy in a mixture of styrene (St, 4-vinyl benzyl chloride (VBC, and ethyl 2-bromoisobutyrate. Tests of the solubilities of CuBr/Bpy and CuBr2/Bpy under various conditions revealed that both temperature and solvent polarity were factors affecting the solubility of these copper complexes. Accordingly, we obtained different polymer topologies when performing AT-SCVP in different single solvents. We investigated two different strategies to control the polymer topology in one-pot: varying temperature and varying solvent polarity. In both cases, different fractions of branching revealed the efficacy of varying the polymer topology. To diversify the functionality of the peripheral space, we performed chain extensions of the resulting hyperbranched poly(St-co-VBC macroinitiator (name as: hbPSt MI with either St or tBA (tert-butyl acrylate. The resulting hyperbranched core star polymer had high molecular weights (hbPSt-g-PSt: Mn = 25,000, Đ = 1.77; hbPSt-g-PtBA: Mn = 27,000, Đ = 1.98; hydrolysis of the tert-butyl groups of the later provided a hyperbranched core star polymer featuring hydrophilic poly(acrylic acid segments.

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

Science.gov (United States)

Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (Pdendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

White organic light emitting diodes based on fluorene-carbazole dendrimers

International Nuclear Information System (INIS)

Usluer, Özlem; Demic, Serafettin; Kus, Mahmut; Özel, Faruk; Serdar Sariciftci, Niyazi

2014-01-01

In this paper, we report on theProd. Type: FTP fabrication and characterization of blue and white light emitting devices based on two fluorene-carbazole containing dendrimers and para-sexiphenyl (6P) oligomers. Blue light emitting diodes were fabricated using 9′,9″-(9,9-dioctyl-9H-fluorene-2,7-diyl)bis-9′H-9,3′:6′,9″-tercarbazole (OFC-G2) and 9′,9″-(9,9′-spirobi[fluorene]-2,7-diyl)bis-9′H-9,3′:6′,9″-tercarbazole (SBFC-G2) dendrimers as a hole transport and emissive layer (EML) and 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) as an electron transport layer. White light emitting diodes were fabricated using 6P and these two dendrimers as an EML. OLED device with the structure of ITO/PEDOT:PSS (50 nm)/OFC-G2 (40 nm)/6P (20 nm)/LiF:Al (0.5:100 nm) shows maximum luminance of nearly 1400 cd/m 2 and a Commission Internationale de l'Eclairage chromaticity coordinates of (0.27, 0.30) at 12 V. -- Highlights: • White organic light emitting diodes have been fabricated using two fluorene-carbazole dendrimers and para-sexiphenyl (6P) oligomers. • When only these two dendrimers are used as EML, OLED devices are emitted blue light. • The emission colors of OLED devices change from blue to white when 6P is coated on dendrimer films

Combining metadynamics simulation and experiments to characterize dendrimers in solution

NARCIS (Netherlands)

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

Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

Science.gov (United States)

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.

Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

International Nuclear Information System (INIS)

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.

Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

Science.gov (United States)

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.

Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

Energy Technology Data Exchange (ETDEWEB)

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.

Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

Science.gov (United States)

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

Photoinduced Electron Transfer of PAMAM Dendrimer-Zinc(II) Porphyrin Associates at Polarized Liquid|Liquid Interfaces.

Science.gov (United States)

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.

Mechanism of PAMAM Dendrimers Internalization in Hippocampal Neurons.

Science.gov (United States)

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.

Rational design of dendrimer/lipid nanoassemblies in drug delivery for cancer chemotherapy

Science.gov (United States)

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.