Sample records for releasable polymeric conjugates

  1. New approach in synthesis, characterization and release study of pH-sensitive polymeric micelles, based on PLA-Lys- b-PEGm, conjugated with doxorubicin

    Efthimiadou, E. K.; Tapeinos, C.; Bilalis, P.; Kordas, G.


    Amphiphilic block copolymers are well established as building blocks for the preparation of micellar drug carriers. The functional polymer micelles possess several advantages, such as high drug efficiency, targeted delivery, and minimized cytotoxicity. The synthesis of block copolymers using nano-structured templates has emerged as a useful and versatile approach for preparing drug carriers. Here, we report the synthesis of a smart polymeric compound of a diblock PLA-Lys- b-PEG copolymer containing doxorubicin. We have synthesized functionalized diblock copolymers, with lysinol, poly(lactide) and monomethoxy poly(ethylene glycol) via thermal ring-opening polymerization and a subsequent six-step substitution reaction. A variety of spectroscopic methods were employed here to verify the product of our synthesis. 1H-Nuclear magnetic resonance and Fourier transform infrared studies validated the expected synthesis of copolymers. Doxorubicin is chemically loaded into micelles, and the ex vitro release can be evaluated either in weak acidic or in SBF solution by UV-vis spectroscopy. Dynamic light scattering, thermo gravimetric analysis, and size exclusion chromatography have also been used.

  2. In vitro drug release and biological evaluation of biomimetic polymeric micelles self-assembled from amphiphilic deoxycholic acid–phosphorylcholine–chitosan conjugate

    Wu, Minming; Guo, Kai; Dong, Hongwei; Zeng, Rong, E-mail:; Tu, Mei; Zhao, Jianhao


    Novel biomimetic amphiphilic chitosan derivative, deoxycholic acid–phosphorylcholine–chitosan conjugate (DCA–PCCs) was synthesized based on the combination of Atherton–Todd reaction for coupling phosphorylcholine (PC) and carbodiimide coupling reaction for linking deoxycholic acid (DCA) to chitosan. The chemical structure of DCA–PCCs was characterized by {sup 1}H and {sup 31}P nuclear magnetic resonance (NMR). The self-assembly of DCA–PCCs in water was analyzed by fluorescence measurements, dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM) technologies. The results confirmed that the amphiphilic DCA–PCCs can self-assemble to form nanosized spherical micelles with biomimetic PC shell. In vitro biological evaluation revealed that DCA–PCCs micelles had low toxicity against NIH/3T3 mouse embryonic fibroblasts as well as good hemocompatibility. Using quercetin as a hydrophobic model drug, drug loading and release study suggested that biomimetic DCA–PCCs micelles could be used as a promising nanocarrier avoiding unfavorable biological response for hydrophobic drug delivery applications. - Highlights: • DCA–PCCs with phosphorylcholine and deoxycholic acid was synthesized. • DCA–PCCs can self-assemble to form spherical micelles in aqueous system. • DCA–PCCs micelles had excellent cytocompatibility and hemocompatibility. • DCA–PCCs micelles loaded with quercetin exhibited a sustained drug release behavior.

  3. CO-releasing molecule (CORM) conjugate systems.

    Kautz, Anna Christin; Kunz, Peter C; Janiak, Christoph


    The development of CORMs (CO-releasing molecules) as a prodrug for CO administration in living organisms has attracted significant attention. CORMs offer the promising possibility of a safe and controllable release of CO in low amounts triggered by light, ligands, enzymes, etc. For the targeting of specific tissues or diseases and to prevent possible side effects from metals and other residues after CO release, these CORMs are attached to biocompatible systems, like peptides, polymers, nanoparticles, dendrimers, protein cages, non-wovens, tablets, and metal-organic frameworks. We discuss in this review the known CORM carrier conjugates, in short CORM conjugates, with covalently-bound or incorporated CORMs for medicinal and therapeutic applications. Most conjugates are nontoxic, show increasing half-lives of CO release, and make use of the EPR-effect, but still show problems because of a continuous background of CO release and the absence of an on/off-switch for the CO release.

  4. Lyophilized Oral Sustained Release Polymeric Nanoparticles of Nateglinide

    Kaleemuddin, Mohammad; Srinivas, Prathima


    The objective of this study is to formulate lyophilized oral sustained release polymeric nanoparticles of nateglinide in order to decrease dosing frequency, minimize side effects, and increase bioavailability...

  5. Electrochemically polymerized conjugated polymer films: Stability improvement and surface functionalization

    Wei, Bin

    Conjugated polymers have been widely used in various applications including organic solar cells, electrochromic devices, chemical sensors, and biomedical devices. Poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives have received considerable interest because of their low oxidation potential, relatively high chemical stability, and high conductivity. Electrochemical deposition is a convenient method for precisely fabricating conjugated polymer thin films. Here, we report the stability improvement and surface functionalization of electrochemically polymerized PEDOT films. The long-term performance of PEDOT coatings is limited by their relatively poor stability on various inorganic substrates. Two different methods were used to improve the stability of PEDOT coatings, one involved using carboxylic acid functionalized EDOT (EDOT-acid) as adhesion promoter. EDOT-acid molecules were chemically bonded onto activated metal oxide substrates via chemisorption. PEDOT was then polymerized onto the EDOT-acid modified substrates, forming covalently bonded coatings. An aggressive ultrasonication test confirmed the significantly improved adhesion of the PEDOT films on electrodes with EDOT-acid treatment over those without treatment. The other method was to use an octa-ProDOT-functionalized POSS derivative (POSSProDOT) as cross-linker. PEDOT copolymer films were electrochemically deposited with various concentrations of POSS-ProDOT. The optical, morphological and electrochemical properties of the copolymer films could be systematically tuned with the incorporation of POSS-ProDOT. Significantly enhanced electrochemical and mechanical stability of the copolymers were observed at intermediate levels of POSS-ProDOT content (3.1 wt%) via chronic stimulation tests. Surface functionalization of conducting polymer films provides a potential means for systematically tailoring their chemical and physical properties. We have synthesized, polymerized and characterized a dialkene

  6. Self-assembled polymeric nanoparticle of PEGylated chitosan-ceramide conjugate for systemic delivery of paclitaxel.

    Battogtokh, Gantumur; Ko, Young Tag


    Chitosan has been widely explored as one of the most favorable biomaterials for various pharmaceutical applications due to its biodegradability and biocompatibility. Here, we report novel PEGylated-chitosan-ceramide (PEG-CS-CE) that forms stable polymeric nanoparticles capable of functioning as efficient carriers of hydrophobic drug molecules. The chitosan-ceramide conjugate (CS-CE) was linked with amine-polyethyleneglycol (NH2-PEG2000) by using dicyclohexylcarbodiimide/N-hydroxysuccinimide (DCC-NHS) to obtain PEG-CS-CE that could exhibit steric stabilization in biological environments. The structure of the conjugate was determined by proton ((1)H) NMR and FT-IR spectrometry. Under suitable conditions, the PEG-CS-CE self-assembled to form colloidally stable nanoparticles with a mean diameter of ∼ 200 nm. Further, hydrophobic anti-tumor agent paclitaxel (PTX) was incorporated into the polymeric nanoparticle with 90% loading efficiency and 11.3% loading capacity via an emulsion-solvent evaporation method. The PTX-loaded PEG-CS-CE nanoparticle showed sustained release and exhibited higher cellular uptake and a comparable cytotoxic efficacy to that of free PTX on B16F10 melanoma and MCF-7 human breast adenocarcinoma cell lines. The empty nanoparticle showed no toxicity, indicating that the co-polymer is safe to use in drug delivery. The polymeric nanoparticle PEG-CS-CE developed by us represent promising nanocarriers of hydrophobic drug molecules.

  7. Nucleobase-templated polymerization: copying the chain length and polydispersity of living polymers into conjugated polymers.

    Lo, Pik Kwan; Sleiman, Hanadi F


    Conjugated polymers synthesized by step polymerization mechanisms typically suffer from poor molecular weight control and broad molecular weight distributions. We report a new method which uses nucleobase recognition to read out and efficiently copy the controlled chain length and narrow molecular weight distribution of a polymer template generated by living polymerization, into a daughter conjugated polymer. Aligning nucleobase-containing monomers on their complementary parent template using hydrogen-bonding interactions, and subsequently carrying out a Sonogashira polymerization, leads to the templated synthesis of a conjugated polymer. Remarkably, this daughter strand is found to possess a narrow molecular weight distribution and a chain length nearly equivalent to that of the parent template. On the other hand, nontemplated polymerization or polymerization with the incorrect template generates a short conjugated oligomer with a significantly broader molecular weight distribution. Hence, nucleobase-templated polymerization is a useful tool in polymer synthesis, in this case allowing the use of a large number of polymers generated by living methods, such as anionic polymerization, controlled radical polymerizations (NMP, ATRP, and RAFT) and other mechanisms to program the structure, length, and molecular weight distribution of polymers normally generated by step polymerization methods and significantly enhance their properties.

  8. Polylactide conjugates of camptothecin with different drug release abilities.

    Oledzka, Ewa; Horeglad, Paweł; Gruszczyńska, Zuzanna; Plichta, Andrzej; Nałęcz-Jawecki, Grzegorz; Sobczak, Marcin


    Camptothecin-polylactide conjugates (CMPT-PLA) were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79) via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled design of the PLA microstructure, and allow in the case of CMPT-PLA conjugates for the development of highly controlled biodegradable CMPT systems-important delivery systems for anti-cancer agents.

  9. Polylactide Conjugates of Camptothecin with Different Drug Release Abilities

    Ewa Oledzka


    Full Text Available Camptothecin-polylactide conjugates (CMPT-PLA were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79 via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled design of the PLA microstructure, and allow in the case of CMPT-PLA conjugates for the development of highly controlled biodegradable CMPT systems—important delivery systems for anti-cancer agents.

  10. Conjugation of diisocyanate side chains to dimethacrylate reduces polymerization shrinkage and increases the hardness of composite resins

    Yih-Dean Jan


    Conclusion: Conjugation of diisocyanate side chains to dimethacrylate represents an effective means of reducing polymerization shrinkage and increasing the surface hardness of dental composite resins.

  11. Application of advanced polymeric materials for controlled release pesticides

    Rahim, M.; Hakim, M. R.; Haris, H. M.


    The objective of this work was to study the capability of advanced polymeric material constituted by chitosan and natural rubber matrices for controlled release of pesticides (1-hydroxynaphthalene and 2-hydroxynaphthalene) in aqueous solution. The released amount of pesticides was measured spectrophotometrically from the absorbance spectra applying a standardized curve. The release of the pesticides was studied into refreshing and non-refreshing neutral aqueous media. Interestingly, formulation successfully indicated a consistent, controlled and prolonged release of pesticides over a period of 35 days.

  12. Dual release of proteins from porous polymeric scaffolds

    Sohier, J.; Vlugt, T.J.H.; Cabrol, N.; Blitterswijk, van C.; Groot, de K.; Bezemer, J.M.


    To create porous scaffolds releasing in a controlled and independent fashion two different proteins, a novel approach based on protein-loaded polymeric coatings was evaluated. In this process, two water-in-oil emulsions are forced successively through a prefabricated scaffold to create coatings, con

  13. Enzymatic Polymerization of an Ibuprofen-Containing Monomer and Subsequent Drug Release.

    Stebbins, Nicholas D; Yu, Weiling; Uhrich, Kathryn E


    Novel ibuprofen-containing monomers comprising naturally occurring and biocompatible compounds were synthesized and subsequently polymerized via enzymatic methods. Through the use of a malic acid sugar backbone, ibuprofen was attached as a pendant group, and then subsequently polymerized with a linear aliphatic diol (1,3-propanediol, 1,5-pentanediol, or 1,8-octanediol) as comonomer using lipase B from Candida antarctica, a greener alternative to traditional metal catalysts. Polymer structures were elucidated by nuclear magnetic resonance and infrared spectroscopies, and thermal properties and molecular weights were determined. All polymers exhibited sustained ibuprofen release, with the longer chain, more hydrophobic diols exhibiting the slowest release over the 30 d study. Polymers were deemed cytocompatible using mouse fibroblasts, when evaluated at relevant therapeutic concentrations. Additionally, ibuprofen retained its chemical integrity throughout the polymerization and in vitro hydrolytic degradation processes. This methodology of enzymatic polymerization of a drug presents a more environmentally friendly synthesis and a novel approach to bioactive polymer conjugates. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Controlled release of ethylene via polymeric films for food packaging

    Pisano, Roberto; Bazzano, Marco; Capozzi, Luigi Carlo; Ferri, Ada; Sangermano, Marco


    In modern fruit supply chain a common method to trigger ripening is to keep fruits inside special chambers and initiate the ripening process through administration of ethylene. Ethylene is usually administered through cylinders with inadequate control of its final concentration in the chamber. The aim of this study is the development of a new technology to accurately regulate ethylene concentration in the atmosphere where fruits are preserved: a polymeric film, containing an inclusion complex of α-cyclodextrin with ethylene, was developed. The complex was prepared by molecular encapsulation which allows the entrapment of ethylene into the cavity of α-cyclodextrin. After encapsulation, ethylene can be gradually released from the inclusion complex and its release rate can be regulated by temperature and humidity. The inclusion complex was dispersed into a thin polymeric film produced by UV-curing. This method was used because is solvent-free and involves low operating temperature; both conditions are necessary to prevent rapid release of ethylene from the film. The polymeric films were characterized with respect to thermal behaviour, crystalline structure and kinetics of ethylene release, showing that can effectively control the release of ethylene within confined volume.

  15. Synthesis of ordered conjugated polycyclic aromatic hydrocarbon polymers through polymerization reaction on Au(111)

    Wang, Zhongping; Zhao, Huiling; Lu, Yan;


    One-dimensional pi-conjugated polymer chains with variable lengths have been synthesized successfully via thermal polymerization reaction on the Au(111) surface. Such polymer chains form parallel arrays along specific directions according to the initial assembly orientations of the close-packed Br...

  16. Utilization of Nitrones in Radical Polymerizations and Polymer Conjugations

    Ranieri Lynn, Kayte


    Much research has been performed in the last 10 years on the use of nitrones in synthetic polymer chemistry. Nitrone polymer chemistry represents an additional tool to the “polymer toolbox”, which contributes to the advancement of modern polymer science and technology. In this present thesis, four interconnecting themes centered on the use of nitrones in radical polymerizations and coupling have been investigated. (1) Synthesize nitrones with various functionalities. (2) Utilize controlled ra...

  17. Conjugate polymers and electronic conductive polymers; Polymeres conjugues et polymeres conducteurs electroniques

    Attias, A.J. [Universite Pierre et Marie Curie, Lab. de Chimie Macromoleculaire, UMR 7610 - CNRS, 75 - Paris (France)


    In some certain conditions a plastic material can become conductive (synthetic metal). To become conductive, a polymer must be conjugate (alternance of simple and multiple bonds) and doped (electron removal or addition). This article presents the recent advances and trends of the research on conductive polymers. The role of {pi} electrons in the conjugate systems is recalled in a first part. The description of energy states of conjugate polymers in terms of bands structure allow to consider them as organic semiconductors. Thus, it is possible to generate charged species by doping, charge injection or photo-excitation. These charge carriers, the conduction mechanisms and the related applications are presented. The chemistry and synthesis of these polymers are presented in a second part: 1 - evolution of research; 2 - physics of conductive polymers (role of {pi} electrons in conjugate polymers, {pi}-electrons conjugate compounds, influence of conjugation length and notion of bands structure, charges-doping generation, conductive polymers, chemical doping and electrical conduction, charge injection at the conjugate semiconductor metal-polymer interface: electro-luminescent polymers, charge creation by photo-excitation: polymers for photovoltaic cells); 3 - chemistry of conductive polymers (role of synthesis, monomers choice, other trends). (J.S.)

  18. Nitric oxide-releasing polymeric nanoparticles against Trypanosoma cruzi

    Seabra, A. B.; Kitice, N. A.; Pelegrino, M. T.; Lancheros, C. A. C.; Yamauchi, L. M.; Pinge-Filho, P.; Yamada-Ogatta, S. F.


    Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi (T. cruzi), and the disease remains a major health problem in many Latin American countries. Several papers report that the killing of the parasite is dependent on the production of nitric oxide (NO). The endogenous free radical NO is an important cellular signalling molecule that plays a key role in the defense against pathogens, including T. cruzi. As T. cruzi is able to compromise host macrophages decreasing endogenous NO production, the administration of exogenous NO donors represents an interesting strategy to combat Chagas disease. Thus, the aims of this study were to prepare and evaluate the antimicrobial activity of NO-releasing polymeric nanoparticles against T. cruzi. Biocompatible polymeric nanoparticles composed of chitosan/sodium tripolyphosphate(TPP) were prepared and used to encapsulate mercaptosuccinic acid (MSA), which is a thiol-containing molecule. Nitrosation of free thiols (SH) groups of MSA were performed by the addition of equimolar amount of sodium nitrite (NaNO2), leading to the formation of S-nitroso-MSA-containing nanoparticles. These polymeric nanoparticles act as spontaneous NO donors, with free NO release. The results show the formation of nanoparticles with average hydrodynamic diameter ranging from 270 to 500 nm, average of polydispersity index of 0.35, and encapsulation efficiency in the range of 99%. The NO release kinetics from the S-nitroso-MSA-containing nanoparticles showed sustained and controlled NO release over several hours. The microbicidal activity of S-nitroso-MSA-containing nanoparticles was evaluated by incubating NO-releasing nanoparticles (200 - 600 μg/mL) with replicative and non-infective epimastigote, and non-replicative and infective trypomastigote forms of T. cruzi. In addition, a significant decrease in the percentage of macrophage-infected (with amastigotes) and

  19. Synthesis of Donor-Acceptor Conjugated Polymers by "CLICK" Polymerization for OPV applications

    Brandt, Rasmus Guldbæk; Yu, Donghong

    The intent of this study was to utilize the Copper(I)-catalyzed Azide Alkyne Cycloaddition (CuAAC) as a polymerization technique (“Click” Polymerization) for synthesizing novel π-conjugated low band gap polymers for organic photovoltaic applications (OPV). The chosen approach was to synthesize...... an alternating electron donating (donor, D) and electron withdrawing (acceptor, A) co-polymer. The chosen monomers were well known units, and the novelty lies in using the monomer units with the click methodology. An insoluble alternating copolymer consisting of 2,7-diazido-9,9-dioctyl-9Hflourene and 1...

  20. Prazosin-Conjugated Matrices Based on Biodegradable Polymers and α-Amino Acids—Synthesis, Characterization, and in Vitro Release Study

    Ewa Oledzka


    Full Text Available Novel and promising macromolecular conjugates of the α1-adrenergic blocker prazosin were directly synthesized by covalent incorporation of the drug to matrices composed of biodegradable polymers and α-amino acids for the development of a polymeric implantable drug delivery carrier. The cyto- and genotoxicity of the synthesized matrices were evaluated using a bacterial luminescence test, protozoan assay, and Salmonella typhimurium TA1535. A new urethane bond was formed between the hydroxyl end-groups of the synthesized polymer matrices and an amine group of prazosin, using 1,1′-carbonyldiimidazole (CDI as a coupling agent. The structure of the polymeric conjugates was characterized by various spectroscopy techniques. A study of hydrogen nuclear magnetic resonance (1H-NMR and differential scanning calorimetry (DSC thermodiagrams indicated that the presence of prazosin pendant groups in the macromolecule structures increased the polymer’s rigidity alongside increasing glass transition temperature. It has been found that the kinetic release of prazosin from the obtained macromolecular conjugates, tested in vitro under different conditions, is strongly dependent on the physicochemical properties of polymeric matrices. Furthermore, the presence of a urethane bond in the macromolecular conjugates allowed for obtaining a relatively controlled release profile of the drug. The obtained results confirm that the pharmacokinetics of prazosin might be improved through the synthesis of polymeric conjugates containing biomedical polymers and α-amino acids in the macromolecule.

  1. New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into reduction-sensitive micelles for triggered drug release

    Yang, Hui-Kang [DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Li-Ming, E-mail: [DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006 (China)


    For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N-carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with α-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential. - Graphical abstract: New amphiphilic glycopolypeptide conjugate containing the disulfide bond could self-assemble in aqueous solution into reduction-sensitive micelles for triggered release of an anticancer drug (methotrexate, MTX) in the presence of 10 mM 1,4-dithio-DL-threitol (DTT). - Highlights: • Amphiphilic glycopolypeptide conjugate containing disulfide bond was prepared. • Such a conjugate self assembled in aqueous solution into nanosize micelles. • The resultant micelles could encapsulate effectively methotrexate drug. • The drug-loaded micelles showed a reduction-sensitive drug release behavior.

  2. Controlled Radical Polymerization as an Enabling Approach for the Next Generation of Protein-Polymer Conjugates.

    Pelegri-O'Day, Emma M; Maynard, Heather D


    Protein-polymer conjugates are unique constructs that combine the chemical properties of a synthetic polymer chain with the biological properties of a biomacromolecule. This often leads to improved stabilities, solubilities, and in vivo half-lives of the resulting conjugates, and expands the range of applications for the proteins. However, early chemical methods for protein-polymer conjugation often required multiple polymer modifications, which were tedious and low yielding. To solve these issues, work in our laboratory has focused on the development of controlled radical polymerization (CRP) techniques to improve synthesis of protein-polymer conjugates. Initial efforts focused on the one-step syntheses of protein-reactive polymers through the use of functionalized initiators and chain transfer agents. A variety of functional groups such as maleimide and pyridyl disulfide could be installed with high end-group retention, which could then react with protein functional groups through mild and biocompatible chemistries. While this grafting to method represented a significant advance in conjugation technique, purification and steric hindrance between large biomacromolecules and polymer chains often led to low conjugation yields. Therefore, a grafting from approach was developed, wherein a polymer chain is grown from an initiating site on a functionalized protein. These conjugates have demonstrated improved homogeneity, characterization, and easier purification, while maintaining protein activity. Much of this early work utilizing CRP techniques focused on polymers made up of biocompatible but nonfunctional monomer units, often containing oligoethylene glycol meth(acrylate) or N-isopropylacrylamide. These branched polymers have significant advantages compared to the historically used linear poly(ethylene glycols) including decreased viscosities and thermally responsive behavior, respectively. Recently, we were motivated to use CRP techniques to develop polymers with

  3. Synthesis and Characterization of Sodium Alginate Conjugate and Study of Effect of Conjugation on Drug Release from Matrix Tablet.

    Satheeshababu, B K; Mohamed, I


    The aim of the present research work to study the effect of conjugation of the polymer on drug release from the matrix tablets. Sodium alginate L-cysteine conjugate was achieved by covalent attachment of thiol group of L-cysteine with the primary amino group of sodium alginate through the amide bonds formed by primary amino groups of the sodium alginate and the carboxylic acid group of L-cysteine. The synthesised sodium alginate L-cysteine conjugate was characterised by determining of charring point, Fourier transmission-infrared and differential scanning calorimetric analysis. To study the effect of conjugation on drug release pattern, the matrix tablets were prepared using various proportions of sodium alginate and sodium alginate L-cysteine conjugate along with atorvastatin calcium as model drug. The wet granulation technique was adopted and prepared matrix tablets were evaluated for various physical parameters. The in vitro drug release study results suggested that tablet formulated in combination of sodium alginate and sodium alginate L-cysteine conjugate S4 showed 100% after 8 h drug release whereas formulated with only sodium alginate S0 released 40% in 8 h.

  4. Synthesis and Characterization of Sodium Alginate Conjugate and Study of Effect of Conjugation on Drug Release from Matrix Tablet

    Satheeshababu, B. K.; Mohamed, I.


    The aim of the present research work to study the effect of conjugation of the polymer on drug release from the matrix tablets. Sodium alginate L-cysteine conjugate was achieved by covalent attachment of thiol group of L-cysteine with the primary amino group of sodium alginate through the amide bonds formed by primary amino groups of the sodium alginate and the carboxylic acid group of L-cysteine. The synthesised sodium alginate L-cysteine conjugate was characterised by determining of charrin...

  5. A robust and versatile photoinduced living polymerization of conjugated and unconjugated monomers and its oxygen tolerance.

    Xu, Jiangtao; Jung, Kenward; Atme, Amir; Shanmugam, Sivaprakash; Boyer, Cyrille


    Controlled/living radical polymerization techniques have transformed polymer chemistry in the last few decades, affording the production of polymers with precise control over both molecular weights and architectures. It is now possible to synthesize almost an infinite variety of macromolecules using nonspecialized equipment, finding applications in high-tech industry. However, they have several shortcomings. Until recently, living radical polymerizations could not be controlled by an external stimulus, such as visible light, pH, mechanical, chemical, etc. Moreover, they are usually sensitive to trace amounts of oxygen in the system. In this Article, we report a photoinduced living polymerization technique, which is able to polymerize a large range of monomers, including conjugated and unconjugated monomers, using ultralow concentrations of an iridium-based photoredox catalyst (typically 1 ppm to monomers) and a low energy visible LED as the light source (1-4.8 W, λ(max) = 435 nm). The synthesis of homopolymers with molecular weights ranging from 1000 to 2,000,000 g/mol was successfully achieved with narrow molecular weight distributions (M(w)/M(n) < 1.3). In addition, chain extensions of poly(methacrylate)s, poly(styrene), poly(N-vinyl pyrrolidinone), poly(vinyl ester)s, and poly(acrylate)s were performed to prepare diblock copolymers. The reusability of the catalyst was demonstrated by the synthesis of a decablock polymer by multiple chain extensions. Most importantly, this process was employed to prepare well-defined polymers and multiblock copolymers in the presence of air.

  6. Synthesis of Conjugated Hyperbranched Polytriazoles Containing Truxene Units by Click Polymerization

    李冬至; 王欣; 贾玉涛; 王爱卿; 武永刚


    It has been a challenge to synthesize high molecular weight and soluble conjugated hyperbranched poly(1,2,3-triazole)s (hb-PTAs). In this paper a series of soluble hyperbranched polytriazoles, whose num- ber-average molecular weight (Mn) and polydispersity index ranged in (1.2--3.3)× 104 and 1.7--3.0, respectively, were synthesized with A2 d-B3 approach. In the polymerization process, diazides A1--A4 and triyne B1 were used as A2 and B3 monomers; Cu(I)-catalyst, THF and water were used as their reaction system. At room temperature the final molecular weight could be controlled through reaction time, so finally we obtained soluble conjugated hyper- branched poly(1,2,3-triazole)s hb-PTAs (1--4). The polymers were soluble in common organic solvents, and all emitted blue light; the films of polymers emitted yellow and blue light, due to the difference in the aggregation of their chromophoric units in the solid state. The thermal properties of the final copolymers were analyzed by differ- ential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).

  7. Enhanced delivery of the RAPTA-C macromolecular chemotherapeutic by conjugation to degradable polymeric micelles.

    Blunden, Bianca M; Lu, Hongxu; Stenzel, Martina H


    Macromolecular ruthenium complexes are a promising avenue to better and more selective chemotherapeutics. We have previously shown that RAPTA-C [RuCl2(p-cymene)(PTA)], with the water-soluble 1,3,5-phosphaadamantane (PTA) ligand, could be attached to a polymer moiety via nucleophilic substitution of an available iodide with an amide in the PTA ligand. To increase the cell uptake of this macromolecule, we designed an amphiphilic block copolymer capable of self-assembling into polymeric micelles. The block copolymer was prepared by ring-opening polymerization of d,l-lactide (3,6-dimethyl-1,4-dioxane-2,5-dione) using a RAFT agent with an additional hydroxyl functionality, followed by the RAFT copolymerization of 2-hydroxyethyl acrylate (HEA) and 2-chloroethyl methacrylate (CEMA). The Finkelstein reaction and reaction with PTA led to polymers that can readily react with the dimer of RuCl2(p-cymene) to create a macromolecular RAPTA-C drug. RAPTA-C conjugation, micellization, and subsequent cytotoxicity and cell uptake of these polymeric moieties was tested on ovarian cancer A2780, A2780cis, and Ovcar-3 cell lines. Confocal microscopy images confirmed cell uptake of the micelles into the lysosome of the cells, indicative of an endocytic pathway. On average, a 10-fold increase in toxicity was found for the macromolecular drugs when compared to the RAPTA-C molecule. Furthermore, the cell uptake of ruthenium was analyzed and a significant increase was found for the micelles compared to RAPTA-C. Notably, micelles prepared from the polymer containing fewer HEA units had the highest cytotoxicity, the best cell uptake of ruthenium and were highly effective in suppressing the colony-forming ability of cells.

  8. Self-assembled nanoparticles of glycol chitosan – Ergocalciferol succinate conjugate, for controlled release

    Quinones, Javier Perez; Gothelf, Kurt Vesterager; Kjems, Jørgen


    Glycol chitosan was linked to vitamin D2 hemisuccinate (ergocalciferol hemisuccinate) for controlled release through water-soluble carbodiimide activation. The resulting conjugate formed self-assembled nanoparticles in aqueous solution with particle size of 279 nm and ergocalciferol hemisuccinate...

  9. Cross-Linked Dependency of Boronic Acid-Conjugated Chitosan Nanoparticles by Diols for Sustained Insulin Release

    Nabil A. Siddiqui


    Full Text Available Boronic acids have been widely investigated for their potential use as glucose sensors in glucose responsive polymeric insulin delivery systems. Interactions between cyclic diols and boronic acids, anchored to polymeric delivery systems, may result in swelling of the delivery system, releasing the drug. In this study, 4-formylphenylboronic acid conjugated chitosan was formulated into insulin containing nanoparticles via polyelectrolyte complexation. The nanoparticles had an average diameter of 140 ± 12.8 nm, polydispersity index of 0.17 ± 0.1, zeta potential of +19.1 ± 0.69 mV, encapsulation efficiency of 81% ± 1.2%, and an insulin loading capacity of 46% ± 1.8% w/w. Changes in size of the nanoparticles and release of insulin were type of sugar- and concentration-dependent. High concentration of diols resulted in a sustained release of insulin due to crosslink formation with boronic acid moieties within the nanoparticles. The formulation has potential to be developed into a self-regulated insulin delivery system for the treatment of diabetes.

  10. Safety and Efficacy of Dextran-Rosmarinic Acid Conjugates as Innovative Polymeric Antioxidants in Skin Whitening: What Is the Evidence?

    Ortensia I. Parisi


    Full Text Available Background: Melanins are high molecular weight pigments responsible for the mammalian skin and hair colour and play a key role in skin protection from UV radiation; however, their overproduction and excessive accumulation lead to pigmentation problems including melasma, freckles, uneven colouring, and age spots. Therefore, the modulation of melanin synthesis represents a critical issue in medicine and cosmetology. In the present study, an innovative polymeric antioxidant to be used as skin whitening agent is developed by the conjugation of dextran with rosmarinic acid. Methods: Dextran-rosmarinic acid conjugates (DEX-RA were synthesized in a one-pot method starting from Origanum vulgare aqueous leaf extract and dextran. The total polyphenol content and the antioxidant activity were assessed by Folin-Ciocalteau assay and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH and bleaching tests, respectively. The efficacy of DEX-RA was evaluated by inhibition of tyrosinase activity, in vitro diffusion and stability studies and in vivo studies. The biocompatibility of the conjugates was investigated by 3-[4,5-Dimethylthiaoly]-2,5-diphenyltetrazoliumbromide (MTT and EPISKIN™ model. Results: Efficacy and safety studies confirmed the antioxidant and tyrosinase inhibitory activities and the biocompatibility of the synthesized conjugates. Conclusion: The polymeric conjugates, comparing to the free antioxidant, show a long-lasting efficacy combined to an enhanced stability resulting in an improved performance of the cosmetic formulations prepared using this innovative whitening agent as a bioactive ingredient.


    谭文长; 吴望一; 严宗毅; 温功碧


    An approximate analytical solution of moving boundary problem for diffusion release of drug from a cylinder polymeric matrix was obtained by use of refined integral method. The release kinetics has been analyzed for non-erodible matrices with perfect sink condition. The formulas of the moving boundary and the fractional drug release were given.The moving boundary and the fractional drug release have been calculated at various drug loading levels, and the calculated results were in good agreement with those of experiments.The comparison of the moving boundary in spherical, cylinder, planar matrices has been completed. An approximate formula for estimating the available release time was presented.These results are useful for the clinic experiments. This investigation provides a new theoretical tool for studying the diffusion release of drug from a cylinder polymeric matrix and designing the controlled released drug.

  12. Protein-Nanocrystal Conjugates Support a Single Filament Polymerization Model in R1 Plasmid Segregation

    Choi, Charina L.; Claridge, Shelley A.; Garner, Ethan C.; Alivisatos, A. Paul; Mullins, R. Dyche


    To ensure inheritance by daughter cells, many low-copy number bacterial plasmids, including the R1 drug-resistance plasmid, encode their own DNA segregation systems. The par operon of plasmid R1 directs construction of a simple spindle structure that converts free energy of polymerization of an actin-like protein, ParM, into work required to move sister plasmids to opposite poles of rod-shaped cells. The structures of individual components have been solved, but little is known about the ultrastructure of the R1 spindle. To determine the number of ParM filaments in a minimal R1 spindle, we used DNA-gold nanocrystal conjugates as mimics of the R1 plasmid. Wefound that each end of a single polar ParM filament binds to a single ParR/parC-gold complex, consistent with the idea that ParM filaments bind in the hollow core of the ParR/parC ring complex. Our results further suggest that multifilament spindles observed in vivo are associated with clusters of plasmidssegregating as a unit.


    Mariana A. Melaj


    Full Text Available The main purpose of this work was to optimize the preparation conditions of solid polymeric matrix based on Chitosan and Xanthan, to be used in the controlled release of fertilizers. KNO3 was chosen as model agrochemical to be released. Both individual polymers and the Xanthan:Chitosan complex are biocompatible, leaving a residue on the soil which is non-toxic. The influence of different variables on the release pattern was studied: the type of polymer, the pressed conditions of the tablets and the presence of a drug-free polymeric coating. The polymer that presented a more promising release profile was Xanthan. The compression pressure applied to prepare the tablets was a more relevant variable than the compression time, in its effect on the kinetics of release. It was determined that the coating of the polymer matrix with crosslinked chitosan-glutaraldehyde allows getting a larger release time.

  14. Immobilization and controlled release of drug using plasma polymerized thin film

    Myung, Sung-Woon [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju (Korea, Republic of); Jung, Sang-Chul [Department of Environmental Engineering, Sunchon National University, Sunchon 540-742 (Korea, Republic of); Kim, Byung-Hoon, E-mail: [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju (Korea, Republic of)


    In this study, plasma polymerization of acrylic acid was employed to immobilize drug and control its release. Doxorubicin (DOX) was immobilized covalently on the glass surface deposited with plasma polymerized acrylic acid (PPAAc) thin film containing the carboxylic group. At first, the PPAAc thin film was coated on a glass surface at a pressure of 1.33 Pa and radio frequency (RF) discharge power of 20 W for 10 min. DOX was immobilized on the PPAAc deposition in a two environment of phosphate buffer saline (PBS) and dimethyl sulfoxide (DMSO) solutions. The DOX immobilized surface was characterized by scanning electron microscope, atomic force microscope and attenuated total reflection Fourier transform infrared spectroscopy. The DOX molecules were more immobilized in PBS than DMSO solution. The different immobilization and release profiles of DOX result from the solubility of hydrophobic DOX in aqueous and organic solutions. Second, in order to control the release of the drug, PPAAc thin film was covered over DOX dispersed layer. Different thicknesses and cross-linked PPAAc thin films by adjusting deposition time and RF discharge power were covered on the DOX layer dispersed. PPAAc thin film coated DOX layer reduced the release rate of DOX. The thickness control of plasma deposition allows controlling the release rate of drug. - Highlights: • Doxorubicin was immobilized on the surface of plasma polymerized acrylic acid thin film. • Release profile of doxorubicin was affected by aqueous and organic solutions. • Plasma polymerized acrylic acid thin film can be used to achieve controlled release.

  15. Controlled-release NPK fertilizer encapsulated by polymeric membranes.

    Jarosiewicz, Anna; Tomaszewska, Maria


    The commercial granular fertilizer NPK6-20-30 was coated using polysulfone (PSF), polyacrylonitrile (PAN), and cellulose acetate (CA). The coatings were formed from the polymer solutions by the phase inversion technique. Measurements of the thickness and porosity of the prepared coatings and a microphotographic observation of the coatings were performed. The physical properties of the coatings influence the release rate of macronutrients which are present in the core of the coated fertilizer. In the case of PAN coating with 60.45% porosity, prepared from a 16% polymer solution, 100% of NH(4)(+) and P(2)O(5) was released after 4 h of test and 99.7% of K(+) after 5 h of test, whereas in the case of coating with 48.8% porosity, 31.8% of NH(4)(+), 16.7% of P(2)O(5), and 11.6% of K(+) was released after 5 h. In all experiments, different selectivities of the coatings in terms of the release of components were observed. The release of potassium through the coatings made of PSF and PAN was the slowest. The same tendency was observed for the release of nitrogen through a coating of CA. The release of fertilizer active components was the slowest in the case of PSF. The lowest porosity coating was prepared from the 18% PSF solution.

  16. Chain propagation and termination mechanisms for polymerization of conjugated polar alkenes by [Al]-based frustrated Lewis pairs

    He, Jianghua


    A combined experimental and theoretical study on mechanistic aspects of polymerization of conjugated polar alkenes by frustrated Lewis pairs (FLPs) based on N-heterocyclic carbene (NHC) and Al(C6F5)3 pairs is reported. This study consists of three key parts: structural characterization of active propagating intermediates, propagation kinetics, and chain-termination pathways. Zwitterionic intermediates that simulate the active propagating species in such polymerization have been generated or isolated from the FLP activation of monomers such as 2-vinylpyridine and 2-isopropenyl-2-oxazoline-one of which, IMes+-CH2C(Me)=(C3H2NO)Al(C6F5)3 - (2), has been structurally characterized. Kinetics performed on the polymerization of 2-vinylpyridine by ItBu/Al(C6F5)3 revealed that the polymerization follows a zero-order dependence on monomer concentration and a first-order dependence on initiator (ItBu) and activator [Al(C6F5)3] concentrations, indicating a bimolecular, activated monomer propagation mechanism. The Lewis pair polymerization of conjugate polar alkenes such as methacrylates is accompanied by competing chain-termination side reactions; between the two possible chain-termination pathways, the one that proceeds via intramolecular backbiting cyclization involving nucleophilic attack of the activated ester group of the growing polymer chain by the O-ester enolate active chain end to generate a six-membered lactone (δ-valerolactone)-terminated polymer chain is kinetically favored, but thermodynamically disfavored, over the pathway leading to the -ketoester-terminated chain, as revealed by computational studies.

  17. Synthesis, characterization and the release kinetics of antiproliferative agents from polyamidoamine conjugates.

    Aderibigbe, B A; Sadiku, E R; Ray, S S; Mbianda, X Y; Fotsing, M C; Jayaramudu, J; Owonubi, S J


    Polyamidoamine conjugates containing curcumin and bisphosphonate were synthesized via a one-pot aqueous phase Michael addition reaction. In the design of the conjugate, bisphosphonate formed an integral part of the polymer carrier backbone. Curcumin was incorporated onto the polyamidoamine backbone via piperazine linker. The conjugates were characterized by Fourier transform spectroscopy, energy-dispersive X-ray analysis, atomic force spectroscopy and nuclear magnetic resonance spectroscopy and it confirmed the successful incorporation of the antiproliferative agents onto the carriers. The weight percentage incorporation of bisphosphonate to the carriers was found to be between 2.56% and 3.34%. The in vitro release studies of curcumin from the polyamidoamine conjugate were performed in dialysis bag at selected pH values. The release of curcumin was significantly slower at pH 7.4 when compared to pH 5.8. The release profiles indicate that the conjugates are more stable at pH 7.4 and are potential sustained drug-delivery systems for combination therapy.

  18. Nitrogen-containing microporous conjugated polymers via carbazole-based oxidative coupling polymerization: preparation, porosity, and gas uptake.

    Chen, Qi; Liu, De-Peng; Luo, Min; Feng, Li-Juan; Zhao, Yan-Chao; Han, Bao-Hang


    Facile preparation of microporous conjugated polycarbazoles via carbazole-based oxidative coupling polymerization is reported. The process to form the polymer network has cost-effective advantages such as using a cheap catalyst, mild reaction conditions, and requiring a single monomer. Because no other functional groups such as halo groups, boric acid, and alkyne are required for coupling polymerization, properties derived from monomers are likely to be fully retained and structures of final polymers are easier to characterize. A series of microporous conjugated polycarbazoles (CPOP-2-7) with permanent porosity are synthesized using versatile carbazolyl-bearing 2D and 3D conjugated core structures with non-planar rigid conformation as building units. The Brunauer-Emmett-Teller specific surface area values for these porous materials vary between 510 and 1430 m(2) g(-1) . The dominant pore sizes of the polymers based on the different building blocks are located between 0.59 and 0.66 nm. Gas (H2 and CO2 ) adsorption isotherms show that CPOP-7 exhibits the best uptake capacity for hydrogen (1.51 wt% at 1.0 bar and 77 K) and carbon dioxide (13.2 wt% at 1.0 bar and 273 K) among the obtained polymers. Furthermore, its high CH4 /N2 and CO2 /N2 adsorption selectivity gives polymer CPOP-7 potential application in gas separation.

  19. Acyclic Diene Metathesis (ADMET Polymerization for Precise Synthesis of Defect-Free Conjugated Polymers with Well-Defined Chain Ends

    Tahmina Haque


    Full Text Available This accounts introduces unique characteristics by adopting the acyclic diene metathesis (ADMET polymerization for synthesis of conjugated polymers, poly(arylene vinylenes, known as promising molecular electronics. The method is more suitable than the other methods in terms of atom efficiency affording defect-free, stereo-regular (exclusive trans polymers with well-defined chain ends; the resultant polymers possess better property than those prepared by the conventional methods. The chain ends (vinyl group in the resultant polymer prepared by ruthenium-carbene catalyst(s can be modified by treating with molybdenum-alkylidene complex (olefin metathesis followed by addition of various aldehyde (Wittig type cleavage, affording the end-functionalized polymers exclusively. An introduction of initiating fragment, the other conjugated segment, and one-pot synthesis of end-functionalized block copolymers, star shape polymers can be achieved by adopting this methodology.

  20. Modulation of release kinetics by plasma polymerization of ampicillin-loaded β-TCP ceramics

    Labay, C.; Buxadera-Palomero, J.; Avilés, M.; Canal, C.; Ginebra, M. P.


    Beta-tricalcium phosphate (β-TCP) bioceramics are employed in bone repair surgery. Their local implantation in bone defects puts them in the limelight as potential materials for local drug delivery. However, obtaining suitable release patterns fitting the required therapeutics is a challenge. Here, plasma polymerization of ampicillin-loaded β-TCP is studied for the design of a novel antibiotic delivery system. Polyethylene glycol-like (PEG-like) coating of β-TCP by low pressure plasma polymerization was performed using diglyme as precursor, and nanometric PEG-like layers were obtained by simple and double plasma polymerization processes. A significant increase in hydrophobicity, and the presence of plasma polymer was visible on the surface by SEM and quantified by XPS. As a main consequence of the plasma polymerisation, the release kinetics were successfully modified, avoiding burst release, and slowing down the initial rate of release leading to a 4.5 h delay in reaching the same antibiotic release percentage, whilst conservation of the activity of the antibiotic was simultaneously maintained. Thus, plasma polymerisation on the surface of bioceramics may be a good strategy to design controlled drug delivery matrices for local bone therapies.

  1. Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study

    Tan, Donna [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Zhao Bin [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore)]. E-mail:; Yang Yiyan [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, 04-01, The Nanos, Singapore 138669 (Singapore)


    Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2-3 h of alertness coupled with side effects whereas a longer effect of 8-12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved.

  2. Glutathione-garlic sulfur conjugates: slow hydrogen sulfide releasing agents for therapeutic applications.

    Bhuiyan, Ashif Iqbal; Papajani, Vilma Toska; Paci, Maurizio; Melino, Sonia


    Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the proliferation of tumor cells. In the present study, we optimized a new protocol for the extraction of water-soluble compounds from garlic at low temperatures and the production of glutathionyl-OSC conjugates during the extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in vivo metabolism of OSCs and represent active molecules able to affect cellular metabolism. Water-soluble extracts, with (GSGaWS) or without (GaWS) glutathione conjugates, were here produced and tested for their ability to release hydrogen sulfide (H2S), also in the presence of reductants and of thiosulfate:cyanide sulfurtransferase (TST) enzyme. Thus, the TST catalysis of the H2S-release from garlic OSCs and their conjugates has been investigated by molecular in vitro experiments. The antiproliferative properties of these extracts on the human T-cell lymphoma cell line, HuT 78, were observed and related to histone hyperacetylation and downregulation of GAPDH expression. Altogether, the results presented here pave the way for the production of a GSGaWS as new, slowly-releasing hydrogen sulfide extract for potential therapeutic applications.

  3. Glutathione-Garlic Sulfur Conjugates: Slow Hydrogen Sulfide Releasing Agents for Therapeutic Applications

    Ashif Iqbal Bhuiyan


    Full Text Available Natural organosulfur compounds (OSCs from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the proliferation of tumor cells. In the present study, we optimized a new protocol for the extraction of water-soluble compounds from garlic at low temperatures and the production of glutathionyl-OSC conjugates during the extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in vivo metabolism of OSCs and represent active molecules able to affect cellular metabolism. Water-soluble extracts, with (GSGaWS or without (GaWS glutathione conjugates, were here produced and tested for their ability to release hydrogen sulfide (H2S, also in the presence of reductants and of thiosulfate:cyanide sulfurtransferase (TST enzyme. Thus, the TST catalysis of the H2S-release from garlic OSCs and their conjugates has been investigated by molecular in vitro experiments. The antiproliferative properties of these extracts on the human T-cell lymphoma cell line, HuT 78, were observed and related to histone hyperacetylation and downregulation of GAPDH expression. Altogether, the results presented here pave the way for the production of a GSGaWS as new, slowly-releasing hydrogen sulfide extract for potential therapeutic applications.

  4. Melt-processed polymeric cellular dosage forms for immediate drug release.

    Blaesi, Aron H; Saka, Nannaji


    The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

  5. Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release

    Shao, Jingxin; Xuan, Mingjun; Si, Tieyan; Dai, Luru; He, Qiang


    Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid release of encapsulated water-soluble drug. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Real time in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demonstrates the biocompatibility and biodegradation of these biointerfacing GNR-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controlled release, biological friendliness and credible biosafety.Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid

  6. Polymeric macroporous formulations for the control release of mosquitocidal Bacillus sphaericus ISPC-8.

    Tripathi, Anuj; Hadapad, Ashok B; Hire, Ramesh S; Melo, Jose S; D'Souza, Stanislaus F


    Bio-polymeric mosquitocidal formulations were developed for the control release of Bacillus sphaericus ISPC-8 by the immobilization of its spore-crystal complex onto the macroporous polymeric matrices. The biodegradable formulations were synthesized at sub-zero temperature using natural polymeric substrates like agarose, alginate, cellulose, non-adsorbent cotton, wooden cork powder and also magnetite nanoparticles. The obtained polymeric matrices were morphologically characterized, which showed 85-90% porosity, uniform pores distribution, high permeability and controlled degradation (19-30%) in 4 weeks depending upon the composition of formulations. Further, the polymeric macroporous formulations were tested for persistence of mosquitocidal activity against Culex quinquefasciatus larvae. Unformulated B. sphaericus ISPC-8 spores retained 54% of larvicidal activity after 7 days, which completely reduced after 35 days of treatment. However, the immobilized B. sphaericus spores in agarose-alginate formulations showed high larvicidal activity on day 7 and retained about 45% activity even after 35 days of treatments. Studies on UV-B and pH dependent inactivation of toxins and spore viability showed that these formulations were significantly protecting the spores as compared to the unformulated spores, which suggest its potential application for the mosquito control program.

  7. Recent Developments in the Synthesis of Biomacromolecules and their Conjugates by Single Electron Transfer-Living Radical Polymerization.

    Lligadas, Gerard; Grama, Silvia; Percec, Virgil


    Single electron transfer-living radical polymerization (SET-LRP) represents a robust and versatile tool for the synthesis of vinyl polymers with well-defined topology and chain end functionality. The crucial step in SET-LRP is the disproportionation of the Cu(I)X generated by activation with Cu(0) wire, powder, or nascent Cu(0) generated in situ into nascent, extremely reactive Cu(0) atoms and nanoparticles and Cu(II)X2. Nascent Cu(0) activates the initiator and dormant chains via a homogeneous or heterogeneous outer-sphere single-electron transfer mechanism (SET-LRP). SET-LRP provides an ultrafast polymerization of a plethora of monomers (e.g., (meth)-acrylates, (meth)-acrylamides, styrene, and vinyl chloride) including hydrophobic and water insoluble to hydrophilic and water soluble. Some advantageous features of SET-LRP are (i) the use of Cu(0) wire or powder as readily available catalysts under mild reaction conditions, (ii) their excellent control over molecular weight evolution and distribution as well as polymer chain ends, (iii) their high functional group tolerance allowing the polymerization of commercial-grade monomers, and (iv) the limited purification required for the resulting polymers. In this Perspective, we highlight the recent advancements of SET-LRP in the synthesis of biomacromolecules and of their conjugates.

  8. In vitro Fluoride Release and Tensile Bond Strength of a Polymeric Intra-Buccal Bioadhesive

    Vinicius PEDRAZZI; LARA, Elza Helena Guimaraes; PANZERI, Heitor; John H Collett; ISSA, Joao Paulo Mardegan


    The intra-buccal polymeric bioadhesive systems that can stay adhered to the oral soft tissues for drug programmed release, with the preventive and/or therapeutic purpose has been employed for large clinical situations. A system based on hydroxypropyl methyl cellulose/Carbopol 934`/magnesium stearate (HPMC/Cp/StMg) was developed having the sodium fluoride as active principle. This kind of system was evaluated according to its resistance to the removal by means of physical test of tensile stren...

  9. Cellulose conjugated FITC-labelled mesoporous silica nanoparticles: intracellular accumulation and stimuli responsive doxorubicin release

    Hakeem, Abdul; Zahid, Fouzia; Duan, Ruixue; Asif, Muhammad; Zhang, Tianchi; Zhang, Zhenyu; Cheng, Yong; Lou, Xiaoding; Xia, Fan


    Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS-MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay.Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS-MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08753h

  10. Preparation of acetylsalicylic acid-acylated chitosan as a novel polymeric drug for drug controlled release.

    Liu, Changkun; Wu, Yiguang; Zhao, Liyan; Huang, Xinzheng


    The acetylsalicylic acid-acylated chitosan (ASACTS) with high degree of substitution (DS) was successfully synthesized, and characterized with FTIR, (1)H NMR and elemental analysis methods. The optimum synthesis conditions were obtained which gave the highest DS (about 60%) for ASACTS. Its drug release experiments were carried out in simulated gastric and intestine fluids. The results show that the drugs in the form of acetylsalicylic acid (ASA) and salicylic acid (SA) were released in a controlled manner from ASACTS only in simulated gastric fluid. The release profile can be best fitted with logistic and Weibull model. The research results reveal that ASACTS can be a potential polymeric drug for the controlled release of ASA and SA in the targeted gastric environment.

  11. The Release Behavior and Kinetic Evaluation of Tramadol HCl from Chemically Cross Linked Ter Polymeric Hydrogels

    Muhammad A Malana


    Full Text Available Background and the purpose of the study: Hydrogels, being stimuli responsive are considered to be effective for targeted and sustained drug delivery. The main purpose for this work was to study the release behavior and kinetic evaluation of Tramadol HCl from chemically cross linked ter polymeric hydrogels.MethodsTer-polymers of methacrylate, vinyl acetate and acrylic acid cross linked with ethylene glycol dimethacrylate (EGDMA were prepared by free radical polymerization. The drug release rates, dynamic swelling behavior and pH sensitivity of hydrogels ranging in composition from 1-10 mol % EGDMA were studied. Tramadol HCl was used as model drug substance. The release behavior was investigated at pH 8 where all formulations exhibited non-Fickian diffusion mechanism.Results and major conclusion: Absorbency was found to be more than 99% indicating good drug loading capability of these hydrogels towards the selected drug substance. Formulations designed with increasing amounts of EGDMA had a decreased equilibrium media content as well as media penetrating velocity and thus exhibited a slower drug release rate. Fitting of release data to different kinetic models indicate that the kinetic order shifts from the first to zero order as the concentration of drug was increased in the medium, showing gradual independency of drug release towards its concentration. Formulations with low drug content showed best fitness with Higuchi model whereas those with higher concentration of drug followed Hixson-Crowell model with better correlation values indicating that the drug release from these formulations depends more on change in surface area and diameter of tablets than that on concentration of the drug. Release exponent (n derived from Korse-Meyer Peppas equation implied that the release of Tramadol HCl from these formulations was generally non-Fickian (n>0.5>1 showing swelling controlled mechanism. The mechanical strength and controlled release capability of

  12. The release behavior and kinetic evaluation of tramadol HCl from chemically cross linked Ter polymeric hydrogels

    Malana Muhammad A


    Full Text Available Abstract Background and the purpose of the study Hydrogels, being stimuli responsive are considered to be effective for targeted and sustained drug delivery. The main purpose for this work was to study the release behavior and kinetic evaluation of Tramadol HCl from chemically cross linked ter polymeric hydrogels. Methods Ter-polymers of methacrylate, vinyl acetate and acrylic acid cross linked with ethylene glycol dimethacrylate (EGDMA were prepared by free radical polymerization. The drug release rates, dynamic swelling behavior and pH sensitivity of hydrogels ranging in composition from 1-10 mol% EGDMA were studied. Tramadol HCl was used as model drug substance. The release behavior was investigated at pH 8 where all formulations exhibited non-Fickian diffusion mechanism. Results and major conclusion Absorbency was found to be more than 99% indicating good drug loading capability of these hydrogels towards the selected drug substance. Formulations designed with increasing amounts of EGDMA had a decreased equilibrium media content as well as media penetrating velocity and thus exhibited a slower drug release rate. Fitting of release data to different kinetic models indicate that the kinetic order shifts from the first to zero order as the concentration of drug was increased in the medium, showing gradual independency of drug release towards its concentration. Formulations with low drug content showed best fitness with Higuchi model whereas those with higher concentration of drug followed Hixson-Crowell model with better correlation values indicating that the drug release from these formulations depends more on change in surface area and diameter of tablets than that on concentration of the drug. Release exponent (n derived from Korse-Meyer Peppas equation implied that the release of Tramadol HCl from these formulations was generally non-Fickian (n > 0.5 > 1 showing swelling controlled mechanism. The mechanical strength and controlled

  13. Resveratrol immobilization and release in polymeric hydrogels; Incorporacao e liberacao de resveratrol em hidrogeis polimericos

    Momesso, Roberta Grazzielli Ramos Alves Passarelli


    Resveratrol (3, 4', 5-trihydroxystilbene) is a polyphenolic produced by a wide variety of plants in response to injury and found predominantly in grape skins. This active ingredient has been shown to possess benefits for the health, such as the antioxidant capacity which is related to the prevention of several types of cancer and skin aging. However, the oral bioavailability of resveratrol is poor and makes its topical application interesting. The purpose of this study was to immobilize resveratrol in polymeric hydrogels to obtain a release device for topical use. The polymeric matrices composed of poli(N-vinyl-2-pyrrolidone) (PVP), poly(ethyleneglycol) (PEG) and agar or PVP and glycerol irradiated at 20 kGy dose were physical-chemically characterized by gel fraction and swelling tests and its preliminary biocompatibility by in vitro test of cytotoxicity using the technique of neutral red uptake. Due to low solubility of resveratrol in water, the addition of 2% ethanol to the matrices was verified. All matrices showed a high crosslinking degree, capacity of swelling and the preliminary cytotoxicity test showed nontoxicity effect. The devices were obtained by resveratrol immobilization in polymeric matrices, carried out in a one-or-two-steps process, that is, before or after irradiation, respectively. The one step resveratrol devices were characterized by gel fraction, swelling tests and preliminary biocompatibility, and their properties were maintained even after the resveratrol incorporation. The devices containing 0,05% of resveratrol obtained by one-step process and 0,1% of resveratrol obtained by two-steps process were submitted to the release test during 24 h. Resveratrol quantification was done by high performance liquid chromatography (HPLC). The results obtained in the kinetics of release showed that only the devices obtained by two-step process release the resveratrol, which demonstrate antioxidant capacity after the release. (author)

  14. Effect of various penetration enhancers concentrations on diclafenac sodium release from cellulose acetate phthalate polymeric film

    El-Nahas Hanan


    Full Text Available An investigation was conducted to evaluate the influence of different penetration enhancers in various concentrations on the release of diclofenac sodium (DFS as a water-soluble drug from Cellulose acetate phthalate polymeric films containing 50% w/w PEG 600 as plasticizer, to choose the most appropriate enhancer and its optimum concentration to be used to achieve the maximum release and permeation of the drug. The addition of various enhancers, as isopropylmyristate (IPM; 0.2_5% w/w, oleic acid (OA; 0.2_5% w/w and linoleic acid (LOA; 0.2_5% w/w, Tween 80 (T80;1_10% w/w and transcutol, (TC; 1_10% w/w enhanced the DFS release from the polymeric films. The enhancement ratio of the penetration enhancers used in the formulation of DFS were found to increase in the order of IPM>LOA>OA>T80>TC. (56.2, 54.1, 50, 48.7 and 48%, respectively. In vitro permeation studies were performed using rabbit abdominal skin as the permeating membrane. The results indicated that maximum permeation was obtained at 24hrs (0.5% IPM, 0.2% LOA, 1% OA, 0.5% T80 and 10% TC, increased skin permeation of DFS by 4.46, 4.06, 3.37, 1.65 and 1.49 time, respectively. IPM was found to be the most efficient enhancer. The results obtained from ANOVA test indicate that the difference in drug permeation rates is highly significant compared to the control formulation (P<0.05. The mechanism of drug release from the polymeric films obey Higuchi′s model.

  15. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna


    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  16. Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin

    Liu CW


    Full Text Available Chia Wen Liu,1,2 Wen Jen Lin11Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei; 2Drug Delivery Department, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, TaiwanBackground: This study was performed to develop a functional poly(D,L-lactide-co-glycolide-poly(ethylene glycol (PLGA-PEG-bearing amino-active end group for peptide conjugation.Methods and results: PLGA was preactivated following by copolymerization with PEG diamine. The resulting amphiphilic PLGA-PEG copolymer bearing 97.0% of amino end groups had a critical micelle concentration of 3.0 × 10-8 mol/L, and the half-effective inhibition concentration (IC50 of the prepared PLGA-PEG nanoparticles was >100 mg/mL, which was much higher than that of PLGA nanoparticles (1.02 ± 0.37 mg/mL. The amphiphilic properties of PLGA-PEG spontaneously formed a core-shell conformation in the aqueous environment, and this special feature provided the amino group on the PEG chain scattered on the surface of PLGA-PEG nanoparticles for efficient peptide conjugation. The peptide-conjugated PLGA-PEG nanoparticles showed three-fold higher uptake than peptide-free PLGA-PEG nanoparticles in a SKOV3 cell line with high expression of epidermal growth factor receptor. Both peptide-conjugated and peptide-free PLGA-PEG nanoparticles were used as nanocarriers for delivery of doxorubicin. Although the rate of release of doxorubicin from both nanoparticles was similar, drug release at pH 4.0 (500 U lipase was faster than at pH 7.4. The IC50 of doxorubicin-loaded peptide-conjugated PLGA-PEG nanoparticles in SKOV3 cells (0.05 ± 0.03 µg/mL was much lower (by 62.4-fold than that of peptide-free PLGA-PEG nanoparticles (3.12 ± 1.44 µg/mL.Conclusion: This in vivo biodistribution study in SKOV3 tumor-bearing mice was further promising in that accumulation of doxorubicin in tumor tissue was in the order of peptide-conjugated

  17. Synthesis, Chemosensory Properties, and Self-Assembly of Terpyridine-Containing Conjugated Polycarbazole through RAFT Polymerization and Heck Coupling Reaction

    Po-Chih Yang


    Full Text Available We report the responsive fluorescence chemosensory phenomena of a carbazole-functionalized crosslinked polymer (PCaT with pendent terpyridine (tpy groups as receptors of metal ions. The polymer was synthesized using Heck polymerization between 3,6-dibromide groups in a carbazole-based polymer (PC2Br and divinyl tpy monomer. The effects of the polymeric structure on the optical and chemosensory properties of the PCaT were compared with those of a carbazole-tpy alternating conjugated polymer (PCT. Photoluminescence titrations demonstrated that the PCaT and PCT had the high sensing ability toward Fe3+ ions, with Stern–Volmer constants of 8.10 × 104 and 6.68 × 104 M−1, respectively. The limit of detection (LOD toward Fe3+ of the PCaT and PCT was estimated to be 1.31 × 10−6 and 1.81 × 10−6 M, respectively, and the superior LOD of the PCaT was ascribed to its lowly crosslinked structure. The fluorescence of the solutions of these polymers that were quenched by Fe3+ ions recovered when trace CN− anions were added because of the high stability constant of the CN−–Fe3+ complex. Micellar aggregates with a mean diameter of approximately 239.5 nm were formed by dissolving the PCaT in tetrahydrofuran (THF solution. Our results suggest that the PCaT is a promising material for chemosensory applications.

  18. Reduction-sensitive liposomes from a multifunctional lipid conjugate and natural phospholipids: reduction and release kinetics and cellular uptake.

    Goldenbogen, Björn; Brodersen, Nicolai; Gramatica, Andrea; Loew, Martin; Liebscher, Jürgen; Herrmann, Andreas; Egger, Holger; Budde, Bastian; Arbuzova, Anna


    The development of targeted and triggerable delivery systems is of high relevance for anticancer therapies. We report here on reduction-sensitive liposomes composed of a novel multifunctional lipidlike conjugate, containing a disulfide bond and a biotin moiety, and natural phospholipids. The incorporation of the disulfide conjugate into vesicles and the kinetics of their reduction were studied using dansyl-labeled conjugate 1 in using the dansyl fluorescence environmental sensitivity and the Förster resonance energy transfer from dansyl to rhodamine-labeled phospholipids. Cleavage of the disulfide bridge (e.g., by tris(2-carboxyethyl)phosphine (TCEP), dithiothreitol (DTT), l-cysteine, or glutathione (GSH)) removed the hydrophilic headgroup of the conjugate and thus changed the membrane organization leading to the release of entrapped molecules. Upon nonspecific uptake of vesicles by macrophages, calcein release from reduction-sensitive liposomes consisting of the disulfide conjugate and phospholipids was more efficient than from reduction-insensitive liposomes composed only of phospholipids. The binding of streptavidin to the conjugates did not interfere with either the subsequent reduction of the disulfide bond of the conjugate or the release of entrapped molecules. Breast cancer cell line BT-474, overexpressing the HER2 receptor, showed a high uptake of the reduction-sensitive doxorubicin-loaded liposomes functionalized with the biotin-tagged anti-HER2 antibody. The release of the entrapped cargo inside the cells was observed, implying the potential of using our system for active targeting and delivery. © 2011 American Chemical Society

  19. Design and synthesis of pyrazole-oxindole conjugates targeting tubulin polymerization as new anticancer agents.

    Kamal, Ahmed; Shaik, Anver Basha; Jain, Nishant; Kishor, Chandan; Nagabhushana, Ananthamurthy; Supriya, Bhukya; Bharath Kumar, G; Chourasiya, Sumit S; Suresh, Yerramsetty; Mishra, Rakesh K; Addlagatta, Anthony


    A series of twenty one compounds with pyrazole and oxindole conjugates were synthesized by Knoevenagel condensation and investigated for their antiproliferative activity on different human cancer cell lines. The conjugates are comprised of a four ring scaffold; the structural isomers 12b and 12c possess chloro-substitution in the D ring. Among the congeners 12b, 12c, and 12d manifested significant cytotoxicity and inhibited tubulin assembly. Treatments with 12b, 12c and 12d resulted in accumulation of cells in G2/M phase, disruption of microtubule network, and increase in cyclin B1 protein. Zebrafish screening revealed that 12b, and 12d caused developmental defects. Docking analysis demonstrated that the congeners occupy the colchicine binding pocket of tubulin.

  20. Assessment of Palmitoyl and Sulphate Conjugated Glycol Chitosan for Development of Polymeric Micelles

    Ikram Ullah Khan


    Full Text Available Introduction: Amphiphilic copolymers are capable of forming core shell-like structures at the critical micellar concentration (CMC; hence, they can serve as drug carriers. Thus, in the present work, polymeric micelles based on novel chitosan derivative were synthesized. Methods: Block copolymer of palmitoyl glycol chitosan sulfate (PGCS was prepared by grafting palmitoyl and sulfate groups serving as hydrophobic and hydrophilic fractions, respectively. Then, fourier transform infrared spectra (FTIR and spectral changes in iodine/iodide mixture were carried out. Results: FTIR studies confirmed the formation of palmitoyl glycol chitosan sulfate (PGCS and spectral changes in iodine/iodide mixture indicated CMC which lies in the range of 0.003-0.2 mg/ml. Conclusion: Therefore, our study indicated that polymeric micelles based on palmitoyl glycol chitosan sulphate could be used as a prospective carrier for water insoluble drugs.

  1. CoCl2 reinforced polymeric nanocomposites of conjugated polymer (polyaniline) and its conductive properties

    M Majhi; R B Choudhary; P Maji


    Polyaniline (PANI) was synthesized by chemical oxidative polymerization of aniline using ammonium persulphate as an oxidant in acidic aqueous medium. Cobalt chloride hexahydrate (CoCl2⋅6H2O)-doped PANI composite was synthesized by in-situ oxidative polymerization process by using various concentrations of CoCl2. Its chemical, structural and morphological properties were examined by X-ray diffraction, energydispersive X-ray spectroscopy, Fourier transform infrared spectroscopy and field-emission scanning electron microscopy techniques. These results confirmed the successful formation of PANI and CoCl2-doped PANI nanocomposites. The morphology of CoCl2-doped PANI nanocomposite was found to be spherical in nature. The dielectric properties were examined using LCR-HITESTER in the frequency range 50 Hz–5 MHz. The optical properties were examined by UV–visible spectroscopic techniques in the wavelength range of 200–800 nm. The high dielectric properties and alternating current conductivity of the composite was studied in the temperature range 313–373 K. It was found that the synthesized polymeric nanocomposite owned fairly suitable dielectric and optical properties for its application in actuators, conductive paints and for many other purposes.

  2. Influence of hydrophobe on the release behavior of vinyl acetate miniemulsion polymerization.

    Park, Soo-Jin; Kim, Ki-Seok


    Poly(vinyl acetate) (PVAc) nanoparticles containing antibiotic have been prepared by miniemulsion polymerization. To compare the effect of hydrophobe types, hexadecane and poly(vinyl acetate) were used as hydrophobe. The particle characteristics as the manufacturing condition were examined by particle size analyzer. As a result, the diameter of PVAc latexes was adjusted between 80 and 260 nm by homogenization conditions and amounts of surfactant. Also, the miniemulsion by using hexadecane showed the more long shelf stability and led to the more small particle size after polymerization, as compared with the case of using poly(vinyl acetate). This indicated that the use of poly(vinyl acetate) as a hydrophobe could not make the stable emulsion, but it could avoid volatile organic chemical problems in the final product. From the release profile of drug through UV spectra, the drug release was very slow and it could be seen that the release of drug encapsulated with PVAc was occurred with the polymer degradation.

  3. Evaluation of the effects of methotrexate released from polymeric implants in solid Ehrlich tumor.

    de Fátima Pereira, Adriana; Mara da Costa, Vivian; Cristina Magalhães Santos, Millene; Maciel de A Ribeiro, Rosy Iara; Gabriela Silva, Ana; Carmo Horta Pinto, Flávia; Vieira Teixeira Vidigal, Paula; Rodrigues Da Silva, Gisele


    In this study, the effects of the controlled and sustained release of methotrexate from poly(ɛ-caprolactone) implants were evaluated in the solid Ehrlich tumor. The drug locally leached from the implantable devices was capable of reducing the tumor growth and the necrotic areas of the tumor site. Furthermore, the methotrexate exerted its anti-tumor effect probably by the recruitment of neutrophils at the tumor site, which assisted in modulating the growth of the tumor. The polymeric implants containing methotrexate could be a chemotherapic alternative to treat locally solid tumors with lower systemic side effects. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Optically active conjugated polymer from solvent chirality transfer polymerization in monoterpenes.

    Kim, Hyojin; Lee, Daehoon; Lee, Seul; Suzuki, Nozomu; Fujiki, Michiya; Lee, Chang-Lyoul; Kwak, Giseop


    Disubstituted acetylene monomers [1,2-diphenylacetylenes (DPAs: DPA-pC1, DPA-mC1, DPA-pC8); 1-phenyl-2-hexylacetylene (PHA-pC1)] are tested for asymmetric polymerization in chiral monoterpenes used as solvents and compared with the corresponding monosubstituted acetylene monomer [1-phenylacetylene (PA-pC1)]. DPA-pC1 containing a trimethylsilyl group in the para-position of the phenyl ring produces an optically active polymer with a large Cotton effect, despite the absence of a stereogenic center. The polymer sample obtained by polymerization in 87% ee (-)-α-pinene shows the strongest CD signal (gCD value at 385 nm: ∼3.2 × 10⁻³). The Cotton bands of the polymers obtained in (-)- and (+)-α-pinenes show the opposite sign in the CD signals. Theoretical calculations show that only the cis-cisoid model adopts a helical conformation. A time-correlated single photon counting experiment shows that the emission of the chiral polymer originates from a virtually single excited species with a 98% component fraction. This polymer solution does not show any significant decrease in gCD value over a wide temperature range of 20 to 80 °C. No noticeable decrease in the gCD value is detected when the polymer solution is kept at relatively low temperatures for a prolonged period (35 d). In contrast, the other polymers show no CD signal.

  5. Detection of adenosine triphosphate through polymerization-induced aggregation of actin-conjugated gold/silver nanorods

    Liao, Yu-Ju; Shiang, Yen-Chun; Chen, Li-Yi; Hsu, Chia-Lun; Huang, Chih-Ching; Chang, Huan-Tsung


    We have developed a simple and selective nanosensor for the optical detection of adenosine triphosphate (ATP) using globular actin-conjugated gold/silver nanorods (G-actin-Au/Ag NRs). By simply mixing G-actin and Au/Ag NRs (length ˜56 nm and diameter ˜12 nm), G-actin-Au/Ag NRs were prepared which were stable in physiological solutions (25 mM Tris-HCl, 150 mM NaCl, 5.0 mM KCl, 3.0 mM MgCl2 and 1.0 mM CaCl2; pH 7.4). Introduction of ATP into the G-actin-Au/Ag NR solutions in the presence of excess G-actin induced the formation of filamentous actin-conjugated Au/Ag NR aggregates through ATP-induced polymerization of G-actin. When compared to G-actin-modified spherical Au nanoparticles having a size of 13 nm or 56 nm, G-actin-Au/Ag NRs provided better sensitivity for ATP, mainly because the longitudinal surface plasmon absorbance of the Au/Ag NR has a more sensitive response to aggregation. This G-actin-Au/Ag NR probe provided high sensitivity (limit of detection 25 nM) for ATP with remarkable selectivity (>10-fold) over other adenine nucleotides (adenosine, adenosine monophosphate and adenosine diphosphate) and nucleoside triphosphates (guanosine triphosphate, cytidine triphosphate and uridine triphosphate). It also allowed the determination of ATP concentrations in plasma samples without conducting tedious sample pretreatments; the only necessary step was simple dilution. Our experimental results are in good agreement with those obtained from a commercial luciferin-luciferase bioluminescence assay. Our simple, sensitive and selective approach appears to have a practical potential for the clinical diagnosis of diseases (e.g. cystic fibrosis) associated with changes in ATP concentrations.

  6. Folate-targeted paclitaxel-conjugated polymeric micelles inhibits pulmonary metastatic hepatoma in experimental murine H22 metastasis models

    Zhang Y


    Full Text Available Yan Zhang,1 Hui Zhang,2 Wenbin Wu,2 Fuhong Zhang,3,4 Shi Liu,3 Rui Wang,3 Yingchun Sun,1 Ti Tong,1 Xiabin Jing3 1Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China; 2Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu, People's Republic of China; 3State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, People's Republic of China; 4Department of Otolaryngology, The First Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China Abstract: Hepatocellular carcinoma shows low response to most conventional chemotherapies; additionally, extrahepatic metastasis from hepatoma is considered refractory to conventional systemic chemotherapy. Target therapy is a promising strategy for advanced hepatoma; however, targeted accumulation and controlled release of therapeutic agents into the metastatic site is still a great challenge. Folic acid (FA and paclitaxel (PTX containing composite micelles (FA-M[PTX] were prepared by coassembling the FA polymer conjugate and PTX polymer conjugate. The main purpose of this study is to investigate the inhibitory efficacy of FA-M(PTX on the pulmonary metastasis of intravenously injected murine hepatoma 22 (H22 on BALB/c mice models. The lung metastatic burden of H22 were measured and tissues were analyzed by immunohistochemistry and histology (hematoxylin and eosin stain, followed by survival analysis. The results indicated that FA-M(PTX prevented pulmonary metastasis of H22, and the efficacy was stronger than pure PTX and simple PTX-conjugated micelles. In particular, the formation of lung metastasis colonies in mice was evidently inhibited, which was paralleled with the downregulated expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. Furthermore, the mice bearing pulmonary metastatic hepatoma in the FA

  7. Magnetically stimulated ciprofloxacin release from polymeric microspheres entrapping iron oxide nanoparticles

    Sirivisoot S


    Full Text Available Sirinrath Sirivisoot,1 Benjamin S Harrison2 1Biological Engineering Program, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, Bangkok, Thailand; 2Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA Abstract: To extend the external control capability of drug release, iron oxide nanoparticles (NPs encapsulated into polymeric microspheres were used as magnetic media to stimulate drug release using an alternating magnetic field. Chemically synthesized iron oxide NPs, maghemite or hematite, and the antibiotic ciprofloxacin were encapsulated together within polycaprolactone microspheres. The polycaprolactone microspheres entrapping ciprofloxacin and magnetic NPs could be triggered for immediate drug release by magnetic stimulation at a maximum value of 40%. Moreover, the microspheres were cytocompatible with fibroblasts in vitro with a cell viability percentage of more than 100% relative to a nontreated control after 24 hours of culture. Macrophage cell cultures showed no signs of increased inflammatory responses after in vitro incubation for 56 hours. Treatment of Staphylococcus aureus with the magnetic microspheres under an alternating (isolating magnetic field increased bacterial inhibition further after 2 days and 5 days in a broth inhibition assay. The findings of the present study indicate that iron oxide NPs, maghemite and hematite, can be used as media for stimulation by an external magnetic energy to activate immediate drug release. Keywords: antibacterial, maghemite, hematite, Staphylococcus aureus

  8. Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension.

    Saigal, Aparna; Ng, Wai Kiong; Tan, Reginald B H; Chan, Sui Yung


    Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million. The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective. The latter drugs act by dilating systemic and pulmonary arterial vascular beds and, with sustained long-term usage, altering pulmonary remodelling. They are administered as IV infusions or inhalation solutions. Despite their clinical effectiveness, prostanoids have short half-lives requiring frequent administration of 6-9 times daily and thus suffer from poor compliance. Controlled release inhalation delivery systems for treatment of PAH, ranging from liposomes, biodegradable nano- and microparticles, formation of co-precipitates and complexation with cyclodextrins, are explored. Arising from these formulation strategies, we developed novel polymeric microspheres for inhalation to reduce dosing frequency and improve medication compliance. These microspheres are designed with release modifiers, to reside in the lung which is the site of drug action for a longer duration so as to release the drug slowly and consistently over a prolonged period. This could lead to the development of the first commercially available controlled release inhalation product.

  9. Noninvasive fluorescence resonance energy transfer imaging of in vivo premature drug release from polymeric nanoparticles.

    Zou, Peng; Chen, Hongwei; Paholak, Hayley J; Sun, Duxin


    Understanding in vivo drug release kinetics is critical for the development of nanoparticle-based delivery systems. In this study, we developed a fluorescence resonance energy transfer (FRET) imaging approach to noninvasively monitor in vitro and in vivo cargo release from polymeric nanoparticles. The FRET donor dye (DiO or DiD) and acceptor dye (DiI or DiR) were individually encapsulated into poly(ethylene oxide)-b-polystyrene (PEO-PS) nanoparticles. When DiO (donor) nanoparticles and DiI (acceptor) nanoparticles were coincubated with cancer cells for 2 h, increased FRET signals were observed from cell membranes, suggesting rapid release of DiO and DiI to cell membranes. Similarly, increased FRET ratios were detected in nude mice after intravenous coadministration of DiD (donor) nanoparticles and DiR (acceptor) nanoparticles. In contrast, another group of nude mice i.v. administrated with DiD/DiR coloaded nanoparticles showed decreased FRET ratios. Based on the difference in FRET ratios between the two groups, in vivo DiD/DiR release half-life from PEO-PS nanoparticles was determined to be 9.2 min. In addition, it was observed that the presence of cell membranes facilitated burst release of lipophilic cargos while incorporation of oleic acid-coated iron oxide into PEO-PS nanoparticles slowed the release of DiD/DiR to cell membranes. The developed in vitro and in vivo FRET imaging techniques can be used to screening stable nanoformulations for lipophilic drug delivery.

  10. Synthesis and Biological Evaluation of a New Polymeric Conjugate and Nanocarrier with Osteotropic Properties

    Rosario Pignatello


    Full Text Available Bone-seeking (osteotropic drug delivery systems (ODDS represent an interesting solution for targeting different types of drugs to the bones. In particular, anticancer and antibacterial agents could take advantage of such therapeutic strategy. We have recently developed an innovative approach to this aim: a new osteotropic biomaterial was prepared, based on the conjugation of a poly(lactide-co-glycolide (PLGA with the bisphosphonate drug alendronate (PLGA-ALE; its hemo- and cytocompatibility were verified. Starting with this copolymer, an osteotropic nanoparticle system (NP was produced for the targeted delivery of antineoplastic drugs to osteolytic bone metastases; in particular, doxorubicin was tested as a model drug. The in vitro and in vivo results of the new ODDS are validated in this article. All the experimental data confirmed that the drug retained its activity after loading in the PLGA-ALE NP; they can be thus considered a new promising strategy for active targeting of drugs to bone tissues in different pathological situations.

  11. From the N-Heterocyclic Carbene-Catalyzed Conjugate Addition of Alcohols to the Controlled Polymerization of (Meth)acrylates.

    Ottou, Winnie Nzahou; Bourichon, Damien; Vignolle, Joan; Wirotius, Anne-Laure; Robert, Fredéric; Landais, Yannick; Sotiropoulos, Jean-Marc; Miqueu, Karinne; Taton, Daniel


    Among various N-heterocyclic carbenes (NHCs) tested, only 1,3-bis(tert-butyl)imidazol-2-ylidene (NHC(tBu) ) proved to selectively promote the catalytic conjugate addition of alcohols onto (meth)acrylate substrates. This rather rare example of NHC-catalyzed 1,4-addition of alcohols was investigated as a simple means to trigger the polymerization of both methyl methacrylate and methyl acrylate (MMA and MA, respectively). Well-defined α-alkoxy poly(methyl (meth)acrylate) (PM(M)A) chains, the molar masses of which could be controlled by the initial [(meth)acrylate]0/[ROH]0 molar ratio, were ultimately obtained in N,N-dimethylformamide at 25 °C. A hydroxyl-terminated poly(ethylene oxide) (PEO-OH) macro-initiator was also employed to directly access PEO-b-PMMA amphiphilic block copolymers. Investigations into the reaction mechanism by DFT calculations revealed the occurrence of two competitive concerted pathways, involving either the activation of the alcohol or that of the monomer by NHC(tBu) .

  12. Rationally Engineering Phototherapy Modules of Eosin-Conjugated Responsive Polymeric Nanocarriers via Intracellular Endocytic pH Gradients.

    Liu, Guhuan; Hu, Jinming; Zhang, Guoying; Liu, Shiyong


    Spatiotemporal switching of respective phototherapy modes at the cellular level with minimum side effects and high therapeutic efficacy is a major challenge for cancer phototherapy. Herein we demonstrate how to address this issue by employing photosensitizer-conjugated pH-responsive block copolymers in combination with intracellular endocytic pH gradients. At neutral pH corresponding to extracellular and cytosol milieu, the copolymers self-assemble into micelles with prominently quenched fluorescence emission and low (1)O2 generation capability, favoring a highly efficient photothermal module. Under mildly acidic pH associated with endolysosomes, protonation-triggered micelle-to-unimer transition results in recovered emission and enhanced photodynamic (1)O2 efficiency, which synergistically actuates release of encapsulated drugs, endosomal escape, and photochemical internalization processes.

  13. Effects of Polymeric Additives on the Crystallization and Release Behavior of Amorphous Ibuprofen

    Su Yang Lee


    Full Text Available Some polymeric additives were studied to understand their effects on the amorphous phase of ibuprofen (IBU, used as a poorly water soluble pharmaceutical model compound. The amorphous IBU in bulk, as well as in nanopores (diameter ~24 nm of anodic aluminum oxide, was examined with the addition of poly(acrylic acid, poly(N-vinyl pyrrolidone, or poly(4-vinylphenol. Results of bulk crystallization showed that they were effective in limiting the crystal growth, while the nucleation of the crystalline phase in contact with water was nearly instantaneous in all cases. Poly(N-vinyl pyrrolidone, the most effective additive, was in specific interaction with IBU, as revealed by IR spectroscopy. The addition of the polymers was combined with the nanoscopic confinement to further stabilize the amorphous phase. Still, the IBU with addition of polymeric additives showed sustained release behavior. The current study suggested that the inhibition of the crystal nucleation was probably the most important factor to stabilize the amorphous phase and fully harness its high solubility.

  14. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    Blaesi, Aron H; Saka, Nannaji


    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration.

  15. Accelerated ketoprofen release from polymeric matrices: importance of the homogeneity/heterogeneity of excipient distribution.

    Gue, E; Willart, J F; Muschert, S; Danede, F; Delcourt, E; Descamps, M; Siepmann, J


    Polymeric matrices loaded with 10-50% ketoprofen were prepared by hot-melt extrusion or spray-drying. Eudragit E, PVP, PVPVA and HPMC were studied as matrix formers. Binary "drug-Eudragit E" as well as ternary "drug-Eudragit E-PVP", "drug-Eudragit E-PVPVA" and "drug-Eudragit E-HPMC" combinations were investigated and characterized by optical macro/microscopy, SEM, particle size measurements, mDSC, X-ray diffraction and in vitro drug release studies in 0.1 M HCl. In all cases ketoprofen release was much faster compared to a commercially available product and the dissolution of the drug powder (as received). Super-saturated solutions were obtained, which were stable during at least 2 h. Importantly, not only the composition of the systems, but also their inner structure potentially significantly affected the resulting ketoprofen release kinetics: For instance, spray-drying ternary ketoprofen:Eudragit E:HPMC combinations led to a more homogenous HPMC distribution within the systems than hot-melt extrusion, as revealed by mDSC and X-ray diffraction. This more homogenous HPMC distribution resulted in more pronounced hindrance for water and drug diffusion and, thus, slower drug release from spray-dried powder compared to hot-melt extrudates of identical composition. This "homogeneity/heterogeneity effect" even overcompensated the "system size effect": the surface exposed to the release medium was much larger in the case of the spray-dried powder. All formulations were stable during storage at ambient conditions in open vials.

  16. Study of the prolonged release of theopylline from polymeric matrices based on grafted chitosan with acrylamide.

    Tapia, C; Costa, E; Terraza, C; Munita, A M; Yazdani-Pedram, M


    The aim of this work was to study the performance of chitosan (CB) grafted with acrylamide (CB-g-A) as prolonged drug release matrix as compared with unmodified chitosan. A non-pH dependent swelling behaviour for the matrix tablets based on grafted chitosan was observed. The overlaping between degree of swelling measured by weighing (DSw) and measured by increase of diameter (DSd) up to 240 minutes showed that the swelling process could be isotropic. The non-pH dependent swelling behaviour of these matrices could be explained by the partial substitution of amine groups of the chitosan chain by acrylamide. The grafting reaction provides an ionizable amine group by a neutral amide group which make the matrix non pH-dependent. On the contrary, the matrix tablet based on chitosan showed a pH dependent swelling behaviour where the swelling process could be anisotropic. The higher degree of erosion and swelling of the formulation based on CB-g-A600 (%G = 600) compared with the formulation based on chitosan and CB-g-A418 (%G = 418) could explain the higher fraction of theopylline released. For all formulations studied in this work, the amount of theopylline released from the matrix tablets was found to be controlled by a combination of the diffusion process and relaxation of the polymeric structure. These results match with the controlled swelling behaviour and low degree of erosion observed for these systems.

  17. Anti-inflammatory drug incorporation into polymeric nano-hybrids for local controlled release.

    Sammartino, G; Marenzi, G; Tammaro, L; Bolognese, A; Calignano, A; Costantino, U; Califano, L; Mastrangelo, F; Tetè, S; Vittoria, V


    In this paper we present the formulation, preparation and characterization of new polymeric composite materials containing a nano-hybrid to be used for the controlled molecular delivery of an anti-inflammatory molecule, Diclofenac. The nano-hybrid consists of a layer of double hydroxide of an Mg-Al hydrotalcite type, in which we replaced the chloride anions present in the host galleries with Diclofenac anions by a simple ion-exchange reaction. Different amounts of the hybrid material were incorporated in polycaprolactone and processed as films of 0.15 mm thickness. The composite materials were analyzed by X-ray diffractometry, thermogravimetry and for their mechanical properties, and showed properties even better than those for the pristine polymer. The release process of the anti-inflammatory molecules was very interesting and promising for tuneable drug delivery. It consists of two stages: a first stage, very rapid as a burst in which a small fraction of the drug is released, and of a second stage that is much slower, extending for longer and longer periods. The parameters influencing the drug release were individuated and discussed.

  18. Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

    Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz de; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo


    Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants. PMID:26346969

  19. Synthesis of phenstatin/isocombretastatin-chalcone conjugates as potent tubulin polymerization inhibitors and mitochondrial apoptotic inducers.

    Kamal, Ahmed; Kumar, G Bharath; Vishnuvardhan, M V P S; Shaik, Anver Basha; Reddy, Vangala Santhosh; Mahesh, Rasala; Sayeeda, Ibrahim Bin; Kapure, Jeevak Sopanrao


    A series of phenstatin/isocombretastatin–chalcones were synthesized and screened for their cytotoxic activity against various human cancer cell lines. Some representative compounds exhibited significant antiproliferative activity against a panel of sixty human cancer cell lines of the NCI, with GI50 values in the range of 0.11 to 19.0 μM. Three compounds (3b, 3c and 3e) showed a broad spectrum of antiproliferative efficacy on most of the cell lines in the sub-micromolar range. In addition, all the synthesized compounds (3a–l and 4a–l) displayed moderate to excellent cytotoxicity against breast cancer cells such as MCF-7 and MDA-MB-231 with IC50 values in the range of 0.5 to 19.9 μM. Moreover, the tubulin polymerization assay and immunofluorescence analysis results suggest that some of these compounds like 3c and 3e exhibited significant inhibitory effect on the tubulin assembly with an IC50 value of 0.8 μM and 0.6 μM respectively. A competitive binding assay suggested that these compounds bind at the colchicine-binding site of tubulin. A cell cycle assay revealed that these compounds arrest at the G2/M phase and lead to apoptotic cell death. Furthermore, this was confirmed by Hoechst 33258 staining, activation of caspase 9, DNA fragmentation, Annexin V-FITC and mitochondrial membrane depolarization. Molecular docking studies indicated that compounds like 3e occupy the colchicine binding site of tubulin.

  20. Conjugation of Hyaluronic Acid onto Surfaces via the Interfacial Polymerization of Dopamine to Prevent Protein Adsorption.

    Huang, Renliang; Liu, Xia; Ye, Huijun; Su, Rongxin; Qi, Wei; Wang, Libing; He, Zhimin


    A versatile, convenient, and cost-effective method that can be used for grafting antifouling materials onto different surfaces is highly desirable in many applications. Here, we report the one-step fabrication of antifouling surfaces via the polymerization of dopamine and the simultaneous deposition of anionic hyaluronic acid (HA) on Au substrates. The water contact angle of the Au surfaces decreased from 84.9° to 24.8° after the attachment of a highly uniform polydopamine (PDA)/HA hybrid film. The results of surface plasmon resonance analysis showed that the Au-PDA/HA surfaces adsorbed proteins from solutions of bovine serum albumin, lysozyme, β-lactoglobulin, fibrinogen, and soybean milk in ultralow or low amounts (4.8-31.7 ng/cm(2)). The hydrophilicity and good antifouling performance of the PDA/HA surfaces is attributable to the HA chains that probably attached onto their upper surface via hydrogen bonding between PDA and HA. At the same time, the electrostatic repulsion between PDA and HA probably prevents the aggregation of PDA, resulting in the formation of a highly uniform PDA/HA hybrid film with the HA chains (with a stretched structure) on the upper surface. We also developed a simple method for removing this PDA/HA film and recycling the Au substrates by using an aqueous solution of NaOH as the hydrolyzing agent. The Au surface remained undamaged, and a PDA/HA film could be redeposited on the surface, with the surface exhibiting good antifouling performance even after 10 such cycles. Finally, it was found that this grafting method is applicable to other substrates, including epoxy resins, polystyrene, glass, and steel, owing to the strong adhesion of PDA with these substrates.

  1. Targeted delivery and pH-triggered release of a saporin toxin conjugated to transferrin via a DNA i-motif

    Liu, Tianqiang


    mechanism was studied by immobilizing the saporin i-motif conjugates on DNA origami, where the release was imaged by atomic force microscopy. In vitro studies demonstrated that the DNA-linked saporin-transferrin conjugates dramatically enhanced cell uptake and cytotoxicity. Furthermore, conjugates that were...

  2. In vivo pharmacological evaluation of a lactose-conjugated luteinizing hormone releasing hormone analogue.

    Moradi, Shayli Varasteh; Varamini, Pegah; Steyn, Frederik; Toth, Istvan


    In the current study, the efficacy and pharmacokinetic profile of lactose-conjugated luteinizing hormone releasing hormone (LHRH) was examined following oral administration in male rats. A rapid and sensitive liquid chromatography/mass spectrometry technique was developed and applied for measuring the concentration of lactose[Q(1)][w(6)]LHRH (compound 1) in rat plasma in order to allow measurement of pharmacokinetic parameters. LH release was evaluated using a sandwich ELISA. Maximum serum concentration (Cmax = 0.11 μg/ml) was reached at 2h (Tmax) following oral administration of the compound at 10mg/kg. The half-life was determined to be 2.6h. The absolute bioavailability of the orally administered compound was found to be 14%, which was a remarkable improvement compared to zero-to-low oral bioavailability of the native peptide. Compound 1 was effective in stimulating LH release at 20mg/kg after oral administration. The method was validated at a linear range of 0.01-20.0 μg/ml and a correlation coefficient of r(2) ≥ 0.999. The accuracy and precision values showed the reliability and reproducibility of the method for evaluation of the pharmacokinetic parameters. These findings showed that the lactose derivative of LHRH has a therapeutic potential to be further developed as an orally active therapeutics for the treatment of hormone-dependent diseases.

  3. Release of DNA oligonucleotides and their conjugates from controlled-pore glass under thermolytic conditions.

    Grajkowski, Andrzej; Cieślak, Jacek; Norris, Scott; Freedberg, Darón I; Kauffman, Jon S; Duff, Robert J; Beaucage, Serge L


    The sequential functionalization of long-chain alkylamine controlled-pore glass (CPG) with a 3-hydroxypropyl-(2-cyanoethyl)thiophosphoryl linker and a dinucleoside phosphorotetrazolide leads to a uniquely engineered support for solid-phase synthesis. Unlike conventional succinylated-CPG supports, this support is designed to allow oligonucleotide deprotection and elimination of deprotection side-products to proceed without release of the oligonucleotide. When needed, the DNA oligonucleotide can be thermolytically released in 2 hr under essentially neutral conditions. The modified CPG support has been successfully employed in the synthesis of both native and fully phosphorothioated DNA 20-mers. On the basis of reversed-phase HPLC and electrophoretic analyses, the purity of the released oligonucleotides is comparable to that of identical oligonucleotides synthesized from succinylated-CPG supports, in terms of both shorter-than-full-length oligonucleotide contaminants and overall yields. The detailed preparation of DNA oligonucleotides conjugated with exemplary reporter or functional groups, either at the 3'-terminus or at both 3'- and 5'-termini, is also described.

  4. Organocatalytic conjugate-addition polymerization of linear and cyclic acrylic monomers by N-heterocyclic carbenes: Mechanisms of chain initiation, propagation, and termination

    Zhang, Yuetao


    This contribution presents a full account of experimental and theoretical/computational investigations into the mechanisms of chain initiation, propagation, and termination of the recently discovered N-heterocyclic carbene (NHC)-mediated organocatalytic conjugate-addition polymerization of acrylic monomers. The current study specifically focuses on three commonly used NHCs of vastly different nucleophilicity, 1,3-di-tert-butylimidazolin-2-ylidene (ItBu), 1,3- dimesitylimidazolin-2-ylidene (IMes), and 1,3,4-triphenyl-4,5-dihydro-1H-1,2,4- triazol-5-ylidene (TPT), and two representative acrylic monomers, the linear methyl methacrylate (MMA) and its cyclic analog, biomass-derived renewable γ-methyl-α-methylene-γ-butyrolactone (MMBL). For MMA, there exhibits an exquisite selectivity of the NHC structure for the three types of reactions it promotes: enamine formation (single-monomer addition) by IMes, dimerization (tail-to-tail) by TPT, and polymerization by ItBu. For MMBL, all three NHCs promote no dimerization but polymerization, with the polymerization activity being highly sensitive to the NHC structure and the solvent polarity. Thus, ItBu is the most active catalyst of the series and converts quantitatively 1000-3000 equiv of MMBL in 1 min or 10 000 equiv in 5 min at room temperature to MMBL-based bioplastics with a narrow range of molecular weights of Mn = 70-85 kg/mol, regardless of the [MMBL]/[ItBu] ratio employed. The ItBu-catalyzed MMBL polymerization reaches an exceptionally high turnover frequency up to 122 s -1 and a high initiator efficiency value up to 1600%. Unique chain-termination mechanisms have been revealed, accounting for the production of relative high-molecular-weight linear polymers and the catalytic nature of this NHC-mediated conjugate-addition polymerization. Computational studies have provided mechanistic insights into reactivity and selectivity between two competing pathways for each NHC-monomer zwitterionic adduct, namely enamine

  5. State of the art, challenges and perspectives in the design of nitric oxide-releasing polymeric nanomaterials for biomedical applications.

    Seabra, Amedea B; Justo, Giselle Z; Haddad, Paula S


    Recently, an increasing number of publications have demonstrated the importance of the small molecule nitric oxide (NO) in several physiological and pathophysiological processes. NO acts as a key modulator in cardiovascular, immunological, neurological, and respiratory systems, and deficiencies in the production of NO or its inactivation has been associated with several pathologic conditions, ranging from hypertension to sexual dysfunction. Although the clinical administration of NO is still a challenge owing to its transient chemical nature, the combination of NO and nanocarriers based on biocompatible polymeric scaffolds has emerged as an efficient approach to overcome the difficulties associated with the biomedical administration of NO. Indeed, significant progress has been achieved by designing NO-releasing polymeric nanomaterials able to promote the spatiotemporal generation of physiologically relevant amounts of NO in diverse pharmacological applications. In this review, we summarize the recent advances in the preparation of versatile NO-releasing nanocarriers based on polymeric nanoparticles, dendrimers and micelles. Despite the significant innovative progress achieved using nanomaterials to tailor NO release, certain drawbacks still need to be overcome to successfully translate these research innovations into clinical applications. In this regard, this review discusses the state of the art regarding the preparation of innovative NO-releasing polymeric nanomaterials, their impact in the biological field and the challenges that need to be overcome. We hope to inspire new research in this exciting area based on NO and nanotechnology.

  6. Chloroaluminium phthalocyanine polymeric nanoparticles as photosensitisers: photophysical and physicochemical characterisation, release and phototoxicity in vitro.

    de Paula, Carina Silva; Tedesco, Antonio Cláudio; Primo, Fernando Lucas; Vilela, José Mário Carneiro; Andrade, Margareth Spangler; Mosqueira, Vanessa Carla Furtado


    Nanoparticles of poly(d,l-lactide-co-glycolide), poly(d,l-lactide) and polyethylene glycol-block-poly(d,l-lactide) were developed to encapsulate chloroaluminium phthalocyanine (AlClPc), a new hydrophobic photosensitiser used in photodynamic therapy (PDT). The mean nanoparticle size varied from 115 to 274 nm, and the encapsulation efficiency ranged from 57% to 96% due to drug precipitation induced by different types of polymer. All nanoparticle formulations presented negative zeta potential values (-37 mV to -59 mV), explaining their colloidal stability. The characteristic photophysical parameters were analysed: the absorption spectrum profile, fluorescence quantum yield and transient absorbance decay, with similar values for free and nanoparticles of AlClPc. The time-resolved spectroscopy measurements for AlClPc triplet excited state lifetimes indicate that encapsulation in nanocapsules increases triplet lifetime, which is advantageous for PDT efficiency. A sustained release profile over 168 h was obtained using external sink method. An in vitro phototoxic effect higher than 80% was observed in human fibroblasts at low laser light doses (3 J/cm(2)) with 10 μM of AlClPc. The AlClPc loaded within polymeric nanocapsules presented suitable physical stability, improved photophysical properties, sustained released profile and suitable activity in vitro to be considered a promising formulation for PDT.

  7. Quinoline based polymeric drug for biological applications: synthesis, characterization, antimicrobial, and drug releasing studies.

    Uma, P; Suresh, J; Selvaraj, Revathy; Karthik, S; Arun, A


    Novel acrylate monomer of quinoline-based chalcone 1-(4-(7-chloroquinolin-4-ylamino)phenyl) acrylate (CPA) was synthesized using (4-(2-chloroquinolin-5-ylamino)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (CPE) and acryloyl chloride. CPA is characterized by different techniques like IR, (1)H NMR and UV-visible spectrometry techniques. Poly(CPA), poly(CPA-co-AA) and poly(CPA-co-HEA) are prepared by solution polymerization technique using CPA, acrylic acid (AA) and hydroxyethylacrylate (HEA), respectively. The antimicrobial activities of the compounds are tested using four different micro-organisms. In vitro cumulative drug release studies are done using UV visible spectroscopic technique. The molecular weights of these polymers are found to be around 5000 g/mol. The synthesized polymers showed two stages of thermal decomposition temperature centred around 220 and 350 °C, respectively. The antimicrobial activity of the polymer sample is found to be very high and especially for gram-negative bacteria with a minimum value of 3.91 μg/mL. The in vitro drug-releasing rate is dependent on the comonomer, pH and temperature of the medium.

  8. Self-assembled nanoparticles of modified-chitosan conjugates for the sustained release of dl-α-tocopherol

    Quinones, Javier Perez; Gothelf, Kurt Vesterager; Kjems, Jørgen


    Synthetic O6-succinylated chitosan and commercial glycol chitosan were covalently linked to dl-α-tocopheryl monoesters for controlled release of vitamin E. These conjugates formed self-assembled nanoparticles in aqueous solution with 254–496 nm mean diameters and dl-α-tocopherol contents between 27...

  9. Facile Synthesis of Well-Defined MDMO-PPV Containing (TriBlock—Copolymers via Controlled Radical Polymerization and CuAAC Conjugation

    Neomy Zaquen


    Full Text Available A systematic investigation into the chain transfer polymerization of the so-called radical precursor polymerization of poly(p-phenylene vinylene (PPV materials is presented. Polymerizations are characterized by systematic variation of chain transfer agent (CTA concentration and reaction temperature. For the chain transfer constant, a negative activation energy of −12.8 kJ·mol−1 was deduced. Good control over molecular weight is achieved for both the sulfinyl and the dithiocarbamate route (DTC. PPVs with molecular weights ranging from thousands to ten thousands g·mol−1 were obtained. To allow for a meaningful analysis of the CTA influence, Mark–Houwink–Kuhn–Sakurada (MHKS parameters were determined for conjugated MDMO-PPV ([2-methoxy-5-(3',7'-dimethyloctyloxy]-1,4-phenylenevinylene to α = 0.809 and k = 0.00002 mL·g−1. Further, high-endgroup fidelity of the CBr4-derived PPVs was proven via chain extension experiments. MDMO-PPV-Br was successfully used as macroinitiator in atom transfer radical polymerization (ATRP with acrylates and styrene. A more polar PPV counterpart was chain extended by an acrylate in single-electron transfer living radical polymerization (SET-LRP. In a last step, copper-catalyzed azide alkyne cycloaddition (CuAAC was used to synthesize block copolymer structures. Direct azidation followed by macromolecular conjugation showed only partial success, while the successive chain extension via ATRP followed by CuAAC afforded triblock copolymers of the poly(p-phenylene vinylene-block-poly(tert-butyl acrylate-block-poly(ethylene glycol (PPV-b-PtBuA-b-PEG.

  10. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH)

    Obayemi, J.D. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Materials Science and Engineering, Kwara State University, Malete, Kwara State (Nigeria); Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Danyuo, Y. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Electronics and Electricals Engineering, Nigerian Turkish Nile University, Abuja (Nigeria); Odusanya, O.S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY 10453 (United States); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Malatesta, K. [Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States); Soboyejo, W.O., E-mail: [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States)


    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV–Visible (UV–Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. - Highlights: • Biosynthesis of MNPs with clinically relevant sizes between 10 and 60 nm. • New insights into the effects of pH and processing time on nanoparticle shapes and sizes. • Successful conjugation of biosynthesized magnetite nanoparticles to LHRH ligands. • Conjugated BMNPs that are monodispersed with potential biomedical relevance. • Magnetic properties of biosynthesized MNPs suggest potential for MRI enhancement.


    HAO Guangjie; SHEN Xiaoyi; LIANG Zhiwu; GUO Tianying; ZHANG Banghua


    Poly(styrene-glycidyl methacrylate) particles having bowl-shaped hollow structures were synthesized by swollen seed emulsion polymerization. The PS emulsion synthesized through soap-free emulsion polymerization was swollen by toluene, and then the mixture of second monomers was added under polymerization condition. So a thin shell of poly(styrene-glycidyl methacrylate) cross-linked by triethylene glycol diacrylate was formed around the swollen PS particle. The bowl-shaped particles were obtained after the collapsing of the thin shell when the toluene emanated from the particles, but the shapes were effected by the degrees of cross-linking. The shape of the particles was observed by SEM. The release behavior of solvent from the particles was examined by TG.

  12. Glucose-induced release of glycosylpoly(ethylene glycol) insulin bound to a soluble conjugate of concanavalin A.

    Liu, F; Song, S C; Mix, D; Baudys, M; Kim, S W


    Treatment of diabetes mellitus by insulin injections provides long-term control of the disease but lacks any feedback response to glucose concentration changes, which finally leads to a number of life-threatening conditions. The purpose of this study was to improve and optimize an implantable, concanavalin A (Con A) based, glucose-responsive insulin delivery system studied earlier [Jeong, S. Y., Kim, S. W., Holmberg, D. L., and McRea, J. C. (1985) J. Controlled Release 2, 143-152], which can be used for long-term diabetes treatment. To optimize the "insulin component" of the delivery system, we prepared PheB1 insulin amino group monosubstituted monoglucosylpoly(ethylene glycol) (G-PEG) insulin conjugates (PEG M(r) 600 or 2000), which showed preserved bioactivity, significantly improved solubility and solution stability at neutral pH, and substantially suppressed hexamerization/dimerization. To improve the delivery system further, we synthesized and characterized a conjugate of Con A and monomethoxypoly(ethylene glycol) (mPEG, M(r) 5000) grafted hydrophilic poly(vinylpyrrolidone-co-acrylic acid) (PVPAA) with M(r) of 250,000. The optimal conjugate contained around eight PEG chains and two to three Con A tetramers attached through the amide bonds to the PVPAA chain. The Con A sugar binding characteristics were preserved, and, more importantly, Con A solubility at pH 7.4 substantially increased. This also holds true for a complex formed by the Con A conjugate and G-PEG insulin, which is soluble and does not precipitate under the physiologically relevant conditions under which the complex formed by the Con A conjugate and glycosyl insulin immediately precipitates. Finally, no leakage of the Con A conjugate from a membrane device was detected. Preliminary in vitro release experiments with Con A conjugate and G-PEG insulin complex enclosed in the membrane device showed a pulsative, reversible release pattern for G-PEG insulin in response to glucose challenges of 50-500 mg

  13. Antibiotic Conjugated Fluorescent Carbon Dots as a Theranostic Agent for Controlled Drug Release, Bioimaging, and Enhanced Antimicrobial Activity

    Mukeshchand Thakur


    Full Text Available A novel report on microwave assisted synthesis of bright carbon dots (C-dots using gum arabic (GA and its use as molecular vehicle to ferry ciprofloxacin hydrochloride, a broad spectrum antibiotic, is reported in the present work. Density gradient centrifugation (DGC was used to separate different types of C-dots. After careful analysis of the fractions obtained after centrifugation, ciprofloxacin was attached to synthesize ciprofloxacin conjugated with C-dots (Cipro@C-dots conjugate. Release of ciprofloxacin was found to be extremely regulated under physiological conditions. Cipro@C-dots were found to be biocompatible on Vero cells as compared to free ciprofloxacin (1.2 mM even at very high concentrations. Bare C-dots (∼13 mg mL−1 were used for microbial imaging of the simplest eukaryotic model—Saccharomyces cerevisiae (yeast. Bright green fluorescent was obtained when live imaging was performed to view yeast cells under fluorescent microscope suggesting C-dots incorporation inside the cells. Cipro@C-dots conjugate also showed enhanced antimicrobial activity against both model gram positive and gram negative microorganisms. Thus, the Cipro@C-dots conjugate paves not only a way for bioimaging but also an efficient new nanocarrier for controlled drug release with high antimicrobial activity, thereby serving potential tool for theranostics.

  14. Complex comprised of dextran magnetite and conjugated cisplatin exhibiting selective hyperthermic and controlled-release potential

    Akinaga Sonoda


    Full Text Available Akinaga Sonoda1, Norihisa Nitta1, Ayumi Nitta-Seko1, Shinich Ohta1, Shigeyuki Takamatsu2, Yoshio Ikehata3, Isamu Nagano3, Jun-ichiro Jo4, Yasuhiko Tabata4, Masashi Takahashi1, Osamu Matsui3, Kiyoshi Murata11Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga, 520-2192, Japan; 2Department of Radiology, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa Ishikawa, 920-8641, Japan; 3Department of Natural Science and Technology, Graduate School of Engineering, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan; 4Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Shogoin kawara-machi 53, Sakyo-ku 606-8507, Kyoto, JapanAbstract: We developed a dextran-magnetite conjugated cisplatin (DM-Cis complex for use in thermal ablation and as a chemotherapeutic drug. To produce DM-Cis we reacted Cis with 1 mL DM (56 mg/mL iron. The temperature rise of DM-Cis was measured in vitro and in vivo under a portable induction-heating (IH device. Platinum desorption from DM-Cis over 24 hours was measured in bovine serum. In in vivo accumulation and magnet and exothermic experiments we used four rat groups. In group 1 we delivered DM-Cis intraperitoneally (ip and placed magnets subcutaneously (sc. In group 2 we injected saline (ip and placed magnets (sc. In group 3 we injected DM-Cis (ip and placed a sc incision (sham. The control (group 4 received an ip injection of saline. Rectus abdominis muscle tissue was stained with hematoxylin-eosin and iron-stained tissue areas (µm2 were calculated. The maximum platinum concentration in DM-Cis was approximately 105.6 µg/mL. Over 24 hours, 33.48% of platinum from DM-Cis was released. There was a significant difference (P < 0.05 in the iron-stained area between group 1 and the other groups. The temperature in muscle tissue registered a maximum of 56°C after about 4 min. DM-Cis may represent a

  15. Preparation and characterization of 1-naphthylacetic acid-silica conjugated nanospheres for enhancement of controlled-release performance

    Ao, Mingming; Zhu, Yuncong; He, Shun; Li, Deguang; Li, Pingliang; Li, Jianqiang; Cao, Yongsong


    Chemical pesticides have been widely used to increase the yield and quality of agricultural products as they are efficient, effective, and easy to apply. However, the rapid degradation and low utilization ratio of conventional pesticides has led to environmental pollution and resource waste. Nano-sized controlled-release formulations (CRFs) can provide better penetration through the plant cuticle and deliver the active ingredients efficiently to the targeted tissue. In this paper we reported novel conjugated nanospheres derived from 1-naphthylacetic acid (NNA), 3-aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate and their application as a controlled-release plant growth regulator. The NNA and APTES conjugate was prepared through a covalent cross-linking reaction and subsequent hydrolyzation and polycondensation to synthesize NNA-silica nanospheres. The release data indicated that the release of NNA was by non-Fickian transport and increased as particle size decreased. It was also found that the acidity-alkalinity was enhanced and as the temperature increased, the release of the active ingredient was faster. The nanoconjugate displayed a better efficacy in promoting root formation than NNA technical. The present study provides a novel synthesis route for CRFs comprising a pesticide, with long-duration sustained-release performance and good environmental compatibility. This method may be extended to other pesticides that possess a carboxyl group.

  16. Conjugation chemistry through acetals toward a dextran-based delivery system for controlled release of siRNA

    Cui, Lina


    New conjugation chemistry for polysaccharides, exemplified by dextran, was developed to enable the attachment of therapeutic or other functional moieties to the polysaccharide through cleavable acetal linkages. The acid-lability of the acetal groups allows the release of therapeutics under acidic conditions, such as that of the endocytic compartments of cells, regenerating the original free polysaccharide in the end. The physical and chemical behavior of these acetal groups can be adjusted by modifying their stereoelectronic and steric properties, thereby providing materials with tunable degradation and release rates. We have applied this conjugation chemistry in the development of water-soluble siRNA carriers, namely acetal-linked amino-dextrans, with various amine structures attached through either slow- or fast-degrading acetal linker. The carriers with the best combination of amine moieties and structural composition of acetals showed high in vitro transfection efficiency and low cytotoxicity in the delivery of siRNA. © 2012 American Chemical Society.

  17. Fabrication of nonfouling, bactericidal, and bacteria corpse release multifunctional surface through surface-initiated RAFT polymerization

    Wang B


    Full Text Available Bailiang Wang,1,2 Zi Ye,1 Yihong Tang,1 Yuemei Han,1 Quankui Lin,1,2 Huihua Liu,2 Hao Chen,1,2 Kaihui Nan1,2 1School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 2Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou, People’s Republic of China Abstract: Infections after surgery or endophthalmitis are potentially blinding complications caused by bacterial adhesion and subsequent biofilm formation on the intraocular lens. Neither single-function anti-adhesion surface nor contacting killing surface can exhibit ideal antibacterial function. In this work, a novel (2-(dimethylamino-ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine (p (DMAEMA-co-MPC brush was synthesized by “grafting from” method through reversible–addition fragmentation chain transfer polymerization. 1-Bromoheptane was used to quaternize the p (DMAEMA-co-MPC brush coating and to endow the surface with bactericidal function. The success of the surface functionalization was confirmed by atomic force microscopy, water contact angle, and spectroscopic ellipsometry. The quaternary ammonium salt units were employed as efficient disinfection that can eliminate bacteria through contact killing, whereas the 2-methacryloyloxyethyl phosphorylcholine units were introduced to suppress unwanted nonspecific adsorption. The functionalized poly(dimethyl siloxane surfaces showed efficiency in reducing bovine serum albumin adsorption and in inhibiting bacteria adhesion and biofilm formation. The copolymer brushes also demonstrated excellent bactericidal function against gram-positive (Staphylococcus aureus bacteria measured by bacteria live/dead staining and shake-flask culture methods. The surface biocompatibility was evaluated by morphology and activity measurement with human lens epithelial cells in vitro. The achievement of the p (DMAEMA+-co-MPC copolymer brush coating with nonfouling, bactericidal, and

  18. Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs.

    Ni, Jiang; Tian, Fengchun; Dahmani, Fatima Zohra; Yang, Hui; Yue, Deren; He, Shuwang; Zhou, Jianping; Yao, Jing


    The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans-retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by (1)H NMR with a degree of substitution of Cur of 4.52-10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (∼200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher Ka and Peff than CsA suspension in the duodenum and jejunum segments (p absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs.

  19. Evaluation of antibacterial activity of nitric oxide-releasing polymeric particles against Staphylococcus aureus and Escherichia coli from bovine mastitis.

    Cardozo, Viviane F; Lancheros, Cesar A C; Narciso, Adélia M; Valereto, Elaine C S; Kobayashi, Renata K T; Seabra, Amedea B; Nakazato, Gerson


    Bovine mastitis is a serious veterinary disease that causes great loss to the dairy industry worldwide. It is a major infectious disease and is difficult to manage and control. Furthermore, emerging multidrug resistant bacteria that cause mastitis have complicated such management. The free radical nitric oxide (NO) is a potent antimicrobial agent. Thus, the aims of this study were to prepare and evaluate the antibacterial activity of nitric oxide-releasing polymeric particles against Staphylococcus aureus (MBSA) and Escherichia coli (MBEC), which were isolated from bovine mastitis. Fifteen MBSA isolates and fifteen MBEC were collected from subclinical and clinical bovine mastitis. Biocompatible polymeric particles composed of alginate/chitosan or chitosan/sodium tripolyphosphate (TPP) were prepared and used to encapsulate mercaptosuccinic acid (MSA), which is a thiol-containing molecule. Nitrosation of thiol groups of MSA-containing particles formed S-nitroso-MSA particles, which are NO donors. The NO release kinetics from the S-nitroso-MSA particles showed sustained and controlled NO release over several hours. The antibacterial activity of NO-releasing particles was evaluated by incubating the particles with an MBSA multi-resistant strain, which is responsible for bovine mastitis. The minimum inhibitory concentration for S-nitroso-MSA-alginate/chitosan particles against MBSA ranged from 125 μg/mL to 250 μg/mL. The results indicate that NO-releasing polymeric particles are an interesting approach to combating bacteria resistance in bovine mastitis treatment and prevention. Copyright © 2014. Published by Elsevier B.V.

  20. Tetrapeptide-coumarin conjugate 3D networks based on hydrogen-bonded charge transfer complexes: gel formation and dye release.

    Guo, Zongxia; Gong, Ruiying; Jiang, Yi; Wan, Xiaobo


    Oligopeptide-based derivatives are important synthons for bio-based functional materials. In this article, a Gly-(L-Val)-Gly-(L-Val)-coumarin (GVGV-Cou) conjugate was synthesized, which forms 3D networks in ethanol. The gel nanostructures were characterized by UV-vis spectroscopy, FT-IR spectroscopy, X-ray diffraction (XRD), SEM and TEM. It is suggested that the formation of charge transfer (CT) complexes between the coumarin moieties is the main driving force for the gel formation. The capability of the gel to encapsulate and release dyes was explored. Both Congo Red (CR) and Methylene Blue (MB) can be trapped in the CT gel matrix and released over time. The present gel might be used as a functional soft material for guest encapsulation and release.

  1. Spray-dried powders improve the controlled release of antifungal tioconazole-loaded polymeric nanocapsules compared to with lyophilized products

    Ribeiro, Roseane Fagundes [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS, 97105-900 (Brazil); Motta, Mariana Heldt [Curso de Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS, 97105-900 (Brazil); Härter, Andréia Pisching Garcia; Flores, Fernanda Cramer [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS, 97105-900 (Brazil); Beck, Ruy Carlos Ruver [Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000 (Brazil); Schaffazick, Scheila Rezende [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS, 97105-900 (Brazil); and others


    This work aimed to obtain solid formulations from polymeric nanocapsules and nanoemulsions containing tioconazole, a broad spectrum antifungal drug. Two dehydration methods were used: spray-drying and freeze-drying, using lactose as adjuvant (10%, w/v). The liquid formulations had a mean particle size around 206 nm and 182 nm for nanocapsules and nanoemulsions, respectively, and an adequate polydispersity index. Tioconazole content was close to the theoretical amount (1.0 mg/mL). After drying, the content ranged between 98 and 102% with a mean nanometric size of the dried products after redispersion. Scanning electron microscopy showed that the particles are rounded, sphere-shaped for the dried products obtained by spray-drying, and shapeless and irregular shapes for those obtained by freeze-drying. In the microbiological evaluation, all dried products remained active against the yeast Candida albicans when compared to the original systems. The dried products obtained by spray-drying from nanocapsules presented better control of the tioconazole release when compared to the freeze-drying products. - Highlights: • Polymeric nanocapsule suspensions containing tioconazole were submitted to spray-drying and freeze-drying. • Dried products from nanocapsule suspensions were stable for 30 days. • Release studies showed that the dried products presented greater control of drug release compared to the original suspension.

  2. Sustained Release of Mitomycin C from Its Conjugate with Single-Walled Carbon Nanotubes Associated by Pegylated Peptide.

    Ohta, Takahisa; Hashida, Yasuhiko; Yamashita, Fumiyoshi; Hashida, Mitsuru


    A novel sustained release formulation of mitomycin C (MMC) was developed by employing single-walled carbon nanotubes (SWCNTs) wrapped by designed peptide with polyethylene glycol (PEG) modification (pegylation) as a nano-scale molecular platform. The amino groups of polycationic and amphiphilic H-(-Cys-Trp-Lys-Gly-)(-Lys-Trp-Lys-Gly-)6-OH [CWKG(KWKG)6] peptide associated with SWCNTs were modified using PEG with 12 units (PEG12) to improve the dispersion stability of the composite. Then thiol groups of peptide were conjugated with MMC using N-ε-maleimidocaproic acid (EMCA) as a linker via transformation of aziridine group of MMC. The obtained SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC composites particularly that with 13.6% PEG modification extent of amino groups, showed good dispersion stability both in water and in a cell culture medium for 24 h. The release of MMC from SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC was confirmed to follow first-order kinetics being accelerated by the pH increase in good agreement with the results observed for MMC-dextran conjugate with the same conjugation structure. The SWCNTs-CWKG(KWKG)6-(PEG)12 composite exhibited a considerably low cytotoxicity against cultured human lung adenocarcinoma epithelial cell line (A549). In contrast, SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC demonstrated delayed but relatively corresponding antitumor activity with free MMC at the same concentration. The results suggested the potential role of SWCNTs-CWKG(KWKG)6-(PEG)12 as a carrier for a controlled release drug delivery system (DDS).

  3. Release of Extracellular Polymeric Substance and Disintegration of Anaerobic Granular Sludge under Reduced Sulfur Compounds-Rich Conditions

    Takuro Kobayashi


    Full Text Available The effect of reduced form of sulfur compounds on granular sludge was investigated. Significant release of extracellular polymeric substance (EPS from the granular sludge occurred in the presence of sulfide and methanethiol according to various concentrations. Granular sludge also showed a rapid increase in turbidity and decrease in diameter in accordance with sulfide concentration during the long-term shaking, suggesting that the strength of the granules was reduced with high-concentration sulfide. A continuous experiment of up-flow anaerobic sludge blanket reactors with different concentrations of sulfide (10, 200, 500 mg-S/L influence demonstrated that the reactor fed with higher concentration of sulfide allowed more washout of small particle-suspended solid (SS content and soluble carbohydrate and protein, which were considered as EPS released from biofilm. Finally, the presence of sulfide negatively affected methane production, chemical oxygen demand removal and sludge retention in operational performance.

  4. Self-quenched covalent fluorescent dye-nucleic acid conjugates as polymeric substrates for enzymatic nuclease assays.

    Trubetskoy, Vladimir S; Hagstrom, James E; Budker, Vladimir G


    A fluorescent method is described for assessing nuclease activity. The technique is based on the preparation of quenched fluorophore-nucleic acid covalent conjugates and their subsequent dequenching due to degradation by nucleases. The resulting fluorescence increase can be measured by a spectrofluorometer and exhibits subpicogram per milliliter sensitivity level for RNase A and low picogram per milliliter level for DNase I. The method is adaptable for quantitative nuclease inhibitor testing.

  5. Thermo-reversible morphology and conductivity of a conjugated polymer network embedded in polymeric self-assembly

    Han, Youngkyu; Carrillo, Jan-Michael Y.; Zhang, Zhe; Li, Yunchao; Hong, Kunlun; Sumpter, Bobby G.; Ohl, Michael; Paranthaman, Mariappan Parans; Smith, Gregory S.; Do, Changwoo

    Self-assembly of block copolymers provides opportunities to create nano hybrid materials, utilizing self-assembled micro-domains with a variety of morphology and periodic architectures as templates for functional nano-fillers. Here we report new progress towards the fabrication of a thermally responsive conducting polymer self-assembly made from a water-soluble poly(thiophene) derivative with short PEO side chains and Pluronic L62 solution in water. The structural and electrical properties of conjugated polymer-embedded nanostructures were investigated by combining SANS, SAXS, CGMD simulations, and impedance spectroscopy. The L62 solution template organizes the conjugated polymers by stably incorporating them into the hydrophilic domains thus inhibiting aggregation. The changing morphology of L62 during the micellar-to-lamellar phase transition defines the embedded conjugated polymer network. The conductivity is strongly coupled to the structural change of the templating L62 phase and exhibits thermally reversible behavior with no signs of quenching of the conductivity at high temperature. The research was sponsored by the Scientific User Facilities Division, Office of BES, U.S. DOE and Laboratory Directed Research and Development Program of ORNL, managed by UT-Battelle, LLC.

  6. Electrochemically controlled release of molecular guests from redox responsive polymeric multilayers and devices

    Song, J.; Janczewski, D.; Ma, Y.; Ingen, van L.; Ee Sim, C.; Goh, Q; Xu, J.; Vancso, G.J.


    A novel platform technology for a tunable molecular payload release, employing complex release profiles, from electrode surfaces is reported. Organometallic poly(ferrocenylsilanes) (PFSs), featuring redox responsive ferrocene units in their main chain, are used as a carrier medium to prepare thin fi

  7. Lenghty reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) polymeric micelles and gels for sustained release of antifungal drugs.

    Figueroa-Ochoa, Edgar B; Villar-Alvarez, Eva M; Cambón, Adriana; Mistry, Dharmista; Llovo, José; Attwood, David; Barbosa, Silvia; Soltero, J F Armando; Taboada, Pablo


    In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. A unified multicomponent stress-diffusion model of drug release from non-biodegradable polymeric matrix tablets.

    Salehi, Ali; Zhao, Jin; Cabelka, Tim D; Larson, Ronald G


    We propose a new transport model of drug release from hydrophilic polymeric matrices, based on Stefan-Maxwell flux laws for multicomponent transport. Polymer stress is incorporated in the total mixing free energy, which contributes directly to the diffusion driving force while leading to time-dependent boundary conditions at the tablet interface. Given that hydrated matrix tablets are dense multicomponent systems, extended Stefan-Maxwell (ESM) flux laws are adopted to ensure consistency with the Onsager reciprocity principle and the Gibbs-Duhem thermodynamic constraint. The ESM flux law for any given component takes into account the friction exerted by all other species and is invariant with respect to reference velocity, thus satisfying Galilean translational invariance. Our model demonstrates that penetrant-induced plasticization of polymer chains partially or even entirely offsets the steady decline of chemical potential gradients at the tablet-medium interface that drive drug release. Utilizing a Flory-Huggins thermodynamic model, a modified form of the upper convected Maxwell constitutive equation for polymer stress and a Fujita-type dependence of mutual diffusivities on composition, depending on parameters, Fickian, anomalous or case II drug transport arises naturally from the model, which are characterized by quasi-power-law release profiles with exponents ranging from 0.5 to 1, respectively. A necessary requirement for non-Fickian release in our model is that the matrix stress relaxation time is comparable to the time scale for water diffusion. Mutual diffusivities and their composition dependence are the most decisive factors in controlling drug release characteristics in our model. Regression of the experimental polymer dissolution and drug release profiles in a system of Theophylline/cellulose (K15M) demonstrate that API-water mutual diffusivity in the presence of excipient cannot generally be taken as a constant.

  9. Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets.

    Samy, Wael; Elnoby, Ayman; El-Gowelli, Hanan M; Elgindy, Nazik


    Purpose: Desvenlafaxine succinate (DSV) is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current work aimed to prepare controllable release DSV matrix to reduce DSV side effects related to its initial burst. Methods: Fifteen DSV matrix formulations were prepared using different polymers, polymer/drug ratios and matrix excipients and characterized using Differential Scanning Calorimetry (DSC), infrared (IR) spectroscopy, water uptake and in vitro DSV release. The release kinetics were calculated to determine the drug release mechanism. Ex-vivo DSV absorption via rat intestinal mucosal cells and the calculation of the apparent permeability coefficient (Papp) were performed using everted sac technique. Results: Maltodextrin was the best matrix excipient (F7 and F10) showing acceptable decrease in the initial burst compared to the innovator. The addition of negatively charged polymers sodium carboxy methyl cellulose (SCMC) or sodium alginate resulted in an interaction that was proved by DSC and IR findings. This interaction slowed DSV release. F10 showed an excellent absorption of more than 80% of DSV after 4 h and the highest similarity factor with the innovator (84.7). Conclusion: A controllable release pattern of DSV was achieved using Methocel, Maltodextrin and SCMC. The obtained results could be used as a platform to control the release of cationic water soluble drugs that suffer from side effects associated with their initial burst after oral administration.

  10. Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets

    Wael Samy


    Full Text Available Purpose: Desvenlafaxine succinate (DSV is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current work aimed to prepare controllable release DSV matrix to reduce DSV side effects related to its initial burst. Methods: Fifteen DSV matrix formulations were prepared using different polymers, polymer/drug ratios and matrix excipients and characterized using Differential Scanning Calorimetry (DSC, infrared (IR spectroscopy, water uptake and in vitro DSV release. The release kinetics were calculated to determine the drug release mechanism. Ex-vivo DSV absorption via rat intestinal mucosal cells and the calculation of the apparent permeability coefficient (Papp were performed using everted sac technique. Results: Maltodextrin was the best matrix excipient (F7 and F10 showing acceptable decrease in the initial burst compared to the innovator. The addition of negatively charged polymers sodium carboxy methyl cellulose (SCMC or sodium alginate resulted in an interaction that was proved by DSC and IR findings. This interaction slowed DSV release. F10 showed an excellent absorption of more than 80% of DSV after 4 h and the highest similarity factor with the innovator (84.7. Conclusion: A controllable release pattern of DSV was achieved using Methocel, Maltodextrin and SCMC. The obtained results could be used as a platform to control the release of cationic water soluble drugs that suffer from side effects associated with their initial burst after oral administration.

  11. Applications of Natural Polymeric Materials in Solid Oral Modified-Release Dosage Forms.

    Li, Liang; Zhang, Xin; Gu, Xiangqin; Mao, Shirui


    Solid oral modified-release dosage forms provide numerous advantages for drug delivery compared to dosage forms where the drugs are released and absorbed rapidly following ingestion. Natural polymers are of particular interest as drug carriers due to their good safety profile, biocompatibility, biodegradability, and rich sources. This review described the current applications of important natural polymers, such as chitosan, alginate, pectin, guar gum, and xanthan gum, in solid oral modified-release dosage forms. It was shown that natural polymers have been widely used to fabricate solid oral modified-release dosage forms such as matrix tablets, pellets and beads, and especially oral drug delivery systems such as gastroretentive and colon drug delivery systems. Moreover, chemical modifications could overcome the shortcomings associated with the use of natural polymers, and the combination of two or more polymers presented further advantages compared with that of single polymer. In conclusion, natural polymers and modified natural polymers have promising applications in solid oral modified-release dosage forms. However, commercial products based on them are still limited. To accelerate the application of natural polymers in commercial products, in vivo behavior of natural polymers-based solid oral modified-release dosage forms should be deeply investigated, and meanwhile quality of the natural polymers should be controlled strictly, and the influence of formulation and process parameters need to be understood intensively.

  12. Accelerated ketoprofen release from spray-dried polymeric particles: importance of phase transitions and excipient distribution.

    Gue, Emilie; Muschert, Susanne; Willart, Jean-Francois; Danede, Florence; Delcourt-Debruyne, Elisabeth; Descamps, Marc; Siepmann, Juergen


    HPMC-, PVPVA- and PVP-based microparticles loaded with 30% ketoprofen were prepared by spray drying suspensions or solutions in various water:ethanol blends. The inlet temperature, drying gas and feed flow rates were varied. The resulting differences in the ketoprofen release rates in 0.1 M HCl could be explained based on X-ray diffraction, mDSC, SEM and particle size analysis. Importantly, long term stable drug release could be provided, being much faster than: (i) drug release from a commercial reference product, (ii) the respective physical drug:polymer mixtures, as well as (iii) the dissolution of ketoprofen powder as received. In addition, highly supersaturated release media were obtained, which did not show any sign for re-crystallization during the observation period. Surprisingly, spraying suspensions resulted in larger microparticles exhibiting faster drug release compared to spraying solutions, which resulted in smaller particles exhibiting slower drug release. These effects could be explained based on the physico-chemical characteristics of the systems.

  13. Development of an original method to study drug release from polymeric nanocapsules in the skin.

    Weiss-Angeli, Valeria; Bourgeois, Sandrine; Pelletier, Jocelyne; Guterres, Silvia Stanisçuaski; Fessi, Hatem; Bolzinger, Marie-Alexandrine


    This study aimed to investigate the distribution and release profile in the skin of a lipophilic model molecule, octylmethoxycinnamate (OMC), loaded in poly(epsilon-caprolactone) nanocapsules (NC) by the Franz cell method. Nanocapsules were formulated in a hydroxyethylcellulose gel and compared to the same gel containing 5% of free OMC as control. A new extraction method was used to discriminate the OMC still entrapped in the NC from free OMC released in the skin strata. The OMC extraction from the skin was performed using acetonitrile, which broke the NC, or isopropyl myristate, which kept the NC intact. When isopropylmyristate was used to determine the OMC released from NC, the results showed that more than 80% of the OMC was released from the NC at the skin surface after 6 h, whereas only 30% was released in the stratum corneum and epidermis. It is suggested that the mechanism of release is different at the surface and in viable skin, probably due to the different local environments surrounding the NC. The small amount of OMC that reached the dermis was no longer encapsulated, suggesting that the NC did not reach the dermis. The viable epidermis seemed to be the limiting barrier against NC diffusion into the skin.

  14. Polymeric micelles for acyclovir drug delivery.

    Sawdon, Alicia J; Peng, Ching-An


    Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ɛ-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200nm and the CMCs of ACV-PCL-MPEG and ACV-PCL-chitosan were 2.0mgL(-1) and 6.6mgL(-1), respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were non-toxic.

  15. Novel pH-sensitive polysialic acid based polymeric micelles for triggered intracellular release of hydrophobic drug.

    Zhang, Wuxia; Dong, Dongqi; Li, Peng; Wang, Dongdong; Mu, Haibo; Niu, Hong; Duan, Jinyou


    Polysialic acid (PSA), a non-immunogenic and biodegradable natural polymer, is prone to hydrolysis under endo-lysosomal pH conditions. Here, we synthesized an intracellular pH-sensitive polysialic acid-ursolic acid conjugate by a condensation reaction. To further test the drug loading capability, we prepared paclitaxel-loaded polysialic acid-based amphiphilic copolymer micelle (PTX-loaded-PSAU) by a nanoprecipitation method. Results showed PTX-loaded-PSAU exhibited well-defined spherical shape and homogeneous distribution. The drug-loading was 4.5% with an entrapment efficiency of 67.5%. PTX released from PTX-loaded-PSAU was 15% and 42% in 72 h under simulated physiological condition (pH 7.4) and mild acidic conditions (pH 5.0), respectively. In addition, In vitro cytotoxicity assay showed that PTX-loaded-PSAU retained anti-tumor (SGC-7901) activity with a cell viability of 53.8% following 72 h incubation, indicating PTX-loaded-PSAU could efficiently release PTX into the tumor cells. These results indicated that the pH-responsive biodegradable PTX-loaded-PSAU possess superior extracellular stability and intracellular drug release ability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Sustained-release microsphere formulation containing an agrochemical by polyurethane polymerization during an agitation granulation process.

    Terada, Takatoshi; Tagami, Manabu; Ohtsubo, Toshiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru


    In this report, a new solventless microencapsulation method by synthesizing polyurethane (PU) from polyol and isocyanate during an agglomeration process in a high-speed mixing apparatus was developed. Clothianidin (CTD), which is a neonicotinoid insecticide and highly effective against a wide variety of insect pests, was used as the model compound. The microencapsulated samples covered with PU (CTD microspheres) had a median diameter of dispersed in PU. Although voids appeared in the CTD microspheres after CTD release, the spherical shape of the microspheres remained stable and no change in its framework was observed. The experimental release data were highly consistent with the Baker-Lonsdale model derived from drug release of spherical monolithic dispersions and consistent with the computed tomography measurements.

  17. Mathematical Models for Controlled Drug Release Through pH-Responsive Polymeric Hydrogels.

    Manga, Ramya D; Jha, Prateek K


    Hydrogels consisting of weakly charged acidic/basic groups are ideal candidates for carriers in oral delivery, as they swell in response to pH changes in the gastrointestinal tract, resulting in drug entrapment at low pH conditions of the stomach and drug release at high pH conditions of the intestine. We have developed 1-dimensional mathematical models to study the drug release behavior through pH-responsive hydrogels. Models are developed for 3 different cases that vary in the level of rigor, which together can be applied to predict both in vitro (drug release from carrier) and in vivo (drug concentration in the plasma) behavior of hydrogel-drug formulations. A detailed study of the effect of hydrogel and drug characteristics and physiological conditions is performed to gain a fundamental insight into the drug release behavior, which may be useful in the design of pH-responsive drug carriers. Finally, we describe a successful application of these models to predict both in vitro and in vivo behavior of docetaxel-loaded micelle in a pH-responsive hydrogel, as reported in a recent experimental study. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Biocompatible silver nanoparticles embedded in a PEG-PLA polymeric matrix for stimulated laser light drug release

    Neri, F.; Scala, A.; Grimato, S.; Santoro, M.; Spadaro, S.; Barreca, F.; Cimino, F.; Speciale, A.; Saija, A.; Grassi, G.; Fazio, E.


    The laser-induced release of a well-known hepatoprotective drug (silibinin, SLB) from a temperature-sensitive polymeric composite loaded with silver nanoparticles (Ag NPs) was investigated. The surface chemistry tuning and the specific design of Ag NPs are fundamental in view of the engineering of specific stimuli-responsive systems, able to control drug release in response to external stimuli. The release profiles of SLB from the newly synthesized PEG-PLA@Ag composite show strong dependences on laser wavelength and Ag NPs' Surface Plasmon Resonance (SPR). The resonant laser light excites the SPR of the NPs and the absorbed energy is converted into heat due to electron-photon collisions. The heat generated from the nanometer-sized metal particles embedded within the polymer is efficient and strongly localized. The nanovector, irradiated by a relatively low-intensity laser but tuned specifically to the metal NPs' SPR, releases the encapsulated drug with a higher efficiency than that not irradiated or irradiated with a laser wavelength far from the metal SPR. A combination of analytical techniques including UV-Vis, NMR, and FT-IR spectroscopy and scanning/transmission electron microscopy has been used to study the structural and morphological properties of the composite. The controllable specificity of this approach and the possibility of the SPR-mediated localized photothermal effect to be usefully applied in aqueous environments are the relevant advances of the proposed system for photothermal therapies that make use of visible optical radiation or for the drug delivery in proximity of the tumor cells.

  19. Platinum(IV) complexes conjugated with phenstatin analogue as inhibitors of microtubule polymerization and reverser of multidrug resistance.

    Huang, Xiaochao; Huang, Rizhen; Gou, Shaohua; Wang, Zhimei; Liao, Zhixin; Wang, Hengshan


    Pt(IV) complexes comprising a phenstatin analogue, as dual-targeting Pt(IV) prodrug, were designed and synthesized. They were found not only to carry the DNA binding platinum warhead into the tumor cells, but also to have a small molecular unit to inhibit tubulin polymerization. In vitro evaluation results revealed that Pt(IV) complexes showed better and more potent activity against the test human cancer cells including cisplatin resistant cell lines than their corresponding Pt(II) counterparts. In addition, the Pt(IV) derivative of cisplatin, complex 10, exhibited highly selective inhibition in human cancer cells and displayed no obvious toxicity to two human normal cell lines, respectively. Mechanism study suggested that complex 10 induced cell-cycle arrest at the G2/M phase and caused apoptotic cell death of human lung cancer NCI-H460 cells through the mitochondrial mediated pathway. Moreover, complex 10 effectively inhibited the tumor growth in the NCI-H460 xenograft model. Copyright © 2017. Published by Elsevier Ltd.

  20. Encapsulation and controlled release from core-shell nanoparticles fabricated by plasma polymerization

    Shahravan, Anaram; Matsoukas, Themis


    Core-shell nanostructures have been synthesized by plasma deposition in radio-frequency plasma reactor. Silica and KCl nanoparticles were encapsulated by deposition of isopropanol-based films of amorphous hydrogenated carbon. Through control of the deposition time, under constant deposition rate of 1 nm/min, particles are encapsulated in a layer of plasma polymer with thickness between 15 and 100 nm. Films are robust, chemically inert, thermally stable up to 250°C. The permeability of the shells is determined by depositing films of various thickness onto KCl nanoparticles and monitoring the dissolution of the core in aqueous solution. The dissolution profile is characterized by an initial rapid release, followed by a slow release that lasts up to 30 days for the thickest films. The profile is analyzed by Fickian diffusion through a spherical matrix. We find that this model captures very accurately the entire release profile except for the first 12 hours during which, the dissolution rate is higher than that predicted by the model. The overall diffusion coefficient for the dissolution of KCl is 3 × 10-21 m2/s.

  1. Conjugating an anticancer drug onto thiolated hyaluronic acid by acid liable hydrazone linkage for its gelation and dual stimuli-response release.

    Fu, Chaoping; Li, Hailiang; Li, Nannan; Miao, Xiangwan; Xie, Minqiang; Du, Wenjun; Zhang, Li-Ming


    A prodrug gelation strategy was developed for the sustained and dual stimuli-response release of doxorubicin hydrochloride (DOX·HCl), a commonly used anticancer drug. For this purpose, the chemical conjugation of DOX·HCl onto thiolated hyaluronic acid (HA) was carried out by an acid liable hydrazone linkage and verified by (1)H NMR analyses. When exposed to the air, such a polysaccharide conjugate showed unique self-gelation ability in aqueous solution. The gelation time and extent depended mainly on the content of thiol groups on thiolated HA. The resultant hydrogel exhibited a dominant elastic response and a thixotropic property. In particular, it could release sustainably conjugated DOX·HCl in dual pH- and reduction-responsive modes. The cumulative drug release was found to be significantly accelerated under the conditions mimicking the intracellular environments of cancer cells. The in vitro cytotoxicity assays for the human nasopharyngeal carcinoma CNE2 cells treated with various release media confirmed the effectiveness of this conjugate hydrogel for cancer cell inhibition.

  2. Relationship between Surface Properties and In Vitro Drug Release from Compressed Matrix Containing Polymeric Materials with Different Hydrophobicity Degrees

    Cristhian J. Yarce


    Full Text Available This work is the continuation of a study focused on establishing relations between surface thermodynamic properties and in vitro release mechanisms using a model drug (ampicillin trihydrate, besides analyzing the granulometric properties of new polymeric materials and thus establishing the potential to be used in the pharmaceutical field as modified delivery excipients. To do this, we used copolymeric materials derived from maleic anhydride with decreasing polarity corresponding to poly(isobutylene-alt-maleic acid (hydrophilic, sodium salt of poly(maleic acid-alt-octadecene (amphiphilic, poly(maleic anhydride-alt-octadecene (hydrophobic and the reference polymer hydroxyl-propyl-methyl-cellulose (HPMC. Each material alone and in blends underwent spectroscopic characterization by FTIR, thermal characterization by DSC and granulometric characterization using flow and compaction tests. Each tablet was prepared at different polymer ratios of 0%, 10%, 20%, 30% and 40%, and the surface properties were determined, including the roughness by micro-visualization, contact angle and water absorption rate by the sessile drop method and obtaining Wadh and surface free energy (SFE using the semi-empirical models of Young–Dupré and  Owens-Wendt-Rabel-Käelbe (OWRK, respectively. Dissolution profiles were determined simulating physiological conditions in vitro, where the kinetic models of order-zero, order-one, Higuchi and Korsmeyer–Peppas were evaluated. The results showed a strong relationship between the proportion and nature of the polymer to the surface thermodynamic properties and kinetic release mechanism.

  3. Controlled release of 5-fluorouracil or mitomycin-c from polymer matrix: Preparation by radiation polymerization and in vivo evaluation of the anticancer drug/polymer composites

    Li, Ximing; Shen, Weiming; Liu, Chengjie; Nishimoto, Sei-Ichi; Kagiya, Tsutomu

    Polymer tablets containing anticancer drugs such as 5-fluorouracil (5-FU) and mitomycin-C (MMC) have been prepared to evaluate the drug-release characteristics in vitro and the effect on local control of mouse solid tumors in vivo. Radiation-induced polymerization of hydrophilic monomers (2-hydroxyethyl methacrylate and related monomers) at low temperature (-80°C) was performed to immobilize 5-FU or MMC in the polymer matrix. The drug was dispersed as microcrystallines within the polymer matrix. The rate of drug release in vitro in buffer solution (pH7.0, 37°C) increased with increase in hydrophilicity of polymer matrix. Appropriate amount of crosslinks within the polymer matrix, as formed by ethylene glycol dimethacrylate (2G) added in the polymerization system, was effective to control the rate of drug release. The drug release became faster upon the addition of increasing amount of water in the radiation-induced polymerization. The tablet consisting of drug/polymer was buried surgically near solid tumors of striate muscle sarcoma (S180) transplanted to Kunming mice and the therapeutic effect of slow releasing drugs was evaluated in vivo by reference to intraperitoneal (i.p.) injection of the corresponding drugs. The slow releasing drugs led to high chemotherapeutic gain for local control of solid tumors with remarkable reduction of toxic side effect of the drugs.

  4. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    Andhariya, Nidhi; Upadhyay, Ramesh; Mehta, Rasbindu; Chudasama, Bhupendra


    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor—folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  5. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    Andhariya, Nidhi, E-mail: [Thapar University, School of Physics and Materials Science (India); Upadhyay, Ramesh [Charotar University of Science and Technology, P.D. Patel Institute of Applied Sciences (India); Mehta, Rasbindu [Maharaja Krishnakumarsinhji Bhavnagar University, Department of Physics (India); Chudasama, Bhupendra, E-mail: [Thapar University, School of Physics and Materials Science (India)


    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor-folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  6. A rapamycin-releasing perivascular polymeric sheath produces highly effective inhibition of intimal hyperplasia.

    Yu, Xiaohua; Takayama, Toshio; Goel, Shakti A; Shi, Xudong; Zhou, Yifan; Kent, K Craig; Murphy, William L; Guo, Lian-Wang


    Intimal hyperplasia produces restenosis (re-narrowing) of the vessel lumen following vascular intervention. Drugs that inhibit intimal hyperplasia have been developed, however there is currently no clinical method of perivascular drug-delivery to prevent restenosis following open surgical procedures. Here we report a poly(ε-caprolactone) (PCL) sheath that is highly effective in preventing intimal hyperplasia through perivascular delivery of rapamycin. We first screened a series of bioresorbable polymers, i.e., poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLLA), PCL, and their blends, to identify desired release kinetics and sheath physical properties. Both PLGA and PLLA sheaths produced minimal (PBS buffer. In contrast, PCL sheaths exhibited more rapid and near-linear release kinetics, as well as durable integrity (>90days) as evidenced in both scanning electron microscopy and subcutaneous embedding experiments. Moreover, a PCL sheath deployed around balloon-injured rat carotid arteries was associated with a minimum rate of thrombosis compared to PLGA and PLLA. Morphometric analysis and immunohistochemistry revealed that rapamycin-loaded perivascular PCL sheaths produced pronounced (85%) inhibition of intimal hyperplasia (0.15±0.05 vs 1.01±0.16), without impairment of the luminal endothelium, the vessel's anti-thrombotic layer. Our data collectively show that a rapamycin-loaded PCL delivery system produces substantial mitigation of neointima, likely due to its favorable physical properties leading to a stable yet flexible perivascular sheath and steady and prolonged release kinetics. Thus, a PCL sheath may provide useful scaffolding for devising effective perivascular drug delivery particularly suited for preventing restenosis following open vascular surgery.

  7. Paper-based microfluidics with an erodible polymeric bridge giving controlled release and timed flow shutoff.

    Jahanshahi-Anbuhi, Sana; Henry, Aleah; Leung, Vincent; Sicard, Clémence; Pennings, Kevin; Pelton, Robert; Brennan, John D; Filipe, Carlos D M


    Water soluble pullulan films were formatted into paper-based microfluidic devices, serving as a controlled time shutoff valve. The utility of the valve was demonstrated by a one-step, fully automatic implementation of a complex pesticide assay requiring timed, sequential exposure of an immobilized enzyme layer to separate liquid streams. Pullulan film dissolution and the capillary wicking of aqueous solutions through the device were measured and modeled providing valve design criteria. The films dissolve mainly by surface erosion, meaning the film thickness mainly controls the shutoff time. This method can also provide time-dependent sequential release of reagents without compromising the simplicity and low cost of paper-based devices.

  8. Controlled Synthesis of Camptothecin-Polylactide Conjugates and Nanoconjugates

    Tong, Rong; Cheng, Jianjun


    We report here a unique method of formulating camptothecin-polylactide (CPT-PLA) conjugate nanoparticles, termed nanoconjugates (NCs), through CPT/(BDI)ZnN(TMS)2 [(BDI) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-bisalkyl)-imino)-2-pentene] mediated polymerization of lactide (LA) followed by nanoprecipitation. When CPT was used as the initiator to polymerize LA in the presence of (BDI)ZnN(TMS)2, the polymerization was complete within hours with nearly 100% CPT loading efficiency and 100% LA conversion. CPT loading as high as 19.5% can be achieved for the CPT-polylactide (CPT-PLA) conjugate prepared at a LA/CPT ratio of 10. The steric bulk of the chelating ligands and the type of metals used had a dramatic effect on the initiation of the LA polymerization and the tendency of the ring opening of the CPT lactone. The CPT/(BDI)ZnN(TMS)2-mediated LA polymerization yielded CPT-PLA conjugates with well controlled molecular weights and narrow molecular weight distributions (1.02–1.18). The nanoprecipitation of CPT-PLA led to the formation of NCs around 100 nm in size with narrow particle size distributions. Sustained release of CPT from CPT-PLA NCs was achieved without burst release. CPT-PLA NCs were toxic to PC-3 cells with tunable IC50 possible by adjusting the drug loading of the CPT-PLA NCs. PMID:20000458

  9. Repetitive on-demand drug release from polymeric matrices containing a macroscopic spherical iron core.

    Rovers, Stefan A; Kemmere, Maartje F; Keurentjes, Jos T F; Hoogenboom, Richard


    A system for multiple on-demand drug release has been prepared that can be activated with an alternating magnetic field as external trigger. The core/shell samples have been developed based on a macroscopic spherical iron core coated with a thermoresponsive polymer, poly(styrene-stat-butyl methacrylate), containing ibuprofen as a model drug. During exposure of the samples to the magnetic field (ON state), the release rate of ibuprofen is significantly increased, up to 35 times the release rate without the magnetic field (OFF state). Using one sample or two samples in line with the magnetic field does not influence the ON/OFF ratio of the system, showing the possibility of using multiple samples to increase and tune the drug dose. Increasing the concentration of ibuprofen in the polymer layer is shown to increase the release rate in both the ON and OFF states. Increasing the size of the iron core and, consequently, decreasing the polymer thickness, was found to only increase the release rate during exposure resulting in higher ON/OFF ratios. The developed on demand drug delivery systems represents a promising development towards on demand drug delivery implants. During my chemical engineering studies, it was only during my master thesis work that I decided to continue with PhD research as I really enjoyed doing original research. When coming to the end of my PhD research under supervision of Prof. Ulrich S. Schubert, I developed the ambition to pursue an academic career. Fortunately, I got the opportunity to stay with Prof. Schubert as project leader for the Dutch Polymer Institute (DPI). Within this position, I supervised ten researchers and was able to start developing my independent research lines. Despite that I now advise students to not stay in the same laboratory, this first position allowed me to gain some initial independence and to publish a large number of papers that has been a great benefit in my further career. After two and a half years I needed a new

  10. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

    Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo


    Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition.

  11. Preparation and characterization of ketoprofen loaded eudragit RS polymeric nanoparticles for controlled release

    Anh, Nguyen Tuan; Chi, Nguyen T.; Khai Tran, T.; Tuyen Dao, T. P.; Nhan Le, N. T.; Mau Chien, Dang; Hoai, Nguyen To


    Nanospheres containing ketoprofen (Keto) and polymer eudragit RS were prepared using an emulsion solvent evaporation method. The ultrasonic probe (VCX500, vibracell) was used as a tool to disperse oil phase into aqueous phase leading to water/oil emulsion. Nanoparticles were successfully prepared and their morphologies and diameters were confirmed by transmission electron microscope (TEM) and dynamic light scattering (DLS), respectively. The result showed that particles were spherical with submicron size. The particle size was dependent on the RS concentration, emulsification tools and the types of organic solvents. For the encapsulation ability, Keto-loaded RS nanoparticle showed 9.8% of Keto in nanoparticle, which was evaluated by high-performance liquid chromatography (HPLC). Moreover, the drug release behavior of Keto-loaded eudragit RS nanoparticle was also investigated in vitro at pH 7.4 and compared to referential profenid.

  12. Hydrophobic interactions between polymeric carrier and palmitic acid-conjugated siRNA improve PEGylated polyplex stability and enhance in vivo pharmacokinetics and tumor gene silencing.

    Sarett, Samantha M; Werfel, Thomas A; Chandra, Irene; Jackson, Meredith A; Kavanaugh, Taylor E; Hattaway, Madison E; Giorgio, Todd D; Duvall, Craig L


    Formation of stable, long-circulating siRNA polyplexes is a significant challenge in translation of intravenously-delivered, polymeric RNAi cancer therapies. Here, we report that siRNA hydrophobization through conjugation to palmitic acid (siPA) improves stability, in vivo pharmacokinetics, and tumor gene silencing of PEGylated nanopolyplexes (siPA-NPs) with balanced cationic and hydrophobic content in the core relative to the analogous polyplexes formed with unmodified siRNA, si-NPs. Hydrophobized siPA loaded into the NPs at a lower charge ratio (N(+):P(-)) relative to unmodified siRNA, and siPA-NPs had superior resistance to siRNA cargo unpackaging in comparison to si-NPs upon exposure to the competing polyanion heparin and serum. In vitro, siPA-NPs increased uptake in MDA-MB-231 breast cancer cells (100% positive cells vs. 60% positive cells) but exhibited equivalent silencing of the model gene luciferase relative to si-NPs. In vivo in a murine model, the circulation half-life of intravenously-injected siPA-NPs was double that of si-NPs, resulting in a >2-fold increase in siRNA biodistribution to orthotopic MDA-MB-231 mammary tumors. The increased circulation half-life of siPA-NPs was dependent upon the hydrophobic interactions of the siRNA and the NP core component and not just siRNA hydrophobization, as siPA did not contribute to improved circulation time relative to unmodified siRNA when delivered using polyplexes with a fully cationic core. Intravenous delivery of siPA-NPs also achieved significant silencing of the model gene luciferase in vivo (∼40% at 24 h after one treatment and ∼60% at 48 h after two treatments) in the murine MDA-MB-231 tumor model, while si-NPs only produced a significant silencing effect after two treatments. These data suggest that stabilization of PEGylated siRNA polyplexes through a combination of hydrophobic and electrostatic interactions between siRNA cargo and the polymeric carrier improves in vivo pharmacokinetics and

  13. Freeze-dried mucoadhesive polymeric system containing pegylated lipoplexes: Towards a vaginal sustained released system for siRNA.

    Furst, Tania; Dakwar, George R; Zagato, Elisa; Lechanteur, Anna; Remaut, Katrien; Evrard, Brigitte; Braeckmans, Kevin; Piel, Geraldine


    Topical vaginal sustained delivery of siRNA presents a significant challenge due to the short residence time of formulations. Therefore, a drug delivery system capable to adhere to the vaginal mucosa is desirable, as it could allow a prolonged delivery and increase the effectiveness of the therapy. The aim of this project is to develop a polymeric solid mucoadhesive system, loaded with lipoplexes, able to be progressively rehydrated by the vaginal fluids to form a hydrogel and to deliver siRNA to vaginal tissues. To minimize adhesive interactions with vaginal mucus components, lipoplexes were coated with different derivatives of polyethylene glycol: DPSE-PEG2000, DPSE-PEG750 and ceramide-PEG2000. Based on stability and diffusion properties in simulated vaginal fluids, lipoplexes containing DSPE-PEG2000 were selected and incorporated in hydroxyethyl cellulose (HEC) hydrogels. Solid systems, called sponges, were then obtained by freeze-drying. Sponges meet acceptable mechanical characteristics and their hardness, deformability and mucoadhesive properties are not influenced by the presence of lipoplexes. Finally, mobility and stability of lipoplexes inside sponges rehydrated with vaginal mucus, mimicking in situ conditions, were evaluated by advanced fluorescence microscopy. The release rate was found to be influenced by the HEC concentration and consequently by the viscosity after rehydration. This study demonstrates the feasibility of entrapping pegylated lipoplexes into a solid matrix system for a prolonged delivery of siRNA into the vagina.

  14. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH).

    Obayemi, J D; Dozie-Nwachukwu, S; Danyuo, Y; Odusanya, O S; Anuku, N; Malatesta, K; Soboyejo, W O


    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV-Visible (UV-Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer.

  15. Antimicrobial and Controlled Release Studies of a Novel Nystatin Conjugated Iron Oxide Nanocomposite

    Samer Hasan Hussein-Al-Ali


    Full Text Available Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of antifungal activity. In the present study, we prepared a nystatin nanocomposite (Nyst-CS-MNP by loading nystatin (Nyst on chitosan (CS coated magnetic nanoparticles (MNPs. The magnetic nanocomposites were characterized by X-ray powder diffraction (XRD, Fourier transform infrared spectroscopy (FT-IR, thermogravimetry analysis (TGA, vibrating sample magnetometer (VSM, and scanning electron microscopy (SEM. The XRD results showed that the MNPs and nanocomposite are pure magnetite. The FTIR analysis confirmed the binding of CS on the surface of the MNPs and also the loading of Nyst in the nanocomposite. The Nyst drug loading was estimated using UV-Vis instrumentation and showing a 14.9% loading in the nanocomposite. The TEM size image of the MNPs, CS-MNP, and Nyst-CS-MNP was 13, 11, and 8 nm, respectively. The release profile of the Nyst drug from the nanocomposite followed a pseudo-second-order kinetic model. The antimicrobial activity of the as-synthesized Nyst and Nyst-CS-MNP nanocomposite was evaluated using an agar diffusion method and showed enhanced antifungal activity against Candida albicans. In this manner, this study introduces a novel nanocomposite that can decrease fungus activity on-demand for numerous medical applications.

  16. Impact of physicochemical properties of porous silica materials conjugated with dexamethasone via pH-responsive hydrazone bond on drug loading and release behavior

    Numpilai, Thanapha; Witoon, Thongthai; Chareonpanich, Metta; Limtrakul, Jumras


    The conjugation of dexamethasone (DEX) onto modified-porous silica materials via a pH-responsive hydrazone bond has been reported to be highly efficient method to specifically deliver the DEX to diseased sites. However, the influence of physicochemical properties of porous silica materials has not yet been fully understood. In this paper, the impact of pore sizes, particle sizes and silanol contents on surface functionalization, drug loading and release behavior of porous silica materials conjugated with dexamethasone via pH-responsive hydrazone bond was investigated. The grafting density was found to relate to the number of silanol groups on the surface of porous silica materials. The particle size and macropores of the porous silica materials played an vital role on the drug loading and release behavior. Although the porous silica materials with larger particle sizes possessed a lower grafting density, a larger amount of drug loading could be achieved. Moreover, the porous silica materials with larger particle sizes showed a slower release rate of DEX due to a longer distance for cleaved DEX diffusion out of pores. DEX release rate exhibited pH-dependent, sustained release. At pH 4.5, the amount of DEX release within 10 days could be controlled in the range of 12.74-36.41%, depending on the host material. Meanwhile, less than 1.5% of DEX was released from each of type of the porous silica materials at pH 7.4. The results of silica dissolution suggested that the degradation of silica matrix did not significantly affect the release rate of DEX. In addition, the kinetic modeling studies revealed that the DEX releases followed Korsmeyer-Peppas model with a release exponent (n) ranged from 0.3 to 0.47, indicating a diffusion-controlled release mechanism.

  17. Study of the nature and of the properties of paramagnetic centers observed by electron spin resonance in conjugated polymers; Etude de la nature des propriete des centres paramagnetiques observes par resonance paramagnetique electronique dans les polymeres conjugues

    Nechtschein, M. [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires


    Conjugated polymers contain paramagnetic centers. It is established that these centers are free radicals and a model which defines their electronic structure is proposed. The interactions between these centers are studied, notably by dynamic polarisation experiments. Finally it is shown that the centers have catalytic properties. (author) [French] Les polymeres conjugues contiennent des centres paramagnetiques. L'origine radicalaire de ces centres est etablie et un modele precisant leur structure electronique est propose. Les interactions entre ces centres sont etudiees, notamment a l'aide d'experiences de polarisation dynamique. Des proprietes catalytiques sont mises en evidence. (auteur)

  18. Preparation, characterization and in vitro release kinetics of polyaspartamide-based conjugates containing antimalarial and anticancer agents for combination therapy

    Aderibigbe, BA


    Full Text Available Malaria is treated by combination of two drugs in order to overcome drug resistance. Antimalarials have been found to be more effective by combining them with low doses of anticancer drugs. Polymer-drug conjugates containing aminoquinoline...

  19. Synthesis, recognition and evaluation of molecularly imprinted polymer nanoparticle using miniemulsion polymerization for controlled release and analysis of risperidone in human plasma samples

    Asadi, Ebadullah; Azodi-Deilami, Saman; Abdouss, Majid [Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Kordestani, Davood [Razi University, Kermanshah (Iran, Islamic Republic of); Rahimi, Alireza [Research Institute of Petroleum Industry (RIPI), Tehran (Iran, Islamic Republic of); Asadi, Somayeh [Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of)


    We prepared high selective imprinted nanoparticle polymers by a miniemulsion polymerization technique, using risperidone as the template, MAA as the functional monomers, and TRIM as the cross-linker in acetonitrile as solvent. The morphology of the nanoparticles determined by scanning electron microscopy (SEM) images and drug release, binding properties and dynamic light scattering (DLS) of molecularly imprinted polymers (MIPs) were studied. Controlled release of risperidone from nanoparticles was investigated through in 1% wt sodium dodecyl sulfate aqueous solution and by measuring the absorbance by HPLC-UV. The results showed that the imprinted nanoparticles exhibited a higher binding level and slower release rate than non-imprinted nanoparticles, which contributed to interaction of risperidone with imprinted cavities within nanoparticles. Furthermore, the results from HPLC showed good precision (5% for 50.0 µg L{sup -1}) and recoveries (between 86-91) using MIP from human plasma samples.

  20. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    Wen-Hao Wei


    Full Text Available Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD chemical conjugate with different degree of substitution (DS of deoxycholic acid (DOCA were prepared. The degree of substitution (DS was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX as the model drug. The human cervical cancer (HeLa cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE, which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.

  1. In vitro investigation of self-assembled nanoparticles based on hyaluronic acid-deoxycholic acid conjugates for controlled release doxorubicin: effect of degree of substitution of deoxycholic acid.

    Wei, Wen-Hao; Dong, Xue-Meng; Liu, Chen-Guang


    Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin-mediated cancer therapy.

  2. The stability and controlled release of I-ascorbic acid encapsulated in poly (ethyl-2-cyanoacrylate) nanocapsules prepared by interfacial polymerization of water-in-oil microemulsions.

    Zhang, Su-Ning; Chen, Tao; Guo, Yi-Guang; Zhang, Jian; Song, Xiaoqiu; Zhou, Lei


    The L-ascorbic acid (AA) was encapsulated into biodegradable and biocompatible poly(ethyl-2-cyanoacrylate) (PECA) nanocapsules by interfacial polymerization of water-in-oil (W/O) microemulsions. The influences of surfactant concentration, pH value of the dispersed aqueous phase, and W/O ratio on nanocapsule size were discussed. The stability and in vitro release of encapsulated AA were also investigated. The results show that nanocapsules could be obtained under the conditions with low pH value, high fraction of aqueous phase, and appropriate surfactant concentration. The encapsulated AA was protected by nanocapsules from oxidation and presented superior storage stability in aqueous medium than pure AA. Releasing AA from the inner core of nanocapsules could be controlled by adjusting the enzyme hydrolysis extent of the PECA wall.

  3. Characterizations of plasticized polymeric film coatings for preparing multiple-unit floating drug delivery systems (muFDDSs with controlled-release characteristics.

    Sheng-Feng Hung

    Full Text Available Effervescent multiple-unit floating drug delivery systems (muFDDSs consisting of drug (lorsartan- and effervescent (sodium bicarbonate-containing pellets were characterized in this study. The mechanical properties (stress and strain at rupture, Young's modulus, and toughness of these plasticized polymeric films of acrylic (Eudragit RS, RL, and NE and cellulosic materials (ethyl cellulose (EC, and Surelease were examined by a dynamic mechanical analyzer. Results demonstrated that polymeric films prepared from Surelease and EC were brittle with less elongation compared to acrylic films. Eudragit NE films were very flexible in both the dry and wet states. Because plasticizer leached from polymeric films during exposure to the aqueous medium, plasticization of wet Eudragit RS and RL films with 15% triethyl citrate (TEC or diethyl phthalate (DEP resulted in less elongation. DEP might be the plasticizer of choice among the plasticizers examined in this study for Eudragit RL to provide muFDDSs with a short time for all pellets to float (TPF and a longer period of floating. Eudragit RL and RS at a 1∶1 ratio plasticized with 15% DEP were optimally selected as the coating membrane for the floating system. Although the release of losartan from the pellets was still too fast as a result of losartan being freely soluble in water, muFDDSs coated with Eudragit RL and RS at a 1∶1 ratio might have potential use for the sustained release of water-insoluble or the un-ionized form of drugs from gastroretentive drug delivery systems.

  4. Thermolytic release of covalently linked DNA oligonucleotides and their conjugates from controlled-pore glass at near neutral pH.

    Grajkowski, Andrzej; Cieślak, Jacek; Kauffman, Jon S; Duff, Robert J; Norris, Scott; Freedberg, Darón I; Beaucage, Serge L


    The functionalization of long chain alkylamine controlled-pore glass (CPG) with a 3-hydroxypropyl-(2-cyanoethyl)thiophosphoryl linker and its conversion to the support 7 has led to the synthesis of DNA oligonucleotides and their 3'- or (3',5')-conjugates. Indeed, CPG support 7 has been successfully employed in the synthesis of both native and fully phosphorothioated DNA 20-mers. Unlike conventional succinylated CPG supports, this distinctively functionalized support allows oligonucleotide deprotection and removal of the deprotection side products to proceed without releasing the oligonucleotide into the aqueous milieu. When freed from deprotection side products, the DNA oligonucleotide is thermolytically released from the support within 2 h under nearly neutral conditions (pH 7.2, 90 degrees C). The quality of these oligonucleotides is comparable to that of identical oligonucleotides synthesized from succinylated CPG supports in terms of shorter than full length oligonucleotide contaminants and overall yields. The versatility of the thermolytic CPG support 7 is further demonstrated by the synthesis of a DNA oligonucleotide (20-mer) and its conjugation with an azido and alkynyl groups at both 5'-and 3'-termini, respectively. The functionality of the (3',5')-heteroconjugated oligonucleotide 18 is verified by its circularization to the DNA oligonucleotide 19 under "click" chemistry conditions.

  5. Dual-layered nanogel-coated hollow lipid/polypeptide conjugate assemblies for potential pH-triggered intracellular drug release.

    Wen-Hsuan Chiang

    Full Text Available To achieve effective intracellular anticancer drug delivery, the polymeric vesicles supplemented with the pH-responsive outlayered gels as a delivery system of doxorubicin (DOX were developed from self-assembly of the lipid/polypeptide adduct, distearin grafted poly(γ-glutamic acid (poly(γ-GA, followed by sequential deposition of chitosan and poly(γ-GA-co-γ-glutamyl oxysuccinimide-g-monomethoxy poly(ethylene glycol in combination with in situ covalent cross-linking on assembly surfaces. The resultant gel-caged polymeric vesicles (GCPVs showed superior performance in regulating drug release in response to the external pH change. Under typical physiological conditions (pH 7.4 and 37 °C at which the γ-GA/DOX ionic pairings remained mostly undisturbed, the dense outlayered gels of GCPVs significantly reduced the premature leakage of the uncomplexed payload. With the environmental pH being reduced from pH 7.4 to 4.7, the drug liberation was appreciably promoted by the massive disruption of the ionic γ-GA/DOX complexes along with the significant swelling of nanogel layers upon the increased protonation of chitosan chain segments. After being internalized by HeLa cells via endocytosis, GCPVs exhibited cytotoxic effect comparable to free DOX achieved by rapidly releasing the payload in intracellular acidic endosomes and lysosomes. This strongly implies the great promise of such unique GCPVs as an intracellular drug delivery carrier for potential anticancer treatment.

  6. Characterization of naproxen-polymer conjugates for drug-delivery.

    Forte, Gianpiero; Chiarotto, Isabella; Giannicchi, Ilaria; Loreto, Maria Antonietta; Martinelli, Andrea; Micci, Roberta; Pepi, Federico; Rossi, Serena; Salvitti, Chiara; Stringaro, Annarita; Tortora, Luca; Vecchio Ciprioti, Stefano; Feroci, Marta


    The synthesis and the characterization of three new naproxen decorated polymers are described. A versatile and general approach is employed to link the drug to polymers, affording the derivatives with a very high degree of purity. The release of the drug from the conjugates proved to be exceptionally slow, even in acidic aqueous media, and the kinetic of the process seems to be triggered by their solubility in water. On the other hand, the interesting outcome of the first ex vivo drug release experiments on human blood samples makes this preliminary study valuable for future investigations on the use of these polymeric prodrugs in in vivo treatment of inflammatory states.

  7. Conjugated Linoleic Acids Mediate Insulin Release through Islet G Protein-coupled Receptor FFA1/GPR40

    Schmidt, Johannes; Liebscher, Kathrin; Merten, Nicole


    Among dietary components, conjugated linoleic acids (CLAs) have attracted considerable attention as weight loss supplements in the Western world because they reduce fat stores and increase muscle mass. However, a number of adverse effects are also ascribed to the intake of CLAs such as aggravatio...... in widely used nutraceuticals, a finding with significant implication for development of FFA1 modulators to treat type 2 diabetes....

  8. Controlled Release of Antimicrobial ClO2 Gas from a Two-Layer Polymeric Film System.

    Bai, Zhifeng; Cristancho, Diego E; Rachford, Aaron A; Reder, Amy L; Williamson, Alexander; Grzesiak, Adam L


    We report a two-component label system comprising a chlorite-containing polymer film and an acid-containing polymer film that can release antimicrobial ClO2 gas upon adhering the two films together to enable a reaction of the chlorite and acid under moisture exposure. The chlorite-containing film comprises a commercial acrylate-based pressure-sensitive adhesive polymer impregnated with sodium chlorite. The acid-containing film comprises a commercial poly(vinyl alcohol) polymer loaded with tartaric acid. Both of the films were prepared on low ClO2-absorbing substrate films from stable aqueous systems of the polymers with high reagent loading. Rapid and sustained releases of significant amounts of ClO2 gas from the label system were observed in an in situ quantification system using UV-vis spectroscopy. It was found that the ClO2 release is slower at a lower temperature and can be accelerated by moisture in the atmosphere and the films. Controlled release of ClO2 gas from the label system was demonstrated by tailoring film composition and thickness. A model was developed to extract release kinetics and revealed good conversions of the label system. This two-component system can potentially be applied as a two-part label without premature release for applications in food packaging.

  9. A Novel Active Targeting Preparation, Vinorelbine Tartrate (VLBT Encapsulated by Folate-Conjugated Bovine Serum Albumin (BSA Nanoparticles: Preparation, Characterization and in Vitro Release Study

    Xinyang Yu


    Full Text Available Vinorelbine tartrate (VLBT, as a kind of high hydrophilic and temperature-induced degradation drug, was prepared into nanoparticles by a desolvation procedure. Bovine serum albumin (BSA, as a drug carrier, was stabilized by chemical cross-linking with glutaraldehyde. Firstly, the optimization process of preparing VLBT-loaded BSA nanoparticles (VLBT-BSANPs was accomplished using response surface methodology (RSM by desolvation. Then VLBT-BSANPs were conjugated with folate, namely Fa-BSANPs-VLBT. Hence targeting drug carrier delivery system loading VLBT was produced. In this study, the characteristics of the nanoparticles, such as the amount of folate conjugation, surface morphology, surface chemistry, physical status of VLBT in Fa-BSANPs-VLBT, stability of Fa-BSANPs-VLBT with mannitol and in vitro drug release behavior were all investigated. The VLBT-BSANPs were obtained under optimum conditions, with a mean particle size (MPS of 155.4 nm and a zeta potential (ZP of −32.97 mV at a pH value of 5.4. Drug loading efficiency (DLE and drug entrapment efficiency (DEE of this obtained drug were approximately 45.6% and 90.6%, respectively.

  10. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

    Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria


    Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

  11. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH Peptide

    Pooria Mansoori


    Full Text Available Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.


    Furqan Muhammad, Iqbal; Mahmood, Ahmad; Aysha, Rashid


    A super-absorbent hydrogel was developed by crosslinking of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and acrylic acid with hydroxypropyl methylcellulose (HPMC) for controlled release drug delivery of captopril, a well known antihypertensive drug. Acrylic acid and AMPS were polymerized and crosslinked with HPMC by free radical polymerization, a widely used chemical crosslinking method. N,N'-methylenebisacrylamide (MBA) and potassium persulfate (KPS) were added as cross-linker and initiator, respectively. The hydrogel formulation was loaded with captopril (as model drug). The concentration of captopril was monitored at 205 nm using UV spectrophotometer. Equilibrium swelling ratio was determined at pH 2, 4.5 and 7.4 to evaluate the pH responsiveness of the formed hydrogel. The super-absorbent hydrogels were evaluated by FTIR, SEM, XRD, and thermal analysis (DSC and TGA). The formation of new copolymeric network was determined by FTIR, XRD, TGA and DSC analysis. The hydrogel formulations with acrylic acid and AMPS ratio of 4: 1 and lower amounts of crosslinker had shown maximum swelling. Moreover, higher release rate of captopril was observed at pH 7.4 than at pH 2, because of more swelling capacity of copolymer with increasing pH of the aqueous medium. The present research work confirms the development of a stable hydrogel comprising of HPMC with acrylic acid and AMPS. The prepared hydrogels exhibited pH sensitive behav-ior. This superabsorbent composite prepared could be a successful drug carrier for treating hypertension.

  13. Design of Controlled Release Non-erodible Polymeric Matrix Tablet Using Microwave Oven-assisted Sintering Technique.

    Patel, Dm; Patel, Bk; Patel, Ha; Patel, Cn


    The objective of the present study was to evaluate the effect of sintering condition on matrix formation and subsequent drug release from polymer matrix tablet for controlled release. The present study highlights the use of a microwave oven for the sintering process in order to achieve more uniform heat distribution with reduction in time required for sintering. We could achieve effective sintering within 8 min which is very less compared to conventional hot air oven sintering. The tablets containing the drug (propranolol hydrochloride) and sintering polymer (eudragit S-100) were prepared and kept in a microwave oven at 540 watt, 720 watt and 900 watt power for different time periods for sintering. The sintered tablets were evaluated for various tablet characteristics including dissolution study. Tablets sintered at 900 watt power for 8 min gave better dissolution profile compared to others. We conclude that microwave oven sintering is better than conventional hot air oven sintering process in preparation of controlled release tablets.

  14. Photocatalytic thin films coupled with polymeric microcapsules for the controlled-release of volatile agents upon solar activation

    Oliveira, L. F.; Marques, J.; Coutinho, P. J. G.; Parpot, P.; Tavares, C. J.


    This work reportson the application of solar-activated photocatalytic thin films that allow the controlled-release of volatile agents (e.g., insecticides, repellents) from the interior of adsorbedpolymericmicrocapsules. In order to standardize the tests, a quantification of the inherent controlled-release of a particular volatile agent is determined by gas chromatography coupled to mass spectroscopy, so that an application can be offered to a wide range of supports from various industrial sectors, such as in textiles (clothing, curtains, mosquito nets). This technology takes advantage of the established photocatalytic property of titanium dioxide (TiO2) for the use as an active surface/site to promote the controlled-release of a specific vapor (volatile agentfrom within the aforementioned microcapsules.

  15. Synthesis, Characterization, and Polymerization of New Ferrocene- Fluorene Complexes. A Novel High-Molecular Weight Conjugated Polymer with Pendant Ferrocene Groups


    similar to copolymer 4. Cyclic voltametry of complex 5 shows two reversible oxidation events, one at +0.11 V (two-electron event) and another at +0.71 V...unlimited9 a S two oxidation events, one at +0.11 V and the other at +0.71 V (relative to the ferrocene/ferrocenium couple). Cyclic voltammetry of...thermal and cyclic voltammetry behavior. To our knowledge, this is the first conjugated organic polymer backbone to possess pendant ferrocene moieties

  16. Polymeric emulsion and crosslink-mediated synthesis of super-stable nanoparticles as sustained-release anti-tuberculosis drug carriers.

    Choonara, Yahya E; Pillay, Viness; Ndesendo, Valence M K; du Toit, Lisa C; Kumar, Pradeep; Khan, Riaz A; Murphy, Caragh S; Jarvis, Debbie-Leigh


    This study focused on evaluating four emulsion-based processing strategies for polymeric nanoparticle synthesis to explicate the mechanisms of nanoparticle formation and the influence on achieving sustained-release of two anti-tuberculosis drugs, isoniazid and rifampicin. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were formulated with and without sorbitan mono-oleate as a stabilizer using emulsion-solvent-surfactant-evaporation (ESSE) and emulsion-solvent-evaporation (ESE) approaches. An alginate solution gelled by ionic crosslinking with calcium chloride was employed to prepare alginate hydrogel nanoparticles via reverse-emulsion-cationic-gelification (RECG) and reverse-emulsion-surfactant-cationic-gelification (RESCG) approaches. In vitro drug release analysis was performed. The size, zeta potential and morphology of the nanoparticles were analyzed. Molecular mechanics energy relationships (MMER) were employed to explore the spatial disposition of alginate and PLGA with respect to the emulsifying profile of sorbitan monooleate and to corroborate the experimental findings. Results revealed that particle size of the PLGA nanoparticles was influenced by the stabilizer concentration. Nanoparticles synthesized by the ESSE approach had smaller sizes of 240±8.7 nm and 195.5±5.4 nm for rifampicin- and isoniazid-loaded nanoparticles, respectively. This was a substantial size reduction from nanoparticles generated by the ESE approach (>1000 nm). The RESCG approach produced stable and higher nanoparticle yields with desirable size (277±1.0 nm; 289±1.2 nm), a low polydispersity index (27.1±0.3 mV; 28.5±0.5 mV) and drug entrapment efficiency of 73% and 75% for isoniazid and rifampicin, respectively. Drug release from the ESSE and RESCG synthesized nanoparticles displayed desirable release of the two anti-TB drugs with sustained zero-order kinetics over a period of 8h. MMER supported the mechanisms of nanoparticle formation with a sphericalized interlaced network

  17. Redox and pH dual-responsive PEG and chitosan-conjugated hollow mesoporous silica for controlled drug release

    Jiao, Jian; Li, Xian; Zhang, Sha; Liu, Jie; Di, Donghua [Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016 (China); Zhang, Ying [School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, PR China. (China); Zhao, Qinfu, E-mail: [Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016 (China); Wang, Siling, E-mail: [Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016 (China)


    In this paper, a hollow mesoporous silica nanoparticles (HMSN) was used as the drug vehicle to develop the redox and pH dual stimuli-responsive delivery system, in which the chitosan (CS), a biodegradable cationic polymer, was grafted on the surface of HMSN via the cleavable disulfide bonds. CS was chosen as the gatekeeper mainly due to its appropriate molecular weight as well as possessing abundant amino groups which could be protonated in the acidic condition to achieve pH-responsive drug release. In addition, the PEG was further grafted on the surface of CS to increase the stability and biocompatibility under physiological conditions. The DOX loaded DOX/HMSN-SS-CS@PEG had a relatively high drug loading efficiency up to 32.8%. In vitro release results indicated that DOX was dramatically blocked within the mesopores of HMSN-SS-CS@PEG in pH 7.4 PBS without addition of GSH. However, the release rate of DOX was markedly increased after the addition of 10 mM GSH or in pH 5.0 release medium. Moreover, the release of DOX was further improved in pH 5.0 PBS with 10 mM GSH. The HMSN-SS-CS@PEG could markedly decrease the hemolysis percent and protein adsorption, and increase the biocompatibility and stability of HMSN compared with the HMSN-SS-CS and bare HMSN. This work suggested an exploration about HMSN based stimuli-responsive drug delivery and these results demonstrated that HMSN-SS-CS@PEG exhibited dual-responsive drug release property and could be used as a promising carrier for cancer therapy. - Highlights: • Hollow mesoporous silica nanoparticles (HMSN) were used as a drug carrier. • Chitosan (CS) and PEG were grafted on the surface of HMSN via disulfide bonds. • The DOX loaded DOX/HMSN-SS-CS@PEG had a high drug loading efficiency up to 32.8%. • DOX/HMSN-SS-CS@PEG showed redox/pH dual-responsive drug release property in vitro. • The grafted PEG could increase the biocompatibility and stability of HMSN.

  18. Beta-cyclodextrins conjugated magnetic Fe{sub 3}O{sub 4} colloidal nanoclusters for the loading and release of hydrophobic molecule

    Lv, Shaonan; Song, Yubei; Song, Yaya; Zhao, Zhigang; Cheng, Changjing, E-mail:


    Herein, we report a facile method to prepare beta-cyclodextrin (β-CD)-conjugated magnetic Fe{sub 3}O{sub 4} colloidal nanocrystal clusters (Fe{sub 3}O{sub 4}@GLY-CD) using (3-glycidyloxypropyl) trimethoxysilane (GLY) as the intermediate linker. The resulting Fe{sub 3}O{sub 4}@GLY-CD was characterized by several methods including Fourier transform infrared (FT-IR) spectroscopy, field-emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and vibrating sample magnetometer (VSM). In addition, the loading and release properties of the synthesized Fe{sub 3}O{sub 4}@GLY-CD for the hydrophobic molecule 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) were also investigated. The results show that the Fe{sub 3}O{sub 4}@GLY-CD has a spherical structure with an average diameter of 186 nm and high saturated magnetism of 51.2 emu/g. The grafting of β-CD onto Fe{sub 3}O{sub 4} colloidal nanocrystal clusters can markedly increase the loading capacity of ANS because of β-CD/ANS inclusion complex formation. The in vitro delivery profile shows that the release of ANS from the Fe{sub 3}O{sub 4}@GLY-CD nanosystem exhibits an initial burst followed by a slow and steady release. Moreover, Fe{sub 3}O{sub 4}@GLY-CD also demonstrates a temperature-dependent release behavior for ANS owing to the effect of temperature on the association constants of β-CD/ANS inclusion complexes. The developed magnetic hybrid nanomaterial is expected to find potential applications in several fields including separation science and biomedicine.

  19. Study of a controlled release polymeric system based on Pluronic P123: Spectroscopic characterization and theoretical model approach

    Arroyo, E.; Luque, P. A.; Cosio, M.; Soto, C.; Villarreal, R.; Nava, O.; Olivas, A.


    This work reports the profiles of drug release systems based on different polymers for the potential use as a skin anti-inflammatory. The materials used for the encapsulation of indomethacin were Pluronic P123 with various combinations of poly-ethylene-glycol and poly-N-vinyl pyrrolidone. These systems were characterized via Fourier transform infrared spectrometry and high resolution transmission electron microscopy. The morphology showed the treated polymers as spheres. Drug loadings were carried out via the absorption in solution method; this load was of a 1:10 wt ratio indomethacin to polymers. Drug release tests were performed via the dialysis method pH 7.2 phosphate buffered saline at 32 °C. The drug concentration was determined via UV-Vis spectroscopy, and additionally, a theoretical model was developed based on diffusion equations to describe the phenomenon. Comparison between the experimental results and theory was close to 5%.

  20. NC-6301, a polymeric micelle rationally optimized for effective release of docetaxel, is potent but is less toxic than native docetaxel in vivo

    Harada M


    Full Text Available Mitsunori Harada,1 Caname Iwata,2 Hiroyuki Saito,1 Kenta Ishii,1 Tatsuyuki Hayashi,1 Masakazu Yashiro,3 Kosei Hirakawa,3 Kohei Miyazono,2 Yasuki Kato,1 Mitsunobu R Kano21Research Division, NanoCarrier Co, Ltd, Chiba, Japan; 2Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; 3Department of Surgical Oncology, Osaka City University, Osaka, JapanAbstract: Drug release rate is an important factor in determining efficacy and toxicity of nanoscale drug delivery systems. However, optimization of the release rate in polymeric micellar nanoscale drug delivery systems has not been fully investigated. In this study NC-6301, a poly(ethylene glycol-poly(aspartate block copolymer with docetaxel (DTX covalently bound via ester link, was synthesized with various numbers of DTX molecules bound to the polymer backbone. The number of DTX molecules was determined up to 14 to achieve an optimal release rate, based upon the authors' own pharmacokinetic model using known patient data. Efficacy and toxicity of the formulation was then tested in animals. When administered three times at 4-day intervals, the maximum tolerated doses of NC-6301 and native DTX were 50 and 10 mg/kg, respectively, in nude mice. Tissue distribution studies of NC-6301 in mice at 50 mg/kg revealed prolonged release of free DTX in the tumor for at least 120 hours, thus supporting its effectiveness. Furthermore, in cynomolgus monkeys, NC-6301 at 6 mg/kg three times at 2-week intervals showed marginal toxicity, whereas native DTX, at 3 mg/kg with the same schedule, induced significant decrease of food consumption and neutrophil count. NC-6301 at 50 mg/kg in mice also regressed a xenografted tumor of MDA-MB-231 human breast cancer. Native DTX, on the other hand, produced only transient and slight regression of the same tumor xenograft. NC-6301 also significantly inhibited growth of OCUM-2MLN human scirrhous gastric carcinoma in an orthotopic mouse

  1. Surface functional polymers by post-polymerization modification using diarylcarbenes: introduction, release and regeneration of hydrogen peroxide and bactericidal activity.

    Griffiths, Jon-Paul; Maliha, Bushra; Moloney, Mark G; Thompson, Amber L; Hussain, Ishtiaq


    Functionalized diarylcarbenes are excellent reactive intermediates suitable for the direct surface modification of organic polymers, and these may be used to introduce urea and thiourea functions onto polystyrene at loading levels of up to 2.3 x 10(13) molecules/cm(2). These functions are capable of the reversible binding and release of peroxide at loading levels of up to 0.6 mmol/g and give polymers that display biocidal activity against a spectrum of gram-positive and gram-negative bacteria.

  2. Conjugated Linoleic Acids Mediate Insulin Release through Islet G Protein-coupled Receptor FFA1/GPR40*

    Schmidt, Johannes; Liebscher, Kathrin; Merten, Nicole; Grundmann, Manuel; Mielenz, Manfred; Sauerwein, Helga; Christiansen, Elisabeth; Due-Hansen, Maria E.; Ulven, Trond; Ullrich, Susanne; Gomeza, Jesús; Drewke, Christel; Kostenis, Evi


    Among dietary components, conjugated linoleic acids (CLAs) have attracted considerable attention as weight loss supplements in the Western world because they reduce fat stores and increase muscle mass. However, a number of adverse effects are also ascribed to the intake of CLAs such as aggravation of insulin resistance and the risk of developing diabetes. However, the mechanisms accounting for the effects of CLAs on glucose homeostasis are incompletely understood. Herein we provide evidence that CLAs specifically activate the cell surface receptor FFA1, an emerging therapeutic target to treat type 2 diabetes. Using different recombinant cellular systems engineered to stably express FFA1 and a set of diverse functional assays including the novel, label-free non-invasive dynamic mass redistribution technology (Corning® Epic® biosensor), both CLA isomers cis-9, trans-11-CLA and trans-10, cis-12-CLA were found to activate FFA1 in vitro at concentrations sufficient to also account for FFA1 activation in vivo. Each CLA isomer markedly increased glucose-stimulated insulin secretion in insulin-producing INS-1E cells that endogenously express FFA1 and in primary pancreatic β-cells of wild type but not FFA1−/− knock-out mice. Our findings establish a clear mechanistic link between CLAs and insulin production and identify the cell surface receptor FFA1 as a molecular target for CLAs, explaining their acute stimulatory effects on insulin secretion in vivo. CLAs are also revealed as insulinotropic components in widely used nutraceuticals, a finding with significant implication for development of FFA1 modulators to treat type 2 diabetes. PMID:21339298

  3. A new method for the production of gelatin microparticles for controlled protein release from porous polymeric scaffolds.

    Ozkizilcik, Asya; Tuzlakoglu, Kadriye


    Tissue engineering using scaffolds and growth factors is a crucial approach in bone regeneration and repair. The combination of bioactive agents carrying microparticles with porous scaffolds can be an efficient solution when controlled release of bio-signalling molecules is required. The present study was based on a recent approach using a biodegradable scaffold and protein-loaded microparticles produced in an innovative manner in which protein loss is minimized during the loading process. Bovine serum albumin (BSA)-loaded gelatin microparticles were obtained by grinding freeze-dried membranes of gelatin and BSA. Porous scaffolds (250-355 µm pore size) produced from a polyactide (PLLA) and polycaprolactone (PCL) blend by salt leaching/supercritical CO₂ methods were used for the experiments. Gelatin microparticles containing three different BSA amounts were incorporated into the porous scaffolds by using a surfactant. In vitro release profiles showed up to 90% protein loading efficiency. This novel method appears to be an effective approach for producing particles that can minimize protein loss during the loading process.

  4. Polymeric nanoparticles loaded with the 3,5,3´-triiodothyroacetic acid (Triac, a thyroid hormone: factorial design, characterization, and release kinetics

    dos Santos KC


    Full Text Available Karen C dos Santos,1 Maria Fatima GF da Silva,1 Edenir R Pereira-Filho,1 Joao B Fernandes,1 Igor Polikarpov,2 Moacir R Forim11Department of Chemistry, Federal University of Sao Carlos, Sao Carlos, 2Physics Institute of Sao Carlos, University of Sao Paulo, Sao Carlos, Sao Paulo, BrazilAbstract: This present investigation deals with the development and optimization of polymeric nanoparticle systems loaded with 3,5,3´-triiodothyroacetic acid (Triac. A 211–6 fractional factorial design and another 22 factorial design were used to study the contrasts on particle size distribution, morphology, surface charge, drug content, entrapment efficiency, and in vitro drug release profiles. The independent variables were the concentration of Triac, type and quantity of both polymer and oil, quantity of Span™ 60 and Tween® 80, volume of solvent and water, and velocity of both magnetic stirring and the transfer of the organic phase into the aqueous solution. The results of optimized formulations showed a narrow size distribution with a polydispersity index lower than 0.200. The particle sizes were on average 159.6 nm and 285.6 nm for nanospheres and nanocapsules, respectively. The zeta potential was higher than 20 mV (in module and the entrapment efficiency was nearly 100%. A high-performance liquid chromatography method was developed, validated, and efficiently applied to Triac quantification in colloidal suspension. The main independent variables were the type and quantity of the polymer and oil. In vitro drug release profile depicted several features to sustain Triac release. Different formulations showed various release rates indicating an interaction between Triac and other formulation compounds such as polymer and/or oil quantity. Two different models were identified (biexponential and monoexponential that allowed the control of both the release rate and Triac concentration. Thus, the prepared nanoparticles described here may be of clinical importance

  5. Effect of functionalization of polymeric nanoparticles incorporated with whole attenuated rabies virus antigen on sustained release and efficacy

    Kiran Nivedh


    Full Text Available Nanovaccines introduced a new dimension to prevent or cure diseases in an efficient and sustained manner. Various polymers have been used for the drug delivery to increase the therapeutic value with minimal side effects. Thus the present study incorporates both nanotechnology and polymers for the drug delivery. Poly(d,l-lactic-co-glycolic acid-b-poly(ethylene glycol was incorporated with the rabies whole attenuated viral antigen using double emulsion (W/O/W method and characterized by Scanning Electron Microscopy (SEM and Atomic Force Microscopy (AFM. Chitosan-PEG nanoparticles incorporated with the rabies whole attenuated virus antigen (CS-PEG NP-RV Ag. were prepared using Ionic Gelation method. The CS-PEG NP-RV Ag. was surface modified with biocompatible polymers such as Acacia, Bovine Serum Albumin (BSA, Casein, Ovalbumin and Starch by Ionic Gelation method. The morphology was confirmed by SEM and Transmission Electron Microscopy (TEM. The surface modification was confirmed by Fourier Transform Infrared Spectroscopy (FTIR, Zeta potential. The size distribution of CS-PEG-RV Ag. and surface modified CS-PEG-RV Ag. by respective biocompatible polymers was assessed by Zetasizer. Release profile of both stabilized nanoparticles was carried out by modified centrifugal ultrafiltration method which showed the sustained release pattern of the Rabies Ag. Immune stimulation under in-vitro condition was studied using rosette assay and phagocytosis assay. In-vitro toxicity using human blood and genotoxicity using human blood DNA was also studied to assess the toxicity of the nanoformulations. The results of these studies infer that PLGA-b-PEG nanoparticles, CS-PEG and surface modified CS-PEG nanoparticles may be an efficient nanocarrier for the RV Ag. to elicit immune response sustainably with negligible toxic effect to the human system.

  6. Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep.

    Lee, Chang H; Rodeo, Scott A; Fortier, Lisa Ann; Lu, Chuanyong; Erisken, Cevat; Mao, Jeremy J


    Regeneration of complex tissues, such as kidney, liver, and cartilage, continues to be a scientific and translational challenge. Survival of ex vivo cultured, transplanted cells in tissue grafts is among one of the key barriers. Meniscus is a complex tissue consisting of collagen fibers and proteoglycans with gradient phenotypes of fibrocartilage and functions to provide congruence of the knee joint, without which the patient is likely to develop arthritis. Endogenous stem/progenitor cells regenerated the knee meniscus upon spatially released human connective tissue growth factor (CTGF) and transforming growth factor-β3 (TGFβ3) from a three-dimensional (3D)-printed biomaterial, enabling functional knee recovery. Sequentially applied CTGF and TGFβ3 were necessary and sufficient to propel mesenchymal stem/progenitor cells, as a heterogeneous population or as single-cell progenies, into fibrochondrocytes that concurrently synthesized procollagens I and IIα. When released from microchannels of 3D-printed, human meniscus scaffolds, CTGF and TGFβ3 induced endogenous stem/progenitor cells to differentiate and synthesize zone-specific type I and II collagens. We then replaced sheep meniscus with anatomically correct, 3D-printed scaffolds that incorporated spatially delivered CTGF and TGFβ3. Endogenous cells regenerated the meniscus with zone-specific matrix phenotypes: primarily type I collagen in the outer zone, and type II collagen in the inner zone, reminiscent of the native meniscus. Spatiotemporally delivered CTGF and TGFβ3 also restored inhomogeneous mechanical properties in the regenerated sheep meniscus. Survival and directed differentiation of endogenous cells in a tissue defect may have implications in the regeneration of complex (heterogeneous) tissues and organs.

  7. Effects of early vaccination with a gonadotropin releasing factor analog-diphtheria toxoid conjugate on boar taint and growth performance of male pigs.

    Kantas, D; Papatsiros, V; Tassis, P; Tzika, E; Pearce, M C; Wilson, S


    The aim of this study was to evaluate safety (in terms of detecting possible adverse clinical effects attributable to vaccination), efficacy, and effects on growth performance of a gonadotropin releasing factor analog-diphtheria toxoid conjugate (commercially distributed as Improvac; Zoetis, Zaventem, Belgium) in male pigs raised in a commercial Greek farm. A total of 1,230 male pigs was enrolled in 16 weekly batches and allocated to 3 groups: barrows (castrated on the next day after birth [study Day 0]), pigs vaccinated with the above-mentioned product, and intact boars. Vaccinated pigs were injected subcutaneously with 2 mL of the anti-gonadotropin releasing factor (GnRF) vaccine at 9 to 11 wk of age (60-78 d) and 15 to 17 wk of age (102-120 d) and slaughtered at 22 to 25 wk of age (152-176 d). No clinical abnormalities or adverse events attributable to vaccination occurred. Mean BW of vaccinated pigs was 6% greater compared with barrows at slaughter (P vaccinated pigs had greater ADG than barrows from castration to slaughter (8%). In detail, a lower ADG from first to second vaccination (-12%; P vaccination to slaughter (P vaccinated pigs and intact boars was not significantly different throughout the study, except from first to second vaccination (boars greater; P = 0.0059) and second vaccination to slaughter (vaccinates greater; P = 0.0390). Feed conversion ratio of barrows was 11 and 8% greater compared with vaccinated pigs (P = 0.0005) and boars (P = 0.0062) from first to second vaccination but was 23 to 26% lower compared with vaccinated pigs (P vaccination to slaughter and 7 to 9.5% lower from the second vaccination to slaughter (P = 0.0029 and P = 0.0003 for vaccinates and intact boars, respectively). At slaughter, the belly fat androstenone concentration of all vaccinated pigs and 64% of intact boars was below 200 ng/g. Belly fat skatole concentration was below 20 ng/g in samples from all groups. In conclusion, vaccination against GnRF using the Gn

  8. Fluorescent polymeric assemblies as stimuli-responsive vehicles for drug controlled release and cell/tissue imaging

    Chang, Ying; Li, Yang; Yu, Shirong; Mao, Jie; Liu, Cheng; Li, Qi; Yuan, Conghui; He, Ning; Luo, Weiang; Dai, Lizong


    Polymer assemblies with good biocompatibility, stimuli-responsive properties and clinical imaging capability are desirable carriers for future biomedical applications. Herein, we report on the synthesis of a novel anthracenecarboxaldehyde-decorated poly(N-(4-aminophenyl) methacryl amide-oligoethyleneglycolmonomethylether methacrylate) (P(MAAPAC-MAAP-MAPEG)) copolymer, comprising fluorescent chromophore and acid-labile moiety. This copolymer can assemble into micelles in aqueous solution and shows a spherical shape with well-defined particle size and narrow particle size distribution. The pH-responsive property of the micelles has been evaluated by the change of particle size and the controlled release of guest molecules. The intrinsic fluorescence property endows the micelles with excellent cell/tissue imaging capability. Cell viability evaluation with human hepatocellular carcinoma BEL-7402 cells demonstrates that the micelles are nontoxic. The cellular uptake of the micelles indicates a time-dependent behavior. The H22-tumor bearing mice treated with the micelles clearly exhibits the tumor accumulation. These multi-functional nanocarriers may be of great interest in the application of drug delivery.

  9. BioMig--A Method to Evaluate the Potential Release of Compounds from and the Formation of Biofilms on Polymeric Materials in Contact with Drinking Water.

    Wen, Gang; Kötzsch, Stefan; Vital, Marius; Egli, Thomas; Ma, Jun


    In contact with water, polymeric materials (plastics) release compounds that can support suspended microbial growth and/or biofilm formation. The different methods presently used in the European Union to test plastics take 7-16 weeks to obtain a result. In industry, this delays material and product development as well as quality testing. Therefore, we developed a method package (BioMig) that allows testing of plastic materials with high reproducibility in 2 weeks for their potential biofilm (or biomass) formation and release of carbonaceous migration products when in contact with water. BioMig consists of (i) an extended migration potential test (seven times for 24 h at 60 °C), based on the European norm EN 12873-1 and the German UBA (Umweltbundesamt) guideline, and (ii) a biomass formation potential (BFP) test (14 days at 30 °C), which is a modified version of the Dutch biofilm production potential test. In the migration potential test, the amount of carbon released into water by the specimen is quantified by monitoring total and assimilable organic carbon over time; furthermore, the modular design of the test also allows one to assess additional parameters such as pathogen growth potential on the migration water or toxic effects on microbial growth. Flow cytometry (FCM)-based total cell counting (TCC) is used to quantify microbial growth in suspension and on surfaces after removal with mild sonication without affecting cell integrity. The BFP test allows one to determine both the planktonic (pBFP) and the sessile (sBFP) cell fractions. The sBFP consists of surface-attached cells after removal (>90% efficiency). Results for four standard test materials (PE-Xa, PE-Xc, EPDM 2%, and EPDM 20%), plus positive (PVC-P) and negative (glass) controls are presented. FCM-based TCC demonstrates that the release of growth-supporting carbon and proliferation of surface-attached cells stops increasing and stabilizes after 14 days of incubation; this allows for faster

  10. Self-Assembled Polymeric Micelles Based on Hyaluronic Acid-g-Poly(d,l-lactide-co-glycolide Copolymer for Tumor Targeting

    Gyung Mo Son


    Full Text Available Graft copolymer composed hyaluronic acid (HA and poly(d,l-lactide-co-glycolide (PLGA (HAgLG was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA to have amine end group in the end of chain (PLGA-amine. PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50–200 nm. Doxorubicin (DOX-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting.

  11. Influence of oxygen and long term storage on the profile of volatile compounds released from polymeric multilayer food contact materials sterilized by gamma irradiation

    Salafranca, Jesús, E-mail: [Aragón Institute of Engineering Research (I3A), EINA, Department of Analytical Chemistry, University of Zaragoza, María de Luna 3 (Torres Quevedo Bldg.), 50018 Zaragoza (Spain); Clemente, Isabel, E-mail: [Aragón Institute of Engineering Research (I3A), EINA, Department of Analytical Chemistry, University of Zaragoza, María de Luna 3 (Torres Quevedo Bldg.), 50018 Zaragoza (Spain); Isella, Francesca, E-mail: [Goglio S.p.A. Packaging Division, Via dell' Industria 7, 21020 Daverio (Italy); Nerín, Cristina, E-mail: [Aragón Institute of Engineering Research (I3A), EINA, Department of Analytical Chemistry, University of Zaragoza, María de Luna 3 (Torres Quevedo Bldg.), 50018 Zaragoza (Spain); Bosetti, Osvaldo, E-mail: [Goglio S.p.A. Packaging Division, Via dell' Industria 7, 21020 Daverio (Italy)


    Highlights: • 13 different food-use multilayers unirradiated and gamma-irradiated were studied. • 60–80 compounds/sample were identified by SPME–GC–MS even after 8-month storage. • Volatile profile of air- and N{sub 2}-filled bags greatly differed after irradiation. • Principal component analysis classified the samples into 4 groups. • Migration from irradiated materials to vapor phase was much lower than EU limits. - Abstract: The profile of volatile compounds released from 13 different multilayer polymeric materials for food use, before and after their exposure to gamma radiation, has been assessed by solid-phase microextraction–gas chromatography–mass spectrometry. Thermosealed bags of different materials were filled with either air or nitrogen to evaluate the oxygen influence. One-third of the samples were analyzed without irradiation, whereas the rest were irradiated at 15 and 25 kGy. Half of the samples were processed just after preparation and the other half was stored for 8 months at room temperature prior to analysis. Very significant differences between unirradiated and irradiated bags were found. About 60–80 compounds were released and identified per sample. A huge peak of 1,3-ditertbutylbenzene was present in most of the irradiated samples. An outstanding reproducibility in all the variables evaluated (chromatograms, oxygen percentage, volume of bags) was noticed. Independently of filling gas, the results of unirradiated materials were almost identical. In contrast, the chromatographic profile and the odor of irradiated bags filled with nitrogen were completely different to those filled with air. Principal component analysis was performed and 86.9% of the accumulated variance was explained with the first two components. The migration of compounds from irradiated materials to the vapor phase was much lower than the limits established in the Commission Regulation (EU) No 10/2011.

  12. Synthesis of ciprofloxacin-conjugated poly (L-lactic acid) polymer for nanofiber fabrication and antibacterial evaluation

    Parwe, Sharad P; Chaudhari, Priti N; Mohite, Kavita K; Selukar, Balaji S; Nande, Smita S; Garnaik, Baijayantimala


    Ciprofloxacin was conjugated with polylactide (PLA) via the secondary amine group of the piperazine ring using PLA and 7-(4-(2-Chloroacetyl) piperazin-1-yl)-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid. Zinc prolinate, a biocompatible catalyst was synthesized, characterized, and used in ring opening polymerization of L-lactide. Five different kinds of OH-terminated poly(L-lactide) (two-, three-, four-, six-arm, star-shaped) homopolymers were synthesized by ring opening polymerization of L-lactide in the presence of dodecanol, glycerol, pentaerythritol, dipentaerythritol as initiator and zinc prolinate as a catalyst. The structures of the polymers and conjugates were thoroughly characterized by means of gel permeation chromatography, matrix-assisted laser desorption/ionization – time of flight mass spectrometry, and nuclear magnetic resonance spectroscopy. PLA (molecular weight =100,000) and ciprofloxacin conjugated PLA were used for fabrication of nonwoven nanofiber mat (diameter ranges; 150–400 nm) having pore size (62–102 nm) using electrospinning. The microbiological assessment shows that the release of ciprofloxacin possesses antimicrobial activity. The drug-release behavior of the mat was studied to reveal potential application as a drug delivery system. The result shows that the ciprofloxacin release rates of the PLA conjugate nonwoven nanofiber mat could be controlled by the drug loading content and the release medium. The development of a biodegradable ciprofloxacin system, based on nonwoven nanofiber mat, should be of great interest in drug delivery systems. PMID:24741303

  13. Dual targeting of a thermosensitive nanogel conjugated with transferrin and RGD-containing peptide for effective cell uptake and drug release

    Quan Changyun; Chang Cong; Wei Hua; Chen Changsheng; Xu Xiaoding; Cheng Sixue; Zhang Xianzheng; Zhuo Renxi, E-mail: [Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072 (China)


    In this paper, both arginine-glycine-aspartic acid (RGD)-containing peptide and transferrin (Tf) were conjugated to the thermosensitive poly(N-isopropylacrylamide-co-propyl acrylic acid) (poly(NIPAAm-co-PAAc)) nanogel to prepare a dual-targeting drug carrier. The obtained nanogel was characterized in terms of fluorescence spectroscopy, UV-vis spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). In order to track the dual-ligand conjugated nanogel, fluorescein isothiocyanate (FITC) was further conjugated to the nanogel. A cell internalization experiment showed that the dual-ligand conjugated nanogel exhibited obviously enhanced endocytosis by HeLa cells as compared with non-tumorous cells (COS-7 cells). The drug-loaded dual-ligand conjugated nanogel could be transported efficiently into the target tumor cells and the anti-tumor effect was enhanced significantly, suggesting that the dual-ligand conjugated nanogel has great potential as a tumor targeting drug carrier.

  14. Binding and Release between Polymeric Carrier and Protein Drug: pH-Mediated Interplay of Coulomb Forces, Hydrogen Bonding, van der Waals Interactions, and Entropy.

    De Luca, Sergio; Chen, Fan; Seal, Prasenjit; Stenzel, Martina H; Smith, Sean C


    The accelerating search for new types of drugs and delivery strategies poses challenge to understanding the mechanism of delivery. To this end, a detailed atomistic picture of binding between the drug and carrier is quintessential. Although many studies focus on the electrostatics of drug-vector interactions, it has also been pointed out that entropic factors relating to water and counterions can play an important role. By carrying out extensive molecular dynamics simulations and subsequently validating with experiments, we shed light herein on the binding in aqueous solution between a protein drug and polymeric carrier. We examined the complexation between the polymer poly(ethylene glycol) methyl ether acrylate-b-poly(carboxyethyl acrylate (PEGMEA-b-PCEA) and the protein egg white lysozyme, a system that acts as a model for polymer-vector/protein-drug delivery systems. The complexation has been visualized and characterized using contact maps and hydrogen bonding analyses for five independent simulations of the complex, each running over 100 ns. Binding at physiological pH is, as expected, mediated by Coulombic attraction between the positively charged protein and negatively charged carboxylate groups on the polymer. However, we find that consideration of electrostatics alone is insufficient to explain the complexation behavior at low pH. Intracomplex hydrogen bonds, van der Waals interactions, as well as water-water interactions dictate that the polymer does not release the protein at pH 4.8 or indeed at pH 3.2 even though the Coulombic attractions are largely removed as carboxylate groups on the polymer become titrated. Experiments in aqueous solution carried out at pH 7.0, 4.5, and 3.0 confirm the veracity of the computed binding behavior. Overall, these combined simulation and experimental results illustrate that coulomb interactions need to be complemented with consideration of other entropic forces, mediated by van der Waals interactions and hydrogen bonding

  15. Emerging Technologies of Polymeric Nanoparticles in Cancer Drug Delivery

    Erik Brewer


    Full Text Available Polymeric nanomaterials have the potential to improve upon present chemotherapy delivery methods. They successfully reduce side effects while increasing dosage, increase residence time in the body, offer a sustained and tunable release, and have the ability to deliver multiple drugs in one carrier. However, traditional nanomaterial formulations have not produced highly therapeutic formulations to date due to their passive delivery methods and lack of rapid drug release at their intended site. In this paper, we have focused on a few “smart” technologies that further enhance the benefits of typical nanomaterials. Temperature and pH-responsive drug delivery devices were reviewed as methods for triggering release of encapsulating drugs, while aptamer and ligand conjugation were discussed as methods for targeted and intracellular delivery, with emphases on in vitro and in vivo works for each method.

  16. Polymeric microspheres

    Walt, David R.; Mandal, Tarun K.; Fleming, Michael S.


    The invention features core-shell microsphere compositions, hollow polymeric microspheres, and methods for making the microspheres. The microspheres are characterized as having a polymeric shell with consistent shell thickness.

  17. A core cross-linked polymeric micellar platium(IV) prodrug with enhanced anticancer efficiency.

    Hou, Jie; Shang, Jincai; Jiao, Chengbin; Jiang, Peiyue; Xiao, Huijie; Luo, Lan; Liu, Tongjun


    A core cross-linked polymeric micellar cisplatin(IV) conjugate prodrug is prepared by attaching the cisplatin(IV) to mPEG-b-PLL biodegradable copolymers to form micellar nanoparticles that can disintegrate to release the active anticancer agent cisplatin(II) in a mild reducing environment. Moreover, in vitro studies show that this cisplatin(IV) conjugate prodrug displays enhanced cytotoxicity against HepG2 cancer cells compared with cisplatin(II). Further studies demonstrate that the high cellular uptake and platinum-DNA adduct of this cisplatin(IV) conjugate prodrug can induce more cancer-cell apoptosis than cisplatin(II), which is responsible for its enhanced anticancer activity.

  18. Ampicillin-Ester Bonded Branched Polymers: Characterization, Cyto-, Genotoxicity and Controlled Drug-Release Behaviour

    Ewa Oledzka


    Full Text Available The development and characterization of novel macromolecular conjugates of ampicillin using branched biodegradable polymers has been described in this study. The conjugates have been prepared coupling the β-lactam antibiotic with branched polymer matrices based on the natural oligopeptide core. The cyto- and genotoxicity of the synthesized polymers were evaluated with a bacterial luminescence test, two protozoan assays and Salmonella typhimurium TA1535. The presence of a newly formed covalent bond between the drug and the polymer matrices was confirmed by 1H-NMR and FTIR studies. A drug content (15.6 and 10.2 mole % in the macromolecular conjugates has been determined. The obtained macromolecular products have been subjected to further in vitro release studies. The total percentage of ampicillin released after 21 days of incubation was nearly 60% and 14% and this resulted from the different physicochemical properties of the polymeric matrices. This is the first report on the application of branched biodegradable polymeric matrices for the covalent conjugation of ampicillin. The obtained results showed that the synthesized macromolecular drug-conjugates might slowly release the active drug molecule and improve the pharmacokinetics of ampicillin.

  19. 壳寡糖-聚乳酸阿霉素胶团体外缓释性能考察%Evaluation of Delayed Release Efficiency in Vitro of Adriamycin Chitosan-Polylactic Acid Polymeric Micelles



    Objective Evaluate the ef iciency of delayed release in vitro of adriamycin chitosan-polylactic acid polymeric micel es.Methods Hypersound dispersion method to prepare the polymeric micel es. Adriamycin as a model drug was then incorporated into the micel es by dialysis. Evaluate the ef iciency of delayed release of adriamycin chitosan-polylactic acid polymeric micel es by in vitro investigation. Results The CSO-PLA micel es with 5000 molecule weight of PLA loading Adr displayed more sustained-release characteristic.Conclusion The micel es loading Adr displayed sustained-release characteristic in vitro. The CSO-PLA (PLA with molecule weight 5000) micel es loading Adr displayed significant sustained-release characteristic.%目的:考察阿霉素壳寡糖-聚乳酸嫁接物胶团的缓释性能。方法以超声分散法制备嫁接物胶团;以阿霉素为模型药物,透析法制备载药胶团。进行载药胶团体外释放实验,考察壳寡糖-聚乳酸共聚物胶团的缓释性能。结果在壳寡糖-聚乳酸嫁接物中,聚乳酸分子量为5000的两种壳寡糖-聚乳酸嫁接物载药胶团体外释放缓释效果明显。结论壳寡糖-聚乳酸聚合物胶团具有显著的缓释特征。其中聚乳酸分子量为5000的壳寡糖-聚乳酸嫁接物,缓释效果更明显。

  20. Synthesis of ciprofloxacin-conjugated poly (L-lactic acid polymer for nanofiber fabrication and antibacterial evaluation

    Parwe SP


    Full Text Available Sharad P Parwe, Priti N Chaudhari, Kavita K Mohite, Balaji S Selukar, Smita S Nande, Baijayantimala Garnaik Polymer Science and Engineering Division, National Chemical Laboratory, Pune, India Abstract: Ciprofloxacin was conjugated with polylactide (PLA via the secondary amine group of the piperazine ring using PLA and 7-(4-(2-Chloroacetyl piperazin-1-yl-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid. Zinc prolinate, a biocompatible catalyst was synthesized, characterized, and used in ring opening polymerization of L-lactide. Five different kinds of OH-terminated poly(L-lactide (two-, three-, four-, six-arm, star-shaped homopolymers were synthesized by ring opening polymerization of L-lactide in the presence of dodecanol, glycerol, pentaerythritol, dipentaerythritol as initiator and zinc prolinate as a catalyst. The structures of the polymers and conjugates were thoroughly characterized by means of gel permeation chromatography, matrix-assisted laser desorption/ionization – time of flight mass spectrometry, and nuclear magnetic resonance spectroscopy. PLA (molecular weight =100,000 and ciprofloxacin conjugated PLA were used for fabrication of nonwoven nanofiber mat (diameter ranges; 150–400 nm having pore size (62–102 nm using electrospinning. The microbiological assessment shows that the release of ciprofloxacin possesses antimicrobial activity. The drug-release behavior of the mat was studied to reveal potential application as a drug delivery system. The result shows that the ciprofloxacin release rates of the PLA conjugate nonwoven nanofiber mat could be controlled by the drug loading content and the release medium. The development of a biodegradable ciprofloxacin system, based on nonwoven nanofiber mat, should be of great interest in drug delivery systems. Keywords: zinc prolinate, ciprofloxacin conjugated polylactides, CP-PLA, electrospinning, nonwoven nanofibers, drug release, antibacterial activity, MDR

  1. RGD-peptide conjugated inulin-ibuprofen nanoparticles for targeted delivery of Epirubicin.

    Zhang, Luzhong; Li, Guicai; Gao, Ming; Liu, Xin; Ji, Bing; Hua, Ruheng; Zhou, Youlang; Yang, Yumin


    Recently, chemotherapy-based polymeric nanoparticles have been extensively investigated for solid tumor treatment. Tumor targeted nanoparticles demonstrated great potential for improved accumulation in the tumor tissue, superior anticancer activity and reduced side effects. Thus, inulin-ibuprofen polymer was synthesized by esterification between inulin and ibuprofen, and RGD targeted epirubicin (EPB) loaded nanoparticles were prepared by the self-assembly of inulin-ibuprofen polymer and in situ encapsulation of EPB. RGD conjugated EPB loaded nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). The EPB release from the nanoparticles showed pH-dependent profile and accelerated by the decreased pH value, which would favor the effective drug delivery in vivo. Intracellular uptake analysis suggested that RGD conjugated nanoparticles could be easily internalized by the cancer cells. In vitro cytotoxicity revealed that RGD conjugated EPB loaded nanoparticles exhibited the better antitumor efficacy compared with non-conjugated nanoparticles. More importantly, RGD conjugated EPB loaded nanoparticles showed superior anticancer effects and reduced toxicity than free EPB and non-conjugated nanoparticles by in vivo antitumor activity, EPB biodistribution and histology analysis.

  2. Charge transport in polymeric transistors

    Alberto Salleo


    Full Text Available Polymeric semiconductors have attracted much attention because of their possible use as active materials in printed electronics. Thin-film transistors (TFTs are a convenient tool for studying charge-transport physics in conjugated polymers. Two families of materials are reviewed here: fluorene copolymers and polythiophenes. Because charge transport is highly anisotropic in molecular conductors, the electrical properties of conjugated polymers are strongly dependent on microstructure. Molecular weight, polydispersity, and regioregularity all affect morphology and charge-transport in these materials. Charge transport models based on microstructure are instrumental in identifying the electrical bottlenecks in these materials.

  3. Polymer-coated echogenic lipid nanoparticles with dual release triggers.

    Nahire, Rahul; Haldar, Manas K; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H; Katti, Kalpana S; Gange, Kara N; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku


    Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer-coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 min simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin-loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging.

  4. A free-standing, sheet-shaped, "hydrophobic" biomaterial containing polymeric micelles formed from poly(ethylene glycol)-poly(lactic acid) block copolymer for possible incorporation/release of "hydrophilic" compounds.

    Moroishi, Hitomi; Yoshida, Chikara; Murakami, Yoshihiko


    Sheet-shaped materials with a large contact area relative to the drug targeting site lead to advantages over conventional particle-shaped drug carriers and have several advantages for their biomedical applications. The present study proposes a methodology for preparing a novel sheet-shaped "hydrophobic" and biocompatible biomaterial in which polymeric micelles are uniformly dispersed for the incorporation of "hydrophilic" compounds into the sheet. The methoxy-terminated poly(ethylene glycol)-block-poly(lactic acid) block copolymer (CH(3)O-PEG-b-PLA) was successfully synthesized by means of the anionic ring-opening polymerization of both ethylene oxide and dl-lactide. CH(3)O-PEG-b-PLA was self-assembled and formed stable micelle-like w/o emulsion with a hydrophilic inner core in organic solvents. A sheet-shaped material containing a hydrophilic inner space for incorporating hydrophilic compounds was obtained by spin-coating both the micelle solution and a sheet-forming polymer. Fluorescent images of the sheet proved that polymeric micelles providing hydrophilic spaces were uniformly dispersed in the hydrophobic sheet. The facile technique presented in this paper can be a tool for fabricating sheet-shaped biomaterials that have a hydrophilic inner core and, consequently, that are suitable for the sustained release of hydrophilic compounds.

  5. Synthesis, structural and in vitro studies of well-dispersed monomethoxy-poly(ethylene glycol)-honokiol conjugate micelles

    Qiu Neng; Cai Lulu; Xie Dachun; Wang Guangcheng; Wu Wenshuang; Chen Lijuan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Zhang Yongkui; Song Hang [Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Yin Huabin, E-mail: [Department of Electronics and Electrical Engineering, University of Glasgow, Glasgow G12 8QQ (United Kingdom)


    Honokiol, an active principle extracted from Magnolia officinalis, has great potential as a cancer treatment. However, its poor water solubility greatly hampers its delivery to the tumor sites at an effective concentration. In this study, an amphiphilic polymer-drug conjugate was successfully prepared by condensation of low molecular weight monomethoxy-poly(ethylene glycol) (MPEG)-2000 with honokiol (HK) through an ester linkage to increase the hydrophilicity of honokiol. The MPEG-honokiol (MPEG-HK) conjugate prepared formed nano-sized micelles, with a mean particle size of less than 20 nm (MPEG-HK, 360 {mu}g ml{sup -1}) in water, which could be well dispersed in water. The nanoparticles obtained were characterized by particle size distribution, morphology and zeta potential. The stability and hydrolysis profile of the polymeric pro-drug in phosphate-buffered saline (PBS) and plasma were also studied and the results showed that only 20% of the conjugated honokiol was released in 2.0 h in beagle dog plasma, while in PBS the time required to reach 20% of honokiol release was >200 h. Meanwhile, the inhibitory activity of the honokiol conjugate was found to be retained in vitro against LL/2 cell lines with an IC50 value of 10.7 {mu}g ml{sup -1}. These results suggest that the polymer-drug conjugate provides a potential new approach to hydrophobic drugs, such as honokiol, in formulation design.

  6. Ultrasound-Mediated Polymeric Micelle Drug Delivery.

    Xia, Hesheng; Zhao, Yue; Tong, Rui


    The synthesis of multi-functional nanocarriers and the design of new stimuli-responsive means are equally important for drug delivery. Ultrasound can be used as a remote, non-invasive and controllable trigger for the stimuli-responsive release of nanocarriers. Polymeric micelles are one kind of potential drug nanocarrier. By combining ultrasound and polymeric micelles, a new modality (i.e., ultrasound-mediated polymeric micelle drug delivery) has been developed and has recently received increasing attention. A major challenge remaining in developing ultrasound-responsive polymeric micelles is the improvement of the sensitivity or responsiveness of polymeric micelles to ultrasound. This chapter reviews the recent advance in this field. In order to understand the interaction mechanism between ultrasound stimulus and polymeric micelles, ultrasound effects, such as thermal effect, cavitation effect, ultrasound sonochemistry (including ultrasonic degradation, ultrasound-initiated polymerization, ultrasonic in-situ polymerization and ultrasound site-specific degradation), as well as basic micellar knowledge are introduced. Ultrasound-mediated polymeric micelle drug delivery has been classified into two main streams based on the different interaction mechanism between ultrasound and polymeric micelles; one is based on the ultrasound-induced physical disruption of the micelle and reversible release of payload. The other is based on micellar ultrasound mechanochemical disruption and irreversible release of payload.

  7. Polysaccharide-modified synthetic polymeric biomaterials.

    Baldwin, Aaron D; Kiick, Kristi L


    This review presents an overview of polysaccharide-conjugated synthetic polymers and their use in tissue-engineered scaffolds and drug-delivery applications. This topic will be divided into four categories: (1) polymeric materials modified with non-mammalian polysaccharides such as alginate, chitin, and dextran; (2) polymers modified with mammalian polysaccharides such as hyaluronan, chondroitin sulfate, and heparin; (3) multi-polysaccharide-derivatized polymer conjugate systems; and (4) polymers containing polysaccharide-mimetic molecules. Each section will discuss relevant conjugation techniques, analysis, and the impact of these materials as micelles, particles, or hydrogels used in in-vitro and in-vivo biomaterial applications. (c) 2010 Wiley Periodicals, Inc.

  8. Polymeric nanoparticles: the future of nanomedicine.

    Banik, Brittany L; Fattahi, Pouria; Brown, Justin L


    Polymeric nanoparticles (NPs) are one of the most studied organic strategies for nanomedicine. Intense interest lies in the potential of polymeric NPs to revolutionize modern medicine. To determine the ideal nanosystem for more effective and distinctly targeted delivery of therapeutic applications, particle size, morphology, material choice, and processing techniques are all research areas of interest. Utilizations of polymeric NPs include drug delivery techniques such as conjugation and entrapment of drugs, prodrugs, stimuli-responsive systems, imaging modalities, and theranostics. Cancer, neurodegenerative disorders, and cardiovascular diseases are fields impacted by NP technologies that push scientific boundaries to the leading edge of transformative advances for nanomedicine.

  9. Condensation Polymerization

    S Ramakrishnan


    The very idea that large polymer molecules can indeed existwas hotly debated during the early part of the 20th century.As highlighted by Sivaram in his articles on Carothersand Flory, Staudinger’s macromolecular hypothesis was finallyaccepted, and the study of polymers gained momentumbecause of the remarkable efforts of the these two individualswho laid down the foundations concerning the processes thatled to the formation of large polymer molecules, and to thosethat led to an understanding of many of their extraordinaryphysical properties. Condensation polymerizations, as thename suggests, utilizes bond-forming reactions that generatea small molecule condensate, which often needs to be continuouslyremoved to facilitate the formation of the polymer. Inthis article, I shall describe some of the essential principles ofcondensation polymerizations or more appropriately calledstep-growth polymerizations; and I will also describe someinteresting extensions that lead to the formation of polymernetworks and highly branched polymers.

  10. Polymer-Chlorambucil Drug Conjugates: A Dynamic Platform of Anticancer Drug Delivery.

    Saha, Biswajit; Haldar, Ujjal; De, Priyadarsi


    Recently, polymer drug conjugates (PDCs) have attracted considerable attention in the treatment of cancer. In this work, a simple strategy has been developed to make PDCs of an antitumor alkylating agent, chlorambucil, using a biocompatible disulphide linker. Chlorambucil-based chain transfer agent was used to prepare various homopolymers and block copolymers in a controlled fashion via reversible addition-fragmentation chain transfer polymerization. Chlorambucil conjugated block copolymer, poly(polyethylene glycol monomethyl ether methacrylate)-b-poly(methyl methacrylate), formed nanoaggregates in aqueous solutions, which are characterized by dynamic light scattering and field emission-scanning electron microscopy. Finally, the simplicity of the design is exemplified by performing a release study of chlorambucil under reducing condition by using D,L-dithiothreitol. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Synthesis, characterization, and in vivo evaluation of poly(ethylene oxide-co-glycidol)-platinate conjugate.

    Zhou, Ping; Li, Zhongyu; Chau, Ying


    Poly(ethylene oxide-co-glycidol) (poly(EO-co-Gly)), a member of polyether polyol (PEP), resembles polyethylene glycol (PEG) in the polymer backbone but distinguishes itself by having multiple pendent groups along the main chain. We showed that this new bioconjugation material is biocompatible by its lack of toxicity on fibroblast cell growth, inactivity in hemolysis, and the absence of side effects after injection in mice. The usefulness of poly(EO-co-Gly) as a polymeric drug carrier was demonstrated via the preparation and characterization of a new anticancer polymer-drug conjugate, poly(EO-co-Gly)-platinate. The drug loading was 9.1-12.6% (cisplatin/conjugate w/w), at least four times higher than a PEG conjugate of similar molecular weight. The aqueous solubility of cisplatin was increased by around 10 folds after conjugation. Platinum complexes were released from the conjugate in a sustained manner over 2 days. The release of active drugs was confirmed by the antitumor activity of poly(EO-co-Gly)-platinate in vitro against HONE-1 (human nasopharyngeal carcinoma) and MCF-7 (human breast cancer), albeit at a potency lower than free cisplatin. Poly(EO-co-Gly)-platinate improved the therapeutic index of cisplatin in vivo. The conjugate had a similar antitumor activity as free cisplatin in nude mice bearing HONE-1 xenografts, and achieved 52% inhibition of tumor growth at the conclusion of the study. While free cisplatin injection caused a severe loss in body weight (>20%), poly(EO-co-Gly)-platinate resulted in mild side effects. These findings support that poly(EO-co-Gly) is a suitable drug carrier.

  12. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis.

    Nam, Joon; Kim, Wooseong; Lee, Sunyoung; Jeong, Seongkeun; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin


    Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine.

  13. Polymerization and photochromism of ammonium molybdate in porous glass

    Pak, V. N.; Borisov, A. N.


    Modification of porous glass (PG) plates is carried out by impregnation with aqueous solutions of ammonium molybdate (NH4)2MoO4 with subsequent removal of water at 120°C. A long-wavelength shift of absorption spectra upon accumulation of the salt in PG indicates polymerization of MoO 4 2- anions at low concentrations of the encapsulated salt. Photochromism manifests itself as the anionic forms in PG become larger. UV irradiation of the modified plates causes enhancement of continuous absorption in the visible range. The proposed mechanism of photoreduction of the polianions in PG involves the removal of oxygen atoms from the bridging-Mo-O-Mo-bonds and stabilization of the colored forms by means of conjugation of the electrons released from the 4 d-levels of pentavalent molybdenum.

  14. Design and development of intraocular polymeric implant systems for long-term controlled-release of clindamycin phosphate for toxoplasmic retinochoroiditis

    Lana Tamaddon


    Conclusion: The implant of PLA (I.V. 0.2 containing 20% w/w of clindamycin, was identified as the optimum formulation in providing continuous efficient in-vitro release of clindamycin for about 5 weeks.

  15. In vitro and in vivo evaluation of Alexa Fluor 680-bombesin[7-14]NH2 peptide conjugate, a high-affinity fluorescent probe with high selectivity for the gastrin-releasing peptide receptor.

    Ma, Lixin; Yu, Ping; Veerendra, Bhadrasetty; Rold, Tammy L; Retzloff, Lauren; Prasanphanich, Adam; Sieckman, Gary; Hoffman, Timothy J; Volkert, Wynn A; Smith, Charles J


    Gastrin-releasing peptide (GRP) receptors are overexpressed on several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. Bombesin (BBN), a 14-amino acid peptide that is an analogue of human GRP, binds to GRP receptors with very high affinity and specificity. The aim of this study was to develop a new fluorescent probe based on BBN having high tumor uptake and optimal pharmacokinetics for specific targeting and optical imaging of human breast cancer tissue. In this study, solid-phase peptide synthesis was used to produce H(2)N-glycylglycylglycine-BBN[7-14]NH(2) peptide with the following general sequence: H(2)N-G-G-G-Q-W-A-V-G-H-L-M-(NH(2)). This conjugate was purified by reversed-phase high-performance liquid chromatography and characterized by electrospray-ionization mass spectra. The fluorescent probe Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) conjugate was prepared by reaction of Alexa Fluor 680 succinimidyl ester to H(2)N-G-G-G-BBN[7-14]NH(2) in dimethylformamide (DMF). In vitro competitive binding assays, using (125)I-Tyr(4)-BBN as the radiolabeling gold standard, demonstrated an inhibitory concentration 50% value of 7.7 +/- 1.4 nM in human T-47D breast cancer cells. Confocal fluorescence microscopy images of Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) in human T-47D breast cancer cells indicated specific uptake, internalization, and receptor blocking of the fluorescent bioprobe in vitro. In vivo investigations in SCID mice bearing xenografted T-47D breast cancer lesions demonstrated the ability of this new conjugate to specifically target tumor tissue with high selectivity and affinity.

  16. In Vitro and In Vivo Evaluation of Alexa Fluor 680-Bombesin[7–14]NH2 Peptide Conjugate, a High-Affinity Fluorescent Probe with High Selectivity for the Gastrin-Releasing Peptide Receptor

    Lixin Ma


    Full Text Available Gastrin-releasing peptide (GRP receptors are overexpressed on several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. Bombesin (BBN, a 14–amino acid peptide that is an analogue of human GRP, binds to GRP receptors with very high affinity and specificity. The aim of this study was to develop a new fluorescent probe based on BBN having high tumor uptake and optimal pharmacokinetics for specific targeting and optical imaging of human breast cancer tissue. In this study, solid-phase peptide synthesis was used to produce H2N-glycylglycylglycine-BBN[7–14]NH2 peptide with the following general sequence: H2N-G-G-G-Q-W-A-V-G-H-L-M-(NH2. This conjugate was purified by reversed-phase high-performance liquid chromatography and characterized by electrospray-ionization mass spectra. The fluorescent probe Alexa Fluor 680-G-G-G-BBN[7–14]NH2 conjugate was prepared by reaction of Alexa Fluor 680 succinimidyl ester to H2N-G-G-G-BBN[7–14]NH2 in dimethylformamide (DMF. In vitro competitive binding assays, using 125I-Tyr4-BBN as the radiolabeling gold standard, demonstrated an inhibitory concentration 50% value of 7.7 ± 1.4 nM in human T-47D breast cancer cells. Confocal fluorescence microscopy images of Alexa Fluor 680-G-G-G-BBN[7–14]NH2 in human T-47D breast cancer cells indicated specific uptake, internalization, and receptor blocking of the fluorescent bioprobe in vitro. In vivo investigations in SCID mice bearing xenografted T-47D breast cancer lesions demonstrated the ability of this new conjugate to specifically target tumor tissue with high selectivity and affinity.

  17. Rational design on controlled release ion-exchange polymeric microspheres and polymer-lipid hybrid nanoparticles for the delivery of water-soluble drugs through a multidisciplinary approach

    Li, Yongqiang

    Sulfopropyl dextran sulfate (SP-DS) microspheres and polymer-lipid hybrid nanoparticles (PLN) for the delivery of water-soluble anticancer drugs and P-glycoprotein inhibitors were developed by our group recently and demonstrated effectiveness in local chemotherapy. To optimize the delivery performance of these particulate systems, particularly PLN, an integrated multidisciplinary approach was developed, based on an in-depth understanding of drug-excipient interactions, internal structure, drug loading and release mechanisms, and application of advanced modeling/optimization techniques. An artificial neural networks (ANN) simulator capable of formulation optimization and drug release prediction was developed. In vitro drug release kinetics of SP-DS microspheres, with various drug loading and in different release media, were predicted by ANN. The effects of independent variables on drug release were evaluated. Good modeling performance suggested that ANN is a useful tool to predict drug release from ion-exchange microspheres. To further improve the performance of PLN, drug-polymer-lipid interactions were characterized theoretically and experimentally using verapamil hydrochloride (VRP) as a model drug and dextran sulfate sodium (DS) as a counter-ion polymer. VRP-DS complexation followed a stoichiometric rule and solid-state transformation of VRP were observed. Dodecanoic acid (DA) was identified as the lead lipid carrier material. Based upon the optimized drug-polymer-lipid interactions, PLN with high drug loading capacity (36%, w/w) and sustained release without initial burst release were achieved. VRP remained amorphous and was molecularly dispersed within PLN. H-bonding contributed to the miscibility between the VRP-DS complex and DA. Drug release from PLN was mainly controlled by diffusion and ion-exchange processes. Drug loading capacity and particle size of PLN depend on the formulation factors of the weight ratio of drug to lipid and concentrations of

  18. Synthesis and biological evaluation of benzimidazole-oxindole conjugates as microtubule-targeting agents.

    Kamal, Ahmed; Nagaseshadri, B; Nayak, V Lakshma; Srinivasulu, Vunnam; Sathish, Manda; Kapure, Jeevak Sopanrao; Suresh Reddy, C


    A series of benzimidazole-oxindole conjugates were synthesized and evaluated for their cytotoxic activity. The cytotoxicity assay results suggest that conjugates 5c and 5p exhibit promising cytotoxicity against human breast cancer cell line (MCF-7). The Cell cycle analysis revealed that these conjugates induced cell cycle arrest at G2/M phase in MCF-7 cells. The tubulin polymerization assay results suggested that these conjugates inhibit tubulin polymerization with IC50 values 1.12 and 1.59μM respectively. Immunofluorescence analysis also suggested that these conjugates effectively inhibited the microtubule assembly in MCF-7 cells. Further, molecular docking studies indicated that these conjugates 5c and 5p interact and binds efficiently with the tubulin protein. By and large, the results demonstrated that these benzimidazole-oxindole conjugates possess cytotoxic property by inhibiting the tubulin polymerization.

  19. Effect of varied release kinetics of the osteogenic thrombin peptide TP508 from biodegradable, polymeric scaffolds on bone formation in vivo

    Hedberg, E.L.; Kroese-Deutman, H.C.; Shih, C.K.; Crowther, R.S.; Carney, D.H.; Mikos, A.G.; Jansen, J.A.


    This study was designed to assess the influence of varied release kinetics of the osteogenic thrombin peptide TP508 from osteoconductive poly(propylene fumarate)-based (PPF) composite scaffolds on bone formation in vivo. Four classes of scaffolds were constructed with different TP508 dosages (200, 1

  20. Versatile, Reversible, and Reusable Gel of a Monocholesteryl Conjugated Calix[4]arene as Functional Material to Store and Release Dyes and Drugs Including Doxorubicin, Curcumin, and Tocopherol.

    Bandela, Anil Kumar; Hinge, Vijaya Kumar; Yarramala, Deepthi S; Rao, Chebrolu Pulla


    Gels are interesting soft materials owing to their functional properties leading to potential applications. This paper deals with the synthesis of monocholesteryl derivatized calix[4]arene (G) and its instantaneous gelation at a minimum gelator concentration of 0.6% in 1:1 v/v THF/acetonitrile. The gel shows remarkable thermoreversibility by exhibiting Tgel→sol at ∼48 °C and is demonstrated for several cycles. The gel shows an organized network of nanobundles, while that of the sol shows spherical nanoaggregates in microscopy. A bundle with ∼12 nm diameter possessing hydrophobic pockets in itself is obtained from computationally modeled gel, and hence the gel is suitable for storage and release applications. The guest-entrapped gels exhibit the same microstructures as that observed with simple gels, while fluorescence spectra and molecular mechanics suggests that the drug molecules occupy the hydrophobic pockets. All the entrapped drug molecules are released into water, suggesting a complete recovery of the trapped species. The reusability of the gel for the storage and release of the drug into water is demonstrated for four consecutive cycles, and hence the gel formed from G acts as a functional material that finds application in drug delivery.

  1. Conjugated Polymers for Energy Production

    Livi, Francesco

    arylation (DAr) and direct arylation polymerization (DArP) have been applied to the preparation of PPDTBT, making this polymer readily available in only 4 synthetic steps and thus easily transferable to a large scale-production setup. DArP avoids organometallic species and therefore is an appealing......This dissertation is aimed at developing materials for flexible, large area, ITO-free polymer solar cells (PSCs) fully printed under ambient conditions. A large screening of conjugated polymers, both novel and well-known materials, has been carried out in order to find suitable candidates...... for scalable PSCs fully printed under ambient conditions [Adv. Energy Mater. 2015, 5, 1402186]. PPDTBT resulted to be the conjugated polymer with the best photovoltaic performance within the 104 synthesized macromolecules. Therefore, further studies have been done on such material. The impact of side chain...

  2. Biokompatible Polymere

    Ha, Suk-Woo; Wintermantel, Erich; Maier, Gerhard

    Der klinische Einsatz von synthetischen Polymeren begann in den 60-er Jahren in Form von Einwegartikeln, wie beispielsweise Spritzen und Kathetern, vor allem aufgrund der Tatsache, dass Infektionen infolge nicht ausreichender Sterilität der wiederverwendbaren Artikel aus Glas und metallischen Werkstoffen durch den Einsatz von sterilen Einwegartikeln signifikant reduziert werden konnten [1]. Die Einführung der medizinischen Einwegartikel aus Polymeren erfolgte somit nicht nur aus ökonomischen, sondern auch aus hygienischen Gründen. Wegen der steigenden Anzahl synthetischer Polymere und dem zunehmenden Bedarf an ärztlicher Versorgung reicht die Anwendung von Polymeren in der Medizin von preisgünstigen Einwegartikeln, die nur kurzzeitig intrakorporal eingesetzt werden, bis hin zu Implantaten, welche über eine längere Zeit grossen Beanspruchungen im menschlichen Körper ausgesetzt sind. Die steigende Verbreitung von klinisch eingesetzten Polymeren ist auf ihre einfache und preisgünstige Verarbeitbarkeit in eine Vielzahl von Formen und Geometrien sowie auf ihr breites Eigenschaftsspektrum zurückzuführen. Polymere werden daher in fast allen medizinischen Bereichen eingesetzt.

  3. Preparation of Inert Polystyrene Latex Particles as MicroRNA Delivery Vectors by Surfactant-Free RAFT Emulsion Polymerization.

    Poon, Cheuk Ka; Tang, Owen; Chen, Xin-Ming; Pham, Binh T T; Gody, Guillaume; Pollock, Carol A; Hawkett, Brian S; Perrier, Sébastien


    We present the preparation of 11 nm polyacrylamide-stabilized polystyrene latex particles for conjugation to a microRNA model by surfactant-free RAFT emulsion polymerization. Our synthetic strategy involved the preparation of amphiphilic polyacrylamide-block-polystyrene copolymers, which were able to self-assemble into polymeric micelles and "grow" into polystyrene latex particles. The surface of these sterically stabilized particles was postmodified with a disulfide-bearing linker for the attachment of the microRNA model, which can be released from the latex particles under reducing conditions. These nanoparticles offer the advantage of ease of preparation via a scaleable process, and the versatility of their synthesis makes them adaptable to a range of applications.

  4. Investigation of the apoptotic pathway induced by benzimidazole-oxindole conjugates against human breast cancer cells MCF-7.

    Lakshma Nayak, Vadithe; Nagaseshadri, Bobburi; Vishnuvardhan, M V P S; Kamal, Ahmed


    In our previous studies, benzimidazole-oxindole conjugates were synthesized and evaluated by National Cancer Institute (NCI) for their cytotoxic activity and the new molecules like 5c and 5p were considered as potential leads. These conjugates arrested the cell cycle at G2/M phase and inhibited tubulin polymerization. These observations prompted us to investigate the apoptotic mechanism induced by these lead molecules against human breast cancer cells (MCF-7). Studies like measurement of mitochondrial membrane potential (ΔΨm), generation of reactive oxygen species (ROS) and Annexin V-FITC assay revealed that these compounds induced mitochondrial mediated (intrinsic apoptotic pathway) apoptosis in human breast cancer cells. It was further confirmed by western blot analysis of pro apoptotic protein Bax, anti apoptotic protein Bcl-2, cytochrome c release, caspase-9 activity and cleavage of PARP.

  5. Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

    Kim, Haneul; Jo, Ara; Baek, Seulgi; Lim, Daeun; Park, Soon-Yong; Cho, Soo Kyung; Chung, Jin Woong; Yoon, Jinhwan


    Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.

  6. Synthesis of Novel π-Conjugated Rod-Rod-Rod Triblock Copolymers Containing Poly(3-hexylthiophene and Polyacetylene Segments by Combination of Quasi-Living GRIM and Living Anionic Polymerization

    Tomoya Higashihara


    Full Text Available The first successful synthesis of a new rod-rod-rod triblock copolymer, polyacetylene(PA-b-poly(3-hexylthiophene(P3HT-b-PA could be synthesized by a combination of quasi-living Grignard metathesis (GRIM and living anionic polymerization. We first confirmed that poly(4-tolyl vinyl sulfoxide (PTVS, which is a soluble precursor for PA, could be synthesized by living anionic polymerization in THF at −78 °C, initiated with 3-methyl-1,1-diphenylpentyllithium as the initiator in the presence of in situ-generated lithium enolate. The molecular weights (MWs and polydispersities (PDIs were well controlled (MW = 5,200–27,000, PDI = 1.10–1.22, respectively. A coil-rod-coil triblock copolymer, PTVS-b-P3HT-b-PTVS, (6,000-12,500-6,000 could also be synthesized, initiated with a P3HT-based difunctional macroinitiator in the presence of lithium enolate. GPC-RALLS and 1H NMR analyses confirmed a high degree of structural homogeneity of PTVS-b-P3HT-b-PTVS. A thermal transformation reaction of the polymer was carried out in the film state at 170 °C for 2 h to afford PA-b-P3HT-b-PA quantitatively, as monitored by TGA and FT-IR analyses. The optical and electronic properties as well as the morphological behavior of the block copolymers were investigated by UV-vis spectroscopy, conductivity measurement, and AFM observation.

  7. Ultrasolation of PLGA Polymeric Nanoparticles Released DNA%超声辐照纳米聚合物体外控释 DNA 效果的研究

    张海; 李莹; 李富荣; 许琴


    目的 利用自制携抗体结合前列腺癌细胞,探讨超声辐照PLGA纳米粒(PLGA-NPs)体外控释脱氧核糖核酸(DNA),靶向抑癌作用.方法 通过溶剂蒸干法制备携有前列腺癌雄激素受体抗体的PLGA纳米粒(NPs-PLGA-GFP-AR),包裹有绿色荧光蛋白(GFP)作为标志;加入前列腺癌PC4 2细胞培养2h后,以脉冲波(pulsed wave,PW)、连续波(continuous wave,CW)超声条件进行体外辐照对比,共聚焦荧光显微镜下观测细胞转染效果.结果 NPs摄入未增加,声辐照后绿色荧光蛋白表达急剧明显增加;无超声辐照的癌细胞中5d后始见绿色荧光,超声辐照3d即可见绿色荧光;196 h后肿瘤细胞凋亡.PW1、2、3(Duty Factor,DF为10%、20%、30%,0.05~0.15 W/cm2))组与无超声比较转染率差异显著(P<0.05),10%、20%、30%组间转染率无显著差异(P>0.05);连续波超声辐照CW1、2、3(DF为10、20、30%,声强为0.1~0.25 W/cm2)与无超声组对照组差异显著(P<0.05),但癌细胞脱壁、死亡率高.结论 超声辐照对NPs有体外促降解及靶向控释DNA作用.%Objective To target DNA by using the antibody with androgen receptors, and to inhibit prostate cancer cells to grow. To study ultrasound irradiation PLGA (Polylactic/poly glycolic acid,) nano polymers (NPs) in vitro for the release of deoxyribonucleic acid (DNA) role. Methods We got PLGA nano polymer through the solvent method. With prostate cancer androgen receptors antibodies specific nanoparticles (NPs-PLGA-GFP-AR) , package green fluorescent protein (GFP) as a symbol of; use PW (Pulsed Wave) , CW (Continuous Wave ) ultrasound,and different conditions for ultrasound irradiation in vitro,quantitative monitoring the NPs degradation and release of DNA,and cells transfection under Laser Scanning Confocal Microscope. Results We got the nano-particles join the cell culture of human prostate cancer C4-2 cells (PC4-2) two hours, then take ultrasound irradiation, nano

  8. Synthesis of Conjugated Polymers for Light Emitting and Photovoltalc Applications


    1 Results The initial report of polymeric light-emitting diodes (PLEDs) based on poly(p-phenylenevinylene) gave birth to an intense research effort in conjugated polymers, primarily focused on the development of optoelectronic and electrochemical devices. Significant developments in modern synthetic chemistry, especially the chemistry of carbon-carbon bond formation have allowed the synthesis of various well-defined conjugated polymers and oligomers with optimized physical properties.Meanwhile, these re...

  9. New heparin–indomethacin conjugate with an ester linkage: Synthesis, self aggregation and drug delivery behavior

    Li, Nan-Nan; Zheng, Bing-Na [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Lin, Jian-Tao [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Medical College, Dongguan 523808 (China); Zhang, Li-Ming, E-mail: [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China)


    New heparin–indomethacin conjugate with an ester linkage was prepared by the carbodiimide-mediated condensation reaction, and then characterized by FTIR and {sup 1}HNMR analyses. Due to its amphiphilic character, such a conjugate could self-aggregate into spherical nanoparticles in aqueous system, as confirmed by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. By the in vitro drug release tests, the resultant conjugate nanoparticles were found to have a sustained and esterase-sensitive release behavior for conjugated indomethacin. In addition, the uptake of these conjugate nanoparticles into human nasopharyngeal carcinoma CNE1 cells was confirmed by fluorescence microscopy. - Highlights: • New heparin–indomethacin conjugate with an ester linkage was prepared. • Such a conjugate could self-aggregate into spherical nanoparticles in aqueous system. • The resultant conjugate nanoparticles exhibited an esterase-sensitive drug release behavior. • The resultant conjugate nanoparticles showed the cellular uptake ability in CNE1 cells.

  10. Thermo-inelastic Response of Polymeric Solids


    Public Release; Distribution Unlimited Final Report: Thermo -inelastic Response of Polymeric Solids The views, opinions and/or findings contained in non peer-reviewed journals: Final Report: Thermo -inelastic Response of Polymeric Solids Report Title We the study the impact response of a large...none) Challenges and opportunities in the modeling of thermo -viscoelastic materials, Society of Experimental Mechanics, Greenville, North, Carolina

  11. pH- and NIR Light-Responsive Polymeric Prodrug Micelles for Hyperthermia-Assisted Site-Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment.

    Li, Zuhong; Wang, Haibo; Chen, Yangjun; Wang, Yin; Li, Huan; Han, Haijie; Chen, Tingting; Jin, Qiao; Ji, Jian


    Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR-780 loaded pH-responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine-based biomimetic micellar shell and acid-sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site-specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX-resistant MCF-7/ADR cells. Meanwhile, the tumor site-specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF-7/ADR tumor growth in tumor-bearing mice. These results demonstrate that the well-designed IR-780 loaded polymeric prodrug micelles for hyperthermia-assisted site-specific chemotherapy present an effective approach to reverse drug resistance.

  12. Bioreducible Micelles Self-Assembled from Poly(ethylene glycol-Cholesteryl Conjugate As a Drug Delivery Platform

    Chulsu Baek


    Full Text Available The ability of polymeric micelles to self-assemble into nanosized particles has created interest in their application as potential anticancer drug delivery systems. A poly(ethylene glycol-cholesteryl conjugate (Chol-ss-PEG-ss-Chol connected by cleavable disulfide linkages was synthesized and used as a nanocarrier for in vitro release of doxorubicin (DOX. Owing to its amphiphilic structure, Chol-ss-PEG-ss-Chol was able to self-assemble into micelles with an average diameter 18.6 nm in aqueous solution. The micelles formed large aggregates due to the shedding of the PEG shell through cleavage of disulfide bonds in a reductive environment. The in vitro release studies revealed that Chol-ss-PEG-ss-Chol micelles released 80% and approximately 9% of the encapsulated DOX within 6 h under reductive and non-reductive conditions, respectively. The glutathione (GSH-mediated intracellular drug delivery was investigated in a KB cell line. The cytotoxicity of DOX-loaded micelles indicated a higher cellular anti-proliferative effect against GSH-pretreated than untreated KB cells. Furthermore, confocal laser scanning microscopy (CLSM measurement demonstrated that Chol-ss-PEG-ss-Chol micelles exhibited faster drug release in GSH-pretreated KB cells than untreated KB cells. These results suggest the potential usefulness of disulfide-based polymeric micelles as controlled drug delivery carriers.

  13. Dispositivos poliméricos eletroluminescentes Polymeric light emitting devices

    Hueder P. M. de Oliveira


    Full Text Available Here we present an overview of electroluminescent devices that use conjugated polymers as the active media. The principal components of the devices are described and we show some examples of conjugated polymers and copolymers usually employed in polymeric light emitting devices (PLED. Some aspects of the photo and electroluminescence properties as well as of the energy transfer processes are discussed. As an example, we present some of the photophysical properties of poly(fluorenes, a class of conjugated polymers with blue emission.

  14. Inhibition of surface induced coagulation by preadsorption of albumin-heparin conjugates

    Hennink, W.E.; Kim, S.W.; Feijen, J.


    Surface coatings of the albumin-heparin conjugates were developed to improve the blood compatibility of polymeric materials. Glass, PVC, Biomer and cellulose acetate were coated with albumin-heparin conjugate and its adsorption and desorption behavior on glass in particular was studied using 3H and

  15. Polymeric vehicles for topical delivery and related analytical methods.

    Cho, Heui Kyoung; Cho, Jin Hun; Jeong, Seong Hoon; Cho, Dong Chul; Yeum, Jeong Hyun; Cheong, In Woo


    Recently a variety of polymeric vehicles, such as micelles, nanoparticles, and polymersomes, have been explored and some of them are clinically used to deliver therapeutic drugs through skin. In topical delivery, the polymeric vehicles as drug carrier should guarantee non-toxicity, long-term stability, and permeation efficacy for drugs, etc. For the development of the successful topical delivery system, it is of importance to develop the polymeric vehicles of well-defined intrinsic properties, such as molecular weights, HLB, chemical composition, topology, specific ligand conjugation and to investigate the effects of the properties on drug permeation behavior. In addition, the role of polymeric vehicles must be elucidated in in vitro and in vivo analyses. This article describes some important features of polymeric vehicles and corresponding analytical methods in topical delivery even though the application span of polymers has been truly broad in the pharmaceutical fields.

  16. Conducting Polymeric Materials

    Hvilsted, Søren


    The overall objective of this collection is to provide the most recent developments within the various areas of conducting polymeric materials. The conductivity of polymeric materials is caused by electrically charged particles, ions, protons and electrons. Materials in which electrons...

  17. Polymeric Systems of Antimicrobial Peptides—Strategies and Potential Applications

    Ewa Olędzka


    Full Text Available The past decade has seen growing interest in the investigation of peptides with antimicrobial activity (AMPs. One approach utilized in infection control is incorporation of antimicrobial agents conjugated with the polymers. This review presents the recent developments on polymeric AMP carriers and their potential applications in the biomedical and pharmaceutical fields.

  18. 热聚合法自交联共轭亚油酸囊泡的制备与释药性能%Preparation and Drug Release Properties of the Self-crosslinked Conjugated Linoleic Acid Ufasomes by Thermal Polymerization


    为考察以热聚合法取代紫外辐照法在较高浓度下制备稳定的脂肪酸囊泡的可行性,以可聚合单体共轭亚油酸(CLA)及其钠盐混合物为原料,在水溶液中经pH响应自组装得到共轭亚油酸囊泡(CLA-Ufasome),再通过热聚合法对高浓度CLA-Ufasome自交联进行化学绑定,制备稳定的自交联共轭亚油酸囊泡(CLA-FAV),并采用透射电子显微镜(TEM)和动态激光光散射(DLS)对其进行表征.结果表明,在pH =8.6的条件下,在3~100mmol/L[cvc(CLA)的500倍]的浓度范围内均得到粒径为10~20 nm的CLA-FAV.说明经简单的热聚合法制备的CLA-FAV形貌与紫外法基本一致;该热聚合法CLA-FAV对5-氟尿嘧啶(5-FU)具有良好的包载缓释效果.

  19. Autonomous Indication of Mechanical Damage in Polymeric Coatings.

    Li, Wenle; Matthews, Christopher C; Yang, Ke; Odarczenko, Michael T; White, Scott R; Sottos, Nancy R


    High-resolution in situ autonomous visual indication of mechanical damage is achieved through a microcapsule-based polymeric material system. Upon mechanical damage, ruptured microcapsules release a liquid indicator molecule. A sharp color change from light yellow to bright red is triggered when the liberated indicator 2',7'-dichlorofluorescein reacts with the polymeric coating matrix.

  20. Deciphering conjugative plasmid permissiveness in wastewater microbiomes

    Jacquiod, Samuel Jehan Auguste; Brejnrod, Asker Daniel; Milani, Stefan Morberg


    Wastewater treatment plants (WWTPs) are designed to robustly treat polluted water. They are characterized by ceaseless flows of organic, chemical and microbial matter, followed by treatment steps before environmental release. WWTPs are hotspots of horizontal gene transfer between bacteria via...... still remains largely uncharted. Furthermore, current in vitro methods used to assess conjugation in complex microbiomes do not include in situ behaviours of recipient cells, resulting in partial understanding of transfers. We investigated the in vitro conjugation capacities of WWTP microbiomes from...... diversity of recipient bacterial phyla for the plasmid was observed, especially in WWTP outlets. We also identified permissive bacteria potentially able to cross WWTPs and engage in conjugation before and after water treatment. Bacterial activity and lifestyle seem to influence conjugation extent...

  1. Conjugation of Lectin to Poly(ε-caprolactone-block-glycopolymer Micelles for In Vitro Intravesical Drug Delivery

    Ning Ning Li


    Full Text Available Amphiphilic poly(ε-caprolactone-block-poly[2-(α-d-mannopyranosyloxy ethyl acrylamide] (PCL-b-PManEA block copolymers were synthesized via a combination of ring-opening polymerization (ROP, reversible addition-fragmentation chain transfer (RAFT polymerization and reactive ester-amine reaction. The PCL-b-PManEA block copolymers can self-assemble into micelles and encapsulate anticancer drug doxorubicin (DOX. To enhance mucoadhesive property of the resulting DOX-loaded PCL-b-PManEA micelles, Concanavalin A (ConA lectin was further conjugated with the micelles. Turbidimetric assay using mucin shows that the DOX-loaded PCL-b-PManEA@ConA micelles are mucoadhesive. DOX release from the DOX-loaded PCL-b-PManEA@ConA micelles in artificial urine at 37 °C exhibits an initial burst release, followed by a sustained and slow release over three days. Confocal laser scanning microscope (CLSM images indicate that the DOX-loaded PCL-b-PManEA@ConA micelles can be effectively internalized by UMUC3 human urothelial carcinoma cells. The DOX-loaded PCL-b-PManEA@ConA micelles exhibit significant cytotoxicity to these cells.

  2. New Approaches to Conjugated Polymer Electrodes for Organic Energy Storage

    Lutkenhaus, Jodie


    Conjugated polymers have been explored as electrodes in batteries and pseudocapacitors for over 30 years. Yet, their widespread implementation has been hindered for several reasons such as oxidative stability, low capacity, and rate limitations associated with ionic mobility relative to current state-of-the-art. On the other hand, conjugated polymers have much to offer because of their good electronic conductivity, high Coulombic efficiency, and theoretical capacities comparable to those of metal oxides. Our lab's current goal is to overcome the aforementioned challenges, so that conjugated polymeric electrodes can be suitable used in energy storage for applications such as mechanically flexible energy storage and structural power system. This talk will present several approaches towards synthesis and processing of polyaniline that achieve oxidatively stable, high capacity, ionically mobile electrodes. These approaches include template polymerization, synthesis of nanofibers, and layer-by-layer assembly.

  3. Revisiting conjugate schedules.

    MacAleese, Kenneth R; Ghezzi, Patrick M; Rapp, John T


    The effects of conjugate reinforcement on the responding of 13 college students were examined in three experiments. Conjugate reinforcement was provided via key presses that changed the clarity of pictures displayed on a computer monitor in a manner proportional to the rate of responding. Experiment 1, which included seven parameters of clarity change per response, revealed that responding decreased as the percentage clarity per response increased for all five participants. These results indicate that each participant's responding was sensitive to intensity change, which is a parameter of conjugate reinforcement schedules. Experiment 2 showed that responding increased during conjugate reinforcement phases and decreased during extinction phases for all four participants. Experiment 3 also showed that responding increased during conjugate reinforcement and further showed that responding decreased during a conjugate negative punishment condition for another four participants. Directions for future research with conjugate schedules are briefly discussed.

  4. Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle.

    Eliasof, Scott; Lazarus, Douglas; Peters, Christian G; Case, Roy I; Cole, Roderic O; Hwang, Jungyeon; Schluep, Thomas; Chao, Joseph; Lin, James; Yen, Yun; Han, Han; Wiley, Devin T; Zuckerman, Jonathan E; Davis, Mark E


    Nanoparticles are currently being investigated in a number of human clinical trials. As information on how nanoparticles function in humans is difficult to obtain, animal studies that can be correlative to human behavior are needed to provide guidance for human clinical trials. Here, we report correlative studies on animals and humans for CRLX101, a 20- to 30-nm-diameter, multifunctional, polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in phase 2 clinical trials, and human data from several of the clinical investigations are compared with results from multispecies animal studies. The pharmacokinetics of polymer-conjugated CPT (indicative of the CRLX101 nanoparticles) in mice, rats, dogs, and humans reveal that the area under the curve scales linearly with milligrams of CPT per square meter for all species. Plasma concentrations of unconjugated CPT released from CRLX101 in animals and humans are consistent with each other after accounting for differences in serum albumin binding of CPT. Urinary excretion of polymer-conjugated CPT occurs primarily within the initial 24 h after dosing in animals and humans. The urinary excretion dynamics of polymer-conjugated and unconjugated CPT appear similar between animals and humans. CRLX101 accumulates into solid tumors and releases CPT over a period of several days to give inhibition of its target in animal xenograft models of cancer and in the tumors of humans. Taken in total, the evidence provided from animal models on the CRLX101 mechanism of action suggests that the behavior of CRLX101 in animals is translatable to humans.

  5. Low-melting elemental metal or fusible alloy encapsulated polymerization initiator for delayed initiation

    Hermes, Robert E.


    An encapsulated composition for polymerization includes an initiator composition for initiating a polymerization reaction, and a capsule prepared from an elemental metal or fusible alloy having a melting temperature from about C. to about C. A fluid for polymerization includes the encapsulated composition and a monomer. When the capsule melts or breaks open, the initiator is released.

  6. Acid-catalyzed Furfuryl Alcohol Polymerization: Characterizations of Molecular Structure and Thermodynamic Properties

    Kim, Taejin; Assary, Rajeev A; Marshall, Christopher L; Gosztola, David J.; Curtiss, Larry A; Stair, Peter C


    The liquid-phase polymerization of furfuryl alcohol catalyzed by sulfuric acid catalysts and the identities of molecular intermediates were investigated by using Raman spectroscopy and density functional theory calculation. At room temperature, with an acid catalyst, a vigorous furfuryl alcohol polymerization reaction was observed, whereas even at a high water concentration, furfuryl alcohol was very stable in the absence of an acid catalyst. Theoretical studies were carried out to investigate the thermodynamics of protonation of furfuryl alcohol, initiation of polymerization, and formation of conjugated dienes and diketonic species by using the B3LYP level of theory. A strong aliphatic C=C band observed in the calculated and measured Raman spectra provided crucial evidence to understand the polymerization reaction mechanism. It is confirmed that the formation of a conjugated diene structure rather than a diketone structure is involved in the furfuryl alcohol polymerization reaction.

  7. The release characteristics of a model protein from self-assembled succinimide-terminated poly(lactide-co-glycolide ethylene oxide fumarate) nanoparticles

    Mercado, Angel E.; He, Xuezhong; Xu, Weijie; Jabbari, Esmaiel


    Lactide-co-glycolide-based functionalized nanoparticles (NPs), because of their high surface areas for conjugation and biodegradability, are attractive as carriers for stabilization and sustained delivery of therapeutic agents and protein drugs. The objective of this work was to compare the release characteristics of model molecules encapsulated in NPs produced from poly(lactide-co-glycolide fumarate) (PLGF) macromer with those of model molecules conjugated to NPs produced from succinimide (NHS)-terminated PLGF-NHS macromer. Poly(lactide fumarate) (PLAF), PLGF and poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromers were synthesized by condensation polymerization. The hydroxyl end-groups of PLAF and PLGF macromers were reacted with N,N'-disuccinimidyl carbonate (DSC) to produce succinimide-terminated PLAF-NHS and PLGF-NHS macromers. The macromers were self-assembled by dialysis to form NPs. The amphiphilic PLEOF macromer was used as the surfactant to stabilize the NPs in the process of self-assembly. 1-(2-pyridylazo)-2-naphthol (PAN) was used as a model small molecule for encapsulation in PLAF or PLGF NPs and bovine serum albumin (BSA) was used as a model protein for conjugation to PLAF-NHS and PLGF-NHS NPs. The profile of release of the encapsulated PAN from PLAF and PLGF NPs was non-linear and consisted of a burst release followed by a period of sustained release. The release profile for BSA, conjugated to PLAF-NHS and PLGF-NHS NPs, was linear up to complete degradation of the NPs. PLGF and PLAF NPs degraded in 15 and 28 days, respectively, while PLGF-NHS and PLAF-NHS NPs degraded in 25 and 38 days, which demonstrated that the release was dominated by erosion of the matrix. PLAF-NHS and PLGF-NHS NPs are potentially useful as carriers for sustained in situ release of protein drugs.

  8. Fabrication and manipulation of polymeric magnetic particles with magnetorheological fluid

    Rodriguez-Lopez, Jaime [Centro de Acustica Aplicada y Evaluacion No Destructivos (CAEND), CSIC-UPM, C/Serrano 144, 28006, Madrid (Spain); Shum, Ho Cheung, E-mail: [Department of Mechanical Engineering, University of Hong Kong, 7/F Haking Wong Building, Pokfulam Road (Hong Kong); Elvira, Luis; Montero de Espinosa, Francisco [Centro de Acustica Aplicada y Evaluacion No Destructivos (CAEND), CSIC-UPM, C/Serrano 144, 28006, Madrid (Spain); Weitz, David A., E-mail: [Department of Physics and School of Engineering and Applied Sciences, Harvard University, 9 and 15 Oxford Street, Cambridge, MA 02138 (United States)


    Polymeric magnetic microparticles have been created using a microfluidic device via ultraviolet (UV) polymerization of double emulsions, resulting in cores of magnetorheological (MR) fluids surrounded by polymeric shells. We demonstrate that the resultant particles can be manipulated magnetically to achieve triggered rupture of the capsules. This illustrates the great potential of our capsules for triggered release of active ingredients encapsulated in the polymeric magnetic microparticles. - Highlights: Black-Right-Pointing-Pointer Polymeric microparticles encapsulating MR fluids have been fabricated. Black-Right-Pointing-Pointer A double-emulsion-templated approach using microfluidic techniques has been used. Black-Right-Pointing-Pointer The monodisperse microparticles obtained are easily manipulated under magnetic field. Black-Right-Pointing-Pointer These microparticles have great potential for encapsulation-and-release applications.

  9. Polymerization Using Phosphazene Bases

    Zhao, Junpeng


    In the recent rise of metal-free polymerization techniques, organic phosphazene superbases have shown their remarkable strength as promoter/catalyst for the anionic polymerization of various types of monomers. Generally, the complexation of phosphazene base with the counterion (proton or lithium cation) significantly improves the nucleophilicity of the initiator/chain end resulting in highly enhanced polymerization rates, as compared with conventional metalbased initiating systems. In this chapter, the general features of phosphazenepromoted/catalyzed polymerizations and the applications in macromolecular engineering (synthesis of functionalized polymers, block copolymers, and macromolecular architectures) are discussed with challenges and perspectives being pointed out.

  10. Conjugates of abscisic acid, brassinosteroids, ethylene, gibberellins, and jasmonates.

    Piotrowska, Alicja; Bajguz, Andrzej


    Phytohormones, including auxins, abscisic acid, brassinosteroids, cytokinins, ethylene, gibberellins, and jasmonates, are involved in all aspects of plant growth, and developmental processes as well as environmental responses. However, our understanding of hormonal homeostasis is far from complete. Phytohormone conjugation is considered as a part of the mechanism to control cellular levels of these compounds. Active phytohormones are changed into multiple forms by acylation, esterification or glycosylation, for example. It seems that conjugated compounds could serve as pool of inactive phytohormones that can be converted to active forms by de-conjugation reactions. Some conjugates are thought to be temporary storage forms, from which free active hormones can be released after hydrolysis. It is also believed that conjugation serves functions, such as irreversible inactivation, transport, compartmentalization, and protection against degradation. The nature of abscisic acid, brassinosteroid, ethylene, gibberellin, and jasmonate conjugates is discussed.

  11. Predicting the optical gap of conjugated systems

    Botelho, Andre Leitao

    The adapted Su-Schrieffer-Heeger model is developed in this work as a tool for in silico prediction of the optical gap of pi-conjugated systems for photovoltaic applications. Full transferability of the model ensures reliable predictive power - excellent agreement with 180 independent experimental data points covering virtually all existing conjugated system types with an accuracy exceeding the time-dependent density functional theory, one of the most accurate first-principles methods. Insights on the structure-property relation of conjugated systems obtained from the model lead to guiding rules for optical gap design: 1) fusing aromatic rings parallel to the conjugated path does not significantly lower the optical gap, 2) fusing rings perpendicularly lowers the optical gap of the monomer, but has a reduced benefit from polymerization, and 3) copolymers take advantage of the lower optical gap of perpendicular fused rings and benefit from further optical gap reduction through added parallel fused rings as electronic communicators. A copolymer of parallel and perpendicular benzodithiophenes, differing only in sulfur atom locations, is proposed as a candidate to achieve the optimal 1.2 eV donor optical gap for organic photovoltaics. For small-molecule organic photovoltaics, substituting the end pairs of carbon atoms on pentacene with sulfur atoms is predicted to lower the optical gap from 1.8 eV to 1.1 eV. Furthermore, the model offers an improvement of orders of magnitude in the computational efficiency over commonly used first-principles tools.

  12. Conjugation of metronidazole with dextran: a potential pharmaceutical strategy to control colonic distribution of the anti-amebic drug susceptible to metabolism by colonic microbes

    Kim, Wooseong; Yang, Yejin; Kim, Dohoon; Jeong, Seongkeun; Yoo, Jin-Wook; Yoon, Jeong-Hyun; Jung, Yunjin


    Metronidazole (MTDZ), the drug of choice for the treatment of protozoal infections such as luminal amebiasis, is highly susceptible to colonic metabolism, which may hinder its conversion from a colon-specific prodrug to an effective anti-amebic agent targeting the entire large intestine. Thus, in an attempt to control the colonic distribution of the drug, a polymeric colon-specific prodrug, MTDZ conjugated to dextran via a succinate linker (Dex-SA-MTDZ), was designed. Upon treatment with dextranase for 8 h, the degree of Dex-SA-MTDZ depolymerization (%) with a degree of substitution (mg of MTDZ bound in 100 mg of Dex-SA-MTDZ) of 7, 17, and 30 was 72, 38, and 8, respectively, while that of dextran was 85. Depolymerization of Dex-SA-MTDZ was found to be necessary for the release of MTDZ, because dextranase pretreatment ensures that de-esterification occurs between MTDZ and the dextran backbone. In parallel, Dex-SA-MTDZ with a degree of substitution of 17 was found not to release MTDZ upon incubation with the contents of the small intestine and stomach of rats, but it released MTDZ when incubated with rat cecal contents (including microbial dextranases). Moreover, Dex-SA-MTDZ exhibited prolonged release of MTDZ, which contrasts with drug release by small molecular colon-specific prodrugs, MTDZ sulfate and N-nicotinoyl-2-{2-(2-methyl-5-nitroimidazol-1-yl)ethyloxy}-d,l-glycine. These prodrugs were eliminated very rapidly, and no MTDZ was detected in the cecal contents. Consistent with these in vitro results, we found that oral gavage of Dex-SA-MTDZ delivered MTDZ (as MTDZ conjugated to [depolymerized] dextran) to the distal colon. However, upon oral gavage of the small molecular prodrugs, no prodrugs were detected in the distal colon. Collectively, these data suggest that dextran conjugation is a potential pharmaceutical strategy to control the colonic distribution of drugs susceptible to colonic microbial metabolism. PMID:28243064

  13. Triggered Release from Polymer Capsules

    Esser-Kahn, Aaron P. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Odom, Susan A. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Sottos, Nancy R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Materials Science and Engineering; White, Scott R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Aerospace Engineering; Moore, Jeffrey S. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry


    Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

  14. A transferrin variant as the targeting ligand for polymeric nanoparticles incorporated in 3-D PLGA porous scaffolds.

    Lopes, André M; Chen, Kevin Y; Kamei, Daniel T


    We have developed doxorubicin (DOX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (DP) conjugated with polyethylene glycol (PEG) and transferrin (Tf) to form Tf-PEG-DPs (TPDPs), and incorporated these TPDPs into three-dimensional (3-D) PLGA porous scaffolds to form a controlled delivery system. To our knowledge, this represents the first use of a Tf variant (oxalate Tf) to improve the targeted delivery of drug-encapsulated nanoparticles (NPs) in PLGA scaffolds to PC3 prostate cancer cells. The PLGA scaffolds with TPDPs incorporated have been shown to release drugs for sustained delivery and provided a continuous release of DOX. The MTS assay was also performed to determine the potency of native and oxalate TPDPs, and a 3.0-fold decrease in IC50 values were observed between the native and oxalate TPDPs. The lower IC50 value for the oxalate version signifies greater potency compared to the native version, since a lower concentration of drug was required to achieve the same therapeutic effect. These results suggest that this technology has potential to become a new implantable polymeric device to improve the controlled and targeted drug delivery of Tf-conjugated NPs for cancer therapy.

  15. Co-conjugation vis-à-vis individual conjugation of α-amylase and glucoamylase for hydrolysis of starch.

    Jadhav, Swati B; Singhal, Rekha S


    Two enzymes, α-amylase and glucoamylase have been individually and co-conjugated to pectin by covalent binding. Both the enzyme systems showed better thermal and pH stability over the free enzyme system with the complete retention of original activities. Mixture of individually conjugated enzymes showed lower inactivation rate constant with longer half life than the co-conjugated enzyme system. Individually conjugated enzymes showed an increase of 56.48 kJ/mole and 38.22 kJ/mole in activation energy for denaturation than the free enzymes and co-conjugated enzymes, respectively. Km as well as Vmax of individually and co-conjugated enzymes was found to be higher than the free enzymes. SDS-polyacrylamide gel electrophoresis confirmed the formation of conjugate and co-conjugate as evident by increased molecular weight. Both the enzyme systems were used for starch hydrolysis where individually conjugated enzymes showed highest release of glucose at 60 °C and pH 5.0 as compared to free and co-conjugated enzyme.

  16. Making Polymeric Microspheres

    Rhim, Won-Kyu; Hyson, Michael T.; Chung, Sang-Kun; Colvin, Michael S.; Chang, Manchium


    Combination of advanced techniques yields uniform particles for biomedical applications. Process combines ink-jet and irradiation/freeze-polymerization techniques to make polymeric microspheres of uniform size in diameters from 100 to 400 micrometer. Microspheres used in chromatography, cell sorting, cell labeling, and manufacture of pharmaceutical materials.

  17. Applied bioactive polymeric materials

    Carraher, Charles; Foster, Van


    The biological and biomedical applications of polymeric materials have increased greatly in the past few years. This book will detail some, but not all, of these recent developments. There would not be enough space in this book to cover, even lightly, all of the major advances that have occurred. Some earlier books and summaries are available by two of this book's Editors (Gebelein & Carraher) and these should be consul ted for additional information. The books are: "Bioactive Polymeric Systems" (Plenum, 1985); "Polymeric Materials In Medication" (Plenum, 1985); "Biological Acti vi ties of Polymers" (American Chemical Society, 1982). Of these three, "Bioacti ve Polymeric Systems" should be the most useful to a person who is new to this field because it only contains review articles written at an introductory level. The present book primarily consists of recent research results and applications, with only a few review or summary articles. Bioactive polymeric materials have existed from the creation of life...

  18. Nanostructured conjugated polymers in chemical sensors: synthesis, properties and applications.

    Correa, D S; Medeiros, E S; Oliveira, J E; Paterno, L G; Mattoso, Luiz C


    Conjugated polymers are organic materials endowed with a π-electron conjugation along the polymer backbone that present appealing electrical and optical properties for technological applications. By using conjugated polymeric materials in the nanoscale, such properties can be further enhanced. In addition, the use of nanostructured materials makes possible miniaturize devices at the micro/nano scale. The applications of conjugated nanostructured polymers include sensors, actuators, flexible displays, discrete electronic devices, and smart fabric, to name a few. In particular, the use of conjugated polymers in chemical and biological sensors is made feasible owning to their sensitivity to the physicochemical conditions of its surrounding environment, such as chemical composition, pH, dielectric constant, humidity or even temperature. Subtle changes in these conditions bring about variations on the electrical (resistivity and capacitance), optical (absorptivity, luminescence, etc.), and mechanical properties of the conjugated polymer, which can be precisely measured by different experimental methods and ultimately associated with a specific analyte and its concentration. The present review article highlights the main features of conjugated polymers that make them suitable for chemical sensors. An especial emphasis is given to nanostructured sensors systems, which present high sensitivity and selectivity, and find application in beverage and food quality control, pharmaceutical industries, medical diagnosis, environmental monitoring, and homeland security, and other applications as discussed throughout this review.

  19. A heterostructure composed of conjugated polymer and copper sulfide nanoparticles.

    Narizzano, Riccardo; Erokhin, Victor; Nicolini, Claudio


    A heterostructure formed by a conjugated polymer and semiconducting nanoparticles was produced. The conjugated polymer was synthesized by oxidative copolymerization of 3-thiopheneacetic acid and 3-hexylthiophene, thus obtaining an amphiphilic polythiophene that allows the formation of a stable polymer layer at the air-water interface. Different numbers of monolayers were deposited on solid substrates. CuS nanoparticles were grown directly in the polymeric matrix using the carboxylic groups as nucleation centers. The reactions were monitored by quartz crystal microbalance, Brewster angle, and fluorescence microscopy. The heterostructure showed increased conductivity as compared to the pristine polymer.

  20. Poly(trimethylsilylcyclooctatetraene): A soluble conjugated polyacetylene via olefin metathesis

    Ginsburg, E.J.; Gorman, C.B.; Grubbs, R.H.; Marder, S.R. (California Institute of Technology, Pasadena (USA))


    highly conjugated polymers, such as polyacetylene, polythiophene, and poly(p-phenylene vinylene), have been the subject of intensive research due to their intriguing optical and electronic properties. These parent systems are highly desirable for experimental and theoretical studies due to their simplicity. Their intractability, however, has made characterization an arduous task, and insolubility has severely limited their applications. Researchers have successfully circumvented these obstacles by synthesizing soluble alkyl- and alkoxy-substituted polythiphenes and poly(p-phenylene vinylenes). Analogous soluble highly conjugated polyacetylene derivatives have proven more elusive. The authors report here the synthesis of such a polymer using ring-opening metathesis polymerization (ROMP).


    Yao-wen Bai; Xiao-fang Chen; Dong Zhang; Xin-hua Wan; Qi-feng Zhou


    The photopolymerization of two kinds of prepolyesters containing conjugated diacetylene (PDA-6 and PDA-12)was investigated using DSC. By measuring the endothermic enthalpy of the prepolymers after different UV-irradiation times,the polymerizations were found to follow the first-order rate law which agreed with the results of other investigators using a different method. The endothermic enthalpy measurements of PDA-6 and PDA-12 before UV-irradiation precluded the possibility that the decrease of endothermic enthalpy was caused by thermal polymerization.

  2. Structural studies of novel glycoconjugates from polymerized allergens (allergoids) and mannans as allergy vaccines.

    Manzano, Ana I; Javier Cañada, F; Cases, Bárbara; Sirvent, Sofia; Soria, Irene; Palomares, Oscar; Fernández-Caldas, Enrique; Casanovas, Miguel; Jiménez-Barbero, Jesús; Subiza, José L


    Immunotherapy for treating IgE-mediated allergies requires high doses of the corresponding allergen. This may result in undesired side effects and, to avoid them, hypoallergenic allergens (allergoids) polymerized with glutaraldehyde are commonly used. Targeting allergoids to dendritic cells to enhance cell uptake may result in a more effective immunotherapy. Allergoids coupled to yeast mannan, as source of polymannoses, would be suitable for this purpose, since mannose-binding receptors are expressed on these cells. Conventional conjugation procedures of mannan to proteins use oxidized mannan to release reactive aldehydes able to bind to free amino groups in the protein; yet, allergoids lack these latter because their previous treatment with glutaraldehyde. The aim of this study was to obtain allergoids conjugated to mannan by an alternative approach based on just glutaraldehyde treatment, taking advantage of the mannoprotein bound to the polymannose backbone. Allergoid-mannan glycoconjugates were produced in a single step by treating with glutaraldehyde a defined mixture of allergens derived from Phleum pratense grass pollen and native mannan (non-oxidized) from Saccharomyces cerevisae. Analytical and structural studies, including 2D-DOSY and (1)H-(13)C HSQC nuclear magnetic resonance spectra, demonstrated the feasibility of such an approach. The glycoconjugates obtained were polymers of high molecular weight showing a higher stability than the native allergen or the conventional allergoid without mannan. The allergoid-mannan glycoconjugates were hypoallergenic as detected by the IgE reactivity with sera from grass allergic patients, even with lower reactivity than conventional allergoid without mannan. Thus, stable hypoallergenic allergoids conjugated to mannan suitable for using in immunotherapy can be achieved using glutaraldehyde. In contrast to mannan oxidation, the glutaraldehyde approach allows to preserve mannoses with their native geometry, which may be

  3. Segmented conjugated polymers

    G Padmanaban; S Ramakrishnan


    Segmented conjugated polymers, wherein the conjugation is randomly truncated by varying lengths of non-conjugated segments, form an interesting class of polymers as they not only represent systems of varying stiffness, but also ones where the backbone can be construed as being made up of chromophores of varying excitation energies. The latter feature, especially when the chromophores are fluorescent, like in MEHPPV, makes these systems particularly interesting from the photophysics point of view. Segmented MEHPPV- samples, where x represents the mole fraction of conjugated segments, were prepared by a novel approach that utilizes a suitable precursor wherein selective elimination of one of the two eliminatable groups is affected; the uneliminated units serve as conjugation truncations. Control of the composition x of the precursor therefore permits one to prepare segmented MEHPPV- samples with varying levels of conjugation (elimination). Using fluorescence spectroscopy, we have seen that even in single isolated polymer chains, energy migration from the shorter (higher energy) chromophores to longer (lower energy) ones occurs – the extent of which depends on the level of conjugation. Further, by varying the solvent composition, it is seen that the extent of energy transfer and the formation of poorly emissive inter-chromophore excitons are greatly enhanced with increasing amounts of non-solvent. A typical S-shaped curve represents the variation of emission yields as a function of composition suggestive of a cooperative collapse of the polymer coil, reminiscent of conformational transitions seen in biological macromolecules.

  4. Methotrexate and epirubicin conjugates as potential antitumor drugs

    Szymon Wojciech Kmiecik


    Full Text Available Introduction: The use of hybrid molecules has become one of the most significant approaches in new cytotoxic drug design. This study describes synthesis and characterization of conjugates consisting of two well-known and characterized chemotherapeutic agents: methotrexate (MTX and epirubicin (EPR. The synthesized conjugates combine two significant anticancer strategies: combinatory therapy and targeted therapy. These two drugs were chosen because they have different mechanisms of action, which can increase the anticancer effect of the obtained conjugates. MTX, which is a folic acid analog, has high cytotoxic properties and can serve as a targeting moiety that can reach folate receptors (FRs overexpresing tumor cells. Combination of nonselective drugs such as EPR with MTX can increase the selectivity of the obtained conjugates, while maintaining the high cytotoxic properties.Materials and methods: Conjugates were purified by RP-HPLC and the structure was investigated by MS and MS/MS methods. The effect of the conjugates on proliferation of LoVo, LoVo/Dx, MCF-7 and MV-4-11 human cancer cell lines was determined by SRB or MTT assay.Results: The conjugation reaction results in the formation of monosubstituted (α, γ and disubstituted MTX derivatives. In vitro proliferation data demonstrate that the conjugates synthesized in our study show lower cytotoxic properties than both chemotherapeutics used alone.Discussion: Epirubicin cytotoxicity was not observed in obtained conjugates. Effective drugs release after internalization needs further investigation.

  5. Delivery of antibiotics with polymeric particles.

    Xiong, Meng-Hua; Bao, Yan; Yang, Xian-Zhu; Zhu, Yan-Hua; Wang, Jun


    Despite the wide use of antibiotics, bacterial infection is still one of the leading causes of hospitalization and mortality. The clinical failure of antibiotic therapy is linked with low bioavailability, poor penetration to bacterial infection sites, and the side effects of antibiotics, as well as the antibiotic resistance properties of bacteria. Antibiotics encapsulated in nanoparticles or microparticles made up of a biodegradable polymer have shown great potential in replacing the administration of antibiotics in their "free" form. Polymeric particles provide protection to antibiotics against environmental deactivation and alter antibiotic pharmacokinetics and biodistribution. Polymeric particles can overcome tissue and cellular barriers and deliver antibiotics into very dense tissues and inaccessible target cells. Polymeric particles can be modified to target or respond to particular tissues, cells, and even bacteria, and thereby facilitate the selective concentration or release of the antibiotic at infection sites, respectively. Thus, the delivery of antibiotics with polymeric particles augments the level of the bioactive drug at the site of infection while reducing the dosage and the dosing frequency. The end results are improved therapeutic effects as well as decreased "pill burden" and drug side effects in patients. The main objective of this review is to analyze recent advances and current perspectives in the use of polymeric antibiotic delivery systems in the treatment of bacterial infection.

  6. Bioactive Polymeric Materials for Tissue Repair

    Diane R. Bienek


    Full Text Available Bioactive polymeric materials based on calcium phosphates have tremendous appeal for hard tissue repair because of their well-documented biocompatibility. Amorphous calcium phosphate (ACP-based ones additionally protect against unwanted demineralization and actively support regeneration of hard tissue minerals. Our group has been investigating the structure/composition/property relationships of ACP polymeric composites for the last two decades. Here, we present ACP’s dispersion in a polymer matrix and the fine-tuning of the resin affects the physicochemical, mechanical, and biological properties of ACP polymeric composites. These studies illustrate how the filler/resin interface and monomer/polymer molecular structure affect the material’s critical properties, such as ion release and mechanical strength. We also present evidence of the remineralization efficacy of ACP composites when exposed to accelerated acidic challenges representative of oral environment conditions. The utility of ACP has recently been extended to include airbrushing as a platform technology for fabrication of nanofiber scaffolds. These studies, focused on assessing the feasibility of incorporating ACP into various polymer fibers, also included the release kinetics of bioactive calcium and phosphate ions from nanofibers and evaluate the biorelevance of the polymeric ACP fiber networks. We also discuss the potential for future integration of the existing ACP scaffolds into therapeutic delivery systems used in the precision medicine field.

  7. Polymeric bicontinuous microemulsions

    Bates, F.S.; Maurer, W.W.; Lipic, P.M.


    High molecular weight block copolymers can be viewed as macromolecular surfactants when blended with thermodynamically incompatible homopolymers. This Letter describes the formation of polymeric bicontinuous microemulsions in nurtures containing a model diblock copolymer and two homopolymers...

  8. Chelating polymeric membranes

    Peinemann, Klaus-Viktor


    The present application offers a solution to the current problems associated with recovery and recycling of precious metals from scrap material, discard articles, and other items comprising one or more precious metals. The solution is premised on a microporous chelating polymeric membrane. Embodiments include, but are not limited to, microporous chelating polymeric membranes, device comprising the membranes, and methods of using and making the same.

  9. Qualidade conjugal: mapeando conceitos

    Clarisse Mosmann


    Full Text Available Apesar da ampla utilização do conceito de qualidade conjugal, identifica-se falta de clareza conceitual acerca das variáveis que o compõem. Esse artigo apresenta revisão da literatura na área com o objetivo de mapear o conceito de qualidade conjugal. Foram analisadas sete principais teorias sobre o tema: Troca Social, Comportamental, Apego, Teoria da Crise, Interacionismo Simbólico. Pelos postulados propostos nas diferentes teorias, podem-se identificar três grupos de variáveis fundamentais na definição da qualidade conjugal: recursos pessoais dos cônjuges, contexto de inserção do casal e processos adaptativos. Neste sentido, a qualidade conjugal é resultado do processo dinâmico e interativo do casal, razão deste caráter multidimensional.

  10. Polymers for Protein Conjugation

    Gianfranco Pasut


    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  11. Direct synthesis of trans-polyacetylene films: Dependence on polymerization conditions

    Suruga, K. [Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152 (Japan); Natsume, N. [Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152 (Japan); Nishioka, T. [Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152 (Japan); Ishikawa, K. [Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152 (Japan); Takezoe, H. [Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152 (Japan); Fukuda, A. [Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152 (Japan)


    We tried to prepare trans-polyacetylene films without thermal treatment to obtain the films with conjugated system of long average length and narrow distribution. Polymerization was carried out at{sub r}oom temperature on various conditions. It has been clearly suggested that the decrease in polymerization rate particularly by decreasing aging temperature is effective for the preparation of trans-polyacetylene films without thermal treatment. (orig.)

  12. Synthesis of PNIPA/NVP Hydrogel by Radiation Polymerization and Its Drug Controlled Release%聚(N-异丙基丙烯酰胺)N-乙烯基吡咯烷酮水凝胶的辐射合成及其药物控释性研究

    杨华; 庄银凤; 朱仲祺; 宋伟强; 赵惠东


    采用辐射法制得N-异丙基丙烯酰胺(NIPA)与N-乙烯基吡咯烷酮(NVP)共聚水凝胶. 调节单体配比获得不同的温敏性和耐盐性. 药物释放结果表明,此凝胶对难溶药物乙酰水杨酸具有增溶缓释作用.%Hydrogel of N-isopropylacrylamide and N-vinylpyrrolidone were prepared by radiation polymerization. Different thermoresponsities and salt resistance were achieved by adjusting the monomer ratio of the copolymer. Acetylsalicylic acid proved a model drug of salt resistance in this work. The experimental results showed that the hydrogel was a promising material for causing solubilization and developing a long-term controlled release system.

  13. Advanced Polymeric Materials for High-tech Innovations

    TANG; BenZhong


    High technology is advancing our society and modernizing our life and advanced materials play an important role in the technological innovations. My research group has been working on the development of advanced polymeric materials and in this talk I will report our recent work on the creation of new conjugated polymers with novel molecular structures and unique materials properties.1-18 Our work include the design of molecular structures of monomeric building blocks, development of stable, effective and environmentally benign "green” polymerization catalysts, discovery of new polymerization reactions, synthesis of functional macromolecules, fabrication of nanodimensional composites, assembly and control of hierarchical structures, and construction of electrooptical devices. We have revealed the liquid crystallinity, light emission, photoconductivity, optical limiting, nano-hybridization, solvatochromism, optical activity, self-organization, and biological activity of the linear polyacetylenes and hyperbranched polyarylenes. The utilization of the advanced polymers and their interesting materials properties for high-tech innovations will be discussed.  ……

  14. Advanced Polymeric Materials for High-tech Innovations


    @@ High technology is advancing our society and modernizing our life and advanced materials play an important role in the technological innovations. My research group has been working on the development of advanced polymeric materials and in this talk I will report our recent work on the creation of new conjugated polymers with novel molecular structures and unique materials properties.1-18 Our work include the design of molecular structures of monomeric building blocks, development of stable, effective and environmentally benign "green” polymerization catalysts, discovery of new polymerization reactions, synthesis of functional macromolecules, fabrication of nanodimensional composites, assembly and control of hierarchical structures, and construction of electrooptical devices. We have revealed the liquid crystallinity, light emission, photoconductivity, optical limiting, nano-hybridization, solvatochromism, optical activity, self-organization, and biological activity of the linear polyacetylenes and hyperbranched polyarylenes. The utilization of the advanced polymers and their interesting materials properties for high-tech innovations will be discussed.

  15. Protein encapsulation in polymeric microneedles by photolithography

    Kochhar JS


    Full Text Available Jaspreet Singh Kochhar,1 Shui Zou,2 Sui Yung Chan,1 Lifeng Kang11Department of Pharmacy, 2Department of Chemistry, National University of Singapore, SingaporeBackground: Recent interest in biocompatible polymeric microneedles for the delivery of biomolecules has propelled considerable interest in fabrication of microneedles. It is important that the fabrication process is feasible for drug encapsulation and compatible with the stability of the drug in question. Moreover, drug encapsulation may offer the advantage of higher drug loading compared with other technologies, such as drug coating.Methods and results: In this study, we encapsulated a model protein drug, namely, bovine serum albumin, in polymeric microneedles by photolithography. Drug distribution within the microneedle array was found to be uniform. The encapsulated protein retained its primary, secondary, and tertiary structural characteristics. In vitro release of the encapsulated protein showed that almost all of the drug was released into phosphate buffered saline within 6 hours. The in vitro permeation profile of encapsulated bovine serum albumin through rat skin was also tested and shown to resemble the in vitro release profile, with an initial release burst followed by a slow release phase. The cytotoxicity of the microneedles without bovine serum albumin was tested in three different cell lines. High cell viabilities were observed, demonstrating the innocuous nature of the microneedles.Conclusion: The microneedle array can potentially serve as a useful drug carrier for proteins, peptides, and vaccines.Keywords: poly (ethylene glycol diacrylate, microneedles, protein stability, photolithography, biocompatibility

  16. N-(2-Hydroxypropyl)methacrylamide-based polymer conjugates with pH-controlled activation of doxorubicin for cell-specific or passive tumour targeting. Synthesis by RAFT polymerisation and physicochemical characterisation.

    Chytil, Petr; Etrych, Tomáš; Kříž, Jaroslav; Subr, Vladimír; Ulbrich, Karel


    Controlled radical reversible addition-fragmentation chain transfer (RAFT) polymerisation was used to prepare water-soluble polymer-drug carriers based on copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) with a hydrazide group-containing monomer, showing well-defined structure with narrow molecular weight distribution (approx. 1.1-1.2). The anticancer therapeutic doxorubicin was bound to the polymeric carrier by a hydrazone bond, enabling pH-controlled release under mildly acid conditions that mimics the environment in endosomes/lysosomes of tumour cells. RAFT polymerisation facilitated the synthesis of semitelechelic copolymers, which were used in the synthesis of monoclonal anti-CD20 antibody-polymer-drug conjugate designed for cell-specific tumour targeting. They were also used for producing a biodegradable high-molecular-weight graft polymer-drug conjugate that degrade in the presence of glutathione, which is designed for passive targeting to solid tumours. The conjugates exhibited well-defined structures with narrow molecular weight distributions of approx. 1.3 and pH-controlled drug release.

  17. Free heme and sickle hemoglobin polymerization

    Uzunova, Veselina V.

    This work investigates further the mechanism of one of the most interesting of the protein self-assembly systems---the polymerization of sickle hemoglobin and the role of free heme in it. Polymerization of sickle hemoglobin is the primary event in the pathology of a chronic hemolytic condition called sickle cell anemia with complex pathogenesis, unexplained variability and symptomatic treatment. Auto-oxidation develops in hemoglobin solutions exposed to room temperature and causes release of ferriheme. The composition of such solutions is investigated by mass spectrometry. Heme dimers whose amount corresponds to the initial amounts of heme released from the protein are followed. Differences in the dimer peak height are established for hemoglobin variants A, S and C and depending on the exposure duration. The effects of free heme on polymerization kinetics are studied. Growth rates and two characteristic parameters of nucleation are measured for stored Hb S. After dialysis of polymerizing solutions, no spherulites are detected at moderately high supersaturation and prolonged exposure times. The addition of 0.16-0.26 mM amounts of heme to dialyzed solutions leads to restoration of polymerization. The measured kinetic parameters have higher values compared to the ones before dialysis. The amount of heme in non-dialyzed aged solution is characterized using spectrophotometry. Three methods are used: difference in absorbance of dialyzed and non-dialyzed solutions, characteristic absorbance of heme-albumin complex and absorbance of non-dialyzed solutions with added potassium cyanide. The various approaches suggest the presence of 0.12 to 0.18 mM of free ferriheme in such solutions. Open questions are whether the same amounts of free heme are present in vivo and whether the same mechanism operates intracellulary. If the answer to those questions is positive, then removal of free heme from erythrocytes can influence their readiness to sickle.

  18. Plasma polymerization by Softplasma

    Jiang, J.; Wu, Zhenning; Benter, Maike


    In the late 19th century, the first depositions - known today as plasma polymers, were reported. In the last century, more and more research has been put into plasma polymers. Many different deposition systems have been developed. [1, 2] Shi F. F. broadly classified them into internal electrode......, external electrode, and electrodeless microwave or high frequency reactors. [3] Softplasma™ is an internal electrode plasma setup powered by low frequenc~ gower supply. It was developed in late 90s for surface treatment of silicone rubber. [ ]- 5] It is a low pressure, low electron density, 3D homogenous...... plasma. In this study, we are presenting the surface modification"pf polymers by plasma polymerization using Softplasma™. Softplasma™ can be used for two major types of polymerization: polymerization of vinyl monomers, where plasma acts as initiator; chemical vapour deposition, where plasma acts...

  19. Synthesis of arylpyrazole linked benzimidazole conjugates as potential microtubule disruptors.

    Kamal, Ahmed; Shaik, Anver Basha; Polepalli, Sowjanya; Kumar, G Bharath; Reddy, Vangala Santhosh; Mahesh, Rasala; Garimella, Srujana; Jain, Nishant


    In an attempt to develop potent and selective anticancer agents, a series of twenty arylpyrazole linked benzimidazole conjugates (10a-t) were designed and synthesized as microtubule destabilizing agents. The joining of arylpyrazole to the benzimidazole moiety resulted in a four ring (A, B, C and D) molecular scaffold that comprises of polar heterocyclic rings in the middle associated with rotatable single bonds and substituted aryl rings placed in the opposite directions. These conjugates were evaluated for their ability to inhibit the growth of sixty cancer cell line panel of the NCI. Among these some conjugates like 10a, 10b, 10d, 10e, 10p and 10r exhibited significant growth inhibitory activity against most of the cell lines ranging from 0.3 to 13μM. Interestingly, the conjugate 10b with methoxy group on D-ring expressed appreciable cytotoxic potential. A549 cells treated with some of the potent conjugates like 10a, 10b and 10d arrested cells at G2/M phase apart from activating cyclin-B1 protein levels and disrupting microtubule network. Moreover, these conjugates effectively inhibited tubulin polymerization with IC50 values of 1.3-3.8μM. Whereas, the caspase assay revealed that they activate the casepase-3 leading to apoptosis. Particularly 10b having methoxy substituent induced activity almost 3 folds higher than CA-4. Furthermore, a competitive colchicine binding assay and molecular modeling analysis suggests that these conjugates bind to the tubulin successfully at the colchicine binding site. These investigations reveal that such conjugates having pyrazole and benzimidazole moieties have the potential in the development of newer chemotherapeutic agents.


    P.M. Saville; J.W. White


    Polymeric surfactants are amongst the most widespread of all polymers. In nature, proteins and polysaccharides cause self organization as a result of this surfactancy; in industry, polymeric surfactants play key roles in the food, explosives and surface coatings sectors. The generation of useful nano- and micro-structures in films and emulsions as a result of polymer amphiphilicity and the application of mechanical stress is discussed. The use of X-ray and neutron small angle scattering and reflectivity to measure these structures and their dynamic properties will be described. New results on linear and dendritic polymer surfactants are presented.

  1. Semiconducting polymeric materials

    de Boer, Bert; Facchetti, Antonio


    (Semi)conducting polymers with a pi-conjugated (hetero)aromatic backbone are capable of transporting charge and interact efficiently with light enabling their utilization in a variety of opto-electronic devices. In this report and in the additional papers of this special issue, several classes of pi

  2. Semiconducting polymeric materials

    de Boer, Bert; Facchetti, Antonio


    (Semi)conducting polymers with a pi-conjugated (hetero)aromatic backbone are capable of transporting charge and interact efficiently with light enabling their utilization in a variety of opto-electronic devices. In this report and in the additional papers of this special issue, several classes of

  3. Polymerized and functionalized triglycerides

    Plant oils are useful sustainable raw materials for the development of new chemical products. As part of our research emphasis in sustainability and green polymer chemistry, we have explored a new method for polymerizing epoxidized triglycerides with the use of fluorosulfonic acid. Depending on the ...

  4. Waterborne Polymeric Films.


    Skydrol 500B is a fire resistant hydraulic fluid available from Monsanto and which is primarily tricresyl phosphate. In most cases, the above table...Makromol. Chem. 1979, 82 149.- 23. Ger. Offen 2,804,609; (8/9/79). Bayer AG. 24. Odian, G. "Principles of Polymerization; "McGraw-Hill Book Co.: New York


    V. V. Vlizlo


    Full Text Available The new method for detection of cationic oligoelectrolytes conjugates with oligodeoxyonucleotides, based on free diffusion of these substances in 0.8% agarose gels is developed. It enables to simplify and reduce the cost of visual identification of the best carrier among various polymer compounds and to uncover the fact of complex formation between the interacting agents resulting in formation of a ring precipitation. The universality of the proposed methodological approach is confirmed by interaction of coligodeoxynucleotides with other cationic polymer of natural origin, namely chitosan. Comparative analysis of our approach applicationto turbidimetry data concerning coligodeoxynucleotides complexes and their electrophoresis showed some advantages, among them are the ability to screen simultaneously a large number of polymeric carriers and no need for using of more expensive equipment and materials. To conclude the complexing occurrence it is enough nanomol amounts of oligodeoxynucleotide.

  6. Highly conductive free standing polypyrrole films prepared by freezing interfacial polymerization.

    Qi, Guijin; Huang, Liyan; Wang, Huiliang


    Highly conductive free standing polypyrrole (PPy) films were prepared by a novel freezing interfacial polymerization method. The films exhibit metallic luster and electrical conductivity up to 2000 S cm(-1). By characterizing with SEM, FTIR, Raman and XRD, the high conductivity is attributed to the smooth surface, higher conjugation length and more ordered molecular structure of PPy.

  7. HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

    Shukla, Rameshwer; Thomas, Thommey P; Desai, Ankur M; Kotlyar, Alina; Park, Steve J; Baker, James R Jr [Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, 9220 MSRB III, Box 0648, Ann Arbor, MI 48109 (United States)], E-mail:, E-mail:


    Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket.

  8. Spiropyran main-chain conjugated polymers.

    Sommer, Michael; Komber, Hartmut


    The first main-chain conjugated copolymers based on alternating spiropyran (SP) and 9,9-dioctylfluorene (F8) units synthesized via Suzuki polycondensation (SPC) are presented. The reaction conditions of SPC are optimized to obtain materials of type P(para-SP-F8) with appreciably high molecular weights up to M(w) ≈ 100 kg mol(-1). (13)C NMR is used to identify the random orientation of the non-symmetric SP unit in P(p-SP-F8). Ultrasound-induced isomerization of P(p-SP-F8) to the corresponding merocyanine form P(p-MC-F8) yields a deep-red solution. This isomerization reaction is followed by (1)H NMR in solution using sonication, whereby the color increasingly changes to deep red. The possibility to incorporate multiple SP units into main-chain polymers significantly broadens existing SP-based polymeric architectures.

  9. Conjugation in "Escherichia coli"

    Phornphisutthimas, Somkiat; Thamchaipenet, Arinthip; Panijpan, Bhinyo


    Bacterial conjugation is a genetic transfer that involves cell-to-cell between donor and recipient cells. With the current method used to teach students in genetic courses at the undergraduate level, the transconjugants are identified using bacterial physiology and/or antibiotic resistance. Using physiology, however, is difficult for both…

  10. DNA-cell conjugates

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki


    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  11. Peptide-Carrier Conjugation

    Hansen, Paul Robert


    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  12. Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

    Ding, Hong; Yong, Ken-Tye; Roy, Indrajit; Hu, Rui; Wu, Fang; Zhao, Lingling; Law, Wing-Cheung; Zhao, Weiwei; Ji, Wei; Liu, Liwei; Bergey, Earl J.; Prasad, Paras N.


    In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l - 1. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the αvβ3 integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

  13. Therapeutic Strategies Based on Polymeric Microparticles

    C. Vilos


    Full Text Available The development of the field of materials science, the ability to perform multidisciplinary scientific work, and the need for novel administration technologies that maximize therapeutic effects and minimize adverse reactions to readily available drugs have led to the development of delivery systems based on microencapsulation, which has taken one step closer to the target of personalized medicine. Drug delivery systems based on polymeric microparticles are generating a strong impact on preclinical and clinical drug development and have reached a broad development in different fields supporting a critical role in the near future of medical practice. This paper presents the foundations of polymeric microparticles based on their formulation, mechanisms of drug release and some of their innovative therapeutic strategies to board multiple diseases.

  14. Design, synthesis and evaluation of N-acetyl glucosamine (NAG)-PEG-doxorubicin targeted conjugates for anticancer delivery.

    Pawar, Smita K; Badhwar, Archana J; Kharas, Firuza; Khandare, Jayant J; Vavia, Pradeep R


    Efficacy of anticancer drug is limited by the severe adverse effects induced by drug; therefore the crux is in designing delivery systems targeted only to cancer cells. Toward this objectives, we propose, synthesis of poly(ethylene glycol) (PEG)-doxorubicin (DOX) prodrug conjugates consisting N-acetyl glucosamine (NAG) as a targeting moiety. Multicomponent system proposed here is characterized by (1)H NMR, UV spectroscopy, and HPLC. The multicomponent system is evaluated for in vitro cellular kinetics and anticancer activity using MCF-7 and MDA-MB-231 cells. Molecular modeling study demonstrated sterically stabilized conformations of polymeric conjugates. Interestingly, PEG-DOX conjugate with NAG ligand showed significantly higher cytotoxicity compared to drug conjugate with DOX. In addition, the polymer drug conjugate with NAG and DOX showed enhanced internalization and retention effect in cancer cells, compared to free DOX. Thus, with enhanced internalization and targeting ability of PEG conjugate of NAG-DOX has implication in targeted anticancer therapy.

  15. Electroluminescence and photoluminescence of conjugated polymer films prepared by plasma enhanced chemical vapor deposition of naphthalene

    Rajabi, Mojtaaba; Firouzjah, Marzieh Abbasi; Hosseini, Seyed Iman; Shokri, Babak


    Polymer light-emitting devices were fabricated utilizing plasma polymerized thin films as emissive layers. These conjugated polymer films were prepared by RF Plasma Enhanced Chemical Vapor Deposition (PECVD) using naphthalene as monomer. The effect of different applied powers on the chemical structure and optical properties of the conjugated polymers was investigated. The fabricated devices with structure of ITO/PEDOT:PSS/ plasma polymerized Naphthalene/Alq3/Al showed broadband Electroluminescence (EL) emission peaks with center at 535-550 nm. Using different structural and optical tests, connection between polymers chemical structure and optical properties under different plasma powers has been studied. Fourier transform infrared (FTIR) and Raman spectroscopies confirmed that a conjugated polymer film with a 3-D cross-linked network was developed. By increasing the power, products tended to form as highly cross-linked polymer films. Photoluminescence (PL) spectra of plasma polymers showed different excimerc ...

  16. Benzocaine-loaded polymeric nanocapsules: study of the anesthetic activities.

    De Melo, Nathalie Ferreira Silva; De Araújo, Daniele Ribeiro; Grillo, Renato; Moraes, Carolina Morales; De Matos, Angélica Prado; de Paula, Eneida; Rosa, André Henrique; Fraceto, Leonardo Fernandes


    This paper describes a comparison of different polymeric nanocapsules (NCs) prepared with the polymers poly(D,L-lactide-co-glycolide), poly(L-lactide) (PLA), and poly(ε-caprolactone) and used as carrier systems for the local anesthetic (LA) benzocaine (BZC). The systems were characterized and their anesthetic activities investigated. The results showed particle size distributions with polydispersity indices below 0.135, average diameters up to 120 nm, zeta potentials up to -30 mV, and entrapment efficiencies around 70%. Formulations of BZC using the polymeric NCs presented slower release profiles, compared with that of free BZC. Slowest release (release constant, k = 0.0016 min(-1)) was obtained using the PLA NC system. Pharmacological evaluation showed that encapsulation of BZC in PLA NCs prolonged its anesthetic action. This new formulation could potentially be used in future applications involving the gradual release of local anesthetics (LAs).

  17. Biodegradable Polymeric Nanoparticles as the Delivery Carrier for Drug.

    Zhao, Kai; Li, Dan; Shi, Ci; Ma, Xueling; Rong, Guangu; Kang, Hong; Wang, Xiaohua; Sun, Bin


    Drug research and development has entered into the new epoch of innovation formulation, and the drug delivery system has been in the forefront of pharmaceutical innovation. Nanotechnology is widely used in fiber and textiles, electronics, space, agriculture, forensic science and medical therapeutics. It increasingly plays a significant role in drug delivery system. Compared with traditional delivery system, the nanoparticle drug delivery system has lots of merits, such as the high drug loading ability, the excellent biocompatibility, low toxicity, controlled and targeted drug release. We undertook a structured research of biodegradable polymeric nanoparticles used as delivery carrier for drug using a focused review question and inclusion/exclusion criteria. We have searched the bibliographic databases for peerreviewed research literature. The outstanding characteristics of the screened papers were described respectively, and a systematic content analysis methodology was used to analysis the findings. Seventy-three papers were included in the review, the majority defined leadership and governance approaches that had impacted upon the polymeric nanoparticles as the delivery carrier for drug in therapeutic applications and developments. Seven papers outlined the superiority characteristics of polymeric nanoparticles that applied in the field of vaccine. Forty-seven papers overviewed the application prospects of polymeric nanoparticles used as drug delivery carrier for cancer. These included current advances in research and clinical applications of polymeric nanoparticles. The review identified the drug delivery carrier of biodegradable polymeric nanoparticles, and we described the synthesis methods, applications and challenges of polymeric nanoparticles. The findings of this review identified that the biodegradable polymeric nanoparticles were used as delivery carrier for drug currently. It also indicates that the biodegradable polymeric nanoparticles play an

  18. Protein corona change the drug release profile of nanocarriers: the "overlooked" factor at the nanobio interface.

    Behzadi, Shahed; Serpooshan, Vahid; Sakhtianchi, Ramin; Müller, Beate; Landfester, Katharina; Crespy, Daniel; Mahmoudi, Morteza


    The emergence of nanocarrier systems in drug delivery applications has ushered in rapid development of new classes of therapeutic agents which can provide an essential breakthrough in the fight against refractory diseases. However, successful clinical application of nano-drug delivery devices has been limited mainly due to the lack of control on sustained release of therapeutics from the carriers. A wide range of sophisticated approaches employs the formation of crosslinkable, non-crosslinkable, stimuli-responsive polymer nanocarriers in order to enhance their delivery efficiency. Despite the extensive research conducted on the development of various nanocarriers, the effect of the biological milieu on the drug release profile of these constructs is not yet fully investigated. In particular, the formation of a protein corona on the surface of nanocarriers, when they interact with living organisms in vivo is largely decisive for their biological function. Using a number of synthetized (i.e., superparamagnetic iron oxide nanoparticles and polymeric nanocapsules) and commercialized nanocarriers (i.e., Abraxane®, albumin-bound paclitaxel drug), this study demonstrates that the protein corona can shield the nanocarriers and, consequently, alters the release profile of the drugs from the nanocarriers. More specifically, the protein corona could significantly reduce the burst effect of either protein conjugated nanocarriers or carriers with surface loaded drug (i.e., SPIONs). However, the corona shell only slightly changed the release profile of polymeric nanocapsules. Therefore, the intermediary, buffer effect of the protein shells on the surface of nanoscale carriers plays a crucial role in their successful high-yield applications in vivo.

  19. Novel polymeric scaffolds using protein microbubbles as porogen and growth factor carriers.

    Nair, Ashwin; Thevenot, Paul; Dey, Jagannath; Shen, Jinhui; Sun, Man-Wu; Yang, Jian; Tang, Liping


    Polymeric tissue engineering scaffolds prepared by conventional techniques like salt leaching and phase separation are greatly limited by their poor biomolecule-delivery abilities. Conventional methods of incorporation of various growth factors, proteins, and/or peptides on or in scaffold materials via different crosslinking and conjugation techniques are often tedious and may affect scaffold's physical, chemical, and mechanical properties. To overcome such deficiencies, a novel two-step porous scaffold fabrication procedure has been created in which bovine serum albumin microbubbles (henceforth MB) were used as porogen and growth factor carriers. Polymer solution mixed with MB was phase separated and then lyophilized to create porous scaffold. MB scaffold triggered substantially lesser inflammatory responses than salt-leached and conventional phase-separated scaffolds in vivo. Most importantly, the same technique was used to produce insulin-like growth factor-1 (IGF-1)-eluting porous scaffolds, simply by incorporating IGF-1-loaded MB (MB-IGF-1) with polymer solution before phase separation. In vitro such MB-IGF-1 scaffolds were able to promote cell growth to a much greater extent than scaffold soaked in IGF-1, confirming the bioactivity of the released IGF-1. Further, such MB-IGF-1 scaffolds elicited IGF-1-specific collagen production in the surrounding tissue in vivo. This novel growth factor-eluting scaffold fabrication procedure can be used to deliver a range of single or combination of bioactive biomolecules to substantially promote cell growth and function in degradable scaffold.

  20. Sterically and electrosterically stabilized emulsion polymerization. Kinetics and preparation.

    Capek, Ignác


    The principal subject discussed in the current paper is the radical polymerization in the aqueous emulsions of unsaturated monomers (styrene, alkyl (meth)acrylates, etc.) stabilized by non-ionic and ionic/non-ionic emulsifiers. The sterically and electrosterically stabilized emulsion polymerization is a classical method which allows to prepare polymer lattices with large particles and a narrow particle size distribution. In spite of the similarities between electrostatically and sterically stabilized emulsion polymerizations, there are large differences in the polymerization rate, particle size and nucleation mode due to varying solubility of emulsifiers in oil and water phases, micelle sizes and thickness of the interfacial layer at the particle surface. The well-known Smith-Ewart theory mostly applicable for ionic emulsifier, predicts that the number of particles nucleated is proportional to the concentration of emulsifier up to 0.6. The thin interfacial layer at the particle surface, the large surface area of relatively small polymer particles and high stability of small particles lead to rapid polymerization. In the sterically stabilized emulsion polymerization the reaction order is significantly above 0.6. This was ascribed to limited flocculation of polymer particles at low concentration of emulsifier, due to preferential location of emulsifier in the monomer phase. Polymerization in the large particles deviates from the zero-one approach but the pseudo-bulk kinetics can be operative. The thick interfacial layer can act as a barrier for entering radicals due to which the radical entry efficiency and also the rate of polymerization are depressed. The high oil-solubility of non-ionic emulsifier decreases the initial micellar amount of emulsifier available for particle nucleation, which induces non-stationary state polymerization. The continuous release of emulsifier from the monomer phase and dismantling of the non-micellar aggregates maintained a high level of

  1. Site-Specific Zwitterionic Polymer Conjugates of a Protein Have Long Plasma Circulation.

    Bhattacharjee, Somnath; Liu, Wenge; Wang, Wei-Han; Weitzhandler, Isaac; Li, Xinghai; Qi, Yizhi; Liu, Jinyao; Pang, Yan; Hunt, Donald F; Chilkoti, Ashutosh


    Many proteins suffer from suboptimal pharmacokinetics (PK) that limit their utility as drugs. The efficient synthesis of polymer conjugates of protein drugs with tunable PK to optimize their in vivo efficacy is hence critical. We report here the first study of the in vivo behavior of a site-specific conjugate of a zwitterionic polymer and a protein. To synthesize the conjugate, we first installed an initiator for atom-transfer radical polymerization (ATRP) at the N terminus of myoglobin (Mb-N-Br). Subsequently, in situ ATRP was carried out in aqueous buffer to grow an amine-functionalized polymer from Mb-N-Br. The cationic polymer was further derivatized to two zwitterionic polymers by treating the amine groups of the cationic polymer with iodoacetic acid to obtain poly(carboxybetaine methacrylate) with a one-carbon spacer (PCBMA; C1 ), and sequentially with 3-iodopropionic acid and iodoacetic acid to obtain PCBMA(mix) with a mixture of C1 and C2 spacers. The Mb-N-PCBMA polymer conjugates had a longer in vivo plasma half-life than a PEG-like comb polymer conjugate of similar molecular weights (MW). The structure of the zwitterion plays a role in controlling the in vivo behavior of the conjugate, as the PCBMA conjugate with a C1 spacer had significantly longer plasma circulation than the conjugate with a mixture of C1 and C2 spacers.

  2. Tumor-targeted HPMA copolymer-(RGDfK)-(CHX-A''-DTPA) conjugates show increased kidney accumulation.

    Borgman, Mark P; Coleman, Tomika; Kolhatkar, Rohit B; Geyser-Stoops, Sandra; Line, Bruce R; Ghandehari, Hamidreza


    N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-RGDfK conjugates targeting the alpha(v)beta(3) integrin have shown increased accumulation in solid tumors and promise for selective delivery of radiotherapeutics to sites of angiogenesis- or tumor-expressed alpha(v)beta(3) integrin. An unresolved issue in targeting radiotherapeutics to solid tumors is toxicity to non-target organs. To reduce toxicity of radiolabeled conjugates, we have synthesized HPMA copolymer-RGDfK conjugates with varying molecular weight and charge content to help identify a polymeric structure that maximizes tumor accumulation while rapidly clearing from non-targeted organs. Endothelial cell binding studies showed that copolymer conjugates of approximately 43, 20 and 10 kD actively bind to the alpha(v)beta(3) integrin. Scintigraphic images showed rapid clearance of indium-111 ((111)In) radiolabeled conjugates from the blood pool and high kidney accumulation within 1 h in tumor bearing mice. Biodistribution data confirms images with high accumulation in kidney (max 210% ID/g for 43 kD conjugate) and lower tumor accumulation (max 1.8% ID/g for 43 kD conjugate). While actively binding to the alpha(v)beta(3) integrin in vitro, HPMA copolymer-RGDfK conjugates with increased negative charge through increased CHX-A''-DTPA chelator content in the side chains causes increased kidney accumulation with a loss of tumor accumulation in vivo.

  3. Tumor-Targeted HPMA Copolymer-(RGDfK)-(CHX-A″-DTPA) Conjugates Show Increased Kidney Accumulation

    Borgman, Mark P.; Coleman, Tomika; Kolhatkar, Rohit B.; Geyser-Stoops, Sandra; Line, Bruce R.; Ghandehari, Hamidreza


    N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-RGDfK conjugates targeting the αvβ3 integrin have shown increased accumulation in solid tumors and promise for selective delivery of radiotherapeutics to sites of angiogenesis- or tumor-expressed αvβ3 integrin. An unresolved issue in targeting radiotherapeutics to solid tumors is toxicity to non-target organs. To reduce toxicity of radiolabeled conjugates, we have synthesized HPMA copolymer-RGDfK conjugates with varying molecular weight and charge content to help identify a polymeric structure that maximizes tumor accumulation while rapidly clearing from non-targeted organs. Endothelial cell binding studies showed that copolymer conjugates of approximately 43, 20 and 10 kD actively bind to the αvβ3 integrin. Scintigraphic images showed rapid clearance of indium-111 radiolabeled conjugates from the blood pool and high kidney accumulation within 1 h in tumor bearing mice. Biodistribution data confirms images with high accumulation in kidney (max 210% ID/g for 43 kD conjugate) and lower tumor accumulation (max 1.8% ID/g for 43kD conjugate). While actively binding to the αvβ3 integrin in vitro, HPMA copolymer-RGDfK conjugates with increased negative charge through increased CHX-A″-DTPA chelator content in the side chains causes increased kidney accumulation with a loss of tumor binding in vivo. PMID:18687371

  4. Theory of Digitized Conjugate Surface and Solution to Conjugate Surface

    Xiao Lai-yuan; Liao Dao-xun; Yi Chuan-yun


    In order to meet the needs of designing and processing digitized surfaces, the method to spreading digitized surface has been proposed. The key technique is to solve the problem of digitized conjugate surface. In the paper, the digitized conjugate surface was theoretically investigated, and the solution of conjugate surface based on digitized surface was also studied. The digitized conjugate surface theory was then proposed, and applied to build the model of solving conjugate surface based on digitized surface. A corresponding algorithm was developed. This paper applies the software Conjugater-1.0 that is developed by ourselves to compute the digitized conjugate surfaces of the drum-tooth surface. This study provides theoretical and technical bases for analyzing engagement of digitized surface, simulation and numerical processing technique.

  5. Development, optimization and evaluation of polymeric electrospun nanofiber: A tool for local delivery of fluconazole for management of vaginal candidiasis.

    Sharma, Rahul; Garg, Tarun; Goyal, Amit K; Rath, Goutam


    The present study is designed to explore the localized delivery of fluconazole using mucoadhesive polymeric nanofibers. Drug-loaded polymeric nanofibers were fabricated by the electrospinning method using polyvinyl alcohol (PVA) as the polymeric constituent. The prepared nanofibers were found to be uniform, non-beaded and non-woven, with the diameter of the fibers ranging from 150 to 180 nm. Further drug release studies indicate a sustained release of fluconazole over a period of 6 h. The results of studies on anti-microbial activity indicated that drug-loaded polymeric nanofibers exhibit superior anti-microbial activity against Candida albicans, when compared to the plain drug.

  6. Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer.

    Li, Wei-Ming; Chiang, Chih-Sheng; Huang, Wei-Chen; Su, Chia-Wei; Chiang, Min-Yu; Chen, Jian-Yi; Chen, San-Yuan


    We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers.

  7. 5-Fluorouracil-lipid conjugate: potential candidate for drug delivery through encapsulation in hydrophobic polyester-based nanoparticles.

    Ashwanikumar, N; Kumar, Nisha Asok; Nair, S Asha; Kumar, G S Vinod


    The encapsulation of 5-fluorouracil (5-FU) in hydrophobic polymeric materials is made feasible by a lipid-based prodrug approach. A lipid-5-FU conjugate of 5-FU with palmitic acid was synthesized in two-step process. A synthesized dipalmitoyl derivative (5-FUDIPAL) was characterized using Fourier transform infrared spectroscopy and (1)H-nuclear magnetic resonance. The 5-FUDIPAL was encapsulated in polyester-based polymers by the double emulsion-solvent evaporation method. The nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy and dynamic light scattering. The thermal stability was assessed by differential scanning calorimetry data. In vitro release kinetics measurements of the drug from nanoparticles showed the controlled release pattern over a period of time. Cytotoxicity measurements by MTT assay confirmed that dipalmitoyl derivative in nano formulation successfully inhibited the cell growth. Thus the combined physical and biological evaluation of the different polyester-based nanoparticle containing the modified drug showed a facile approach to delivering 5-FU to the tumour site with enhanced efficacy.

  8. Living olefin polymerization processes

    Schrock, Richard R.; Baumann, Robert


    Processes for the living polymerization of olefin monomers with terminal carbon-carbon double bonds are disclosed. The processes employ initiators that include a metal atom and a ligand having two group 15 atoms and a group 16 atom or three group 15 atoms. The ligand is bonded to the metal atom through two anionic or covalent bonds and a dative bond. The initiators are particularly stable under reaction conditions in the absence of olefin monomer. The processes provide polymers having low polydispersities, especially block copolymers having low polydispersities. It is an additional advantage of these processes that, during block copolymer synthesis, a relatively small amount of homopolymer is formed.

  9. Con-A conjugated mucoadhesive microspheres for the colonic delivery of diloxanide furoate.

    Anande, Nalini M; Jain, Sunil K; Jain, Narendra K


    The aim of the research work was to develop cyst-targeted novel concanavalin-A (Con-A) conjugated mucoadhesive microspheres of diloxanide furoate (DF) for the effective treatment of amoebiasis. Eudragit microspheres of DF were prepared using emulsification-solvent evaporation method. Formulations were characterized for particle size and size distribution, % drug entrapment, surface morphology and in vitro drug release in simulated gastrointestinal (GI) fluids. Eudragit microspheres of DF were conjugated with Con-A. IR spectroscopy and DSC were used to confirm successful conjugation of Con-A to Eudragit microspheres while Con-A conjugated microspheres were further characterized using the parameters of zeta potential, mucoadhesiveness to colonic mucosa and Con-A conjugation efficiency with microspheres. IR studies confirmed the attachment of Con-A with Eudragit microspheres. All the microsphere formulations showed good % drug entrapment (78+/-5%). Zeta potential of Eudragit microspheres and Con-A conjugated Eudragit microspheres were found to be 3.12+/-0.7mV and 16.12+/-0.5mV, respectively. Attachment of lectin to the Eudragit microspheres significantly increases the mucoadhesiveness and also controls the release of DF in simulated GI fluids. Gamma scintigraphy study suggested that Eudragit S100 coated gelatin capsule retarded the release of Con-A conjugated microspheres at low pH and released microspheres slowly at pH 7.4 in the colon.

  10. Novel amphiphilic PEG-hydroxycamptothecin conjugates as glutathione-responsive prodrug nanocapsules for cancer chemotherapy

    Guo, Na; Hao, Tiantian; Shang, Xiuzhuan; Zhang, Tianle; Liu, Huan; Zhang, Qian; Wang, Jing; Jiang, Du; Rong, Yao; Teng, Yuou; Yu, Peng


    A series of novel hydroxycamptothecin (HCPT) conjugates ( 13a-14d), which contained a polyethylene glycol moiety and disulfide bond, were designed and synthesized in five to six steps, with overall yields of 20-39%. The anticancer activities and toxicities of these new conjugates were evaluated using an in vitro MTT assay in K562, HepG2, and HT-29 cell lines and HUVECs. The conjugates displayed enhanced antitumor activity and reduced toxicity in comparison with their parent molecule, HCPT. Among these conjugates, compound 13a exhibited 100-fold better selectivity to the tumor cells than to HUVECs. TEM and DLS experiments demonstrated that 13a formed nanosized micelles with a diameter of approximately 200 nm in aqueous solution and that the conjugate could undergo glutathione-responsive degradation to release HCPT at the tumor site. The improved potency and reduced toxicity of these conjugates may be caused by the enhanced permeation and retention (EPR) effect of nanoparticles.

  11. Phosphazene-promoted anionic polymerization

    Zhao, Junpeng


    In the recent surge of metal-free polymerization techniques, phosphazene bases have shown their remarkable potential as organic promoters/catalysts for the anionic polymerization of various types of monomers. By complexation with the counterion (e.g. proton or lithium cation), phosphazene base significantly improve the nucleophilicity of the initiator/chain-end resulting in rapid and usually controlled anionic/quasi-anionic polymerization. In this review, we will introduce the general mechanism, i.e. in situ activation (of initiating sites) and polymerization, and summarize the applications of such a mechanism on macromolecular engineering toward functionalized polymers, block copolymers and complex macromolecular architectures.

  12. Preparation and Evaluation of Inhalable Itraconazole Chitosan Based Polymeric Micelles

    Esmaeil Moazeni


    Full Text Available Background: This study evaluated the potential of chitosan based polymeric micelles as a nanocarrier system for pulmonary delivery of itraconazole (ITRA.Methods: Hydrophobically modified chitosan were synthesized by conjugation of stearic acid to the hydrophilic depolymerized chitosan. FTIR and 1HNMR were used to prove the chemical structure and physical properties of the depolymerized and the stearic acid grafted chitosan. ITRA was entrapped into the micelles and physicochemical properties of the micelles were investigated. Fluorescence spectroscopy, dynamic laser light scattering andtransmission electron microscopy were used to characterize the physicochemical properties of the prepared micelles. The in vitro pulmonary profile of polymeric micelles was studied by an air-jet nebulizer connected to a twin stage impinger.Results: The polymeric micelles prepared in this study could entrap up to 43.2±2.27 μg of ITRA per milliliter. All micelles showed mean diameter between 120–200 nm. The critical micelle concentration of the stearic acid grafted chitosan was found to be 1.58×10-2 mg/ml. The nebulization efficiency was up to 89% and the fine particle fraction (FPF varied from 38% to 47%. The micelles had enough stability to remain encapsulation of the drug during nebulization process.Conclusions: In vitro data showed that stearic acid grafted chitosan based polymeric micelles has a potential to be used as nanocarriers for delivery of itraconazole through inhalation.

  13. Development of polymeric nanoparticles showing tuneable pH-responsive precipitation

    Vakurov, Alexander, E-mail:; Pchelintsev, Nikolay A., E-mail:; Gibson, Tim, E-mail:; Millner, Paul, E-mail: [Research Institute of Membrane and Systems Biology, University of Leeds (United Kingdom)


    A reverse micellar system comprising dioctyl-sulfosuccinate (AOT)/toluene was used as a template for polymerization of acrylamide/bisacrylamide-based functionalized polymeric nanoparticles. Such nanoparticles were typically sized between 20 and 90 nm and could be synthesized with a wide range of functional groups according to the monomers added to the polymerization mixture. Carboxy nanoparticles with acrylic acid as the functional monomer were synthesized in the reported work. The carboxy nanoparticles were pH sensitive and precipitated at pHs below 4. Modification of carboxy-functionalized polymeric nanoparticles with polyetheleneimine (PEI) resulted in the fabrication of a series of pH-responsive nanoparticles which could precipitate at different pHs and ionic strengths according to the PEI/carboxy ratio in the system. Both non-covalent PEI-nanoparticles conjugates and nanoparticles with covalently linked PEI behaved in this way.

  14. Chimeric Antisense Oligonucleotide Conjugated to α-Tocopherol

    Tomoko Nishina


    Full Text Available We developed an efficient system for delivering short interfering RNA (siRNA to the liver by using α-tocopherol conjugation. The α-tocopherol–conjugated siRNA was effective and safe for RNA interference–mediated gene silencing in vivo. In contrast, when the 13-mer LNA (locked nucleic acid-DNA gapmer antisense oligonucleotide (ASO was directly conjugated with α-tocopherol it showed markedly reduced silencing activity in mouse liver. Here, therefore, we tried to extend the 5′-end of the ASO sequence by using 5′-α-tocopherol–conjugated 4- to 7-mers of unlocked nucleic acid (UNA as a “second wing.” Intravenous injection of mice with this α-tocopherol–conjugated chimeric ASO achieved more potent silencing than ASO alone in the liver, suggesting increased delivery of the ASO to the liver. Within the cells, the UNA wing was cleaved or degraded and α-tocopherol was released from the 13-mer gapmer ASO, resulting in activation of the gapmer. The α-tocopherol–conjugated chimeric ASO showed high efficacy, with hepatic tropism, and was effective and safe for gene silencing in vivo. We have thus identified a new, effective LNA-DNA gapmer structure in which drug delivery system (DDS molecules are bound to ASO with UNA sequences.

  15. Dead Sea Minerals loaded polymeric nanoparticles.

    Dessy, Alberto; Kubowicz, Stephan; Alderighi, Michele; Bartoli, Cristina; Piras, Anna Maria; Schmid, Ruth; Chiellini, Federica


    Therapeutic properties of Dead Sea Water (DSW) in the treatment of skin diseases such as atopic dermatitis, psoriasis and photo aging UV damaged skin have been well established. DSW is in fact rich in minerals such as calcium, magnesium, sodium, potassium, zinc and strontium which are known to exploit anti-inflammatory effects and to promote skin barrier recovery. In order to develop a Dead Sea Minerals (DSM) based drug delivery system for topical therapy of skin diseases, polymeric nanoparticles based on Poly (maleic anhydride-alt-butyl vinyl ether) 5% grafted with monomethoxy poly(ethyleneglycol) 2000 MW (PEG) and 95% grafted with 2-methoxyethanol (VAM41-PEG) loaded with DSM were prepared by means of a combined miniemulsion/solvent evaporation process. The resulting nanoparticles were characterized in terms of dimension, morphology, biocompatibility, salt content and release. Cytocompatible spherical nanoparticles possessing an average diameter of about 300 nm, a time controlled drug release profile and a high formulation yield were obtained.

  16. Matrix metalloproteinases-2/9-sensitive peptide-conjugated polymer micelles for site-specific release of drugs and enhancing tumor accumulation: preparation and in vitro and in vivo evaluation

    Zhang X


    Full Text Available Xiaoyan Zhang, Xiaofei Wang, Weitong Zhong, Xiaoqing Ren, Xianyi Sha, Xiaoling FangKey Laboratory of Smart Drug Delivery, Ministry of Education and People’s Liberation Army of China, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China Abstract: Since elevated expression of matrix metalloproteinase (MMP-2 and MMP-9 is commonly observed in several malignant tumors, MMPs have been widely reported as key factors in the design of drug delivery systems. Several strategies have been proposed to develop MMPs-responsive nanoparticles to deliver chemotherapeutics to malignant solid tumors. A stimuli-responsive drug delivery system, which could be cleaved by MMPs, was proposed in this study. By inserting an MMP-2/9 cleavable oligopeptide GPVGLIGK-NH2 (GK8 as spacer between α-tocopherol succinate (α-TOS and methoxy-polyethylene glycol molecular weight (MW 2000 Da activated by N-hydroxysuccinimide (mPEG2K-NHS, mPEG2K-GK8-α-TOS (TGK was synthesized as the primary ingredient for MMP-2/9-sensitive micelles composed of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS and TGK (n:n =40:60, TGK micelles. mPEG2K-α-TOS (T2K was similarly synthesized as nonsensitive control. The TGK micelles showed better stability than nonsensitive micelles composed of TPGS and T2K (n:n =40:60, T2K micelles owing to the inserted peptide. Fluorescence resonance energy transfer results indicated that TGK micelles could be successfully cleaved by MMP-2/9. Effective drug release was demonstrated in the presence of collagenase type IV, a mixture of MMP-2 and MMP-9. Compared with nonsensitive micelles, docetaxel (DTX-loaded TGK micelles showed a fold higher cellular uptake in HT1080 cells. While the half-maximal inhibitory concentration (IC50 of TGK and T2K micelles were similar (P>0.05 in MCF-7 cells (MMP-2/9 underexpression, the IC50 values of the aforementioned micelles were 0.064±0.006 and 0.122±0.009 µg/mL, respectively, in HT1080 cells (MMP

  17. Gratings in polymeric waveguides

    Mishakov, G.; Sokolov, V.; Kocabas, A.; Aydinli, A.


    Laser-induced formation of polymer Bragg grating filters for Dense Wavelength Division Multiplexing (DWDM) applications is discussed. Acrylate monomers halogenated with both fluorine and chlorine, which possess absorption losses less than 0.25 dB/cm and wide choice of refractive indices (from 1.3 to 1.5) in the 1.5 μm telecom wavelength region were used. The monomers are highly intermixable thus permitting to adjust the refractive index of the composition within +/-0.0001. Moreover they are photocurable under UV exposure and exhibit high contrast in polymerization. These properties make halogenated acrylates very promising for fabricating polymeric waveguides and photonic circuits. Single-mode polymer waveguides were fabricated on silicon wafers using resistless contact lithography. Submicron index gratings have been written in polymer waveguides using holographic exposure with He-Cd laser beam (325 nm) through a phase mask. Both uniform and apodized gratings have been fabricated. The gratings are stable and are not erased by uniform UV exposure. The waveguide gratings possess narrowband reflection spectra in the 1.5 μm wavelength region of 0.4 nm width, nearly rectangular shape of the stopband and reflectivity R > 99%. The fabricated Bragg grating filters can be used for multiplexing/demultiplexing optical signals in high-speed DWDM optical fiber networks.

  18. Nanoencapsulation of blocked isocyanates through aqueous emulsion polymerization


    Full Text Available Blocked isocyanates were successfully encapsulated into polystyrene and hydroxyl and amine functionalized polymeric nanospheres via emulsion polymerization. The nanocapsules were characterized via Fourier transform infrared spectroscopy, differential scanning calorimetry and transmission electronic microscopy. The blocked isocyanates generated free isocyanate functionality upon thermal annealing of nanocapsules. This research establishes a novel encapsulating method for release and retention of free isocyanates in aqueous media. These nanocapsules can provide active isocyanates in coatings and adhesive applications, and represent a novel application of nanoencapsulated materials for controlled or delayed active material utilization.

  19. Poly-cross-linked PEI through aromatically conjugated imine linkages as a new class of pH-responsive nucleic acids packing cationic polymers

    Shun eChen


    Full Text Available Cationic polyimines polymerized through aromatically conjugated bis-imine linkages and intra-molecular cross-linking were found to be a new class of effective transfection materials for their flexibility in structural optimization, responsiveness to intracellular environment, the ability to facilitate endosome escape and cytosol release of the nucleic acids, as well as self-metabolism. When three phthalaldehydes of different substitution positions were used to polymerize highly branched low molecular weight polyethylenimine (PEI-1.8K, the product through ortho-phthalimines (named PPOP showed significantly higher transfection activity than its two tere- and iso-analogues (named PPTP and PPIP. Physicochemical characterization confirmed the similarity of three polyimines in pH-responded degradability, buffer capacity, as well as the size and Zeta potential of the polyplexes formed from the polymers. A mechanistic speculation may be that the ortho-positioned bis-imine linkage of PPOP may only lead to the straight trans-configuration due to steric hindrance, resulting in larger loops of intra-polymer cross-linking and more flexible backbone.

  20. Synthesis and biological evaluation of 1,2,3-triazole linked aminocombretastatin conjugates as mitochondrial mediated apoptosis inducers.

    Kamal, Ahmed; Shaik, Bajee; Nayak, V Lakshma; Nagaraju, Burri; Kapure, Jeevak Sopanrao; Shaheer Malik, M; Shaik, Thokhir Basha; Prasad, B


    A series of 1,2,3-triazole linked aminocombretastatin conjugates were synthesized and evaluated for cytotoxicity, inhibition of tubulin polymerization and apoptosis inducing ability. Most of the conjugates exhibited significant anticancer activity against some representative human cancer cell lines and two of the conjugates 6d and 7c displayed potent cytotoxicity with IC50 values of 53 nM and 44 nM against A549 human lung cancer respectively, and were comparable to combretastatin A-4 (CA-4). SAR studies revealed that 1-benzyl substituted triazole moiety with an amide linkage at 3-position of B-ring of the combretastatin subunit are more active compared to 2-position. G2/M cell cycle arrest was induced by these conjugates 6d and 7c and the tubulin polymerization assay (IC50 of 1.16 μM and 0.95 μM for 6d and 7c, respectively) as well as immunofluorescence analysis showed that these conjugates effectively inhibit microtubule assembly at both molecular and cellular levels in A549 cells. Colchicine competitive binding assay suggested that these conjugates bind at the colchicine binding site of tubulin as also observed from the docking studies. Further, mitochondrial membrane potential, ROS generation, caspase-3 activation assay, Hoechst staining and DNA fragmentation analysis revealed that these conjugates induce cell death by apoptosis.

  1. Organometallic B12-DNA conjugate

    Hunger, Miriam; Mutti, Elena; Rieder, Alexander


    Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets in hum...

  2. Collaborative Research: Polymeric Multiferroics

    Ren, Shenqiang [Temple Univ., Philadelphia, PA (United States). College of Engineering


    The goal of this project is to investigate room temperature magnetism and magnetoelectric coupling of polymeric multiferroics. A new family of molecular charge-transfer crystals has been emerged as a fascinating opportunity for the development of all-organic electrics and spintronics due to its weak hyperfine interaction and low spin-orbit coupling; nevertheless, direct observations of room temperature magnetic spin ordering have yet to be accomplished in organic charge-transfer solids. Furthermore, room temperature magnetoelectric coupling effect hitherto known multiferroics, is anticipated in organic donor-acceptor complexes because of magnetic field effects on charge-transfer dipoles, yet this is also unexplored. The PI seeks to fundamental understanding of the control of organic crystals to demonstrate and explore room temperature multiferroicity. The experimental results have been verified through the theoretical modeling.

  3. PLA-PEG-PLA的微波合成及其磁性载药微球的表征、释药性%Microwave-assisted polymerization of PLA-PEG-PLA and characterization, drug release properties for magnetic drug-loaded microspheres

    李亚瑜; 甄卫军; 汪凌; 刘月娥; 庞桂林


    目的 采用微波法合成PLA-PEG-PLA,并以该嵌段共聚物为基质制备ASA/PLA-PEG-PLA载药微球和ASA-Fe3O4/PLA-PEG-PLA载药微球,考察磁性载药微球和非磁性载药微球的药物缓释性能.方法 通过傅立叶变换红外光谱(FT-IR)、核磁(NMR)对微波法合成的PLA-PEG-PLA的微观结构进行了表征分析.采用乳化-溶剂挥发法制备了ASA/PLA-PEG-PLA载药微球,通过正交设计实验优选载药微球的最佳制备条件,在此基础上利用单微乳法制备的Fe3O4纳米粒子制备了ASA-Fe3O4/PLA-PEG-PLA载药微球.通过透射电子显微镜(TEM)、X-射线衍射(XRD)对Fe3O4纳米粒子进行微观结构表征和性能分析.采用傅立叶变换红外光谱(FT-IR),扫描电子显微镜(SEM)对制备的载药微球进行了微观结构的表征和分析.结果 微波法合成的PLA-PEG-PLA是一种三嵌段共聚物.载药微球呈规则球形,表面光滑,粒径分布较均匀,平均粒径约为20μm.体外模拟释药试验表明ASA/PLA-PEG-PLA载药微球和ASA-Fe3O4/PLA-PEG-PLA载药微球24h释药率分别为69.16%和100%.结论 以微波法合成的PLA-PEG-PLA作为药物载体具有明显的缓释作用.ASA-Fe3O4/PLA-PEG-PLA磁性载药微球比ASA/PLA-PEG-PLA非磁性载药微球具有较快的药物释放速率.%Objective PLA-PEG-PLA was synthesized by microwave-assisted polymerization. Drag-loaded microspheres were prepared by using this copolymer as matrix.The drag release properties of the magnetic drug-loaded microsphere and non-magnetic drag-loaded microsphere were observed. Methods The microstructure of synthesized PLA-PEG-PLA was characterized by FT-IR, 'H-NMR. ASA/PLA-PEG-PLA drag-loaded microspheres were prepared by emulsion-solvent evaporation method. The optimum experimental conditions of drag-loaded microspheres were screened by orthogonal experiment. Magnetic ferroferric oxide(Fe3O4) was prepared by water-in-oil microemulsion processing and characterized by TEM and XRD. The

  4. Light-driven nitrile imine-mediated tetrazole-ene cycloaddition as a versatile platform for fullerene conjugation.

    Sugawara, Yuuki; Jasinski, Nils; Kaupp, Michael; Welle, Alexander; Zydziak, Nicolas; Blasco, Eva; Barner-Kowollik, Christopher


    An efficient methodology for modular fullerene functionalization via the photo-induced nitrile imine-mediated tetrazole-ene cycloaddition (NITEC) is introduced. The versatility and platform character of the method is illustrated by the light-driven reaction of fullerenes with small molecule, polymeric and surface-immobilized tetrazoles. The efficient fullerene conjugation is evidenced via mass spectrometric techniques.

  5. Polymeric nanoparticles for drug delivery and targeting: A comprehensive review

    Natarajan Jawahar


    Full Text Available In the recent years, many modern technologies have been established in the pharmaceutical research and development area. The field of nanotechnology has been revolutionary as substantial and technical, and scientific growth, in basic sciences plus manipulation by physical or chemical process of individual atoms and molecules have widened its horizon. Polymeric nanoparticles with a size in the nanometer range protect drugs against in vitro and in vivo degradation; it releases the drug in a controlled manner and also offers the possibility of drug targeting. The use of polymeric drug nanoparticles is a universal approach to increase the therapeutic performance of poorly soluble drugs in any route of administration. The present review discusses the physico-chemical properties of polymeric nanoparticles, production methods, routes of administration and potential therapeutic applications.

  6. Selective fluorescent detection of aspartic acid and glutamic acid employing dansyl hydrazine dextran conjugate.

    Nasomphan, Weerachai; Tangboriboonrat, Pramuan; Tanapongpipat, Sutipa; Smanmoo, Srung


    Highly water soluble polymer (DD) was prepared and evaluated for its fluorescence response towards various amino acids. The polymer consists of dansyl hydrazine unit conjugated into dextran template. The conjugation enhances higher water solubility of dansyl hydrazine moiety. Of screened amino acids, DD exhibited selective fluorescence quenching in the presence of aspartic acid (Asp) and glutamic acid (Glu). A plot of fluorescence intensity change of DD against the concentration of corresponding amino acids gave a good linear relationship in the range of 1 × 10(-4) M to 25 × 10(-3) M. This establishes DD as a potential polymeric sensor for selective sensing of Asp and Glu.

  7. Novel π-Conjugated Poly(Schiff base) Containing Thiazole and Tetrathiatetrahyd ropentalene Moieties

    江黎明; 孙维林; 沈之荃


    A new kind of π-conjugated heterocyclic poly(Schiff base) was firstly prepared by the condensation reaction between tetrathiatetrahydropentalene-type diketone and bithiazole-diamine in good yields. The polymers were characterized by VPO, FTIR and 1H NMR spectroscopy. A large bathochromic shift was observed in UV-Vis spectra for these polymers due to the π-π* transition in the conjugated main chain. Brief examination indicated that the nitrogen-and sulfur-containing polymers exhibited an excellent chelating tendency to metal ions and the corresponding polymeric complexes would be expected to have potential in applications.

  8. Drug conjugation to cyclic peptide-polymer self-assembling nanotubes.

    Blunden, Bianca M; Chapman, Robert; Danial, Maarten; Lu, Hongxu; Jolliffe, Katrina A; Perrier, Sébastien; Stenzel, Martina H


    We show for the first time how polymeric nanotubes (NTs) based on self-assembled conjugates of polymers and cyclic peptides can be used as an efficient drug carrier. RAPTA-C, a ruthenium-based anticancer drug, was conjugated to a statistical co-polymer based on poly(2-hydroxyethyl acrylate) (pHEA) and poly(2-chloroethyl methacrylate) (pCEMA), which formed the shell of the NTs. Self-assembly into nanotubes (length 200-500 nm) led to structures exhibiting high activity against cancer cells.

  9. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus.

    Lehar, Sophie M; Pillow, Thomas; Xu, Min; Staben, Leanna; Kajihara, Kimberly K; Vandlen, Richard; DePalatis, Laura; Raab, Helga; Hazenbos, Wouter L; Morisaki, J Hiroshi; Kim, Janice; Park, Summer; Darwish, Martine; Lee, Byoung-Chul; Hernandez, Hilda; Loyet, Kelly M; Lupardus, Patrick; Fong, Rina; Yan, Donghong; Chalouni, Cecile; Luis, Elizabeth; Khalfin, Yana; Plise, Emile; Cheong, Jonathan; Lyssikatos, Joseph P; Strandh, Magnus; Koefoed, Klaus; Andersen, Peter S; Flygare, John A; Wah Tan, Man; Brown, Eric J; Mariathasan, Sanjeev


    Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S. aureus within host cells may provide a reservoir relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Here we confirm that intracellular reservoirs of S. aureus in mice comprise a virulent subset of bacteria that can establish infection even in the presence of vancomycin, and we introduce a novel therapeutic that effectively kills intracellular S. aureus. This antibody-antibiotic conjugate consists of an anti-S. aureus antibody conjugated to a highly efficacious antibiotic that is activated only after it is released in the proteolytic environment of the phagolysosome. The antibody-antibiotic conjugate is superior to vancomycin for treatment of bacteraemia and provides direct evidence that intracellular S. aureus represents an important component of invasive infections.

  10. Hierarchically deflated conjugate residual

    Yamaguchi, Azusa


    We present a progress report on a new class of multigrid solver algorithm suitable for the solution of 5d chiral fermions such as Domain Wall fermions and the Continued Fraction overlap. Unlike HDCG \\cite{Boyle:2014rwa}, the algorithm works directly on a nearest neighbour fine operator. The fine operator used is Hermitian indefinite, for example $\\Gamma_5 D_{dwf}$, and convergence is achieved with an indefinite matrix solver such as outer iteration based on conjugate residual. As a result coarse space representations of the operator remain nearest neighbour, giving an 8 point stencil rather than the 81 point stencil used in HDCG. It is hoped this may make it viable to recalculate the matrix elements of the little Dirac operator in an HMC evolution.

  11. Dihydroazulene-buckminsterfullerene conjugates

    Santella, Marco; Mazzanti, Virginia; Jevric, Martyn;


    The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has recently attracted interest as a molecular switch for molecular electronics. In this field, Buckminsterfullerene, C(60), has been shown to be a useful anchoring group for adhering a molecular wire to an electrode. Here we have...... combined the two units with the overall aim to elucidate how C(60) influences the DHA-VHF switching events. Efficient synthetic protocols for making covalently linked DHA-C(60) conjugates were developed, using Prato, Sonogashira, Hay, and Cadiot-Chodkiewicz reactions. These syntheses provide as well...... of DHA to its corresponding VHF. Thus, C(60) was found to significantly quench this conversion when situated closely to the DHA unit....

  12. Fire-Retardant Polymeric Additives

    Williams, Martha K.; Smith, Trent M.


    Polyhydroxyamide (PHA) and polymethoxyamide (PMeOA) are fire-retardant (FR) thermoplastic polymers and have been found to be useful as an additive for imparting fire retardant properties to other compatible, thermoplastic polymers (including some elastomers). Examples of compatible flammable polymers include nylons, polyesters, and acrylics. Unlike most prior additives, PHA and PMeOA do not appreciably degrade the mechanical properties of the matrix polymer; indeed, in some cases, mechanical properties are enhanced. Also, unlike some prior additives, PHA and PMeOA do not decompose into large amounts of corrosive or toxic compounds during combustion and can be processed at elevated temperatures. PMeOA derivative formulations were synthesized and used as an FR additive in the fabrication of polyamide (PA) and polystyrene (PS) composites with notable reduction (>30 percent for PS) in peak heat release rates compared to the neat polymer as measured by a Cone Calorimeter (ASTM E1354). Synergistic effects were noted with nanosilica composites. These nanosilica composites had more than 50-percent reduction in peak heat release rates. In a typical application, a flammable thermoplastic, thermoplastic blend, or elastomer that one seeks to render flame-retardant is first dry-mixed with PHA or PMeOA or derivative thereof. The proportion of PHA or PMeOA or derivative in the mixture is typically chosen to lie between 1 and 20 weight percent. The dry blend can then be melt-extruded. The extruded polymer blend can further be extruded and/or molded into fibers, pipes, or any other of a variety of objects that may be required to be fire-retardant. The physical and chemical mechanisms which impart flame retardancy of the additive include inhibiting free-radical oxidation in the vapor phase, preventing vaporization of fuel (the polymer), and cooling through the formation of chemical bonds in either the vapor or the condensed phase. Under thermal stress, the cyclic hydroxyl/ methoxy

  13. Generalized conjugate gradient squared

    Fokkema, D.R.; Sleijpen, G.L.G. [Utrecht Univ. (Netherlands)


    In order to solve non-symmetric linear systems of equations, the Conjugate Gradient Squared (CGS) is a well-known and widely used iterative method. In practice the method converges fast, often twice as fast as the Bi-Conjugate Gradient method. This is what you may expect, since CGS uses the square of the BiCG polynomial. However, CGS may suffer from its erratic convergence behavior. The method may diverge or the approximate solution may be inaccurate. BiCGSTAB uses the BiCG polynomial and a product of linear factors in an attempt to smoothen the convergence. In many cases, this has proven to be very effective. Unfortunately, the convergence of BiCGSTAB may stall when a linear factor (nearly) degenerates. BiCGstab({ell}) is designed to overcome this degeneration of linear factors. It generalizes BiCGSTAB and uses both the BiCG polynomial and a product of higher order factors. Still, CGS may converge faster than BiCGSTAB or BiCGstab({ell}). So instead of using a product of linear or higher order factors, it may be worthwhile to look for other polynomials. Since the BiCG polynomial is based on a three term recursion, a natural choice would be a polynomial based on another three term recursion. Possibly, a suitable choice of recursion coefficients would result in method that converges faster or as fast as CGS, but less erratic. It turns out that an algorithm for such a method can easily be formulated. One particular choice for the recursion coefficients leads to CGS. Therefore one could call this algorithm generalized CGS. Another choice for the recursion coefficients leads to BiCGSTAB. It is therefore possible to mix linear factors and some polynomial based on a three term recursion. This way one may get the best of both worlds. The authors will report on their findings.


    Zhu Zhenping; Yang Chunzheng; Tarunendu Ghose; Jaroslav Kralovec


    Objective: To analysis the uptake of free MTX and MTX conjugated to tumor specific monoclonal antibody by target and non-target cells. Methods: The folate antagonist methotrexate (MTX) was conjugated to two monoclonal antibodies (Mab) directed against human chronic lymphocytic leukemia (CLL), Dal B01 and Dal B02, by an active ester method. Both conjugates were more cytotoxic toward the target tumor cell line D10-1than to the non-target cell line MOLT-3, and Dal B02-MTX conjugate was more inhibitory to D10-1 cells than free MTX in a 6 h pulse exposure assay. Results: Drug uptake studies revealed that D10-1 cells took up much more Dal B01 and Dal B02-conjugated MTX than free MTX. The amounts of drug taken up by D10-1 cells incubated with Dal B01 and Dal B02-conjugated MTX were always 3 to 5-fold higher than that taken up by MOLT-3 cells, although the latter took up more drug when incubated with free MTX. Furthermore, tumor cells incubated with Dal B01 or Dal B02-conjugated MTX retained much larger amounts of drug for a prolonged period of time than those incubated with free MTX.Conclusion: The enhanced specific cytotoxicity of Dal B01 and Dal B02-MTX conjugates toward target tumor cells is therefore likely due to (Ⅰ) delivery of larger amounts of MTX to target cells when the drug is conjugated to Mab;(ii) longer retention of Mab-conjugated MTX by target cells; and (iii) slow, prolonged release of MTX from the surface-bound or endocytosed conjugates, rendering them into a sustained release dosage form.

  15. Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

    Kurtoglu, Yunus Emre

    The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.

  16. Synthesis and characterization of insulin-5-Fu conjugate,enabling insulin as multi-drug carder via dendritic approach

    Juan Huang; Jian Wei Wang; Tao Gong; Zhi Rong Zhang


    To enable insulin as multi-drug carrier, we designed and synthesized dendritic linker molecule bearing three 5-fluorouracil residues at the branch ends. The new conjugate showed excellent water solubility. The stabilities under different conditions were investigated. The results showed that the conjugate was a potential prodrug to release free 5-Fu.

  17. Controlled Bioactive Molecules Delivery Strategies for Tendon and Ligament Tissue Engineering using Polymeric Nanofibers.

    Hiong Teh, Thomas Kok; Hong Goh, James Cho; Toh, Siew Lok


    The interest in polymeric nanofibers has escalated over the past decade given its promise as tissue engineering scaffolds that can mimic the nanoscale structure of the native extracellular matrix. With functionalization of the polymeric nanofibers using bioactive molecules, localized signaling moieties can be established for the attached cells, to stimulate desired biological effects and direct cellular or tissue response. The inherently high surface area per unit mass of polymeric nanofibers can enhance cell adhesion, bioactive molecules loading and release efficiencies, and mass transfer properties. In this review article, the application of polymeric nanofibers for controlled bioactive molecules delivery will be discussed, with a focus on tendon and ligament tissue engineering. Various polymeric materials of different mechanical and degradation properties will be presented along with the nanofiber fabrication techniques explored. The bioactive molecules of interest for tendon and ligament tissue engineering, including growth factors and small molecules, will also be reviewed and compared in terms of their nanofiber incorporation strategies and release profiles. This article will also highlight and compare various innovative strategies to control the release of bioactive molecules spatiotemporally and explore an emerging tissue engineering strategy involving controlled multiple bioactive molecules sequential release. Finally, the review article concludes with challenges and future trends in the innovation and development of bioactive molecules delivery using polymeric nanofibers for tendon and ligament tissue engineering.

  18. Lectin-conjugated microspheres for eradication of Helicobacter pylori infection and interaction with mucus.

    Adebisi, Adeola O; Conway, Barbara R


    Using second generation mucoadhesives may enhance targeting antibiotics for eradication of Helicobacter pylori from the stomach for the treatment of peptic ulcer. The aim of this research was to prepare and characterise ethylcellulose/chitosan microspheres containing clarithromycin with their surfaces functionalised with concanavalin A to produce a floating-mucoadhesive formulation. The microspheres were prepared using an emulsification-solvent evaporation method. Particle size, surface morphology, in vitro buoyancy profile, zeta potential, drug entrapment efficiency, in vitro drug release and release kinetics of the particles were determined. Lectin was conjugated to the microsphere surface using two-stage carbodiimide activation and confirmed using FTIR, fluorescence studies and zeta potential measurements. Conjugation ranged from 11 to 15 μg Con A/mg microspheres which represents over 56% efficiency although there was some drug loss during the conjugation process. Conjugation did not have a significant effect on the buoyancy and release of drug from the microspheres using a mucus diffusion model with 53% and 40% of drug released from unconjugated and conjugated microspheres within 12h. Conjugation improved mucoadhesion and interaction with porcine gastric mucin compared to unconjugated microspheres. The buoyancy and improved mucoadhesion of the microspheres provides potential for delivery of clarithromycin and other drugs to the stomach.

  19. Organometallic Polymeric Conductors

    Youngs, Wiley J.


    For aerospace applications, the use of polymers can result in tremendous weight savings over metals. Suitable polymeric materials for some applications like EMI shielding, spacecraft grounding, and charge dissipation must combine high electrical conductivity with long-term environmental stability, good processability, and good mechanical properties. Recently, other investigators have reported hybrid films made from an electrically conductive polymer combined with insulating polymers. In all of these instances, the films were prepared by infiltrating an insulating polymer with a precursor for a conductive polymer (either polypyrrole or polythiophene), and oxidatively polymerizing the precursor in situ. The resulting composite films have good electrical conductivity, while overcoming the brittleness inherent in most conductive polymers. Many aerospace applications require a combination of properties. Thus, hybrid films made from polyimides or other engineering resins are of primary interest, but only if conductivities on the same order as those obtained with a polystyrene base could be obtained. Hence, a series of experiments was performed to optimize the conductivity of polyimide-based composite films. The polyimide base chosen for this study was Kapton. 3-MethylThiophene (3MT) was used for the conductive phase. Three processing variables were identified for producing these composite films, namely time, temperature, and oxidant concentration for the in situ oxidation. Statistically designed experiments were used to examine the effects of these variables and synergistic/interactive effects among variables on the electrical conductivity and mechanical strength of the films. Multiple linear regression analysis of the tensile data revealed that temperature and time have the greatest effect on maximum stress. The response surface of maximum stress vs. temperature and time (for oxidant concentration at 1.2 M) is shown. Conductivity of the composite films was measured for

  20. Kumada chain-growth polycondensation as a universal method for synthesis of well-defined conjugated polymers


    Kumada chain-growth polycondensation (KCGP) is a novel method for the synthesis of well-defined conjugated polymers.Because the Ni-catalyst can transfer in an intramolecular process to the propagating chain end,the polymerization follows chain-growth mechanism.With this newly developed method,various conjugated polymers,such as polythiophenes,poly(p-phenylene) (PPP),polypyrrole (PPy),and polyfluorene with controlled molecular weights and relatively narrow polydispersities (PDIs),have been prepared.Especially,the polymerizations for poly(3-alkylthiophene)s (P3ATs),PPP,and PPy exhibited quasi-living characteristics,which allows preparing polymer brushes,fully-conjugated block copolymers,and macroinitiators and macro-reactants for the synthesis of rod-coil block copolymers.In the current review,the progress in this new area is summarized.

  1. High temperature structural, polymeric foams from high internal emulsion polymerization

    Hoisington, M.A.; Duke, J.R.; Apen, P.G.


    In 1982, a high internal phase emulsion (HIPE) polymerization process to manufacture microcellular, polymeric foam systems was patented by Unilever. This patent discloses a polymerization process that occurs in a water-in-oil emulsion in which the water represents at least 76% of the emulsion by volume. The oil phase consists of vinyl monomers such as styrene and acrylates that are crosslinked by divinyl monomers during polymerization. After polymerization and drying to remove the water phase, the result is a crosslinked polymer foam with an open cell microstructure that is homogeneous throughout in terms of morphology, density, and mechanical properties. Since 1982, numerous patents have examined various HIPE polymerized foam processing techniques and applications that include absorbents for body fluids, cleaning materials, and ion exchange systems. All the published HIPE polymerized foams have concentrated on materials for low temperature applications. Copolymerization of styrene with maleic anhydride and N-substituted maleimides to produce heat resistant thermoplastics has been studied extensively. These investigations have shown that styrene will free radically copolymerize with N-substituted maleimides to create an alternating thermoplastic copolymer with a Tg of approximately 200{degrees}C. However, there are many difficulties in attempting the maleimide styrene copolymerization in a HIPE such as lower polymerization temperatures, maleimide solubility difficulties in both styrene and water, and difficulty obtaining a stable HIPE with a styrene/maleimide oil phase. This work describes the preparation of copolymer foams from N-ethylmaleimide and Bis(3-ethyl-5-methyl-4-maleimide-phenyl)methane with styrene based monomers and crosslinking agents.

  2. Polymeric micelles in anticancer therapy : Targeting, imaging and triggered release

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


    Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use

  3. Polymeric micelles in anticancer therapy : Targeting, imaging and triggered release

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


    Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use

  4. Polymeric nanoparticles – a novel solution for delivery of antimicrobial agents

    Grzegorz Michalak


    Full Text Available The increased prevalence of antibiotic-resistant pathogens requires additional efforts to develop new antimicrobial agents and alternative methods to prevent and treat infections. In response to this challenge, a variety of nanotechnology-based tools are currently being designed and thoroughly investigated. To date, a considerable number of studies have reported increased activity of antibiotic-conjugated polymeric nanoparticles against bacteria and fungi associated with various infections, including those caused by drug-resistant pathogens. Importantly, high biocompatibility of these structures coupled with enhanced biological activity and improved pharmacokinetic properties supports the potential of these nanosystems as new tools to treat infections. In this review, we summarize the synthesis of polymer-based nanoparticles and describe their mechanism of action. We also highlight the recent advances in the application of antibiotic-conjugated polymeric nanoparticles as novel antimicrobial agents.

  5. Electroactivity in Polymeric Materials


    Electroactivity in Polymeric Materials provides an in-depth view of the theory of electroactivity and explores exactly how and why various electroactive phenomena occur. The book explains the theory behind electroactive bending (including ion-polymer-metal-composites –IPMCs), dielectric elastomers, electroactive contraction, and electroactive contraction-expansion cycles.  The book also balances theory with applications – how electroactivity can be used – drawing inspiration from the manmade mechanical world and the natural world around us.  This book captures: A complete introduction to electroactive materials including examples and recent developments The theory and applications of numerous topics like electroactive bending of dielectric elastomers and electroactive contraction and expansion New topics, such as biomimetic applications and energy harvesting This is a must-read within the electroactive community, particularly for professionals and graduate students who are interested in the ...

  6. Kinetics of silica polymerization

    Weres, O.; Yee, A.; Tsao, L.


    The polymerization of silicic acid in geothermal brine-like aqueous solutions to produce amorphous silica in colloidal form has been studied experimentally and theoretically. A large amount of high quality experimental data has been generated over the temperature rang 23 to 100{sup 0}C. Wide ranges of dissolved silica concentration, pH, and sodium chloride concentration were covered. The catalytic effects of fluoride and the reaction inhibiting effects of aluminum and boron were studied also. Two basic processes have been separately studied: the formation of new colloidal particles by the homogeneous nucleation process and the deposition of dissolved silica on pre-existing colloidal particles. A rigorous theory of the formation of colloidal particles of amorphous silica by homogeneous nucleation was developed. This theory employs the Lothe-Pound formalism, and is embodied in the computer code SILNUC which quantitatively models the homogeneous nucleation and growth of colloidal silica particles in more than enough detail for practical application. The theory and code were extensively used in planning the experimental work and analyzing the data produced. The code is now complete and running in its final form. It is capable of reproducing most of the experimental results to within experimental error. It is also capable of extrapolation to experimentally inaccessible conditions, i.e., high temperatures, rapidly varying temperature and pH, etc.

  7. Nanostructuring of PEG-fibrinogen polymeric scaffolds.

    Frisman, Ilya; Seliktar, Dror; Bianco-Peled, Havazelet


    Recent studies have shown that nanostructuring of scaffolds for tissue engineering has a major impact on their interactions with cells. The current investigation focuses on nanostructuring of a biocompatible, biosynthetic polymeric hydrogel scaffold made from crosslinked poly(ethylene glycol)-fibrinogen conjugates. Nanostructuring was achieved by the addition of the block copolymer Pluronic F127, which self-assembles into nanometric micelles at certain concentrations and temperatures. Cryo-transmission electron microscopy experiments detected F127 micelles, both embedded within PEGylated fibrinogen hydrogels and in solution. The density of the F127 micelles, as well as their ordering, increased with increasing block copolymer concentration. The mechanical properties of the nanostructured hydrogels were investigated using stress-sweep rheological testing. These tests revealed a correlation between the block copolymer concentration and the storage modulus of the composite hydrogels. In vitro cellular assays confirmed that the increased modulus of the hydrogels did not limit the ability of the cells to form extensions and become spindled within the three-dimensional (3-D) hydrogel culture environment. Thus, altering the nanostructure of the hydrogel may be used as a strategy to control cellular behavior in 3-D through changes in mechanical properties of the environment.

  8. Polymerization of anionic wormlike micelles.

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


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

  9. Effects of polymeric carbohydrates on growth and development in pigs

    Knudsen, Knud Erik Bach


    and lead to different metabolites upon digestion. Pancreatic and mucosal enzymes in the small intestine break down the majority of starch, whereas NSP primarily are degraded by the microflora in the large intestine. Starch degradation leads to the release of glucose, which is absorbed by an active...... absorption process that triggers the release of insulin from the pancreas, whereas the fermentation of NSP to short-chain fatty acids (SCFA; i.e., acetate, propionate, and butyrate) occurs at a slower and more constant rate and with SCFA being absorbed by passive diffusion. Type and amounts of polymeric......, organs, and cells, and thus plays a critically essential role in protein synthesis and muscle growth, as well as lipid synthesis and adipose tissue growth. In conclusion, polymeric carbohydrates influence growth and development through events in the gut and direct and indirect effects of different...

  10. Polymeric Nanoparticles, Nanospheres and Nanocapsules, for Cutaneous Applications

    Adriana R. Pohlmann


    Full Text Available This review presents an overview about pharmaceutical and cosmetic topical products containing polymeric nanoparticles (nanospheres and nanocapsules, reporting the main preparation and characterization methods and the studies of penetration and transport of substances through the skin. The penetration and transport extent of those systems through the skin depends on the ingredients chemical composition, on the encapsulation mechanism influencing the drug release, on the size of nanoparticles and on the viscosity of the formulations. The polymeric nanoparticles are able to modify the activity of drugs, delay and control the drug release, and increase the drug adhesivity or its time of permanence in the skin. Briefly, the nanoparticles can be useful as reservoirs of lipophilic drugs to deliver them in the stratum corneum becoming an important strategy to control their permeation into the skin.

  11. Direct Arylation Strategies in the Synthesis of π-Extended Monomers for Organic Polymeric Solar Cells

    Andrea Nitti; Riccardo Po; Gabriele Bianchi; Dario Pasini


    π-conjugated macromolecules for organic polymeric solar cells can be rationally engineered at the molecular level in order to tune the optical, electrochemical and solid-state morphology characteristics, and thus to address requirements for the efficient solid state device implementation. The synthetic accessibility of monomers and polymers required for the device is getting increasing attention. Direct arylation reactions for the production of the π-extended scaffolds are gaining importance,...

  12. Comparative study of structural and optical properties of pulsed and RF plasma polymerized aniline films

    Barman, Tapan; Pal, Arup R., E-mail:; Chutia, Joyanti


    Graphical abstract: - Highlights: • Pulse DC and RF plasma is used for synthesis of conducting polymer films. • Conjugated structure retention is better at optimum powers in both the processes. • Conjugated structure retention is better in case of RF plasma prepared films. • Band gap is lower in case of RF plasma prepared films at higher power. • Defect in pulse plasma prepared film is less than RF plasma prepared thin films. - Abstract: Plasma polymerization of aniline is carried out by means of continuous RF and pulsed DC glow discharge plasma in a common reactor at different applied powers. The discharge control variables are optimized for good quality film growth and the role of fragmentation of the molecular structure on the structural, optical, morphological and optophysical properties of the deposited plasma polymerized aniline (PPAni) layers is investigated. Retention of the conjugated structure is found to be prominent at optimum applied power to the plasma in both the continuous RF and pulsed DC polymerization techniques. Improvement in conjugated structure and chain length have been observed in both the continuous RF and pulse DC PPAni thin films with the increase in applied power to the plasma up to a certain limit of applied power when working pressure is fixed at 0.15 mbar. A decrease in optical bandgap with the increase in applied power to the plasma is observed in both the pulsed DC and RF PPAni thin films, but it is more significant in case of RF PPAni films. The plasma polymerized aniline thin films are found to emit photoluminescence due to band to band transition and defects generated in the structure.

  13. Redox and pH dual responsive poly(amidoamine) dendrimer-poly(ethylene glycol) conjugates for intracellular delivery of doxorubicin.

    Hu, Wen; Qiu, Lipeng; Cheng, Liang; Hu, Qing; Liu, Yang; Hu, Ziyang; Chen, Dawei; Cheng, Lifang


    To solve the contradiction between long circulation time and effective intracellular drug release, redox and pH-responsive drug delivery system was developed by incorporated redox-sensitive disulfide linkage between poly(amidoamine) dendrimers (PAMAM) and poly(ethylene glycol) (PEG). Doxorubicin (DOX) was loaded into the hydrophobic core of the conjugates to prepare PAMAM-SS-PEG/DOX complexes (PSSP/DOX). In vitro release studies suggested that DOX release from PSSP/DOX complexes followed an redox and acid-triggered manner and increased with increasing PEGylation degree. In vitro cytotoxicity of PSSP/DOX complexes against B16 tumor cells increased with, while cellular uptake decreased with increasing PEGylation degree. Further, intracellular DOX release observation and measurement indicate that the intracellular DOX release played a critical role for the cytotoxicity of DOX-loaded PSSP conjugates. In addition, cellular entry mechanism of the PSSP/DOX study demonstrated that both clathrin- and caveolae-mediated endocytosis were the primary pathways for cellular entry of PSSP/DOX. Finally, in vivo study of PSSP/DOX complexes in B16 tumor-bearing mice indicate that PSSP/DOX could significantly improve antitumor efficiency and present a good safety. The redox and pH-responsive drug delivery system has been demonstrated to be a promising candidate for solid tumor therapy. In previous research, pH-sensitive diblock polymer of poly(ethylene glycol)-poly(2,4,6-trimethoxybenzylidene-pentaerythritol carbonate) (PEG-PTMBPEC) was synthesized to facilitate the intracellular anticancer drug release. However, the nanoparticles based on PEG-PTMBPEC get into the tumor cells just relying on the EPR-mediated passive targeting resulting in the low drug accumulation. Therefore, cRGD peptide modified PEG-PTMBPEC polymeric micelles were developed for specific targeted delivery of doxorubicin (DOX) to neovascular cells and tumor cells simultaneously. The precise intracellular target site

  14. Surface glycosylation of polymeric membranes

    DAI ZhengWei; WAN LingShu; XU ZhiKang


    Surface glycosylation of polymeric membranes has been inspired by the structure of natural biomembranes. It refers to that glycosyl groups are introduced onto the membrane surface by various strategies, which combine the separation function of the membrane with the biological function of the saccharides in one system. In this review, progress in the surface glycosylation of polymeric membranes is highlighted in two aspects, i.e. the glycosylation methods and the potential applications of the surface-glycosylated membranes.

  15. Three-dimensional microfabrication using two-photon polymerization

    Cumpston, Brian H.; Ehrlich, Jeffrey E.; Kuebler, Stephen M.; Lipson, Matthew; Marder, Seth R.; McCord-Maughon, D.; Perry, Joseph W.; Roeckel, Harold; Rumi, Maria Cristina


    Photopolymerization initiated by the simultaneous absorption of two photons is unique in its ability to produce complex three-dimensional (3D) structures from a single, thick photopolymer film. Strong 3D confinement of the polymerization process is not possible in other polymer microfabrication techniques such as LIGA, rapid prototyping, and conventional photoresist technology. Two-photon polymerization also permits the fabrication of 3D structures and the definition of lithographic features on non-planar surfaces. We have developed a wide array of chromophores which hold great promise for 3D microfabrication, as well as other applications, such as two-photon fluorescence imaging and 3D optical data storage. These materials are based on a donor- (pi) -donor, donor-acceptor-donor, or acceptor-donor-acceptor structural motif. The magnitude of the two-photon absorption cross-section, (delta) , and the position of the two-photon absorption maximum, (lambda) (2)max, can be controlled by varying the length of the conjugated bridge and by varying the strength of the donor/acceptor groups. In this way, chromophores have been developed which exhibit strong two- photon absorption in the range of 500 - 975 nm, in some cases as high as 4400 X 10-50 cm4 s/photon-molecule. In the case of donor-(pi) -donor structures, quantum-chemical calculations show that the large absorption cross-sections arise from the symmetric re-distribution of charge from the donor end-groups to the conjugated bridge, resulting in an electronic excited-state which is more delocalized than the ground state. For many of these molecules, two-photon excitation populates a state which is sufficiently reducing that a charge transfer reaction can occur with acrylate monomers. The efficiency of these processes can be described using Marcus theory. Under suitable conditions, such reactions can induce radical polymerization of acrylate resins. Polymerization rates have been measured, and we show that these two

  16. Crosslinked polymer nanoparticles containing single conjugated polymer chains.

    Ponzio, Rodrigo A; Marcato, Yésica L; Gómez, María L; Waiman, Carolina V; Chesta, Carlos A; Palacios, Rodrigo E


    Conjugated polymer nanoparticles are widely used in fluorescent labeling and sensing, as they have mean radii between 5 and 100 nm, narrow size dispersion, high brightness, and are photochemically stable, allowing single particle detection with high spatial and temporal resolution. Highly crosslinked polymers formed by linking individual chains through covalent bonds yield high-strength rigid materials capable of withstanding dissolution by organic solvents. Hence, the combination of crosslinked polymers and conjugated polymers in a nanoparticulated material presents the possibility of interesting applications that require the combined properties of constituent polymers and nanosized dimension. In the present work, F8BT@pEGDMA nanoparticles composed of poly(ethylene glycol dimethacrylate) (pEGDMA; a crosslinked polymer) and containing the commercial conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) were synthesized and characterized. Microemulsion polymerization was applied to produce F8BT@pEDGMA particles with nanosized dimensions in a ∼25% yield. Photophysical and size distribution properties of F8BT@pEDGMA nanoparticles were evaluated by various methods, in particular single particle fluorescence microscopy techniques. The results demonstrate that the crosslinking/polymerization process imparts structural rigidity to the F8BT@pEDGMA particles by providing resistance against dissolution/disintegration in organic solvents. The synthesized fluorescent crosslinked nanoparticles contain (for the most part) single F8BT chains and can be detected at the single particle level, using fluorescence microscopy, which bodes well for their potential application as molecularly imprinted polymer fluorescent nanosensors with high spatial and temporal resolution.

  17. Detection of Salmonella typhi utilizing bioconjugated fluorescent polymeric nanoparticles

    Jain, Swati; Chattopadhyay, Sruti; Jackeray, Richa; Abid, Zainul; Singh, Harpal


    Present work demonstrates effective utilization of functionalized polymeric fluorescent nanoparticles as biosensing probe for the detection of Salmonella typhi bacteria on modified polycarbonate (PC) filters in about 3 h. Antibody modified-PC membranes were incubated with contaminated bacterial water for selective capturing which were detected by synthesized novel bioconjugate probe. Core-shell architecture of polymeric nanoparticles endows them with aqueous stabilization and keto-enolic functionalities making them usable for covalently linking S. typhi antibodies without any crosslinker or activator. Bradford analysis revealed that one nanoparticle has an average of 3.51 × 10-19 g or 21 × 104 bound S. typhi Ab molecules. Analysis of the regions of interest (ROI) in fluorescent micrographs of modified fluoroimmunoassay showed higher detection sensitivity of 5 × 102 cells/mL due to signal amplification unlike conventional naked dye FITC-Ab conjugate. Fluorescence of pyrene dye remained same on immobilization of biomolecules and nanoparticles showed stable fluorescent intensity under prolong exposure to laser owing to protective polymeric layer allowing accurate identification of bacteria. Surface-functionalized PC matrix and fluorescent label NPs permit covalent interactions among biomolecules enhancing signal acquisitions showing higher detection efficiency as compared to conventional microtiter plate-based system. Our novel immunoassay has the potential to be explored as rapid detection method for identifying S. typhi contaminations in water.

  18. Smart linkers in polymer-drug conjugates for tumor-targeted delivery.

    Chang, Minglu; Zhang, Fang; Wei, Ting; Zuo, Tiantian; Guan, Yuanyuan; Lin, Guimei; Shao, Wei


    To achieve effective chemotherapy, many types of drug delivery systems have been developed for the specific environments in tumor tissues. Polymer-drug conjugates are increasingly used in tumor therapy due to several significant advantages over traditional delivery systems. In the fabrication of polymer-drug conjugates, a smart linker is an important component that joins two fragments or molecules together and can be cleared by a specific stimulus, which results in targeted drug delivery and controlled release. By regulating the conjugation between the drug and the nanocarriers, stimulus-sensitive systems based on smart linkers can offer high payloads, certified stability, controlled release and targeted delivery. In this review, we summarize the current state of smart linkers (e.g. disulfide, hydrazone, peptide, azo) used recently in various polymer-drug conjugate-based delivery systems with a primary focus on their sophisticated design principles and drug delivery mechanisms as well as in vivo processes.

  19. Glycyrrhizin conjugated chitosan nanoparticles for hepatocyte-targeted delivery of lamivudine.

    Mishra, Deepak; Jain, Nivrati; Rajoriya, Vaibhav; Jain, Ashish K


    The present study was focused to prepare controlled release glycyrrhizin (GL) conjugated low molecular weight chitosan nanoparticles (CS-NPs) for liver targeting. The hydrophilic antiretroviral drug lamivudine was chosen as a model drug and encapsulated within glycyrrhizin conjugated low molecular weight chitosan nanoparticles (GL-CS-NPs) for liver specificity. First, the low molecular weight chitosan (CS) was synthesized through depolymerization method. The low molecular weight chitosan nanoparticles were prepared by inotropic gelation method. Then glycyrrhizin was conjugated with previously prepared low molecular weight chitosan nanoparticles (CS-NPs) and conjugation was confirmed by Fourier transform infrared (FT-IR) spectroscopy. The prepared GL-CS-NPs were characterized using dynamic light scattering, transmission electron microscopy and FT-IR. The encapsulation efficiency and in-vitro drug release behaviour of drug-loaded GL-CS-NPs were studied using ultra violet spectroscopy and high performance liquid chromatographic methods. Release of lamivudine from the nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. In-vivo biodistribution study suggested the target ability of GL-CS-NPs is better and haematological study shows decline of the tissue damage in comparison with plain drug solution. The experimental results show that the glycyrrhizin conjugated LMWC nanoparticles may be used as a potential drug delivery system with hepatocyte-targeting characteristics. © 2014 Royal Pharmaceutical Society.

  20. Aptamer-Drug Conjugates.

    Zhu, Guizhi; Niu, Gang; Chen, Xiaoyuan


    Western medicine often aims to specifically treat diseased tissues or organs. However, the majority of current therapeutics failed to do so owing to their limited selectivity and the consequent "off-target" side effects. Targeted therapy aims to enhance the selectivity of therapeutic effects and reduce adverse side effects. One approach toward this goal is to utilize disease-specific ligands to guide the delivery of less-specific therapeutics, such that the therapeutic effects can be guided specifically to diseased tissues or organs. Among these ligands, aptamers, also known as chemical antibodies, have emerged over the past decades as a novel class of targeting ligands that are capable of specific binding to disease biomarkers. Compared with other types of targeting ligands, aptamers have an array of unique advantageous features, which make them promising for developing aptamer-drug conjugates (ApDCs) for targeted therapy. In this Review, we will discuss ApDCs for targeted drug delivery in chemotherapy, gene therapy, immunotherapy, photodynamic therapy, and photothermal therapy, primarily of cancer.

  1. Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

    Ding Hong; Yong, Ken-Tye; Roy, Indrajit; Hu Rui; Zhao Lingling; Law, Wing-Cheung; Ji Wei; Liu Liwei; Bergey, Earl J; Prasad, Paras N [Department of Chemistry, Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Wu Fang [Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Zhao Weiwei, E-mail:, E-mail: [Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, NY 14215 (United States)


    In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l{sup -1}. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the {alpha}{sub v{beta}3} integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

  2. Preparing polymeric biomaterials using "click" chemistry techniques

    Lin, Fei

    Significant efforts have been focused on preparing degradable polymeric biomaterials with controllable properties, which have the potential to stimulate specific cellular responses at the molecular level. Click reactions provide a universal tool box to achieve that goal through molecular level design and modification. This dissertation demonstrates multiple methodologies and techniques to develop advanced biomaterials through combining degradable polymers and click chemistry. In my initial work, a novel class of amino acid-based poly(ester urea)s (PEU) materials was designed and prepared for potential applications in bone defect treatment. PEUs were synthesized via interfacial polycondensation, and showed degradability in vivo and possessed mechanical strength superior to conventionally used polyesters. Further mechanical enhancement was achieved after covalent crosslinking with a short peptide crosslinker derived from osteogenic growth peptide (OGP). The in vitro and in an in vivo subcutaneous rat model demonstrated that the OGP-based crosslinkers promoted proliferative activity of cells and accelerated degradation properties of PEUs. As a continuous study, extra efforts were focused on the development of PEUs with functional pendant groups, including alkyne, azide, alkene, tyrosine phenol, and ketone groups. PEUs with Mw exceeding to 100K Da were obtained via interfacial polycondensation, and the concentration of pendent groups was varied using a copolymerization strategy. Electrospinning was used to fabricate PEU nanofiber matrices with mechanical strengths suitable for tissue engineering. A series of biomolecules were conjugated to nanofiber surface following electrospinning using click reactions in aqueous media. The ability to derivatize PEUs with biological motifs using high efficient chemical reactions will significantly expand their use in vitro and in vivo. Based on similar principles, a series of mono- and multifunctionalized polycaprolactone (PCL

  3. Sequential measurements of conjugate observables

    Carmeli, Claudio [Dipartimento di Fisica, Universita di Genova, Via Dodecaneso 33, 16146 Genova (Italy); Heinosaari, Teiko [Department of Physics and Astronomy, Turku Centre for Quantum Physics, University of Turku, 20014 Turku (Finland); Toigo, Alessandro, E-mail:, E-mail:, E-mail: [Dipartimento di Matematica ' Francesco Brioschi' , Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)


    We present a unified treatment of sequential measurements of two conjugate observables. Our approach is to derive a mathematical structure theorem for all the relevant covariant instruments. As a consequence of this result, we show that every Weyl-Heisenberg covariant observable can be implemented as a sequential measurement of two conjugate observables. This method is applicable both in finite- and infinite-dimensional Hilbert spaces, therefore covering sequential spin component measurements as well as position-momentum sequential measurements.

  4. Polymeric nanoparticles based on chitooligosaccharide as drug carriers for co-delivery of all-trans-retinoic acid and paclitaxel.

    Zhang, Jing; Han, Jian; Zhang, Xiuli; Jiang, Jing; Xu, Maolei; Zhang, Daolai; Han, Jingtian


    An amphiphilic all-trans-retinoic acid (ATRA)-chitooligosaccharide (RCOS) conjugate was synthesized to form self-assembled polymeric nanoparticles to facilitate the co-delivery of ATRA and paclitaxel (PTX). The blank RCOS nanoparticles possessed low hemolytic activity and cytotoxicity, and could efficiently load PTX with a drug loading of 22.2% and a high encapsulation efficiency of 71.3%. PTX-loaded RCOS nanoparticles displayed a higher cytotoxicity to HepG2 cells compared to PTX plus ATRA solution when corrected by the accumulated drug release. Cellular uptake profiles of RCOS nanoparticles were evaluated via confocal laser scanning microscope and flow cytometry with FITC as a fluorescent mark. The RCOS nanoparticles could be rapidly and continuously taken up by HepG2 cells via endocytosis and transported into the nucleus, and the uptake rates increased with particle concentration. These results revealed the promising potential of RCOS nanoparticles as drug carriers for co-delivery of ATRA and PTX or other hydrophobic therapeutic agents.

  5. Regulated pH-Responsive Polymeric Micelles for Doxorubicin Delivery to the Nucleus of Liver Cancer Cells.

    Li, Hao; Li, Xian; Zhang, Chao; Sun, Qiquan; Yi, Wei; Wang, Xuan; Cheng, Du; Chen, Shupeng; Liang, Biling; Shuai, Xintao


    A diblock copolymer of poly(ethylene glycol) (PEG) and poly(γ-benzyl L-glutamate) (PBLG), PEG-PBLG, was synthesized via the ring-opening polymerization of γ-benzyl L-glutamate N-carboxyanhydride (BLG-NCA) using allyl-PEG-NH2 as a macroinitiator. After deprotection of the benzyl groups, N,N-diisopropyl ethylenediamine (DIP) was conjugated to poly(L-glutamic acid) (PGA) blocks as side groups. The pendant DIP groups on the PGA blocks greatly enhance the pH-sensitivity of poly(ethylene glycol)-block-poly[N-(N',N'-diisopropylaminoethyl) glutamide] [PEG-PGA(DIP)] micelles, and a higher grafting percentage of DIP favors a faster acid-response. In neutral aqueous solution, the PEG-PGA(DIP) can self-assemble into stable micelles featuring an acid-responsive PGA(DIP) core with the encapsulated anticancer drug doxorubicin (DOX). In an acidic environment, the hydrophobic-hydrophilic transition of the PGA block leads to the gradual expansion and disassembly of these micelles and, consequently, an accelerated release of DOX. Thus, DOX transported by PEG-PGA(DIP) micelles can be entrapped more efficiently into the nuclei of hepatoma Bel 7402 cells.


    Andrea R. Szkurhan; Michael K. Georges


    An overview of aqueous polymerizations, which include emulsion, miniemulsion and suspension polymerizations,under stable free radical polymerization (SFRP) conditions is presented. The success of miniemulsion and suspension SFRP polymerizations is contrasted with the difficulties associated with obtaining a stable emulsion polymerization. A recently developed unique microprecipitation technique is referenced as a means of making submicron sized particles that can be used to achieve a stable emulsion SFRP process.

  7. AS1411 aptamer and folic acid functionalized pH-responsive ATRP fabricated pPEGMA-PCL-pPEGMA polymeric nanoparticles for targeted drug delivery in cancer therapy.

    Lale, Shantanu V; R G, Aswathy; Aravind, Athulya; Kumar, D Sakthi; Koul, Veena


    Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of ∼140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (∼70%) compared to pH 7.4 (∼25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10- and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others.

  8. Reverse saturable absorption studies in polymerized indole - Effect of polymerization in the phenomenal enhancement of third order optical nonlinearity

    Jayakrishnan, K.; Joseph, Antony; Bhattathiripad, Jayakrishnan; Ramesan, M. T.; Chandrasekharan, K.; Siji Narendran, N. K.


    We report our results on the identification of large order enhancement in nonlinear optical coefficients of polymerized indole and its comparative study with reference to its monomer counterpart. Indole monomer shows virtually little third order effects whereas its polymerized version exhibits phenomenal increase in its third order nonlinear optical parameters such as nonlinear refractive index and nonlinear absorption. Open aperture Z-scan trace of polyindole done with Q-switched Nd:YAG laser source (532 nm, 7 ns), shows β value as high as 89 cm/GW at a beam energy of 0.83 GW/cm2. Closed aperture Z-scan done at identical energies reveals nonlinear refractive index of the order of -3.55 × 10-17 m2/W. Band gap measurement of polyindole was done with UV-Vis absorption spectra and compared with that of Indole. FTIR spectra of the monomer and polymerized versions were recorded and relevant bond formations were confirmed from the characteristic peaks. Photo luminescent spectra were investigated to know the emission features of both molecules. Beam energy (I0) versus nonlinear absorption coefficient (β) plot indicates reverse saturable type of absorption behaviour in polyindole molecules. Degenerate Four Wave Mixing (DFWM) plot of polyindole reveals quite a cubic dependence between probe and phase conjugate signal and the resulting χ(3) is comparable with Z-scan results. Optical limiting efficiency of polyindole is comparable with certain derivatives of porphyrins, phthalocyanines and graphene oxides.

  9. Polymeric materials for neovascularization

    DeVolder, Ross John

    Revascularization therapies have emerged as a promising strategy to treat various acute and chronic wounds, cardiovascular diseases, and tissue defects. It is common to either administer proangiogenic growth factors, such as vascular endothelial growth factor (VEGF), or transplant cells that endogenously express multiple proangiogenic factors. Additionally, these strategies utilize a wide variety of polymeric systems, including hydrogels and biodegradable plastics, to deliver proangiogenic factors in a sophisticated manner to maintain a sustained proangiogenic environment. Despite some impressive results in rebuilding vascular networks, it is still a challenging task to engineer mature and functional neovessels in target tissues, because of the increasing complexities involved with neovascularization applications. To resolve these challenges, this work aims to design a wide variety of proangiogenic biomaterial systems with tunable properties used for neovascularization therapies. This thesis describes the design of several biomaterial systems used for the delivery of proangiogenic factors in neovascularization therapies, including: an electrospun/electrosprayed biodegradable plastic patch used for directional blood vessel growth (Chapter 2), an alginate-g-pyrrole hydrogel system that biochemically stimulates cellular endogenous proangiogenic factor expression (Chapter 3), an enzyme-catalyzed alginate-g-pyrrole hydrogel system for VEGF delivery (Chapter 4), an enzyme-activated alginate-g-pyrrole hydrogel system with systematically controllable electrical and mechanical properties (Chapter 5), and an alginate-g-pyrrole hydrogel that enables the decoupled control of electrical conductivity and mechanical rigidity and is use to electrically stimulate cellular endogenous proangiogenic factor expression (Chapter 6). Overall, the biomaterial systems developed in this thesis will be broadly useful for improving the quality of a wide array of molecular and cellular based

  10. In Vitro Evaluation of Doxorubicin Conjugates Based on Sugar Core Nonlinear Polymethacrylates toward Anticancer Drug Delivery.

    Mielańczyk, A; Skonieczna, M; Mielańczyk, Ł; Neugebauer, D


    V-shaped and star-shaped hydroxylamine-functionalized polymethacrylates designed as nanosized conjugates (cancer (MCF-7) treatment. Statistical analysis of MTS assay results showed that the 4-arm conjugate (n(DOX) = 16) was the most effective polymeric system against MCF-7/W (wild type) and MCF-7/R (DOX resistant) cell lines. Apoptosis assay analysis showed that MCF-7/R cells cultured with nonlinear copolymers died due to necrosis and late apoptotis, whereas MCF-7/W cells were in early and late apoptosis. Among all tested conjugates, the most promising results with induction of apoptosis without inducing necrosis in both MCF-7 cell lines were obtained for conjugate based on 4-arm stars with low content of DOX. The cell cycle assay revealed that increase of MMA units in 4-arm copolymers induced MCF-7/R cell arrest in the SubG1 phase. In the same cell line, the corresponding conjugates triggered S and G2/M arrest. Gradual internalization of the chosen conjugate by MCF-7/R cells was monitored via fluorescence microscopy showing its main localization in the cytoplasm.

  11. Development of monodispersed and functional magnetic polymeric liposomes via simple liposome method

    Liang Xiaofei; Wang Hanjie [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China); Jiang Xinguo [Fudan University, School of Pharmacy (China); Chang Jin, E-mail: [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China)


    We are reporting a simple and rapid method to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by octadecyl quaternized carboxymethyl chitosan (OQCMC) and cholesterol. The whole process is only about 25 min with simple thin-film dispersion and solvent evaporation method. Hydrophilic magnetic nanoparticles (LM) and hydrophobic magnetic nanoparticles (BM) can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. A model hydrophobic drug indomethacin can be successfully filled in MCPL with high drug loading capacity 22%. MCPL encapsulating BM also showed strong DNA (pEGFP) binding ability. Drug-loaded MCPL have a long and controlled sustained release profile by changing the number of polymeric lipid layer. These functional MCPL nanospheres can be allowed to serve as ideal candidates for many biomedical applications.Graphical AbstractA simple and rapid liposome method was reported to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by polymeric surfactant, octadecyl quaternized carboxymethyl chitosan (OQCMC), and cholesterol. Hydrophilic Fe{sub 3}O{sub 4} ferrofluid and hydrophobic magnetic nanoparticles can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. Hydrophobic drug indomethacin can be encapsulated into this MCPL with high encapsulating efficiency and with controlled release profile by changing the number of polymeric lipid layer.

  12. A fragment-based approach towards $\\it{ab-initio}$ treatment of polymeric materials



    The broad range of applications of $\\pi$-conjugated polymeric materials in industries such as automobiles, textiles, packaging, medical etc. have led to their extensive studies in both academic and industrial fields. Predicting the structure of these polymers is important for the study of their properties. The present work uses a ‘divide and conquer’-type approach for the $\\it{ab-initio}$ studies of these polymeric systems. The method employs a fragmentation technique with independent fragment optimization for obtaining optimized geometries of the oligomers of various polymeric materials such as polyfuran, polypyrrole, polythiophene and other such $\\pi$-conjugated polymers. A few test calculations performed in the study provide fair concurrence between the energies and the HOMO–LUMO energy gaps obtained using the fragmentation-based approach with those obtained using the full optimization of the whole oligomer. Also, a significant reduction in time complexity occurs for the present fragment-based approach compared to the parent system optimization. The results are encouraging and prompt for studies of large polymeric materials.

  13. Fabrication of biodegradable polymeric nanofibers with covalently attached NO donors.

    Wold, Kathryn A; Damodaran, Vinod B; Suazo, Lucas A; Bowen, Richard A; Reynolds, Melissa M


    Many common wound healing aids are created from biodegradable polymeric materials. Often, these materials are unable to induce complete healing in wounds because of their failure to prevent infection and promote cell growth. This study reports the development of therapeutic materials aimed at overcoming these limitations through the release of a naturally occurring antimicrobial agent from a porous, polymeric fiber scaffold. The antimicrobial character was achieved through the release of nitric oxide (NO) while the porous structure was fabricated through electrospinning polymers into nanofibers. Three variations of the polymer poly(lactic-co-glycolic-co-hydroxymethyl propionic acid) (PLGH) modified to include thiol and NO groups were investigated. Fibers of the modified polymers exhibited smooth, bead free morphologies with diameters averaging between 200 and 410 nm. These fibers were deposited in a random manner to create a highly porous fibrous scaffold. The fibers were found to release NO under physiological pH and temperature and have the capacity to release 0.026 to 0.280 mmol NO g(-1). The materials maintained their fibrous morphological structure after this exposure to aqueous conditions. The sustained morphological stability of the fiber structure coupled to their extended NO release gives these materials great potential for use in wound healing materials.

  14. Development of self-assembled molecular structures on polymeric surfaces and their applications as ultrasonically responsive barrier coatings for on-demand, pulsatile drug delivery

    Kwok, Connie Sau-Kuen

    Nature in the form of DNA, proteins, and cells has the remarkable ability to interact with its environment by processing biological information through specific molecular recognition at the interface. As such, materials that are capable of triggering an appropriate biological response need to be engineered at the biomaterial surface. Chemically and structurally well-defined self-assembled monolayers (SAMs), biomimetics of the lipid bilayer in cell membranes, have been created and studied mostly on rigid metallic surfaces. This dissertation is motivated by the lack of methods to generate a molecularly designed surface for biomedical polymers and thus provides an enabling technology to engineer a polymeric surface precisely at a molecular and cellular level. To take this innovation one step further, we demonstrated that such self-assembled molecular structure coated on drug-containing polymeric devices could act as a stimulus-responsive barrier for controlled drug delivery. A simple, one-step procedure for generating ordered, crystalline methylene chains on polymeric surfaces via urethane linkages was successfully developed. The self-assemblies and molecular structures of these crystalline methylene chains are comparable to the SAM model surfaces, as evidenced by various surface characterization techniques (XPS, TOF-SIMS, and FTIR-ATR). For the first time, these self-assembled molecular structures are shown to function collectively as an ultrasound-responsive barrier membrane for pulsatile drug delivery, including delivery of low-molecular-weight ciprofloxacin and high-molecular-weight insulin. Encouraging results, based on the insulin-activated deoxyglucose uptakes in adipocytes, indicate that the released insulin remained biologically active. Both chemical and acoustic analyses suggest that the ultrasound-assisted release mechanism is primarily induced by transient cavitation, which causes temporary disruption of the self-assembled overlayer, and thus allows

  15. Smart branched polymer drug conjugates as nano-sized drug delivery systems.

    Duro-Castano, A; Movellan, J; Vicent, M J


    Polymer-drug conjugates represent excellent nanopharmaceutical candidates, as they offer multiple advantages related to their intrinsic characteristics. Many of the said characteristics are provided by the covalent bonding between the drug and the polymer. However, their clinical development has been slow and only one polymer-drug conjugate has reached the market, thus there remains an urgent need for the development of new and smart polymeric systems. Desirable characteristics of these new systems include higher molecular weight and degree of homogeneity, predictable conformations in solution, multivalency, and increased drug loading capacity, amongst others. With these aims in mind, branched polymers are ideal candidates due to their unique rheological, mechanical, and biomedical properties derived from their structure, inaccessible for linear polymers. Within this review, the synthetic strategies developed and the main efforts towards branched polymer implementation as carriers for polymer-drug conjugates will be addressed.

  16. Stereospecific olefin polymerization catalysts

    Bercaw, John E.; Herzog, Timothy A.


    A metallocene catalyst system for the polymerization of .alpha.-olefins to yield stereospecific polymers including syndiotactic, and isotactic polymers. The catalyst system includes a metal and a ligand of the formula ##STR1## wherein: R.sup.1, R.sup.2, and R.sup.3 are independently selected from the group consisting of hydrogen, C.sub.1 to C.sub.10 alkyl, 5 to 7 membered cycloalkyl, which in turn may have from 1 to 3 C.sub.1 to C.sub.10 alkyls as a substituent, C.sub.6 to C.sub.15 aryl or arylalkyl in which two adjacent radicals may together stand for cyclic groups having 4 to 15 carbon atoms which in turn may be substituted, or Si(R.sup.8).sub.3 where R.sup.8 is selected from the group consisting of C.sub.1 to C.sub.10 alkyl, C.sub.6 to C.sub.15 aryl or C.sub.3 to C.sub.10 cycloalkyl; R.sup.4 and R.sup.6 are substituents both having van der Waals radii larger than the van der Waals radii of groups R.sup.1 and R.sup.3 ; R.sup.5 is a substituent having a van der Waals radius less than about the van der Waals radius of a methyl group; E.sup.1, E.sup.2 are independently selected from the group consisting of Si(R.sup.9).sub.2, Si(R.sup.9).sub.2 --Si(R.sup.9).sub.2, Ge(R.sup.9).sub.2, Sn(R.sup.9).sub.2, C(R.sup.9).sub.2, C(R.sup.9).sub.2 --C(R.sup.9).sub.2, where R.sup.9 is C.sub.1 to C.sub.10 alkyl, C.sub.6 to C.sub.15 aryl or C.sub.3 to C.sub.10 cycloalkyl; and the ligand may have C.sub.S or C.sub.1 -symmetry. Preferred metals are selected from the group consisting of group III, group IV, group V or lanthanide group elements. The catalysts are used to prepare stereoregular polymers including polypropylene from .alpha.-olefin monomers.

  17. Mechanically controlled radical polymerization initiated by ultrasound

    Mohapatra, Hemakesh; Kleiman, Maya; Esser-Kahn, Aaron Palmer


    In polymer chemistry, mechanical energy degrades polymeric chains. In contrast, in nature, mechanical energy is often used to create new polymers. This mechanically stimulated growth is a key component of the robustness of biological materials. A synthetic system in which mechanical force initiates polymerization will provide similar robustness in polymeric materials. Here we show a polymerization of acrylate monomers initiated and controlled by mechanical energy provided by ultrasonic agitation. The activator for an atom-transfer radical polymerization is generated using piezochemical reduction of a Cu(II) precursor complex, which thus converts a mechanical activation of piezoelectric particles to the synthesis of a new material. This polymerization reaction has some characteristics of controlled radical polymerization, such as narrow molecular-weight distribution and linear dependence of the polymeric chain length on the time of mechanical activation. This new method of controlled radical polymerization complements the existing methods to synthesize commercially useful well-defined polymers.

  18. Stability of guest molecules in urea canal complexes by canal polymerization

    Yoshii, Fumio; Makuuchi, Keizo [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment


    It was found that various organic materials are attracted into urea canal by hexanediol diacrylate (HDDA) and long chain compounds. This means that materials which does not form complex by itself are induced in canal by HDDA and long chain compounds. To include with stability perfumes, insecticides, attractants and repellents in urea canal, leaf alcohol was used as a model compound for guest molecules in the canal. The leaf alcohol from the canal released gradually over many days and the release was inhibited for 15 days by long chain compounds and for 30 days by polymerized HDDA after irradiation. After releasing, the leaf alcohol in the canal remained 25 % stable for long chain compounds and 40 % for polymerized HDDA. The dose required for stabilization of leaf alcohol in the urea canal by canal polymerization of HDDA was 30 kGy. (author).

  19. Physicochemical properties and biocompatibility of a polymer-paclitaxel conjugate for cancer treatment

    Yang D


    Full Text Available Danbo Yang1, Sang Van2, Jian Liu2, Jing Wang1, Xinguo Jiang3, Yiting Wang1, Lei Yu1,2 1Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, China; 2Biomedical Group, Nitto Denko Technical Corporation, Oceanside, CA; 3School of Pharmacy, Fudan University, Shanghai, ChinaBackground: Poly(L-γ-glutamylglutamine paclitaxel (PGG-PTX conjugate is a non-diblock polymeric drug nanoparticle intended to improve the therapeutic index of paclitaxel. The purpose of the present study was to elucidate further the physicochemical properties of PGG-PTX in order to proceed with its clinical development.Methods and results: PGG-PTX was designed by integration of a hydrophobic paclitaxel conjugate through an added hydrophilic glutamic acid onto poly(L-glutamic acid. The addition of a flexible glutamic linker between PGA and paclitaxel resulted in spontaneous self-assembly of a PGG-PTX conjugate into nanoparticles. The PGG-PTX conjugate was stable as a lyophilized solid form. An in vitro viability experiment showed that PGG-PTX was effective after a longer incubation period, the same trend as Taxol. In vitro studies using NCI-H460 and B16F0 cancer cells demonstrated significantly high cellular uptake after 30 minutes of incubation. The in vivo biocompatibility of PGG-PTX conjugate was evaluated in the NCI-H460 tumor model, the assessment of tissue seemed to be normal after 21 days of treatment.Conclusion: These results are encouraging for further development of non-block polymeric paclitaxel nanoparticles for treatment of cancer.Keywords: polymer conjugate, paclitaxel, poly(L-γ-glutamylglutamine, drug delivery, physicochemical properties, nanoparticles

  20. Research study of conjugate materials; Conjugate material no chosa kenkyu



    The paper reported an introductory research on possibilities of new glass `conjugate materials.` The report took up the structure and synthetic process of conjugate materials to be researched/developed, classified them according to structural elements on molecular, nanometer and cluster levels, and introduced the structures and functions. Further, as glasses with new functions to be proposed, the paper introduced transparent and high-strength glass used for houses and vehicles, light modulation glass which realizes energy saving and optical data processing, and environmentally functional glass which realizes environmental cleaning or high performance biosensor. An initial survey was also conducted on rights of intellectual property to be taken notice of in Japan and abroad in the present situation. Reports were summed up and introduced of Osaka National Research Institute, Electrotechnical Laboratory, and National Industrial Research Institute of Nagoya which are all carrying out leading studies of conjugate materials. 235 refs., 135 figs., 6 tabs.

  1. Preparation and evaluation of microcapsules using polymerized rosin as a novel wall forming material.

    Fulzele, S V; Satturwar, P M; Kasliwal, R H; Dorle, A K


    Sustained release diclofenac sodium microcapsules were prepared using polymerized rosin as a novel wall-forming material by a solvent evaporation technique. A novel method developed in our laboratory with the potential for scale-up and production of polymerized rosin microcapsules is detailed. These microcapsules might have application for development of implant/depot systems, primarily due to a sustained/controlled release capability and potential biocompatibility of polymerized rosin. The effect of variables like solvent systems, stirring speed and temperature were previously optimized. The solution system of drug and polymerized rosin dissolved in iso-propyl alcohol and acetone is sprayed with the help of a 0.5 mm nozzle spray gun in liquid paraffin maintained at 60 degrees C in the stirring condition. Varying drug:polymer ratios, namely 1:1, 1:2, 2:1, 1:3 and 3:1, were employed for microcapsule preparation. The prepared microcapsules were evaluated for size, shape, drug content and in vitro drug release. The morphology of microcapsules was characterized by scanning electron microscopy. The microcapsules show sustained release curves at pH 7.4 phosphate buffer for up to 10 h. The data obtained from the dissolution profiles were compared in the light of different kinetics models and the regression coefficients were compared. The in vitro dissolution study confirmed the Higuchi-order release pattern. Particle size and release data analysis from five consecutive batches prepared in the laboratory indicated suitable reproducibility of the proposed solvent evaporation process.

  2. Synthesis, characterization, and in vivo efficacy evaluation of PGG–docetaxel conjugate for potential cancer chemotherapy

    Jiang X


    -dependent manner. However, PGG–DTX showed better antitumor activity in NCI-H460 lung cancer-bearing mice with minimal weight loss compared to that of free DTX.Conclusion: The PGG–DTX conjugate may be considered as an attractive and promising polymeric DTX conjugate for non-small cell lung cancer treatment.Keywords: polymer drug delivery, nanotechnology, nanotherapeutics, drug delivery, nanomedicine, pharmaceutics

  3. Conjugated polymer nanoparticles, methods of using, and methods of making

    Habuchi, Satoshi


    Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

  4. Supramolecular Polymeric Materials Containing Cyclodextrins.

    Nakahata, Masaki; Takashima, Yoshinori; Harada, Akira


    Smart design of polymeric materials may lead to intelligent materials exhibiting unique functional properties. Looking at nature, living systems use specific and reversible intermolecular interactions in realizing complex functions. Hence reversible bonds based on selective molecular recognition can impart artificial materials with unique functional properties. This review mainly focuses on supramolecular polymeric materials based on cyclodextrin-based host-guest interactions. Polymeric materials using molecular recognition at polymer main chain, side chain, and termini are described. Polymers carrying host and guest residues exhibit unique properties such as: 1) formation of macroscopic self-assembly of polymer gels carrying host and guest residues; 2) stimuli-responsive self-healing properties due to the reversible nature of host-guest interactions; and 3) macroscopic motion of artificial muscle cross-linked by host-guest interaction controlled by external stimuli. An overview of recent developments in this new frontier between materials science and life science is given.

  5. Direct Cytoplasmic Delivery and Nuclear Targeting Delivery of HPMA-MT Conjugates in a Microtubules Dependent Fashion.

    Zhong, Jiaju; Zhu, Xi; Luo, Kui; Li, Lian; Tang, Manlin; Liu, Yanxi; Zhou, Zhou; Huang, Yuan


    As the hearts of tumor cells, the nucleus is the ultimate target of many chemotherapeutic agents and genes. However, nuclear drug delivery is always hampered by multiple intracellular obstacles, such as low efficiency of lysosome escape and insufficient nuclear trafficking. Herein, an N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-based drug delivery system was designed, which could achieve direct cytoplasmic delivery by a nonendocytic pathway and transport into the nucleus in a microtubules dependent fashion. A special targeting peptide (MT), derived from an endogenic parathyroid hormone-related protein, was conjugated to the polymer backbone, which could accumulate into the nucleus a by microtubule-mediated pathway. The in vitro studies found that low temperature and NaN3 could not influence the cell internalization of the conjugates. Besides, no obvious overlay of the conjugates with lysosome demonstrated that the polymer conjugates could enter the tumor cell cytoplasm by a nonendocytic pathway, thus avoiding the drug degradation in the lysosome. Furthermore, after suppression of the microtubule dynamics with microtubule stabilizing docetaxel (DTX) and destabilizing nocodazole (Noc), the nuclear accumulation of polymeric conjugates was significantly inhibited. Living cells fluorescence recovery after photobleaching study found that the nuclear import rate of conjugates was 2-fold faster compared with the DTX and Noc treated groups. These results demonstrated that the conjugates transported into the nucleus in a microtubules dependent way. Therefore, in addition to direct cytoplasmic delivery, our peptide conjugated polymeric platform could simultaneously mediate nuclear drug accumulation, which may open a new path for further intracellular genes/peptides delivery.

  6. Surface glycosylation of polymeric membranes


    Surface glycosylation of polymeric membranes has been inspired by the structure of natural biomem-branes. It refers to that glycosyl groups are introduced onto the membrane surface by various strate-gies, which combine the separation function of the membrane with the biological function of the sac-charides in one system. In this review, progress in the surface glycosylation of polymeric membranes is highlighted in two aspects, i.e. the glycosylation methods and the potential applications of the sur-face-glycosylated membranes.

  7. On-demand photoinitiated polymerization

    Boydston, Andrew J; Grubbs, Robert H; Daeffler, Chris; Momcilovic, Nebojsa


    Compositions and methods for adjustable lenses are provided. In some embodiments, the lenses contain a lens matrix material, a masking compound, and a prepolymer. The lens matrix material provides structure to the lens. The masking compound is capable of blocking polymerization or crosslinking of the prepolymer, until photoisomerization of the compound is triggered, and the compound is converted from a first isomer to a second isomer having a different absorption profile. The prepolymer is a composition that can undergo a polymerization or crosslinking reaction upon photoinitiation to alter one or more of the properties of the lenses.

  8. Conjugate Gradient with Subspace Optimization

    Karimi, Sahar


    In this paper we present a variant of the conjugate gradient (CG) algorithm in which we invoke a subspace minimization subproblem on each iteration. We call this algorithm CGSO for "conjugate gradient with subspace optimization". It is related to earlier work by Nemirovsky and Yudin. We apply the algorithm to solve unconstrained strictly convex problems. As with other CG algorithms, the update step on each iteration is a linear combination of the last gradient and last update. Unlike some other conjugate gradient methods, our algorithm attains a theoretical complexity bound of $O(\\sqrt{L/l} \\log(1/\\epsilon))$, where the ratio $L/l$ characterizes the strong convexity of the objective function. In practice, CGSO competes with other CG-type algorithms by incorporating some second order information in each iteration.

  9. Persistence Mechanisms of Conjugative Plasmids

    Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes


    Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting...... the successful propagation and long-term continued existence of these extra-chromosomal elements is extensive. Apart from the accessory genetic elements that may provide plasmid-harboring cells a selective advantage, special focus is placed on the mechanisms conjugative plasmids employ to ensure their stable...... maintenance in the host cell. These importantly include the ability to self-mobilize in a process termed conjugative transfer, which may occur across species barriers. Other plasmid stabilizing mechanisms include the multimer resolution system, active partitioning, and post-segregational-killing of plasmid...

  10. Biodegradable Multiamine Polymeric Vector for siRNA Delivery.

    Yuan, Yuanyuan; Gong, Faming; Cao, Yang; Chen, Weicai; Cheng, Du; Shuai, Xintao


    The gene silencing activity of small interfering RNA (siRNA) has led to their use as tools for target validation and as potential therapeutics for a variety of diseases. A major challenge is the development of vectors with high delivery efficiency and low toxicity. Although poly(ethylenimine) (PEI) has been regarded as the most promising polymeric vector for nucleic acid delivery, the nonbiodegradable structure greatly hinders its clinical application. In the present study, a diblock copolymer, PEG-PAsp(DIP-DETA), of poly(ethylene glycol) (PEG) and poly(L-aspartic acid) (PAsp) randomly grafted with pH-sensitive 2-(diisopropylamino)ethylamine (DIP) and diethylenetriamine (DETA) groups was synthesized via ring-opening polymerization and aminolysis reaction. Similar to polyethylenimine (PEI), the copolymer possesses a multiamine structure that not only allows effective siRNA complexation at neutral pH but also facilitates lysosomal release of siRNA via a proton buffering effect. Moreover, the poly(L-aspartic acid) backbone renders the vector biodegradability, which is not achievable with PEI. This novel polymeric vector can mediate effective intracellular siRNA delivery in various cancer cells. Consequently, the delivery of BCL-2 siRNA resulted in target gene silencing, inducing apoptosis and inhibiting the growth of cancer cells. These results show the potential of this non-PEI based polymeric vector with proton buffering capacity and biodegradability for siRNA delivery in cancer therapy.

  11. Hypercube Solutions for Conjugate Directions


    alternative term that emphasizes the role of A in this definition. We also say that x and y are A-orthogonal. [Ref. 18: p. 410] The method of conjugate...conjugate (A-orthogonal). begin CG u0 =zeros(n) (arbitrary initial guess) Po = r0 = b- Auo for i = 0 : n = pTAp , (denominator used below) ai = (pTri...application, it could characterize water or chemical penetration in soil. We shall continue to use the term "heat equation", though, for the sake of

  12. 可降解高分子纳米空心粒子载中药血竭的工艺方法及体外释放%Preparation methods andin vitro release of Resina Draconis-loaded biodegradable polymeric hollow nanoparticles

    王雪明; 邢长民; 李楠


    water insoluble, it is difficult to be made into injection. Meanwhile, the oral preparation and enemas of Resina Draconis, due to the water insolubility and large particle size, have poorin vivo absorption and very low bioavailability. Polymeric holow nanoparticles have large surface area and strong adsorption characteristics; moreover, the holow core parts can accommodate a large number of guest molecules. Therefore, the holow nanoparticles have a series of peculiar properties based on the microcapsule effect. OBJECTIVE:To review the literatures covering the preparation methods andin vitro release researches on Resina Draconis-loaded biodegradable polymeric holow nanoparticles. METHODS: A computer-based search was performed in PubMed database, Chinese Science and Technology Periodical Database (1989 to 2014), China Academic Conference Papers Database (1986 to 2014), Chinese Dissertations Database (1986 to 2014), China Patent Database (1985 to 2014), Chinese Science and Technology Paper and Citation Database (1999 to 2014), China Journal Ful Text Database (1979 to 2014), China Outstanding Master's Degree Thesis Database (1999 to 2014), Chinese Doctoral Dissertations Ful Text Database (1999 to 2014) for relevant articles by the retrieval key words of “resina draconis, nanoparticles, holow particles, biodegradable polymer” in English and Chinese, respectively. RESULTS AND CONCLUSION:The traditional Chinese medicine Resina Draconis is firstly dissolved in suitable solvents like ethanol, isopropanol or solvents, forming nearly saturated solution. Then the pre-made polymer hollow nanoparticles are dispersed in the solution, with ultrasonic oscilation for a certain time. After separation by high-speed centrifugation, Resina Draconis-loaded nanoparticles can be prepared successfuly. It is of great importance to make the Chinese medicine Resina Draconis into microemulsion nanoparticles, forming “homogeneous solution” in the medium of water, which wil lead to the

  13. A novel polymeric herbicide based on phenoxyacetic acid derivatives

    Wimol Klaichim


    Full Text Available A novel polymeric herbicide based on phenoxyacetic acid derivatives was prepared by the reaction of epoxidised liquid natural rubber (ELNR with 2,4-dichlorophenoxyacetic acid (2,4-D or 2-methyl-4-chlorophenoxyacetic acid(MCPA. The liquid natural rubber (LNR was firstly obtained from the degradation of natural rubber latex with tert-butyl hydroperoxide and cobalt acetylacetonate at 65oC for 72 hrs. The epoxidised liquid natural rubber was prepared from thereaction of LNR with formic acid and hydrogen peroxide at 50oC for 6 hrs. The reaction of epoxidised liquid natural rubber with 2,4-D or MCPA using triethylamine as a catalyst in toluene was performed at 70, 80, and 90oC for 6, 9, 12, 18, and 24hrs. The polymeric herbicides obtained were characterized and the grafting percentage of 2,4-D or MCPA onto liquid natural rubber were also determined by FT-IR and 1H-NMR spectroscopy. It was found that the grafting percentage increased with increasing amount of reactants, temperature, and reaction time. The release of 2,4-D and MCPA from polymeric herbicides was investigated in pH 6, 7, and 8 buffers at room temperature. The results show that the slowest release of 2,4-D and MCPA was found to be constant at pH 7 for 14 and 10 days, respectively.

  14. Functionalization and Polymerization on the CNT Surfaces

    Albuerne, Julio


    In this review we focus on the current status of using carbon nanotube (CNT) as a filler for polymer nanocomposites. Starting with the historical background of CNT, its distinct properties and the surface functionalization of the nanotube, the three different surface polymerization techniques, namely grafting "from", "to" and "through/in between" were discussed. Wider focus has been given on "grafting from" surface initiated polymerizations, including atom transfer radical polymerization (ATRP), reversible addition fragmentation chain-transfer (RAFT) Polymerization, nitroxide mediated polymerization (NMP), ring opening polymerization (ROP) and other miscellaneous polymerization methods. The grafting "to" and "through / in between" also discussed and compared with grafting from polymerization. The merits and shortcomings of all three grafting methods were discussed and the bottleneck issue in grafting from method has been highlighted. Furthermore the current and potential future industrial applications were deliberated. Finally the toxicity issue of CNTs in the final product has been reviewed with the limited available literature knowledge. © 2013 Bentham Science Publishers.

  15. Metal-catalyzed simultaneous chain- and step-growth radical polymerization: marriage of vinyl polymers and polyesters.

    Mizutani, Masato; Satoh, Kotaro; Kamigaito, Masami


    All polymerization reactions are categorized into two large different families, chain- and step-growth polymerizations, which are typically incompatible. Here, we report the simultaneous chain- and step-growth polymerization via the metal-catalyzed radical copolymerization of conjugated vinyl monomers and designed monomers possessing unconjugated C horizontal lineC and active C-Cl bonds. Especially, almost ideal linear random copolymers containing both vinyl polymer and polyester units in a single polymer chain were formed by the CuCl/1,1,4,7,10,10-hexamethyltriethylenetetramine- or RuCp*Cl(PPh(3))(2)-catalyzed copolymerization of methyl acrylate (MA) for the chain-growth polymerization and 3-butenyl 2-chloropropionate (1) for the step-growth polymerization. In contrast, other transition metal catalysts, such as CuCl with tris[2-(dimethylamino)ethyl]amine or N,N,N',N'',N''-pentamethyldiethylenetriamine and FeCl(2)/PnBu(3), resulted in branched structures via the concomitant chain-growth copolymerization of 1 with MA. The polymerization mechanism was studied in detail by NMR and MALDI-TOF-MS analyses of the polymerizations as well as the model reactions. Furthermore, a series of copolymers changing from random to multiblock polymer structures were obtained by varying the feed ratios of the two monomers. These copolymers can be easily degraded into lower molecular weight oligomers or polymers via methanolysis of the ester-linkages in the main chain using sodium carbonate.

  16. The absorption of polymeric composites

    Řídký, R.; Popovič, M.; Rolc, S.; Drdlová, M.; Krátký, J.


    An absorption capacity of soft, viscoelastic materials at high strain rates is important for wide range of practical applications. Nowadays there are many variants of numerical models suitable for this kind of analysis. The main difficulty is in selection of the most realistic numerical model and a correct setup of many unknown material constants. Cooperation between theoretical simulations and real testing is next crucial point in the investigation process. Standard open source material database offer material properties valid for strain rates less than 250 s-1. There are experiments suitable for analysis of material properties with strain rates close to 2000 s-1. The high strain-rate characteristics of a specific porous blast energy absorbing material measured by modified Split Hopkinson Pressure Bar apparatus is presented in this study. Testing these low impedance materials using a metallic split Hopkinson pressure bar setup results in poor signal to noise ratios due to impedance mismatching. These difficulties are overcome by using polymeric Hopkinson bars. Conventional Hopkinson bar analysis cannot be used on the polymeric bars due to the viscoelastic nature of the bar material. One of the possible solution leads to complex and frequency depended Young modulus of testing bars material. This testing technique was applied to materials composed of porous glass/ceramic filler and polymeric binder, with density of 125 - 300 kg/m3 and particle size in range of 50 µm - 2 mm. The achieved material model was verified in practical application of sandwich structure includes polymeric composites under a blast test.

  17. The Viscosity of Polymeric Fluids.

    Perrin, J. E.; Martin, G. C.


    To illustrate the behavior of polymeric fluids and in what respects they differ from Newtonian liquids, an experiment was developed to account for the shear-rate dependence of non-Newtonian fluids. Background information, procedures, and results are provided for the experiment. Useful in transport processes, fluid mechanics, or physical chemistry…

  18. Biodegradable polymeric prodrugs of naltrexone

    Bennet, D.B.; Li, X.; Adams, N.W.; Kim, S.W.; Hoes, C.J.T.; Feijen, J.


    The development of a biodegradable polymeric drug delivery system for the narcotic antagonist naltrexone may improve patient compliance in the treatment of opiate addiction. Random copolymers consisting of the ¿-amino acids N5-(3-hydroxypropyl--glutamine and -leucine were synthesized with equimolar

  19. Buckling of polymerized monomolecular films

    Bourdieu, L.; Daillant, J.; Chatenay, D.; Braslau, A.; Colson, D.


    The buckling of a two-dimensional polymer network at the air-water interface has been evidenced by grazing incidence x-ray scattering. A comprehensive description of the inhomogeneous octadecyltrichlorosilane polymerized film was obtained by atomic force microscopy and x-ray scattering measurements. The buckling occurs with a characteristic wavelength ~=10 μm.

  20. Novel polymeric materials from triglycerides

    Triglycerides are good platforms for new polymeric products that can substitute for petroleum-based materials. As part of our research emphasis in sustainability and green polymer chemistry, we have explored a number of reactions in efforts to produce a wide range of value-added products. In this ...

  1. Polymeric amines and biomedical uses thereof

    Broekhuis, Antonius; Zhang, Youchum; Picchioni, Francesco; Roks, Antonius


    The invention relates to the field of polymers and biomedical applications thereof. In particular, it relates to the use of polymeric amines derived from alternating polyketones.Provided is the use of a polymeric amine for modulating or supporting cellular behavior, said polymeric amine being an alt


    HUANG Zhitang


    This review is a concise survey about the works in our laboratory on the polymerization of aromatic and heterocyclic dinitriles, including the polymerization kinetics and mechanism, synthesis of heterocyclic dinitriles, the structure of polymers, and the correlation between the structures of dinitriles and polymerization rates and thermal performances of polymers.

  3. Glycine Polymerization on Oxide Minerals

    Kitadai, Norio; Oonishi, Hiroyuki; Umemoto, Koichiro; Usui, Tomohiro; Fukushi, Keisuke; Nakashima, Satoru


    It has long been suggested that mineral surfaces played an important role in peptide bond formation on the primitive Earth. However, it remains unclear which mineral species was key to the prebiotic processes. This is because great discrepancies exist among the reported catalytic efficiencies of minerals for amino acid polymerizations, owing to mutually different experimental conditions. This study examined polymerization of glycine (Gly) on nine oxide minerals (amorphous silica, quartz, α-alumina and γ-alumina, anatase, rutile, hematite, magnetite, and forsterite) using identical preparation, heating, and analytical procedures. Results showed that a rutile surface is the most effective site for Gly polymerization in terms of both amounts and lengths of Gly polymers synthesized. The catalytic efficiency decreased as rutile > anatase > γ-alumina > forsterite > α- alumina > magnetite > hematite > quartz > amorphous silica. Based on reported molecular-level information for adsorption of Gly on these minerals, polymerization activation was inferred to have arisen from deprotonation of the NH3 + group of adsorbed Gly to the nucleophilic NH2 group, and from withdrawal of electron density from the carboxyl carbon to the surface metal ions. The orientation of adsorbed Gly on minerals is also a factor influencing the Gly reactivity. The examination of Gly-mineral interactions under identical experimental conditions has enabled the direct comparison of various minerals' catalytic efficiencies and has made discussion of polymerization mechanisms and their relative influences possible Further systematic investigations using the approach reported herein (which are expected to be fruitful) combined with future microscopic surface analyses will elucidate the role of minerals in the process of abiotic peptide bond formation.

  4. An improved approach to poly(ester-carbonate) conjugates.

    Mo, Guojun; Yue, Jun; Ma, Ping'an; Huang, Yubin; Chen, Xuesi; Jing, Xiabin


    A novel poly(ester-carbonate) (P(LA-co-NPC)) with activated pendant carboxyl groups was synthesized by ring-opening polymerization of L-lactide (LA) and 2-methyl-2-(4-nitrophenoxycarbonyl)-propylene carbonate (NPC) with diethyl zinc (ZnEt(2)) as catalyst. GPC and NMR studies confirmed the co-polymer structure. The pendant 4-nitrophenyl carboxylate groups can react with amino-containing molecules, such as 3,6,9-trioxa-1,11-undecanediamine, doxorubicin and chitosan under mild conditions. Therefore, any amino-containing molecules of biomedical interests can be conjugated to P(LA-co-NPC) efficiently and easily. The biocompatibility of the co-polymer was tested using L929 cell line, indicating that P(LA-co-NPC) is a promising biomedical material.

  5. On contravariant product conjugate connections

    A. M. Blaga


    Full Text Available Invariance properties for the covariant and contravariant connections on a Riemannian manifold with respect to an almost product structure are stated. Restricting to a distribution of the contravariant connections is also discussed. The particular case of the conjugate connection is investigated and properties of the extended structural and virtual tensors for the contravariant connections are given.

  6. Actinomycete integrative and conjugative elements

    Poele, Evelien M. te; Bolhuis, Henk; Dijkhuizen, Lubbert


    This paper reviews current knowledge on actinomycete integrative and conjugative elements (AICEs). The best characterised AICEs, pSAM2 of Streptomyces ambofaciens (10.9 kb), SLP1 (17.3 kb) of Streptomyces coelicolor and pMEA300 of Amycolatopsis methanolica (13.3 kb), are present as integrative eleme

  7. Fused thiophene-based conjugated polymers and their use in optoelectronic devices

    Facchetti, Antonio; Marks, Tobin J.; Takai, Atsuro; Seger, Mark; Chen; , Zhihua


    The present teachings relate to polymeric compounds and their use as organic semiconductors in organic and hybrid optical, optoelectronic, and/or electronic devices such as photovoltaic cells, light emitting diodes, light emitting transistors, and field effect transistors. The disclosed compounds generally include as repeating units at least one annulated thienyl-vinylene-thienyl (TVT) unit and at least one other pi-conjugated unit. The annulated TVT unit can be represented by the formula: ##STR00001## where Cy.sup.1 and Cy.sup.2 can be a five- or six-membered carbocyclic ring. The annulated TVT unit can be optionally substituted at any available ring atom(s), and can be covalently linked to the other pi-conjugated unit via either the thiophene rings or the carbocyclic rings Cy.sup.1 and Cy.sup.2. The other pi-conjugated unit can be a conjugated linear linker including one or more unsaturated bonds, or a conjugated cyclic linker including one or more carbocyclic and/or heterocyclic rings.

  8. Glutathione conjugation as a bioactivation reaction

    Bladeren, P.J. van


    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  9. Glutathione conjugation as a bioactivation reaction

    Bladeren, P.J. van


    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  10. Bacteriophytochromes control conjugation in Agrobacterium fabrum.

    Bai, Yingnan; Rottwinkel, Gregor; Feng, Juan; Liu, Yiyao; Lamparter, Tilman


    Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN-GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation.

  11. Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an Overlooked Risk in Plants?

    Fu, Qiuguo; Zhang, Jianbo; Borchardt, Dan; Schlenk, Daniel; Gan, Jay


    Agricultural use of treated wastewater, biosolids, and animal wastes introduces a multitude of contaminants of emerging concerns (CECs) into the soil-plant system. The potential for food crops to accumulate CECs depends largely on their metabolism in plants, which at present is poorly understood. Here, we evaluated the metabolism of naproxen and ibuprofen, two of the most-used human drugs from the Profen family, in Arabidopsis thaliana cells and the Arabidopsis plant. The complementary use of high-resolution mass spectrometry and (14)C labeling allowed the characterization of both free and conjugated metabolites, as well as nonextractable residues. Naproxen and ibuprofen, in their parent form, were conjugated quickly and directly with glutamic acid and glutamine, and further with peptides, in A. thaliana cells. For example, after 120 h, the metabolites of naproxen accounted for >90% of the extractable chemical mass, while the intact parent itself was negligible. The structures of glutamate and glutamine conjugates were confirmed using synthesized standards and further verified in whole plants. Amino acid conjugates may easily deconjugate, releasing the parent molecule. This finding highlights the possibility that the bioactivity of such CECs may be effectively preserved through direct conjugation, a previously overlooked risk. Many other CECs are also carboxylic acids, such as the profens. Therefore, direct conjugation may be a common route for plant metabolism of these CECs, making it imperative to consider conjugates when assessing their risks.

  12. Synthesis and Characterization of Fatty Acid Conjugates of Niacin and Salicylic Acid.

    Vu, Chi B; Bemis, Jean E; Benson, Ericka; Bista, Pradeep; Carney, David; Fahrner, Richard; Lee, Diana; Liu, Feng; Lonkar, Pallavi; Milne, Jill C; Nichols, Andrew J; Picarella, Dominic; Shoelson, Adam; Smith, Jesse; Ting, Amal; Wensley, Allison; Yeager, Maisy; Zimmer, Michael; Jirousek, Michael R


    This report describes the synthesis and preliminary biological characterization of novel fatty acid niacin conjugates and fatty acid salicylate conjugates. These molecular entities were created by covalently linking two bioactive molecules, either niacin or salicylic acid, to an omega-3 fatty acid. This methodology allows the simultaneous intracellular delivery of two bioactives in order to elicit a pharmacological response that could not be replicated by administering the bioactives individually or in combination. The fatty acid niacin conjugate 5 has been shown to be an inhibitor of the sterol regulatory element binding protein (SREBP), a key regulator of cholesterol metabolism proteins such as PCSK9, HMG-CoA reductase, ATP citrate lyase, and NPC1L1. On the other hand, the fatty acid salicylate conjugate 11 has been shown to have a unique anti-inflammatory profile based on its ability to modulate the NF-κB pathway through the intracellular release of the two bioactives.

  13. Precursor polymer approach towards functional conjugated polymer networks and ultrathin film electro-optical applications

    Taranekar, Prasad

    Conjugated polymers are organic semiconductors which are of interest to a wide variety of optical, electronic, opto-electronic, and sensory applications; including light emitting diodes, thin film transistors, photovoltaic cells, and chemical sensors. While conducting polymers have some similarities to conventional polymeric materials, it is clearly the extensive main chain pi-conjugated structure and its implicit electro-optical properties that make it distinct. The same structure, however, gives it "chain stiffness" that affects its physical behavior. As a direct consequence of this, virtually all unsubstituted conducting polymers are found to be intractable and insoluble. This dissertation details the issue of tailoring the electro-optical properties and processability of conjugated polymers via a novel "precursor polymer approach". In this approach, electroactive side group units of either similar or different kind are tethered to a polymeric backbone. This combination determines the eventual electro-optical and electrochemical properties of these polymers including their ability to form ultrathin films. Thus, the desired macroscopic property is transformed by designing new precursor polymer structures, manipulating polymer-based compositions and blends, and the exploration and exploitation of their electrochemical processing conditions. In Chapters 2, 3, and 4, we have used single or binary electroactive compositions of species such as pyrrole, thiophene, carbazole and terthiophene are tethered to a linear polymeric backbone. Besides, the linear approach, in Chapters 5 and 6, we have also explored the use of generational dendrimers as backbone with carbazole units attached as peripheral electroactive groups. These precursor polymers were then subjected to electrochemical cross-linking to generate high optical quality ultrathin films on a conducting substrate such as indium tin oxide (ITO) or Au surfaces. The reaction of such electroactive species inimically

  14. Design and characterization of nanomaterial-biomolecule conjugates

    Yim, Tae-Jin

    In the field of nanobiotechnology, nanoscale dimensions result in physical properties that differ from more conventional bulk material state. The integration of nanomaterials with biomolecules has begun to be used for unique physical properties, and for biological specific recognition, thereby leading to novel nanomaterial-biomolecule conjugates. The direction of this dissertation is to develop biocatalytic nanomaterial-biomolecule conjugates and to characterize them. For this, biological catalysts are employed to combine with nanomaterials. Two large parts include functional ization of nanomaterials with biomolecules and assembly of nanomaterials using a biological catalyst. First part of this thesis work is the exploration of the biocatalytic properties of nanomaterial-biomolecule conjugates. Si nanocolumns have higher surface area which leads more amount of biocatalytis immobilization than flat Si wafer with the same projected area. The enhanced activity of soybean peroxidase (SBP) immobilized onto Si nanocolumns as novel nanostructured supports is focused. Next, the catalytic activity of immobilized DNAzyme onto multiwalled carbon nanotubes (MWNTs) is compared to that in solution phase, and multiple turnovers are examined. The relationship between hybridization efficiency and activity is investigated as a function of surface density of DNAzyme on MWNTs. Then, cellular delivery of silica nanoparticle-protein conjugates is visually confirmed and therefore the intracellular function of a protein delivered by silica nanoparticle-protein conjugates is proved. For one example of the intracellular function, stable SBP immobilized onto silica nanoparticles to activate a prodrug is demonstrated. Second part of this thesis work is the formation of nanostructured materials through the enzymatic assembly of single-walled carbon nanotubes (SWNTs). Enzymatic polymerization of a phenol compound is applied to the bridging of two or more SWNTs functionalized with phenol

  15. Double phase conjugation in tungsten bronze crystals.

    Sharp, E J; Clark Iii, W W; Miller, M J; Wood, G L; Monson, B; Salamo, G J; Neurgaonkar, R R


    In this paper we report a new method for double phase conjugation particularly suited to the tungsten bronze crystal strontium barium niobate. It has also been observed to produce conjugate waves in BaTiO(3) and BSKNN. This new arrangement is called the bridge conjugator because the two beams enter opposing [100] crystal faces and fan together to form a bridge without reflection off a crystal face. Our measurements indicate that the bridge conjugator is competitive with previously reported double phase conjugate mirrors in reflectivity, response time, ease of alignment, and fidelity.

  16. B:b interactions are essential for polymerization of variant fibrinogens with impaired holes 'a'.

    Okumura, N; Terasawa, F; Haneishi, A; Fujihara, N; Hirota-Kawadobora, M; Yamauchi, K; Ota, H; Lord, S T


    Fibrin polymerization is mediated by interactions between knobs 'A' and 'B' exposed by thrombin cleavage, and holes 'a' and 'b' always present in fibrinogen. The role of A:a interactions is well established, but the roles of knob:hole interactions A:b, B:b or B:a remain ambiguous. To determine whether A:b or B:b interactions have a role in thrombin-catalyzed polymerization, we examined a series of fibrinogen variants with substitutions altering holes 'a': gamma364Ala, gamma364His or gamma364Val. We examined thrombin- and reptilase-catalyzed fibrinopeptide release by high-performance liquid chromatography, fibrin clot formation by turbidity, fibrin clot structure by scanning electron microscopy (SEM) and factor (F) XIIIa-catalyzed crosslinking by sodium dodecylsulfate polyacrylamide gel electrophoresis. Thrombin-catalyzed fibrinopeptide A release was normal, but fibrinopeptide B release was delayed for all variants. The variant fibrinogens all showed markedly impaired thrombin-catalyzed polymerization; polymerization of gamma364Val and gamma364His were more delayed than gamma364Ala. There was absolutely no polymerization of any variant with reptilase, which exposed only knobs 'A'. SEM showed that the variant clots formed after 24 h had uniform, ordered fibers that were thicker than normal. Polymerization of the variant fibrinogens was inhibited dose-dependently by the addition of either Gly-Pro-Arg-Pro (GPRP) or Gly-His-Arg-Pro (GHRP), peptides that specifically block holes 'a' and 'b', respectively. FXIIIa-catalyzed crosslinking between gamma-chains was markedly delayed for all the variants. These results demonstrate that B:b interactions are critical for polymerization of variant fibrinogens with impaired holes 'a'. Based on these data, we propose a model wherein B:b interactions participate in protofibril formation.

  17. Proton-Transfer Polymerization by N-Heterocyclic Carbenes: Monomer and Catalyst Scopes and Mechanism for Converting Dimethacrylates into Unsaturated Polyesters

    Hong, Miao


    This contribution presents a full account of experimental and theoretical/computational investigations into the N-heterocyclic carbene (NHC)-catalyzed proton-transfer polymerization (HTP) that converts common dimethacrylates (DMAs) containing no protic groups into unsaturated polyesters. This new HTP proceeds through the step-growth propagation cycles via enamine intermediates, consisting of the proposed conjugate addition–proton transfer–NHC release fundamental steps. This study examines the monomer and catalyst scopes as well as the fundamental steps involved in the overall HTP mechanism. DMAs having six different types of linkages connecting the two methacrylates have been polymerized into the corresponding unsaturated polyesters. The most intriguing unsaturated polyester of the series is that based on the biomass-derived furfuryl dimethacrylate, which showed a unique self-curing ability Four MeO– and Cl–substituted TPT (1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene) derivatives as methanol insertion products, RxTPT(MeO/H) (R = MeO, Cl; x = 2, 3), and two free carbenes (catalysts), OMe2TPT and OMe3TPT, have been synthesized, while OMe2TPT(MeO/H) and OMe2TPT have also been structurally characterized. The structure/reactivity relationship study revealed that OMe2TPT, being both a strong nucleophile and a good leaving group, exhibits the highest HTP activity and also produced the polyester with the highest Mn, while the Cl–substituted TPT derivatives are least active and efficient. Computational studies have provided mechanistic insights into the tail-to-tail dimerization coupling step as a suitable model for the propagation cycle of the HTP. The extensive energy profile was mapped out and the experimentally observed unicity of the TPT-based catalysts was satisfactorily explained with the thermodynamic formation of key spirocyclic species.

  18. [Preparation and drug releasing property of curcumin nanoparticles].

    Liu, Zhan-jun; Han, Gang; Yu, Jiu-gao; Dai, Hong-guang


    To prepare curcumin nanoparticles and evaluate the in vitro release of curcumin. The chitosan-graft-vinyl acetate copolymers were synthesized by free radical polymerization. Curcumin nanoparticles were synthesized by ultrasonic irradiation. The encapsulation efficiency of the nanoparticles and the in vitro release of curcumin were studied. The nanoparticles were discrete and uniform spheres, covered with positive charges. The encapsulation efficiency of nanoparticles was up to 91.6%. The in vitro release profile showed the slower release rate of curcumin. The methods is simple. The nanoparticles possess good physical performance and sustained release character in vitro.

  19. Improved QD-BRET conjugates for detection and imaging

    Xing, Yun; So, Min-kyung; Koh, Ai-leen; Sinclair, Robert; Rao, Jianghong


    Self-illuminating quantum dots, also known as QD-BRET conjugates, are a new class of quantum dots bioconjugates which do not need external light for excitation. Instead, light emission relies on the bioluminescence resonance energy transfer from the attached Renilla luciferase enzyme, which emits light upon the oxidation of its substrate. QD-BRET combines the advantages of the QDs (such as superior brightness & photostability, tunable emission, multiplexing) as well as the high sensitivity of bioluminescence imaging, thus holds the promise for improved deep tissue in vivo imaging. Although studies have demonstrated the superior sensitivity and deep tissue imaging potential, the stability of the QD-BRET conjugates in biological environment needs to be improved for long-term imaging studies such as in vivo cell trafficking. In this study, we seek to improve the stability of QD-BRET probes through polymeric encapsulation with a polyacrylamide gel. Results show that encapsulation caused some activity loss, but significantly improved both the in vitro serum stability and in vivo stability when subcutaneously injected into the animal. Stable QD-BRET probes should further facilitate their applications for both in vitro testing as well as in vivo cell tracking studies. PMID:18468518

  20. Conjugative plasmids of Neisseria gonorrhoeae.

    Emilia Pachulec

    Full Text Available Many clinical isolates of the human pathogen Neisseria gonorrhoeae contain conjugative plasmids. The host range of these plasmids is limited to Neisseria species, but presence of a tetracycline (tetM determinant inserted in several of these plasmids is an important cause of the rapid spread of tetracycline resistance. Previously plasmids with different backbones (Dutch and American type backbones and with and without different tetM determinants (Dutch and American type tetM determinants have been identified. Within the isolates tested, all plasmids with American or Dutch type tetM determinants contained a Dutch type plasmid backbone. This demonstrated that tetM determinants should not be used to differentiate between conjugal plasmid backbones. The nucleotide sequences of conjugative plasmids with Dutch type plasmid backbones either not containing the tetM determinant (pEP5233 or containing Dutch (pEP5289 or American (pEP5050 type tetM determinants were determined. Analysis of the backbone sequences showed that they belong to a novel IncP1 subfamily divergent from the IncP1alpha, beta, gamma, delta and epsilon subfamilies. The tetM determinants were inserted in a genetic load region found in all these plasmids. Insertion was accompanied by the insertion of a gene with an unknown function, and rearrangement of a toxin/antitoxin gene cluster. The genetic load region contains two toxin/antitoxins of the Zeta/Epsilon toxin/antitoxin family previously only found in Gram positive organisms and the virulence associated protein D of the VapD/VapX toxin/antitoxin family. Remarkably, presence of VapX of pJD1, a small cryptic neisserial plasmid, in the acceptor strain strongly increased the conjugation efficiency, suggesting that it functions as an antitoxin for the conjugative plasmid. The presence of the toxin and antitoxin on different plasmids might explain why the host range of this IncP1 plasmid is limited to Neisseria species. The isolated plasmids

  1. Synthesis of doped graphene nanoribbons from molecular and polymeric precursors

    Cloke, Ryan Randal

    As electronic devices continue to shrink and energy problems continue to grow, nanoscale materials are becoming increasingly important. Graphene is a material with exceptional promise to complement silicon in next-generation electronics because of its extraordinary charge carrier mobility, while also finding a role in cutting-edge energy solutions due to its high surface area and conductivity. Improving on this material even further by reducing the width of graphene to nanoscale dimensions with atomically-precise dopant patterns is the subject of this thesis. Nanometer-wide strips of graphene, known as graphene nanoribbons (GNRs), offer the advantages of semiconducting behavior, combined with more accessible surface area compared to bulk graphene (Chapter 1). Additionally, it is demonstrated that GNRs can be doped with atomic precision, allowing for intricate modulation of the electronic properties of this material, which was studied by STM, STS, and nc-AFM (Chapter 2). Controlled growth of GNRs on surfaces is still an outstanding challenge within the field, and to this end, a variety of porphyrin-GNR template materials were synthesized (Chapter 3). The GNRs obtained in this work were also synthesized in solution, and it was shown that these materials possess excellent properties for applications in hydrogen storage, carbon dioxide reduction, and Li-ion batteries (Chapter 4). A prerequisite for solution-synthesized GNRs, conjugated aromatic polymers are an important class of materials in their own right. Therefore, Ring-Opening Alkyne Metathesis Polymerization was developed using conjugated, strained diynes (Chapter 5). The resulting conjugated polymers were explored both for their own materials properties due to a remarkable self-assembly process that was discovered, and also as precursors to GNRs (Chapter 6). This work advances the fundamental understanding of carbon-based nanostructures, as well as the large-scale production of GNRs for next-generation energy

  2. Study on the preirradiation polymerization of vinyl monomers

    Yu-Ming, Liu; Yue-Qi, Yang; Zue-Teh, Ma

    This paper presents mainly the polymerization, copolymerization and crosslinking of monomers off-source induced by peroxides which are formed by high energy irradiation of vinyl monomers such as styrene (St), acrylonitrile (AN), methylmethacrylate (MMA), vinyl acetate (VAc) and 2-hydroxyethyl methacrylate (HEMA). The peroxides produced by irradiation of the above-mentioned monomers can not only induce the monomers themselves, but also another non-irradiated monomer to carry out copolymerization efficiently. The activation energy of peroxide formation, the apparent activation energy of polymerization and the activation energy of peroxide initiation by irradiation of vinyl monomers are: Ef(MMA) = 11, Ef(St) = 9.6, Ef(AN) = 8.5, EMMA = EVA = 11.4, Ei(MMA) = Ei(VA) = 13 kcal/mol. The rate of decomposition of monomer peroxides is smoother than that of BPO during the polymerization and so a smooth kinetic progress is obtained. The initiating ability of forming peroxides by irradiation of the vinyl monomers depends mainly on the chemical structure of the monomers. For instance, the main structure of peroxides formed during preirradiation MMA are: alternating peroxy-copolymer ? and random peroxy-copolymer ? Owing to the peroxy-bond which is unstable and in which homolytic breakage easily occurs to yield a pair of radicals, RO . is formed within the above-mentioned structural compounds, so that they possess stronger initiating reactivity. It is quite evident that the initiating reactivity of AN peroxide will be greatly reduced because of the conjugate double bond. In other words, the initiating ability of AN peroxide is lower than MMA peroxide and St peroxide.

  3. GPCR ligand-dendrimer (GLiDe) conjugates: future smart drugs?

    Jacobson, Kenneth A


    Unlike nanocarriers that are intended to release their drug cargo at the site of action, biocompatibile polyamidoamine (PAMAM) conjugates are designed to act at cell surface G protein-coupled receptors (GPCRs) without drug release. These multivalent GPCR ligand-dendrimer (GLiDe) conjugates display qualitatively different pharmacological properties in comparison with monomeric drugs. They might be useful as novel tools to study GPCR homodimers and heterodimers as well as higher aggregates. The structure of the conjugate determines the profile of biological activity, receptor selectivity, and physical properties such as water solubility. Prosthetic groups for characterization and imaging of receptors can be introduced without loss of affinity. The feasibility of targeting multiple adenosine and P2Y receptors for synergistic effects has been shown. Testing in vivo will be needed to explore the effects on pharmacokinetics and tissue targeting.

  4. Synthesis of novel polymeric nanoparticles for hydrophobic and hydrophilic drug delivery

    Sartor, Marta

    Modern medicine has achieved extraordinary results with the use of nanotechnologies. The combination of the two disciplines created the modern field of nanomedicine, in which drug delivery is one of the most prominent branches. Several aspects are involved in drug delivery; this work will focus on the drug delivery vehicle. In particular three aspects will be investigated: building material, internal structure and material compatibility. In a first project DNA was proposed as an innovative building material. DNA nanoparticles were made from self-folding of long concatameric repeats of a single strand sequence. Nanoparticles with different sequences created a library that was biopanned against dendritic cells (DC). Particles from the enriched library were sequenced and individually tested for affinity towards DC. The use of DNA as building material offers several advantages. For instance DNA binding drugs (such as Doxorubicin) can be easily incorporated, and immunostimulatory sequences (such as GpC) and any other encoding sequence can be integrated within the concatamers. In addition, any other molecule or small particle of interest can be conjugated to a short complementary sequence and hybridized on the outer layer of the DNA nanoparticle. DNA nanoparticles' payloads are limited to hydrophilic drugs. In addition to an hydrophobic payload, some therapies require a high loading and steady release. To achieve such results a gradient structure was created within the core of a polymeric nanoparticle. Physical and chemical gradient were considered. A chemical gradient was created by combining a low molecular weigh polycaprolactone (PCL) to a higher molecular weigh poly(lactic-co-glycolic acid) (PLGA). PCL and PLGA have different degradation rate and hydrophobicity. The particles created by combining the two polymers showed properties (such as loading) dependent on the two polymers' proportion into the composition. The chemical gradient nanoparticles are characterized by




    Full Text Available Here, of great interest to us is a quantitative study of the scattering properties from ramified polymeric systems of arbitrary topology. We consider three types of systems, namely ramified polymers in solution, ramified polymer blends, or ternary mixtures made of two ramified polymers of different chemical nature immersed in a good solvent. To achieve the goal of the study, use is made of the Random Phase Approximation. First we determine the exact expression of the form factor of an ideal ramified polymer of any topology, from which we extract the exact expression of its gyration radius. Using the classical Zimm's formulae and the exact form factor, we determine all scattering properties of these three types of ramified polymeric systems. The main conclusion is that ramification of the chains induces drastic changes of the scattering properties.

  6. Magnetic properties of polymerized diphenyloctatetrayne

    Beristain, Miriam F.; Jimenez-Solomon, Maria F.; Ortega, Alejandra; Escudero, Roberto [Instituto de Investigaciones en Materiales, Universidad Nacional Autonoma de Mexico, Apartado Postal 70-360, Ciudad Universitaria, Mexico DF 04510 (Mexico); Munoz, Eduardo [Instituto de Fisica, Universidad Nacional Autonoma de Mexico, Apartado Postal 20-364, Ciudad Universitaria, Mexico DF 01000 (Mexico); Maekawa, Yasunari; Koshikawa, Hiroshi [High Performance Polymer Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Ogawa, Takeshi, E-mail: [Instituto de Investigaciones en Materiales, Universidad Nacional Autonoma de Mexico, Apartado Postal 70-360, Ciudad Universitaria, Mexico DF 04510 (Mexico)


    A new type of metal-free ferromagnetic carbon material was obtained by thermal polymerization and electron beam irradiation of diphenyloctatetrayne (DPOT). The isothermal magnetic measurements showed hysteresis loops indicating weak but intrinsic ferromagnetism with Curie temperatures of around 600 K. Electron spin resonance spectroscopy showed that the material contained stable free radicals in the range of 10{sup 17}-10{sup 20} radicals g{sup -1} depending on the polymerization process. The ferromagnetism should be due to high radical concentration although no correlation was observed between them. It was shown that an amorphous ferromagnetic carbon could be obtained from a simple crystalline solid by heating at moderate temperatures. Highlights: Black-Right-Pointing-Pointer Diphenyloctatetrayne as a precursor for carbon with high radical concentration. Black-Right-Pointing-Pointer The carbon material consists of sp{sup 2} configuration. Black-Right-Pointing-Pointer A weak intrinsic metal-free ferromagnetism was observed for the carbon products.

  7. 'Reactive' nano-complex coated medical cotton: a facile avenue for tailored release of small molecules.

    Rather, Adil Majeed; Mahato, Sulendar; Maji, Kousik; Gogoi, Neeha; Manna, Uttam


    Controlled and sustained release of drug-like small molecules in an aqueous medium still remains a challenging problem due to rapid infiltration of liquid water in most reported drug release systems. However, internal-superhydrophobicity with an antifouling property extending beyond the surface of a material recently has been recognized as a potential avenue for sustained and extended release of drug-like small molecules. Sluggish removal of metastable trapped air in a superhyrophobic material provides a basis to achieve extended release of encapsulated small molecules. In this article, naturally abundant medical-cotton-extensively used in wound management including control of bleeding, absorbance of secretions and protecting wounds from contamination-is strategically exploited in tailoring (from rapid to extended) the release of small molecules by appropriate modulation of liquid water wettability. Modulation included bio-mimicked adhesive and non-adhesive superhydrophobicity of the medical cotton without erosion of any polymeric material. In this process, amine 'reactive' nano-complexes (RNC) were prepared by just mixing branched poly(ethylenimine) (BPEI) with dipentaerythritol pentaacrylate (5Acl) in ethanol with appropriate compositions. Then they were covalently immobilized on fibrous medical-cotton through a facile and robust 1,4-conjugated addition reaction. Residual acrylate moieties in the immobilized RNC provide an opportunity to tailor water wettability through strategic and appropriate post-chemical modification of RNC-coated medical cotton with a primary amine containing various small molecules. This medical-cotton with tunable wettability was exploited further to control the release rate of small molecules from rapid (100 days) times. A volatile solvent induced transient and reversible switching of anti-fouling properties which allowed further varying the amount of post-loading small molecules into the medical cotton up to 2.36 wt% without

  8. Fabrication of Functional Nano-objects through RAFT Dispersion Polymerization and Influences of Morphology on Drug Delivery.

    Qiu, Liang; Xu, Chao-Ran; Zhong, Feng; Hong, Chun-Yan; Pan, Cai-Yuan


    To study the influence of self-assembled morphologies on drug delivery, four different nano-objects, spheres, nanorods, nanowires, and vesicles having aldehdye-based polymer as core, were successfully prepared via alcoholic RAFT dispersion polymerization of p-(methacryloxyethoxy)benzaldehyde (MAEBA) using poly((N,N'-dimethylamino)ethyl methacrylate) (PDMAEMA) as a macro chain transfer agent (macro-CTA) for the first time. The morphologies and sizes of the four nano-objects were characterized by TEM and DLS, and the spheres with average diameter (D) of 70 nm, the nanorods with D of 19 nm and length of 140 nm, and the vesicles with D of 137 nm were used in the subsequent cellular internalization, in vitro release, and intracellular release of the drug. The anticancer drug doxorubicin (DOX) was conjugated onto the core polymers of nano-objects through condensation reaction between aldehyde groups of the PMAEBA with primary amine groups in the DOX. Because the aromatic imine is stable under neutral conditions, but is decomposed in a weakly acidic solution, in vitro release of the DOX from the DOX-loaded nano-objects was investigated in the different acidic solutions. All of the block copolymer nano-objects show very low cytotoxicity to HeLa cells up to the concentration of 1.2 mg/mL, but the DOX-loaded nano-objects reveal different cell viability and their IC50s increase as the following order: nanorods-DOX nano-objects owing to their too large size to be internalized. Endocytosis tests demonstrate that the internalization of vesicles-DOX by the HeLa cells is faster than that of the nanorods-DOX, and the spheres-DOX are the slowest to internalize among the studied nano-objects. Relatively more nanorods localized in the acidic organelles of the HeLa cells lead to faster intracellular release of the DOX, so the IC50 of nanorods is lower than that of the vesicles-DOX.

  9. Polymeric Microspheres for Medical Applications

    Ketie Saralidze


    Full Text Available Synthetic polymeric microspheres find application in a wide range of medical applications. Among other applications, microspheres are being used as bulking agents, embolic- or drug-delivery particles. The exact composition of the spheres varies with the application and therefore a large array of materials has been used to produce microspheres. In this review, the relation between microsphere synthesis and application is discussed for a number of microspheres that are used for different treatment strategies.

  10. Antitumor efficacy of dexamethasone-loaded core-crosslinked polymeric micelles

    Coimbra, M.; Rijcken, C.J.; Stigter, M.; Hennink, W.E.; Storm, Gerrit; Schiffelers, R.M.


    Abstract In the current study, core-crosslinked polymeric micelles (DEX-PMs) loaded with three different DEX derivatives designed to display different drug release kinetics, were evaluated for cancer therapy and compared to another effective nanomedicine formulation (long-circulating liposomes encap

  11. Influence of extracellular polymeric substances on deposition and redeposition of Pseudomonas aeruginosa to surfaces

    Gomez-Suarez, C; Pasma, J; van der Borden, AJ; Wingender, J; Flemming, HC; Busscher, HJ; van der Mei, HC


    In this study, the role of extracellular polymeric substances (EPS) in the initial adhesion of EPS-producing Pseudomonas aeruginosa SG91 and SG81R1, a non-EPS-producing strain, to substrata with different hydrophobicity was investigated. The release of EPS by SG81 was concurrent with a decrease in s

  12. Fiber bundle phase conjugate mirror

    Ward, Benjamin G.


    An improved method and apparatus for passively conjugating the phases of a distorted wavefronts resulting from optical phase mismatch between elements of a fiber laser array are disclosed. A method for passively conjugating a distorted wavefront comprises the steps of: multiplexing a plurality of probe fibers and a bundle pump fiber in a fiber bundle array; passing the multiplexed output from the fiber bundle array through a collimating lens and into one portion of a non-linear medium; passing the output from a pump collection fiber through a focusing lens and into another portion of the non-linear medium so that the output from the pump collection fiber mixes with the multiplexed output from the fiber bundle; adjusting one or more degrees of freedom of one or more of the fiber bundle array, the collimating lens, the focusing lens, the non-linear medium, or the pump collection fiber to produce a standing wave in the non-linear medium.

  13. Protopanaxadiol aglycone ginsenoside-polyethylene glycol conjugates: synthesis, physicochemical characterizations, and in vitro studies.

    Mathiyalagan, Ramya; Kim, Yeon Ju; Wang, Chao; Jin, Yan; Subramaniyam, Sathiyamoorthy; Singh, Priyanka; Wang, Dandan; Yang, Deok Chun


    Ginsenosides are triterpenoid saponins, which is an active compound responsible for most of the pharmacological effects of ginseng (Panax ginseng Meyer). It is known to have numerous structural and pharmacological properties. However, aqueous solubility and delivery of ginsenosides in targeted region by avoiding undesirable toxicity to normal cell is also of prime importance. The aim of this study was to obtain amphiphilic ginsenoside derivatives in which hydrophilic polymers were conjugated to ginsenosides to enhance the water solubility and targeted delivery. To this end, the hydrophobic protopanaxadiol ginsenoside aglycone (aPPD) was covalently conjugated to the backbone of hydrophilic polyethylene glycol (PEG) through a pH sensitive ester linkage, which was confirmed by (1)H NMR and FTIR. The resultant PPD is covalently conjugated to hydrophilic PEG through esterification (PEG-PPD) forming self-assembled spherical nanoparticles, whose average particle diameter was 189 nm as observed by FE-TEM and particle size analyzer respectively. In vitro release experiments revealed that the release rate of PPD was rapidly increased from the self-assembled nanoparticles under acidic conditions (pH 5.0) than in a physiological buffer (pH 7.4) condition. Furthermore, in vitro cytotoxicity assays revealed that PEG-PPD conjugates exhibited lower cytotoxicity in HT-29 cancer cells compared with PPD alone. Since the slow release of PPD from conjugates is triggered only by acidic environmental conditions, such as those found in extracellular solid tumor tissues, intracellular endosomes, and intracellular lysosomes, the conjugation of PPD may aid its selective delivery to these targets. Overall, results suggest that pH-dependent release of PPD, which expected in reduced cytotoxicity to non-targeted regions, may enhance the overall efficacy of PPD.

  14. Conjugated polyelectrolytes fundamentals and applications

    Liu, Bin


    This is the first monograph to specifically focus on fundamentals and applications of polyelectrolytes, a class of molecules that gained substantial interest due to their unique combination of properties. Combining both features of organic semiconductors and polyelectrolytes, they offer a broad field for fundamental research as well as applications to analytical chemistry, optical imaging, and opto-electronic devices. The initial chapters introduce readers to the synthesis, optical and electrical properties of various conjugated polyelectrolytes. This is followed by chapters on the applica

  15. Co-delivery of doxorubicin and AS1411 aptamer by poly(ethylene glycol)-poly( β-amino esters) polymeric micelles for targeted cancer therapy

    Zhang, Ran; Wang, Shi-Bin; Wu, Wen-Guo; Kankala, Ranjith Kumar; Chen, Ai-Zheng; Liu, Yuan-Gang; Fan, Jing-Qian


    Recently, targeted drug delivery systems (TDDS) have offered a great potential and benefits towards the anti-tumor drug delivery. In this work, we designed the TDDS using a biocompatible poly(ethylene glycol)-poly( β-amino esters) amphiphilic block copolymer (PEG-PAEs) synthesized by Michael addition polymerization for combinatorial therapy. Further, the chemotherapeutic agents' doxorubicin (DOX) and AS1411 DNA aptamer (Apt) are encapsulated in the PEG-PAEs NPs (PDANs) for co-delivery therapeutics. PDANs have shown the monodisperse spherical shape, smooth surface with a net positive charge (average diameter—183.1 ± 27.2 nm, zeta potential—31.2 ± 6.3 mV), and good colloidal stability (critical micelle concentration of PEG-PAEs is about 6.3 μg/mL). The pH-sensitive PAEs endowed PDANs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the localization and cytotoxicity of DOX. AS1411 Apt conjugated PDANs precisely targeted nucleolin and their uptake correlates to a significant activity enhancement only in tumor cells (MCF-7) but not in normal cells (MCF-10A). Thus, PDANs can be a very promising targeted drug delivery platform for effective breast cancer therapy.

  16. Curcumin and Osteosarcoma: Can Invertible Polymeric Micelles Help?

    Avudaiappan Maran


    Full Text Available Systematic review of experimental and clinical data on the use of curcumin in the treatment of osteosarcoma is presented. The current status of curcumin’s therapeutic potential against bone cancer is analyzed in regard to using polymeric micelles (including recently developed invertible, responsive, micelles as a platform for curcumin delivery to treat osteosarcoma. The potential of micellar assemblies from responsive macromolecules in a controlled delivery of curcumin to osteosarcoma cells, and the release using a new inversion mechanism is revealed.

  17. Polymeric and Ceramic Nanoparticles in Biomedical Applications

    Aura-Ileana Moreno-Vega


    Full Text Available Materials in the nanometer size range may possess unique and beneficial properties, which are very useful for different medical applications including stomatology, pharmacy, and implantology tissue engineering. The application of nanotechnology to medicine, known as nanomedicine, concerns the use of precisely engineered materials at this length scale to develop novel therapeutic and diagnostic modalities. Nanomaterials have unique physicochemical properties, such as small size, large surface area to mass ratio, and high reactivity, which are different from bulk materials of the same composition. Polymeric and ceramic nanoparticles have been extensively studied as particulate carriers in the pharmaceutical and medical fields, because they show promise as drug delivery systems as a result of their controlled- and sustained-release properties, subcellular size, and biocompatibility with tissue and cells. These properties can be used to overcome some of the limitations found in traditional therapeutic and diagnostic agents. Nanotechnology is showing promising developments in many areas and may benefit our health and welfare. However, a wide range of ethical issues has been raised by this innovative science. Many authorities believe that these advancements could lead to irreversible disasters if not limited by ethical guidelines.

  18. Release and toxicity of dental resin composite

    Saurabh K Gupta; Saxena, Payal; Pant, Vandana A.; Pant, Aditya B.


    Dental resin composite that are tooth-colored materials have been considered as possible substitutes to mercury-containing silver amalgam filling. Despite the fact that dental resin composites have improved their physico-chemical properties, the concern for its intrinsic toxicity remains high. Some components of restorative composite resins are released in the oral environment initially during polymerization reaction and later due to degradation of the material. In vitro and in vivo studies h...

  19. Polymerization rate and mechanism of ultrasonically initiated emulsion polymerization of n-butyl acrylate.

    Xia, Hesheng; Wang, Qi; Liao, Yongqin; Xu, Xi; Baxter, Steven M; Slone, Robert V; Wu, Shuguang; Swift, Graham; Westmoreland, David G


    The factors affecting the induction period and polymerization rate in ultrasonically initiated emulsion polymerization of n-butyl acrylate (BA) were investigated. The induction period takes only an instant in ultrasonically initiated emulsion polymerization of BA without any added initiator by enhancing the N2 flow rate. Increasing temperature, power output and SDS concentration, decreasing the monomer concentration results in further decreasing induction period and enhanced polymerization rate. Under optimized reaction conditions the conversion of BA reaches 92% in 11 min. The polymerization rate can be controlled by varying reaction parameters. The apparatus of ultrasonically initiated semi-continuous and continuous emulsion polymerization were set up and the feasibility was first studied. Based on the experimental results, a free radical polymerization mechanism for ultrasonically initiated emulsion polymerization was proposed, including the sources of the radicals, the process of radical formation, the locus of polymerization and the polymerization process. Compared with conventional emulsion polymerization, where the radicals come from thermal decomposition of a chemical initiator, ultrasonically initiated emulsion polymerization has attractive features such as no need for a chemical initiator, lower reaction temperature, faster polymerization rate, and higher molecular weight of the polymer prepared.

  20. Aptamer conjugated magnetic nanoparticles as nanosurgeons

    Nair, Baiju G.; Nagaoka, Yutaka; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.


    Magnetic nanoparticles have shown promise in the fields of targeted drug delivery, hyperthermia and magnetic resonance imaging (MRI) in cancer therapy. The ability of magnetic nanoparticles to undergo surface modification and the effect of external magnetic field in the dynamics of their movement make them an excellent nanoplatform for cancer destruction. Surgical removal of cancerous or unwanted cells selectively from the interior of an organ or tissue without any collateral damage is a serious problem due to the highly infiltrative nature of cancer. To address this problem in surgery, we have developed a nanosurgeon for the selective removal of target cells using aptamer conjugated magnetic nanoparticles controlled by an externally applied three-dimensional rotational magnetic field. With the help of the nanosurgeon, we were able to perform surgical actions on target cells in in vitro studies. LDH and intracellular calcium release assay confirmed the death of cancer cells due to the action of the nanosurgeon which in turn nullifies the possibility of proliferation by the removed cells. The nanosurgeon will be a useful tool in the medical field for selective surgery and cell manipulation studies. Additionally, this system could be upgraded for the selective removal of complex cancers from diverse tissues by incorporating various target specific ligands on magnetic nanoparticles.

  1. Supramolecular 1-D polymerization of DNA origami through a dynamic process at the 2-dimensionally confined air-water interface.

    Yonamine, Yusuke; Cervantes-Salguero, Keitel; Minami, Kosuke; Kawamata, Ibuki; Nakanishi, Waka; Hill, Jonathan P; Murata, Satoshi; Ariga, Katsuhiko


    In this study, a Langmuir-Blodgett (LB) system has been utilized for the regulation of polymerization of a DNA origami structure at the air-water interface as a two-dimensionally confined medium, which enables dynamic condensation of DNA origami units through variation of the film area at the macroscopic level (ca. 10-100 cm(2)). DNA origami sheets were conjugated with a cationic lipid (dioctadecyldimethylammonium bromide, 2C18N(+)) by electrostatic interaction and the corresponding LB-film was prepared. By applying dynamic pressure variation through compression-expansion processes, the lipid-modified DNA origami sheets underwent anisotropic polymerization forming a one-dimensionally assembled belt-shaped structure of a high aspect ratio although the thickness of the polymerized DNA origami was maintained at the unimolecular level. This approach opens up a new field of mechanical induction of the self-assembly of DNA origami structures.

  2. Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles

    Dian, Linghui; Yu, Enjiang; Chen, Xiaona; Wen, Xinguo; Zhang, Zhengzan; Qin, Lingzhen; Wang, Qingqing; Li, Ge; Wu, Chuanbin


    To improve its poor aqueous solubility and stability, the potential chemotherapeutic drug quercetin was encapsulated in soluplus polymeric micelles by a modified film dispersion method. With the encapsulation efficiency over 90%, the quercetin-loaded polymeric micelles (Qu-PMs) with drug loading of 6.7% had a narrow size distribution around mean size of 79.00 ± 2.24 nm, suggesting the complete dispersibility of quercetin in water. X-ray diffraction (XRD) patterns illustrated that quercetin was in amorphous or molecular form within PMs. Fourier transform infrared spectroscopy (FTIR) indicated that quercetin formed intermolecular hydrogen bonding with carriers. An in vitro dialysis test showed the Qu-PMs possessed significant sustained-release property, and the formulation was stable for at least 6 months under accelerated conditions. The pharmacokinetic study in beagle dogs showed that absorption of quercetin after oral administration of Qu-PMs was improved significantly, with a half-life 2.19-fold longer and a relative oral bioavailability of 286% as compared to free quercetin. Therefore, these novel soluplus polymeric micelles can be applied to encapsulate various poorly water-soluble drugs towards a development of more applicable therapeutic formulations.

  3. Polymeric insulation post electrodeless dielectrophoresis (iDEP) for the monitoring of water-borne pathogens.

    Lapizco-Encinas, Blanca Hazalia; Shediac, Renee; Fiechtner, Gregory J.; Brazzle, John D.; Cummings, Eric B.; Davalos, Rafael V.; Hachman, John T.; Hunter, Marion C.; McGraw, Gregory J.; Ceremuga, Joseph T.; Chames, Jeffrey; Blake, Simmons; Fintschenko, Yolanda


    We have successfully demonstrated selective trapping, concentration, and release of various biological organisms and inert beads by insulator-based dielectrophoresis within a polymeric microfluidic device. The microfluidic channels and internal features, in this case arrays of insulating posts, were initially created through standard wet-etch techniques in glass. This glass chip was then transformed into a nickel stamp through the process of electroplating. The resultant nickel stamp was then used as the replication tool to produce the polymeric devices through injection molding. The polymeric devices were made of Zeonor{reg_sign} 1060R, a polyolefin copolymer resin selected for its superior chemical resistance and optical properties. These devices were then optically aligned with another polymeric substrate that had been machined to form fluidic vias. These two polymeric substrates were then bonded together through thermal diffusion bonding. The sealed devices were utilized to selectively separate and concentrate a biological pathogen simulants. These include spores that were selectively concentrated and released by simply applying D.C. voltages across the plastic replicates via platinum electrodes in inlet and outlet reservoirs. The dielectrophoretic response of the organisms is observed to be a function of the applied electric field and post size, geometry and spacing. Cells were selectively trapped against a background of labeled polystyrene beads and spores to demonstrate that samples of interest can be separated from a diverse background. We have implemented and demonstrated here a methodology to determine the concentration factors obtained in these devices.

  4. Direct Arylation Strategies in the Synthesis of π-Extended Monomers for Organic Polymeric Solar Cells

    Andrea Nitti


    Full Text Available π-conjugated macromolecules for organic polymeric solar cells can be rationally engineered at the molecular level in order to tune the optical, electrochemical and solid-state morphology characteristics, and thus to address requirements for the efficient solid state device implementation. The synthetic accessibility of monomers and polymers required for the device is getting increasing attention. Direct arylation reactions for the production of the π-extended scaffolds are gaining importance, bearing clear advantages over traditional carbon-carbon forming methodologies. Although their use in the final polymerization step is already established, there is a need for improving synthetic accessibility to implement them also in the monomer synthesis. In this review, we discuss recent examples highlighting this useful strategy.

  5. Engineering live cell surfaces with functional polymers via cytocompatible controlled radical polymerization

    Niu, Jia; Lunn, David J.; Pusuluri, Anusha; Yoo, Justin I.; O'Malley, Michelle A.; Mitragotri, Samir; Soh, H. Tom; Hawker, Craig J.


    The capability to graft synthetic polymers onto the surfaces of live cells offers the potential to manipulate and control their phenotype and underlying cellular processes. Conventional grafting-to strategies for conjugating preformed polymers to cell surfaces are limited by low polymer grafting efficiency. Here we report an alternative grafting-from strategy for directly engineering the surfaces of live yeast and mammalian cells through cell surface-initiated controlled radical polymerization. By developing cytocompatible PET-RAFT (photoinduced electron transfer-reversible addition-fragmentation chain-transfer polymerization), synthetic polymers with narrow polydispersity (Mw/Mn cells using either covalent attachment or non-covalent insertion, while maintaining high cell viability. Compared with conventional grafting-to approaches, these methods significantly improve the efficiency of grafting polymer chains and enable the active manipulation of cellular phenotypes.

  6. Morphological control of conductive polymers utilized electrolysis polymerization technique: trial of fabricating biocircuit.

    Onoda, Mitsuyoshi


    Conductive polymers are a strong contender for making electronic circuits. The growth pattern in conductive polymer synthesis by the electrolysis polymerization method was examined. The growth pattern is deeply related to the coupling reaction of the radical cation and the deprotonation reaction following it and changes suddenly depending on the kind and concentration of the supporting electrolyte and the solvent used. That is, when the electrophilic substitution coupling reaction becomes predominant, the three-dimensional growth form is observed, and when the radical coupling reaction becomes predominant, the two-dimensional growth morphology is observed. In addition, the growth pattern can be comparatively easily controlled by changing the value of the polymerization constant current, and it is considered that the indicator and development for biocircuit research with neuron-type devices made of conjugated polymers was obtained.

  7. Synthesis of Cross-Linked Polymeric Micelle pH Nanosensors

    Ek, Pramod Kumar; Jølck, Rasmus Irming; Andresen, Thomas Lars


    at the micelle shell using CuAAC results in a stabilized micelle pH nanosensor. Compared to the postmicelle modification strategy, the mixed-micellization approach increases the control of the overall composition of the nanosensors.Both approaches provide stable nanosensors with similar pKa profiles and thereby......The design flexibility that polymeric micelles offer in the fabrication of optical nanosensors for ratiometric pH measurements is investigated. pH nanosensors based on polymeric micelles are synthesized either by a mixed-micellization approach or by a postmicelle modification strategy. In the mixed......-micellization approach, self-assembly of functionalized unimers followed by shell cross-linking by copper-catalyzed azide-alkyne cycloaddition (CuAAC) results in stabilized cRGD-functionalized micelle pH nanosensors. In the postmicelle modification strategy, simultaneous cross-linking and fluorophore conjugation...

  8. Bacteria‐Triggered Release of Antimicrobial Agents

    Komnatnyy, Vitaly V.; Chiang, Wen‐Chi; Tolker‐Nielsen, Tim


    Medical devices employed in healthcare practice are often susceptible to microbial contamination. Pathogenic bacteria may attach themselves to device surfaces of catheters or implants by formation of chemically complex biofilms, which may be the direct cause of device failure. Extracellular...... material is demonstrated by the bacteria‐triggered release of antibiotics to control bacterial populations and signaling molecules to modulate quorum sensing. The self‐regulating system provides the basis for the development of device‐relevant polymeric materials, which only release antibiotics...... in dependency of the titer of bacteria surrounding the medical device....

  9. Bacteria-Triggered Release of Antimicrobial Agents

    Komnatnyy, Vitaly V.; Chiang, Wen-Chi; Tolker-Nielsen, Tim


    Medical devices employed in healthcare practice are often susceptible to microbial contamination. Pathogenic bacteria may attach themselves to device surfaces of catheters or implants by formation of chemically complex biofilms, which may be the direct cause of device failure. Extracellular...... material is demonstrated by the bacteria‐triggered release of antibiotics to control bacterial populations and signaling molecules to modulate quorum sensing. The self‐regulating system provides the basis for the development of device‐relevant polymeric materials, which only release antibiotics...... in dependency of the titer of bacteria surrounding the medical device....

  10. Nanoporous Polymeric Grating-Based Biosensors

    Gao, Tieyu


    We demonstrate the utilization of an interferometrically created nanoporous polymeric gratings as a platform for biosensing applications. Aminopropyltriethoxysilane (APTES)-functionalized nanoporous polymeric gratings was fabricated by combining holographic interference patterning and APTES-functionalization of pre-polymer syrup. The successful detection of multiple biomolecules indicates that the biofunctionalized nanoporous polymeric gratings can act as biosensing platforms which are label-free, inexpensive, and applicable as high-throughput assays. Copyright © 2010 by ASME.


    DONG Jianhua; QIU Kunyuan; FENG Xinde


    Polymerization of acrylamide initiated by ceric ammonium nitrate alone has been studied in aqueous medium. The effects of UV light irradiation on the initial rates of polymerization, the activation energy and on the polymer molecular weights have been investigated. Compared with that in the dark, the rate of polymerization under UV light was accelerated to eleven times higher, and the overall activation energy was lowered markedly.

  12. Characterization and molecular cloning of conjugation-regulating sex pheromones in homothallic Closterium.

    Tsuchikane, Yuki; Kokubun, Yume; Sekimoto, Hiroyuki


    Conjugation-regulating pheromones were analyzed in homothallic Closterium for the first time. Members of the Closterium peracerosum-strigosum-littorale complex are unicellular charophycean algae in which there are two modes of zygospore formation: heterothallism and homothallism. A homothallic strain of Closterium (designation, kodama20) forms selfing zygospores via the conjugation of two sister gametangial cells derived from one vegetative cell. Conjugation-promoting and -suppressing activities, against cells at very low (1 x 10(2) cells ml(-1)) and normal (1 x 10(4) cells ml(-1)) cell density, respectively, were detected in the medium in which cells of a normal density had been cultured. Pheromone activities decreased to 20% after incubation at 60 °C for 10  min. The release and action of the pheromones was dependent on light. The culture medium was subjected to gel filtration, and both active substances had an apparent molecular mass of 17  kDa; this was similar to that previously reported for the heterothallic sex-specific pheromone protoplast-release-inducing protein (PR-IP) Inducer. cDNAs encoding the orthologs of PR-IP Inducer were isolated from the homothallic strain. Recombinant PR-IP Inducers produced by yeast cells showed conjugation-promoting activity. These results indicate that conjugation of the homothallic strain is regulated by an ortholog of a heterothallic sex-specific pheromone.

  13. Performance of Doxorubicin-Conjugated Gold Nanoparticles: Regulation of Drug Location.

    Cui, Teng; Liang, Juan-Juan; Chen, Huan; Geng, Dong-Dong; Jiao, Lei; Yang, Jian-Yong; Qian, Hai; Zhang, Can; Ding, Ya


    Drug-conjugated gold nanoparticles (GNPs), which are generally constructed with many molecules of thiol-terminated polyethylene glycol (PEG)-drug decorated on their surfaces via a thiol-Au covalent bond, are promising and efficient nanoprodrugs. However, because of the exposure of the hydrophobic drug molecules on the surface of the conjugate, in vivo stability, opsonization, and subsequent inefficient therapy become the main issues of this system. To solve these problems without complicating the structures of gold conjugates, herein we propose a method to change the relative position of PEG and the drug. A novel gold conjugate (GNP-NHN═Dox-mPEG) with doxorubicin (Dox) shielded by PEGylation on the surface of GNPs is designed. It demonstrates improved solubility, stability, and dispersion and achieves a two-step stimulus-responsive drug release in response to an acidic environment in lysosomes and then esterase in the cytoplasm. This unique manner of release enables the cytoplasm to act as a reservoir for sustained drug delivery into the nucleus to improve antitumor efficacy in vivo. The intratumoral drug concentrations of the conjugate reach 14.4 ± 1.4 μg/g at 8 h, a two-fold increase in the drug concentration compared with that of the doxorubicin hydrochloride group. This molecular design and regulation approach is facile but important in modulating the in vivo performance of nanovehicles and demonstrates its vital potential in developing effective nanoparticle-based drug delivery agents.

  14. Modelling conjugation with stochastic differential equations.

    Philipsen, K R; Christiansen, L E; Hasman, H; Madsen, H


    Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two Enterococcus faecium strains in a rich exhaustible media. The model contains a new expression for a substrate dependent conjugation rate. A maximum likelihood based method is used to estimate the model parameters. Different models including different noise structure for the system and observations are compared using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared to the model without plate conjugation. The modelling approach described in this article can be applied generally when modelling dynamical systems.

  15. Evaluation of the effects of chemically different linkers on hepatic accumulations, cell tropism and gene silencing ability of cholesterol-conjugated antisense oligonucleotides.

    Wada, Shunsuke; Yasuhara, Hidenori; Wada, Fumito; Sawamura, Motoki; Waki, Reiko; Yamamoto, Tsuyoshi; Harada-Shiba, Mariko; Obika, Satoshi


    Cholesterol conjugation of oligonucleotides is an attractive way to deliver the oligonucleotides specifically to the liver. However cholesterol-conjugated antisense oligonucleotides (ASOs) mainly accumulate in non-parenchymal cells (NPCs) such as Kupffer cells. In this study, to increase the hepatic accumulation of cholesterol-conjugated ASOs, we prepared a variety of linkers for cholesterol conjugation to anti-Pcsk9 ASOs and examined their effects on pharmacological parameters. Hepatic accumulation of ASO was dramatically increased with cholesterol conjugation. The increase in hepatic accumulation depended largely on the linker chemistry of each cholesterol-conjugated ASO. In addition to hepatic accumulation, the cell tropism of each cholesterol-conjugated ASO tended to depend on their linker. Although a linker bearing a disulfide bond accumulated mainly in NPCs, hexamethylene succinimide linker accumulated mainly in hepatocytes. To estimate the benefits of releasing ASO from the conjugated cholesterol in hepatocyte, we designed another linker based on hexamethylene succinimide, which has a phosphodiester bond between the linker and the ASO. The cholesterol-conjugated ASO bearing such a phosphodiester bond showed a significantly improved Pcsk9 mRNA inhibitory effect compared to its counterpart, cholesterol-conjugated ASO with a phosphorothioate bond, while the hepatic accumulation of both cholesterol-conjugated ASOs was comparable, indicating the effectiveness of removing the conjugated cholesterol for ASO activity. In toxicity analysis, some of the linkers induced lethal toxicities when they were injected at high concentrations (>600μM). These toxicities were attributed to decreased platelet levels in the blood, suggesting an interaction between cholesterol-conjugated ASO and platelets. Our findings may provide a guideline for the design of molecule-conjugated ASOs. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Near-infrared (NIR) emitting conjugated polymers for biomedical applications (Presentation Recording)

    Repenko, Tatjana; Kuehne, Alexander J. C.


    Fluorescent biomedical markers of today such as dye-infiltrated colloids, microgels and quantum dots suffer from fast bleaching, lack surface functionality (for targets or pharmaceutical agents) and potentially leach heavy metals in case of quantum dots (e.g. Cd). By contrast, conjugated polymer particles are non-cytotoxic, exhibit reduced bleaching, as the entire particle consists of fluorophore, they are hydrophobic and show high quantum yields. Consequently, conjugated polymer particles represent ideal materials for biological applications and imaging. However currently, conjugated polymer particles for biomedical imaging usually lack near-infrared (NIR) emission and are polydisperse. Fluorescent agents with emission in the NIR spectrum are interesting for biomedical applications due to their low photo-damage towards biological species and the ability of NIR radiation to penetrate deep into biological tissue.. I will present the development and synthesis of new conjugated polymers particles with fluorescence in the NIR spectral region for bio-imaging and clinical diagnosis. The particle synthesis proceeds in a one-step Pd or Ni-catalyzed dispersion polymerization of functional NIR emitters. The resulting monodisperse conjugated polymer particles are obtained as a dispersion in a non-hazardous solvent. Different sizes in the sub-micrometer range with a narrow size distribution can be produced. Furthermore biological recognition motifs can be easily attached to the conjugated polymers via thiol-yne click-chemistry providing specific tumor targeting without quenching of the fluorescence. References [1] Kuehne AJC, Gather MC, Sprakel J., Nature Commun. 2012, 3, 1088. [2] Repenko T, Fokong S, De Laporte L, Go D, Kiessling F, Lammers T, Kuehne AJC.,Chem Commun 2015, accepted.

  17. Synthesis of C-5, C-2' and C-4'-neomycin-conjugated triplex forming oligonucleotides and their affinity to DNA-duplexes.

    Tähtinen, Ville; Granqvist, Lotta; Virta, Pasi


    Neomycin-conjugated homopyrimidine oligo 2'-deoxyribonucleotides have been synthesized on a solid phase and their potential as triplex forming oligonucleotides (TFOs) with DNA-duplexes has been studied. For the synthesis of the conjugates, C-5, C-2' and C-4'-tethered alkyne-modified nucleoside derivatives were used as an integral part of the standard automated oligonucleotide chain elongation. An azide-derived neomycin was then conjugated to the incorporated terminal alkynes by Cu(I)-catalyzed 1,3-dipolar cycloaddition (the click chemistry). Concentrated ammonia released the desired conjugates in acceptable purity and yields. The site of conjugation was expectedly important for the Hoogsteen-face recognition: C-5-conjugation showed a notable positive effect, whereas the influence of the C-2' and C-4'-modification remained marginal. In addition to conventional characterization methods (UV- and CD-spectroscopy), (19)F NMR spectroscopy was applied for the monitoring of triplex/duplex/single strand-conversions.

  18. Directional Growth of Polymeric Nanowires

    Thapa, Prem; Flanders, Bret


    This work establishes an innovative electrochemical approach to the template free growth of conducting polypyrrole and polythiophene wires. These polymeric wires exhibit a knobby structure, but persistent growth in a given direction up to 30 μm in length. A long-range component of the applied voltage signal defines the growth-path. Moreover, the presence of this component enables the growth of amorphous nanowires with wire-like geometries. Such wires are employed in a non-invasive methodology for attaining strong mechanical attachments to live cells. This capability is of potential use in the electro-mechanical probing of cell physiological processes.

  19. Marketing NASA Langley Polymeric Materials

    Flynn, Diane M.


    A marketing tool was created to expand the knowledge of LaRC developed polymeric materials, in order to facilitate the technology transfer process and increase technology commercialization awareness among a non-technical audience. The created brochure features four materials, LaRC-CP, LaRC-RP46, LaRC-SI, and LaRC-IA, and highlights their competitive strengths in potential commercial applications. Excellent opportunities exist in the $40 million per year microelectronics market and the $6 billion adhesives market. It is hoped that the created brochure will generate inquiries regarding the use of the above materials in markets such as these.

  20. Novel thiophene-bearing conjugated microporous polymer honeycomb-like porous spheres with ultrahigh iodine uptake.

    Ren, Feng; Zhu, Zhaoqi; Qian, Xin; Liang, Weidong; Mu, Peng; Sun, Hanxue; Liu, Jiehua; Li, An


    Two conjugated microporous polymers containing thiophene-moieties (SCMPs) were obtained by the polymerization of 3,3',5,5'-tetrabromo-2,2'-bithiophene and ethynylbenzene monomers through the palladium-catalyzed Sonogashira-Hagihara crosscoupling reaction. The resulting SCMPs show high thermal stability with a decomposition temperature above 300 °C. Scanning electron microscopy images show that the resulting SCMPs formed as an aggregation composed of micrometer-sized SCMP spheres, in which honeycomb-like porous spheres with penetrated pores on the surface were observed. Taking advantage of such a unique honeycomb-like porous morphology as well as π-conjugated structures, the SCMPs show ultrahigh absorption performance for iodine vapour with an uptake of up to 345 wt% obtained, which is the highest value reported to date for CMPs, thus making the resulting SCMPs ideal absorbent materials for reversible iodine capture to address environmental issues.

  1. Novel hybrid nocodazole analogues as tubulin polymerization inhibitors and their antiproliferative activity

    Kale, Sangram S.; Jedhe, Ganesh S.; Meshram, Sachin N.; Santra, Manas K.; Hamel, Ernest; Sanjayan, Gangadhar J.


    We describe the design, synthesis and SAR profiling of a series of novel combretastatin–nocodazole conjugates as potential anticancer agents. The thiophene ring in the nocodazole moiety was replaced by a substituted phenyl ring from the combretastatin moiety to design novel hybrid analogues. The hydroxyl group at the ortho position in compounds 2, 3 and 4 was used as the conformationally locking tool by anticipated six-membered hydrogen bonding. The bioactivity profiles of all compounds as tubulin polymerization inhibitors and as antiproliferative agents against the A-549 human lung cancer cell line were investigated Compounds 1 and 4 showed μM IC50 values in both assays. PMID:25817588

  2. Synthesis of click-reactive HPMA copolymers using RAFT polymerization for drug delivery applications

    Ebbesen, Morten F; Schaffert, D.H.; Crowley, Michael L


    This study describes a versatile strategy combining reversible addition fragmentation transfer (RAFT) polymerization and click chemistry to synthesize well-defined, reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) for drug delivery applications. A novel azide containing monomer N-(3......-alkyne cycloaddition (CuAAC) was demonstrated by efficient conjugation (up to 92%) of phosphocholine, a near infrared dye, and poly(ethylene glycol) (PEG) with different substitution degrees, either alone or in combination. This study introduces a novel and versatile method to synthesize well-defined click...

  3. Adjusting the inner-structure of polypyrrole nanoparticles through microemulsion polymerization

    Liu Yang [Department of Chemistry, Northeast Normal University, Changchun, Jilin 130024 (China); Chu Ying [Department of Chemistry, Northeast Normal University, Changchun, Jilin 130024 (China)]. E-mail:; Yang Likun [Department of Chemistry, Northeast Normal University, Changchun, Jilin 130024 (China)


    The inner-structure of polypyrrole (PPy) nanoparticles can be straightly adjusted by a simple alcohol-assisted microemulsion polymerization. The characteristic peaks of PPy in infrared spectroscopy (IR) confirm the formation of PPy. The morphology of PPy nanoparticles was characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). UV-vis and Raman spectra exhibit that the conjugation and order of PPy chains were improved directly in the presence of alcohols and adjusted by the alkyl unit of alcohols. These changes in the molecular structure lead to the improvement in the electrical conductivity of as-prepared PPy nanoparticles obviously.

  4. High Vacuum Techniques for Anionic Polymerization

    Ratkanthwar, Kedar


    Anionic polymerization high vacuum techniques (HVTs) are the most suitable for the preparation of polymer samples with well-defined complex macromolecular architectures. Though HVTs require glassblowing skill for designing and making polymerization reactor, it is the best way to avoid any termination of living polymers during the number of steps for the synthesis of polymers with complex structure. In this chapter, we describe the different polymerization reactors and HVTs for the purification of monomers, solvents, and other reagents for anionic polymerization as well as few model reactions for the synthesis of polymers with simple to complex structure.

  5. Comparative cytotoxicity of gold-doxorubicin and InP-doxorubicin conjugates

    Zhang, Xuan; Chibli, Hicham; Kong, Dekun; Nadeau, Jay


    Direct comparisons of different types of nanoparticles for drug delivery have seldom been performed. In this study we compare the physical properties and cellular activity of doxorubicin (Dox) conjugates to gold nanoparticles (Au) and InP quantum dots of comparable diameter. Although the Au particles alone are non-toxic and InP is moderately toxic, Au-Dox is more effective than InP-Dox against the Dox-resistant B16 melanoma cell line. Light exposure does not augment the efficacy of InP-Dox, suggesting that conjugates are breaking down. Electron and confocal microscopy and atomic absorption spectroscopy reveal that over 60% of the Au-Dox conjugates reach the cell nucleus. In contrast, InP-Dox enters cell nuclei to a very limited extent, although liberated Dox from the conjugates does eventually reach the nucleus. These observations are attributed to faster Dox release from Au conjugates under endosomal conditions, greater aggregation of InP-Dox with cytoplasmic proteins, and adherence of InP to membranes. These findings have important implications for design of active drug-nanoparticle conjugates.

  6. Adenosine conjugated lipidic nanoparticles for enhanced tumor targeting.

    Swami, Rajan; Singh, Indu; Jeengar, Manish Kumar; Naidu, V G M; Khan, Wahid; Sistla, Ramakrishna


    Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using phenol-sulfuric acid method. Conjugated SLN were shown to have sustained drug release as compared to unconjugated nanoparticles and drug suspension. Compared with free DTX and unconjugated SLN, ADN conjugated SLN showed significantly higher cytotoxicity of loaded DTX, as evidenced by in vitro cell experiments. The IC50 was 0.41 μg/ml for native DTX, 0.30 μg/ml for unconjugated SLN formulation, and 0.09 μg/ml for ADN conjugated SLN formulation in MCF-7 cell lines. Whereas, in DU-145, there was 2 fold change in IC50 of ADN-SLN as compared to DTX. IC50 was found to be 0.44 μg/ml for free DTX, 0.39 μg/ml for unconjugated SLN and 0.22 μg/ml for ADN-SLN. Annexin assay and cell cycle analysis assay further substantiated the cell cytotoxicity. Fluorescent cell uptake and competitive ligand-receptor binding assay corroborated the receptor mediated endocytosis pathway indicated role of adenosine receptors in internalization of conjugated particles. Pharmacokinetic studies of lipidic


    Ze-da Xu; Yong Zhang; Xing-he Fan; Xin-hua Wan; Qi-feng Zhou


    An optically active monomer containing azobenzene moieties with chiral group (s-2-methyl-butyl), 4-[2-(methacryloyloxy)ethyloxy]-4'-(s-2-methyl-1-butyloxycarbonyl) azobenzene (M1) was synthesized. Polymer (PM1) possessing optical phase conjugated response was obtained by homopolymerization of the optically active monomer (M1) using free radical polymerization. The polymer was very soluble in common solvents and good optical quality films could be easily fabricated by spin coating. The optical phase conjugated responses of the polymer PM1 were measured by degenerate four-wave mixing (DFWM). In comparison with polymer containing no chiral group, it was found from the preliminary measurement of photoisomeric change that optical phase conjugated response of the PM1 in the long-range order hexagonal symmetry microstructure could be easily controlled by choosing the appropriate polarization direction of the irradiating beams (514.5 nm) and the irradiating number, presumably due to the chiral group in the PM1 molecular structure. For the case of the polymer investigated here, a chiral group side chain was introduced to increase optical phase conjugated response intensity with different polarization directions of the irradiating beams, which aims originally at searching for a new photoactive material.

  8. Application of living free radical polymerization for nucleic acid delivery.

    Chu, David S H; Schellinger, Joan G; Shi, Julie; Convertine, Anthony J; Stayton, Patrick S; Pun, Suzie H


    Therapeutic gene delivery can alter protein function either through the replacement of nonfunctional genes to restore cellular health or through RNA interference (RNAi) to mask mutated and harmful genes. Researchers have investigated a range of nucleic acid-based therapeutics as potential treatments for hereditary, acquired, and infectious diseases. Candidate drugs include plasmids that induce gene expression and small, interfering RNAs (siRNAs) that silence target genes. Because of their self-assembly with nucleic acids into virus-sized nanoparticles and high transfection efficiency in vitro, cationic polymers have been extensively studied for nucleic acid delivery applications, but toxicity and particle stability have limited the clinical applications of these systems. The advent of living free radical polymerization has improved the quality, control, and reproducibility of these synthesized materials. This process yields well-defined, narrowly disperse materials with designed architectures and molecular weights. As a result, researchers can study the effects of polymer architecture and molecular weight on transfection efficiency and cytotoxicity, which will improve the design of next-generation vectors. In this Account, we review findings from structure-function studies that have elucidated key design motifs necessary for the development of effective nucleic acid vectors. Researchers have used robust methods such as atom transfer radical polymerization (ATRP), reverse addition-fragmentation chain transfer polymerization (RAFT), and ring-opening metastasis polymerization (ROMP) to engineer materials that enhance extracellular stability and cellular specificity and decrease toxicity. In addition, we discuss polymers that are biodegradable, form supramolecular structures, target specific cells, or facilitate endosomal release. Finally, we describe promising materials with a range of in vivo applications from pulmonary gene delivery to DNA vaccines.

  9. Polymeric Nanosuspensions for Enhanced Dissolution of Water Insoluble Drugs

    Roya Yadollahi


    Full Text Available The aim of the present research is to formulate and evaluate polymeric nanosuspensions containing three model water insoluble drugs, nifedipine (NIF, carbamazepine (CBZ, and ibuprofen (IBU with various physicochemical properties. The nanosuspensions were prepared from hydroxypropyl methylcellulose (HPMC and polyvinylpyrrolidone (PVP by a cosolvent technique with polyethylene glycol (PEG-300 and water as the cosolvents. Physicochemical and morphological characteristics of the nanosuspensions (particle size, polydispersity index, and crystallinity have been correlated with the drug release behaviour. The effects of polymer, drug ratio on the physical, morphological, and dissolution characteristics of the drugs are reported. Drug release is significantly enhanced from the nanosuspensions; for example, the maximum NIF, IBU, and CBZ concentrations after 8-hour dissolution are increased approximately 37, 2, and 1.2 times, respectively, in comparison with the pure powdered drugs. Based on this solubilization enhancement performance, the nanosuspensions have potential for increasing the orally dosed bioavailability of NIF, IBU, and CBZ.

  10. Polymerized rosin: novel film forming polymer for drug delivery.

    Fulzele, S V; Satturwar, P M; Dorle, A K


    Polymerized rosin (PR) a novel film forming polymer is characterized and investigated in the present study for its application in drug delivery. Films were produced by a casting/solvent evaporation method from plasticizer free and plasticizer containing solutions. Films prepared from different formulations were studied for their mechanical (tensile strength, percent elongation and Young's modulus), water vapour transmission and moisture absorption characteristics. Neat PR films were slightly brittle and posed the problem of breaking during handling. Hydrophobic plasticizers, dibutyl sebacate and tributyl citrate, improved the mechanical properties of free films with both the plasticizers showing significant effects on film elongation. Release of diclofenac sodium (model drug) from coated pellets was sustained with high coating levels. Concentration of plasticizer was found to affect the release profile. PR films plasticized with hydrophobic plasticizers could therefore be used in coating processes for the design of oral sustained delivery dosage forms.

  11. Renin release

    Schweda, Frank; Friis, Ulla; Wagner, Charlotte;


    The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located......, salt, and volume overload. In contrast, the events controlling the function of renin-secreting cells at the organ and cellular level are markedly less clear and remain mysterious in certain aspects. The unravelling of these mysteries has led to new and interesting insights into the process of renin...

  12. Celecoxib coupled to dextran via a glutamic acid linker yields a polymeric prodrug suitable for colonic delivery

    Lee Y


    Full Text Available Yonghyun Lee,1,2,* Jungyun Kim,1,* Wooseong Kim,1,* Joon Nam,1,* Seongkeun Jeong,1 Sunyoung Lee,1 Jin-Wook Yoo,1 Min-Soo Kim,1 Yunjin Jung1 1College of Pharmacy, Pusan National University, Busan, 2Bio-Nanomedicine Laboratory, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: Celecoxib, a selective cyclooxygenase-2 inhibitor, is potentially useful for the treatment of colonic diseases such as colorectal cancer and colitis. However, the cardiovascular toxicity of celecoxib limits its routine use in the clinic. Generally, colon-specific delivery of a drug both increases the therapeutic availability in the large intestine and decreases the systemic absorption of the drug, most likely resulting in enhanced therapeutic effects against colonic diseases such as colitis and reduced systemic side effects. To develop a colon-specific prodrug of celecoxib that could reduce its cardiovascular toxicity and improve its therapeutic activity, dextran–glutamic acid–celecoxib conjugate (glutam-1-yl celecoxib-dextran ester [G1CD] was prepared and evaluated. While stable in pH 1.2 and 6.8 buffer solutions and small-intestinal contents, G1CD efficiently released celecoxib in cecal contents. Oral administration of G1CD to rats delivered a larger amount of celecoxib to the large intestine than free celecoxib. G1CD prevented the systemic absorption of celecoxib and did not decrease the serum level of 6-ketoprostaglandin F1α, an inverse indicator of cardiovascular toxicity of celecoxib. Collectively, G1CD may be a polymeric colon-specific celecoxib prodrug with therapeutic and toxicological advantages. Keywords: colon-specific drug delivery, dextran, celecoxib, prodrug, cardiovascular toxicity

  13. Cysteine S-conjugate β-lyases

    Arthur J. L. Cooper; Krasnikov, Boris F.; Pinto, John T.; Bruschi, Sam A.


    Cysteine S-conjugate β-lyases are pyridoxal 5′-phosphate (PLP)-containing enzymes that catalyze the conversion of cysteine S-conjugates [RSCH2CH(NH3+)CO2−] and selenium Se-conjugates [RSeCH2CH(NH3+)CO2−] that contain a leaving group in the β position to pyruvate, ammonium and a sulfur-containing fragment (RSH) or selenium-containing fragment (RSeH), respectively. At least ten PLP enzymes catalyze β-elimination reactions with such cysteine S-conjugates. All are enzymes involved in amino acid m...

  14. The Tcp conjugation system of Clostridium perfringens.

    Wisniewski, Jessica A; Rood, Julian I


    The Gram-positive pathogen Clostridium perfringens possesses a family of large conjugative plasmids that is typified by the tetracycline resistance plasmid pCW3. Since these plasmids may carry antibiotic resistance genes or genes encoding extracellular or sporulation-associated toxins, the conjugative transfer of these plasmids appears to be important for the epidemiology of C. perfringens-mediated diseases. Sequence analysis of members of this plasmid family identified a highly conserved 35kb region that encodes proteins with various functions, including plasmid replication and partitioning. The tcp conjugation locus also was identified in this region, initially based on low-level amino acid sequence identity to conjugation proteins from the integrative conjugative element Tn916. Genetic studies confirmed that the tcp locus is required for conjugative transfer and combined with biochemical and structural analyses have led to the development of a functional model of the Tcp conjugation apparatus. This review summarises our current understanding of the Tcp conjugation system, which is now one of the best-characterized conjugation systems in Gram-positive bacteria.

  15. Modelling conjugation with stochastic differential equations

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo; Hasman, Henrik


    Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two...... using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared...

  16. Test of charge conjugation invariance.

    Nefkens, B M K; Prakhov, S; Gårdestig, A; Allgower, C E; Bekrenev, V; Briscoe, W J; Clajus, M; Comfort, J R; Craig, K; Grosnick, D; Isenhower, D; Knecht, N; Koetke, D; Koulbardis, A; Kozlenko, N; Kruglov, S; Lolos, G; Lopatin, I; Manley, D M; Manweiler, R; Marusić, A; McDonald, S; Olmsted, J; Papandreou, Z; Peaslee, D; Phaisangittisakul, N; Price, J W; Ramirez, A F; Sadler, M; Shafi, A; Spinka, H; Stanislaus, T D S; Starostin, A; Staudenmaier, H M; Supek, I; Tippens, W B


    We report on the first determination of upper limits on the branching ratio (BR) of eta decay to pi0pi0gamma and to pi0pi0pi0gamma. Both decay modes are strictly forbidden by charge conjugation (C) invariance. Using the Crystal Ball multiphoton detector, we obtained BR(eta-->pi0pi0gamma)pi0pi0pi0gamma)<6 x 10(-5) at the 90% confidence level, in support of C invariance of isovector electromagnetic interactions.

  17. Waveguide mutually pumped phase conjugators

    James, S. W.; Youden, K.E.; Jeffrey, P. M.; EASON, R. W.; Chandler, P.J.; Zhang, L.; Townsend, P.D.


    The operation of the Bridge Mutually Pumped Phase Conjugator is reported in a planar waveguide structure in photorefractive BaTiO3. The waveguide was fabricated by the technique of ion implantation. using 1.5 MeV H+ at a dose of 10^16 ions/cm^2. An order of magnitude decrease in response time is observed in the waveguide as compared to typical values obtained in bulk crystals, probably resulting from a combination of the optical confinement within the waveguide, and possibly modification of t...

  18. Short Conjugators in Solvable Groups

    Sale, Andrew W


    We give an upper bound on the size of short conjugators in certain solvable groups. Diestel-Leader graphs, which are a horocyclic product of trees, are discussed briefly and used to study the lamplighter groups. The other solvable groups we look at can be recognised in a similar vein, as groups which act on a horocyclic product of well known spaces. These include the Baumslag-Solitar groups BS(1,q) and semidirect products of Z^n with Z^k. Results can also be applied to the conjugacy of parabolic elements in Hilbert modular groups and to elements in 3-manifold groups.

  19. Comparative evaluation of polymeric and waxy microspheres for combined colon delivery of ascorbic acid and ketoprofen.

    Maestrelli, F; Zerrouk, N; Cirri, M; Mura, P


    The goal of this work was to combine the ketoprofen anti-inflammatory effect with the ascorbic acid antioxidant properties for a more efficient treatment of colonic pathologies. With this aim, microspheres (MS) based on both waxy materials (ceresine, Precirol(®) and Compritol(®)) or hydrophilic biopolymers (pectine, alginate and chitosan) loaded with the two drugs were developed, physicochemically characterized and compared in terms of entrapment efficiency, in vitro release profiles, potential toxicity and drug permeation properties across the Caco-2 cell line. Waxy MS revealed an high encapsulation efficiency of ketoprofen but a not detectable entrapment of ascorbic acid, while polymeric MS showed a good entrapment efficiency of both drugs. All MS need a gastro-resistant coating, to avoid any premature release of the drugs. Ketoprofen release rate from polymeric matrices was clearly higher than from the waxy ones. In contrast, the ASC release rate was higher, due to its high hydro-solubility. Cytotoxicity studies revealed the safety of all the formulations. Transport studies showed that the ketoprofen apparent permeability increased, when formulated with the different MS. In conclusion, only polymeric MS enabled an efficient double encapsulation of both the hydrophilic and lipophilic drugs, and, in addition, presented higher drug release rate and stronger enhancer properties.

  20. Effect of Polymerization Condition on Particle Size Distribution in St/BA/MAA Emulsion Polymerization Process


    A series of St/BA/MAA emulsion polymerizations was carried out. By using PCS (photon correlation spectroscopy), the particle size distribution(PSD) of the whole St/BA/MAA emulsion polymerization process was gotten easily and quickly. The effect of polymerization condition on PSD in St/BA/MAA emulsion process was discussed.

  1. Twin screw extruders as polymerization reactors for a free radical homo polymerization

    Ganzeveld, K.J.; Janssen, L.P.B.M.


    The bulk polymerization of n-butylmethacrylate was investigated in a counter-rotating twin screw extruder. It appeared that the gel effect, occurring with bulk polymerizations, affected the polymerization progress very strongly. Due to this effect the conversion of the reaction is independent of the


    Manjusha Rani


    Full Text Available Chitosan obtained by alkaline deacetylation of chitin is a non-toxic, biocompatible, and biodegradable natural polymer. Chitosan-based hydrogel polymeric beads have been extensively studied as micro- or nano-particulate carriers in the pharmaceutical and medical fields, where they have shown promise for drug delivery as a result of their controlled and sustained release properties, as well as biocompatibility with tissue and cells. To introduce desired properties and enlarge the scope of the potential applications of chitosan, graft copolymerization with natural or synthetic polymers on it has been carried out, and also, various chitosan derivatives have been utilized to form beads. The desired kinetics, duration, and rate of drug release up to therapeutical level from polymeric beads are limited by specific conditions such as beads material and their composition, bead preparation method, amount of drug loading, drug solubility, and drug polymer interaction. The present review summarizes most of the available reports about compositional and structural effects of chitosan-based hydrogel polymeric beads on swelling, drug loading, and releasing properties. From the studies reviewed it is concluded that chitosan-based hydrogel polymeric beads are promising drug delivery systems.

  3. Electrochemical Polymerization of Methylene Green

    ZHU,Hong-Ping; MU,Shao-Lin


    The electrochemical polymerization of methylene green has been carried out using cyclic voltammetry. The electrolytic so lution consisted of 4 × 10-3 mol/L methylene green, 0.1 mol/L NaNO3 and 1 × 10-2 mol/L sodium tetraborate with pH 11.0. The temperature for polymerization is controlled at 60℃. The scan potential is set between -0.2 and 1.2 V (vs. Ag/AgCl with saturated KCl solution). There are an anodic peak and a cathodic peak on the cyclic voltammogram of poly(methylene green) at pH≤3.8. Both peak potentials shift towards nega tive potentials with increasing pH value, and their peak cur rents decrease with increasing pH value. Poly(methylene green) has a good electrochemical activity and stability in aqueous solutions with pH ≤ 3.8. The UV-Visible spectrum and FTIR spectrum of poly (methylene green) are different from those of methylene green.

  4. Schlenk Techniques for Anionic Polymerization

    Ratkanthwar, Kedar


    Anionic polymerization-high vacuum techniques (HVTs) are doubtlessly the most prominent and reliable experimental tools to prepare polymer samples with well-defined and, in many cases, complex macromolecular architectures. Due to the high demands for time and skilled technical personnel, HVTs are currently used in only a few research laboratories worldwide. Instead, most researchers in this filed are attracted to more facile Schlenk techniques. The basic principle of this technique followed in all laboratories is substantially the same, i.e. the use of alternate vacuum and inert gas atmosphere in glass apparatus for the purification/charging of monomer, solvents, additives, and for the manipulation of air-sensitive compounds such as alkyl metal initiators, organometallic or organic catalysts. However, it is executed quite differently in each research group in terms of the structure of Schlenk apparatus (manifolds, connections, purification/storage flasks, reactors, etc.), the use of small supplementary devices (soft tubing, cannulas, stopcocks, etc.) and experimental procedures. The operational methods are partly purpose-oriented while also featured by a high flexibility, which makes it impossible to describe in detail each specific one. In this chapter we will briefly exemplify the application of Schlenk techniques for anionic polymerization by describing the performance of a few experiments from our own work.

  5. Nanoparticles generated by PEG-Chrysin conjugates for efficient anticancer drug delivery.

    Zheng, Hui; Li, Sai; Pu, Yuji; Lai, Yusi; He, Bin; Gu, Zhongwei


    Nanoparticle-based drug delivery systems promise the safety and efficacy of anticancer drugs. Herein, we presented a facile approach to fabricate novel nanoparticles generated by PEG-Chrysin conjugates for the delivery of anticancer drug doxorubicin. Chrysin was immobilized on the terminal group of methoxy poly(ethylene glycol) (mPEG) to form mPEG-Chrysin conjugate. The conjugates were self-assembled into nanoparticles. Doxorubicin (DOX) was loaded in the nanoparticles. The self-assembly, drug release profiles, interactions between nanoparticle and drug, cellular uptake and in vitro anticancer activity of the DOX loaded nanoparticles were investigated. The results showed that the mean diameters of drug loaded nanoparticles were below 200 nm. Strong π-π stacking interaction was tested within the drug loaded nanoparticles. The drug release rate was closely related to the chain length of PEG, shorter PEG chain resulted faster release. The mPEG-Chrysin conjugate was non-toxic to both 3T3 fibroblasts and HepG2 cancer cells. The cellular uptake measurements demonstrated that the mPEG1000-Chrysin nanoparticles exhibited higher capability in endocytosis. The IC50 of drug loaded mPEG1000-Chrysin nanoparticles was 4.4 μg/mL, which was much lower than that of drug loaded mPEG2000-Chrysin nanoparticles (6.8 μg/mL). These nanoparticles provided a new strategy for fabricating antitumor drug delivery systems.

  6. A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for methotrexate delivery.

    Ren, Jin; Fang, Zhengjie; Yao, Li; Dahmani, Fatima Zohra; Yin, Lifang; Zhou, Jianping; Yao, Jing


    The purpose of this study was to develop a novel featured and flexible methotrexate (MTX) formulation, in which MTX was physically entrapped and chemically conjugated in the same drug delivery system. A series of poloxamer-MTX (p-MTX) conjugates was synthesized, wherein MTX was grafted to poloxamer through an ester bond. p-MTX conjugates could self-assemble into micelle-like structures in aqueous environment and the MTX end was in the inner-core of micelles. Moreover, free MTX could be physically entrapped into p-MTX micelles hydrophobic core region to increase the total drug loading. Importantly, the resulting MTX-loaded p-MTX micelles showed a biphasic release of MTX, with a relative fast release of the entrapped MTX (about 6-7h) followed by a sustained release of the conjugated MTX. The pharmacokinetics study showed that the mean residence time (MRT) was extended in the case of MTX-loaded p-MTX micelles, indicating a delayed MTX elimination from the bloodstream and prolonged in vivo residence time. Besides, the area under curve (AUC) of MTX-loaded p-MTX micelles was greater than free MTX, indicating a drug bioavailability improvement. Overall, MTX-loaded p-MTX micelles might be a promising nanosized drug delivery system for the cancer therapy.

  7. Multifunctional nanoparticle-protein conjugates with controllable bioactivity and pH responsiveness

    Liu, Feng; Xue, Lulu; Yuan, Yuqi; Pan, Jingjing; Zhang, Chenjie; Wang, Hongwei; Brash, John L.; Yuan, Lin; Chen, Hong


    The modulation of protein activity is of significance for disease therapy, molecular diagnostics, and tissue engineering. Nanoparticles offer a new platform for the preparation of protein conjugates with improved protein properties. In the present work, Escherichia coli (E. coli) inorganic pyrophosphatase (PPase) and poly(methacrylic acid) (PMAA) were attached together to gold nanoparticles (AuNPs), forming AuNP-PPase-PMAA conjugates having controllable multi-biofunctionalities and responsiveness to pH. By treating with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and regulating the pH, the bioactivity of the conjugate becomes ``on/off''-switchable. In addition, by taking advantage of the ability of AuNPs to undergo reversible aggregation/dispersion, the conjugates can be recycled and reused multiple times; and due to the shielding effect of the PMAA, the conjugated enzyme has high resistance to protease digestion. This approach has considerable potential in areas such as controlled delivery and release of drugs, biosensing, and biocatalysis.The modulation of protein activity is of significance for disease therapy, molecular diagnostics, and tissue engineering. Nanoparticles offer a new platform for the preparation of protein conjugates with improved protein properties. In the present work, Escherichia coli (E. coli) inorganic pyrophosphatase (PPase) and poly(methacrylic acid) (PMAA) were attached together to gold nanoparticles (AuNPs), forming AuNP-PPase-PMAA conjugates having controllable multi-biofunctionalities and responsiveness to pH. By treating with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and regulating the pH, the bioactivity of the conjugate becomes ``on/off''-switchable. In addition, by taking advantage of the ability of AuNPs to undergo reversible aggregation/dispersion, the conjugates can be recycled and reused multiple times; and due to the shielding effect of the PMAA, the conjugated enzyme has high resistance to protease digestion

  8. Preparation of drug-loaded polymeric nanoparticles and evaluation of the antioxidant activity against lipid peroxidation.

    Pohlmann, Adriana R; Schaffazick, Scheila Rezende; Creczynski-Pasa, Tânia B; Guterres, Sílvia S


    Antioxidants have been found to be effective as prophylatic and therapeutic agents for different diseases such as diabetes, cancer, and neurodegenerative disorders. However, antioxidant substances can present poor solubility in water, inefficient permeability, gastrointestinal degradation, first-pass effect, and/or instability during storage. These drawbacks can be potentially circumvented by encapsulating the susceptible antioxidants. Polymeric nanoparticles (nanocapsules or nanospheres) have been used to improve the drug efficacy and release. Our group has shown that the in vitro antioxidant effect of melatonin against lipid peroxidation in microsomes and liposomes can be improved by encapsulation of the antioxidant drug in polymeric nanoparticles.

  9. Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

    Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K., E-mail: [Dr. Hari Singh Gour Vishwavidyalaya, Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences (India)


    Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

  10. Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

    Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K.


    Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

  11. Photoluminescence of Conjugated Star Polymers

    Ferguson, J. B.; Prigodin, N. V.; Epstein, A. J.; Wang, F.


    Higher dimensionality "star" polymers provide new properties beyond those found in their linear analogs. They have been used to improving electronic properties for nonlinear optics through exciton transfer and molecular antenna structures for example (M. Kawa, J. M. J. Frechet, Chem. Mater. 10, 286 (1998).). We report on photoluminescence properties of star polymers with a hyperbranched core (both hyperbranched phenlyene and hyperbranched triphenylamine) and polyhexylthiophene arms. The arm is a conjugated oligomer of polythiophene that has been investigated extensively for metallic like conductivity when doped as well as utilized in field effect transistors in its undoped form (A. Tsumara, H. Koezuka, T. Ando, Appl. Phys. Lett. 49, 1210 (1986).). The cores are respectively, a nonconjugated polymer in the case of hyperbranched phenlyene and a conjugated polymer in the case of hyperbranched triphenylamine. The photoluminesce spectrum (λ_max at 575 nm) is identical for both star polymers with the two electronically different hyperbranched cores and for linear polythiophene alone. We conclude the wave functions of the core and arms do not strongly interact to form states different from their individual states and excitons formed on the hyperbranched cores migrate to the lower bandgap polythiophene before recombining.

  12. Subgap Absorption in Conjugated Polymers

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.


    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.


    Wei-jun Ye; Jason S. Keiper; Joseph M. DeSimone


    Herein, we reported the microemulsion polymerization in supercritical carbon dioxide. With the aid of an anionic phosphate fluorosurfactant (bis-[2-(F-hexyl)ethyl]phosphate sodium), water-soluble/CO2-insoluble acryloxyethyltrimethyl ammonium chloride monomer and N,N'-methylene-bisacrylamide cross-linker were solubilized into CO2 continuous phase via the formation of water-in-CO2 (w/c) microemulsion water pools. Initiated by a CO2-soluble initiator, 2,2'-azo-bisisobutyronitrile (AIBN), cross-linked poly(acryloxyethyltrimethyl ammonium chloride) particles were produced and stabilized in these w/c internal water pools. Nano-sized particles with sizes less than 20 nm in diameter and narrow particle size distributions were obtained.

  14. Inflation and Instability of a Polymeric Membrane

    Hassager, Ole; Kristensen, Susanne Brogaard; Larsen, Johannes Ruben


    We consider an axisymmetric polymeric membrane inflated by a uniform pressure difference acting across the membrane. The polymeric material is described by an arbitrary combination of a viscoelastic and a purely viscous component to the stress. Some viscoelastic materials described by a Mooney...

  15. Inflation and Instability of a Polymeric Membrane

    Neergaard, Jesper; Hassager, Ole


    We consider an axisymmetric polymeric membrane inflated by a uniform pressure difference acting across the membrane. The polymeric materialis described by an arbitrary combination of a viscoelastic and a purely viscous component to the stress. Some viscoelastic materials described by a Mooney...

  16. Understanding Drug Release Data through Thermodynamic Analysis

    Marjorie Caroline Liberato Cavalcanti Freire


    Full Text Available Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas–Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability.

  17. Photoacoustic analysis of dental resin polymerization

    Coloiano, E. C. R.; Rocha, R.; Martin, A. A.; da Silva, M. D.; Acosta-Avalos, D.; Barja, P. R.


    In this work, we use the photoacoustic technique to monitor the curing process of diverse dental materials, as the resins chemically activated (RCA). The results obtained reveal that the composition of a determined RCA significantly alters its activation kinetics. Photoacoustic data also show that temperature is a significant parameter in the activation kinetics of resins. The photoacoustic technique was also applied to evaluate the polymerization kinetics of photoactivated resins. Such resins are photoactivated by incidence of continuous light from a photodiode. This leads to the polymerization of the resin, modifying its thermal properties and, consequently, the level of the photoacoustic signal. Measurements show that the polymerization of the resin changes the photoacoustic signal amplitude, indicating that photoacoustic measurements can be utilized to monitor the polymerization kinetic and the degree of polymerization of photoactivated dental resins.

  18. Fluid Effects in Polymers and Polymeric Composites

    Weitsman, Y Jack


    Fluid Effects in Polymers and Polymeric Composites, written by the late Dr. Y. Jack Weitsman, addresses the wide range of parameters that affect the interaction of fluids with polymers and polymeric composites. The book aims at broadening the scope of available data, mostly limited up to this time to weight-gain recordings of fluid ingress into polymers and composites, to the practical circumstances of fluctuating exposure. Various forms of experimental data are given, in conjunction with theoretical models derived from basic scientific principles, and correlated with severity of exposure conditions and interpreted by means of rationally based theoretical models. The practical implications of the effects of fluids are discussed. The issue of fluid effects on polymers and polymeric composites is of concern to engineers and scientists active in aerospace and naval structures, as an increasing portion of these structures are made of polymeric composites and employ polymeric adhesives as a joining device. While...

  19. Evaluation of gum sandarac as a novel release controlling coating polymer for formulation of sustained release pellets

    Deepak S. Khobragade


    Full Text Available Polymeric coating techniques have been widely used in the pharmaceutical industries for diversified reasons. Various materials are being investigated as polymers as there is scarcity of good polymeric materials to be used in pharmaceutical products. The present study was aimed at evaluating novel natural material gum sandarac, a resin obtained by incision from the stem of Callitris quadrivalvis, Ventenat (N.O. Coniferae Pinaceae as a coating material for developing coated pellets for sustained release of drug and comparing it with  well known ethyl cellulose as hydrophobic polymeric material. Drug layered NPS, drug loaded pellets prepared with extrusion spheronization and NPS coated with drug polymer matrix were used as multi particulate formulation. The results indicate that Gum Sandarac is very efficient in retarding release of drugs from different pellet formulations yielding very superior quality pellet.

  20. The Conjugate Acid-Base Chart.

    Treptow, Richard S.


    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)



    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...


    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G


    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

  3. Bio-Conjugates for Nanoscale Applications

    Villadsen, Klaus

    Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...


    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G


    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence


    Ernst Hairer


    For the numerical treatment of Hamiltonian differential equations, symplectic integra-tors are the most suitable choice, and methods that are conjugate to a symplectic integrator share the same good long-time behavior. This note characterizes linear multistep methods whose underlying one-step method is conjugate to a symplectic integrator. The bounded-hess of parasitic solution components is not addressed.

  6. Kinetic models of conjugated metabolic cycles

    Ershov, Yu. A.


    A general method is developed for the quantitative kinetic analysis of conjugated metabolic cycles in the human organism. This method is used as a basis for constructing a kinetic graph and model of the conjugated citric acid and ureapoiesis cycles. The results from a kinetic analysis of the model for these cycles are given.

  7. Bio-Conjugates for Nanoscale Applications

    Villadsen, Klaus

    Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...

  8. LEDs based on conjugated PPV block copolymers

    Brouwer, H.J.; Hilberer, A.; Krasnikov, V.V.; Werts, M.; Wildeman, J.; Hadziioannou, G.


    A way to control the bandgap in semi-conducting polymers is by preparing polymers with a partially conjugated backbone. In our laboratory, three conjugated copolymers containing PPV trimers as light emitting chromophores have been synthesized, which emit in the blue, green and orange wavelength regi

  9. Tailor-made starch-based conjugates containing well-defined poly(vinyl acetate and its derivative poly(vinyl alcohol


    Full Text Available Reversible addition-fragmentation chain transfer (RAFT polymerization was adopted to synthesize starch-based conjugates that possessed controllable architecture and properties. Starch-based xanthate agent was prepared and applied as chain transfer agent to conduct the living/controlled polymerization (LCP of vinyl acetate, which generated tailor-made conjugates of starch and well-defined poly(vinyl acetate (SVAc. The relevant derivatives, conjugates of starch and chain length-controlled poly(vinyl alcohol (SVA, were obtained subsequently. Various characterizations such as Fourier transform infrared spectra (FTIR, ultraviolet-visible spectroscopy (UV, proton nuclear magnetic resonance (1H NMR, gel permeation chromatography (GPC, X-ray diffraction (XRD, Thermogravimetric analysis (TGA, and dynamic mechanical thermal analysis (DMTA were performed to examine the structure of intermediates and the starch-based conjugates. Static contact angle measurements revealed that the hydrophilic character of starch-based conjugates was tunable. Well-defined SVAc was amphiphilic and it was able to self-assemble into size controllable micelles, which was verified by contact angles, transmission electron microscopy (TEM and dynamic light scattering (DLS tests. SVA exhibited much higher capability to form physically cross-linked hydrogel than starch did. Both the characteristic of SVAc and SVA were chain length-dependent.

  10. A new family of conjugate gradient methods

    Shi, Zhen-Jun; Guo, Jinhua


    In this paper we develop a new class of conjugate gradient methods for unconstrained optimization problems. A new nonmonotone line search technique is proposed to guarantee the global convergence of these conjugate gradient methods under some mild conditions. In particular, Polak-Ribiére-Polyak and Liu-Storey conjugate gradient methods are special cases of the new class of conjugate gradient methods. By estimating the local Lipschitz constant of the derivative of objective functions, we can find an adequate step size and substantially decrease the function evaluations at each iteration. Numerical results show that these new conjugate gradient methods are effective in minimizing large-scale non-convex non-quadratic functions.

  11. Energetic Tuning in Spirocyclic Conjugated Polymers

    Hugo Bronstein


    Full Text Available Precise control of the energy levels in a conjugated polymer is the key to allowing their exploitation in optoelectronic devices. The introduction of spirocycles into conjugated polymers has traditionally been used to enhance their solid state microstructure. Here we present a highly novel method of energetic tuning through the use of electronically active spirocyclic systems. By modifying the size and oxidation state of a heteroatom in an orthogonal spirocycle we demonstrate energetic fine tuning in both the absorption and emission of a conjugated polymer. Furthermore, the synthesis of highly novel triplet-decker spirocyclic conjugated polymers is presented. This new method of energetic manipulation in a conjugated polymer paves the way for future application targeted synthesis of polymers with electronically active spirocycles.

  12. Modeling liquid crystal polymeric devices

    Gimenez Pinto, Vianney Karina

    The main focus of this work is the theoretical and numerical study of materials that combine liquid crystal and polymer. Liquid crystal elastomers are polymeric materials that exhibit both the ordered properties of the liquid crystals and the elastic properties of rubbers. Changing the order of the liquid crystal molecules within the polymer network can induce shape change. These materials are very valuable for applications such as actuators, sensors, artificial muscles, haptic displays, etc. In this work we apply finite element elastodynamics simulations to study the temperature induced shape deformation in nematic elastomers with complex director microstructure. In another topic, we propose a novel numerical method to model the director dynamics and microstructural evolution of three dimensional nematic and cholesteric liquid crystals. Numerical studies presented in this work are in agreement with experimental observations and provide insight into the design of application devices.


    Zhen-zhongYang; Jian-huaRong; DanLi


    Meso-structured(opal and inverse opal) polymeric hydrogels of varied morphology and composition were prepared by using two methods:post-modification of the template-synthesized structured polymers and templatepolymerization of functional monomers.A polyacrylic acid based inverse opal hydrogel was chosen to demonstrate its fast pH response by changing color,which is important in designing tunable photonic crystals.Template effects of the hydrogels on controlling structure of the template-synthesized inorganic materials were discussed.The catalytic effect of acid groups in the templates was emphasized for a preferential formation of TiO2 in the region containing acid groups,which allowed duplicating inorganic colloidal crystals from colloidal crystal hydrogels (or macroporous products from macroporous hydrogels) via one step duplication.


    Zhen-zhong Yang; Jian-hua Rong; Dan Li


    Meso-structured (opal and inverse opal) polymeric hydrogels of varied morphology and composition were prepared by using two methods: post-modification of the template-synthesized structured polymers and templatepolymerization of functional monomers. A polyacrylic acid based inverse opal hydrogel was chosen to demonstrate its fast pH response by changing color, which is important in designing tunable photonic crystals. Template effects of the hydrogels on controlling structure of the template-synthesized inorganic materials were discussed. The catalytic effect of acid groups inthe templates was emphasized for a preferential formation of TiO2 in the region containing acid groups, which allowed duplicating inorganic colloidal crystals from colloidal crystal hydrogels (or macroporous products from macroporous hydrogels) via one step duplication.

  15. Pressure induced polymerization of Formates

    Tschauner, Oliver


    The discovery of pressure induced polymerization of CO2 inspired us to search for C-O based chain structures forming at high pressure. We used salts of carboxylic acids as starting materials and exposed them to pressures between 10 and 30 GPa. Upon heating to temperatures above 1800 K we observed deprotonation and significant changes in the Raman shifts of C-O streching modes. Structure analysis based on powder diffraction patterns collected at sector 16 of the APS showed formation of extended C-O chain structures with the cations of the salts residing in the interchain spaces. These new high pressure polymers are interesting by their mechanical strength and provide basic molecular patterns of organic metallic conductors.

  16. Environment-Responsive Polymeric Hydrogels

    Zhn X. X.; M. Nichifor; Lin H.Y.; D. Avoce


    Some polymers may respond by changing their physico-chemical perperties when the environmental conditions such as pH, temperature and ionic strength are varied. For example,thermosensentive polymers can exhibit a sharp change in solubility in a solvent such as water at a certain temperature known as the lower critical solution temperature (LCST). The responsiveness of the polymeric materials has important technological implications since they can be employed for various applications. The responsiveness of such polymers can be varied by means of copolymerization, chemical modification of the polymer, or the addition of reagents into the solutions. It is interesting and important to tune predictably the responsiveness of the polymers for the different applications. The sensitivity towards the external environment can be modulated by the relative hydrophilicity of the copolymers, hence the chemical structure and composition of the comonomers used.

  17. Positron Emission Tomography Based Analysis of Long-Circulating Cross-Linked Triblock Polymeric Micelles in a U87MG Mouse Xenograft Model and Comparison of DOTA and CB-TE2A as Chelators of Copper-64

    Jensen, Andreas Tue Ingemann; Binderup, Tina; Ek, Pramod Kumar;


    Copolymers of ABC-type (PEG-PHEMA-PCMA) architecture were prepared by atom transfer radical polymerization and formulated as micelles with functionalizable primary alcohols in the shell-region (PHEMA-block) to which the metal-ion chelators DOTA or CB-TE2A were conjugated. Using this micelle system...

  18. Novel liver-specific cholic acid-cytarabine conjugates with potent antitumor activities: Synthesis and biological characterization

    Dan-qi CHEN; Xin WANG; Lin CHEN; Jin-xue HE; Ze-hong MIAO; Jing-kang SHEN


    Aim: Cytarabine is an efficient anticancer agent for acute myelogenous leukemia, but with short plasma half-life and rapid deamination to its inactive metabolite. The aim of this study was to design and synthesize novel cholic acid-cytarabine conjugates to improve its pharmacokinetic parameters.Methods: The in vitro stability of novel cholic acid-cytarabine conjugates was investigated in simulated gastric and intestinal fluid, mouse blood and liver homogenate using HPLC. The portacaval samples of the conjugates were examined in male Sprague-Dawley rats using LC/MS, and in vivo distribution was examined in male Kunming mice using LC/MS. Antitumor activities were tested in HL60 cells using MTT assay.Results: Cholic acid-cytarabine compounds with four different linkers were designed and synthesized. All the four cholic acid-cytarabine conjugates could release cytarabine when incubated with the simulated gastric and intestinal fluid, mouse blood and liver homoge-nate. The conjugates 6,/2, and 16 were present in the portacaval samples, whereas the conjugate 7 was not detected. The conju-gates 6 and 16 showed high specificity in targeting the liver (liver target index 34.9 and 16.3, respectively) and good absorption in vivo, as compared with cytarabine. In cytarabine-sensitive HL60 cells, the conjugates 6, 12, and 16 retained potent antitumor activities.Conclusion: Three novel cholic acid-cytarabine conjugates with good liver-targeting properties and absorption were obtained. Further optimization of the conjugates is needed in the future.

  19. Hemocompatibility of polymeric nanostructured surfaces.

    Leszczak, Victoria; Smith, Barbara S; Popat, Ketul C


    Tissue integration is an important property when inducing transplant tolerance, however, the hemocompatibility of the biomaterial surface also plays an important role in the ultimate success of the implant. Therefore, in order to induce transplant tolerance, it is critical to understand the interaction of blood components with the material surfaces. In this study, we have investigated the adsorption of key blood serum proteins, in vitro adhesion and activation of platelets and clotting kinetics of whole blood on flat polycaprolactone (PCL) surfaces, nanowire (NW) surfaces and nanofiber (NF) surfaces. Previous studies have shown that polymeric nanostructured surfaces improve cell adhesion, proliferation and viability; however it is unclear how these polymeric nanostructured surfaces interact with the blood and its components. Protein adsorption results indicate that while there were no significant differences in total albumin (ALB) adsorption on PCL, NW and NF surfaces, NW surfaces had higher total fibrinogen (FIB) and immunoglobulin-G (IgG) adsorption compared to NF and PCL surfaces. In contrast, NF surfaces had higher surface FIB and IgG adsorption compared to PCL and NW surfaces. Platelet adhesion and viability studies show more adhesion and clustering of platelets on the NF surfaces as compared to PCL and NW surfaces. Platelet activation studies reveal that NW surfaces have the highest percentage of unactivated platelets, whereas NF surfaces have the highest percentage of fully activated platelets. Whole blood clotting results indicate that NW surfaces maintain an increased amount of free hemoglobin during the clotting process compared to PCL and NF surface, indicating less clotting and slower rate of clotting on their surfaces.

  20. Polymeric materials from renewable resources

    Frollini, Elisabete; Rodrigues, Bruno V. M.; da Silva, Cristina G.; Castro, Daniele O.; Ramires, Elaine C.; de Oliveira, Fernando; Santos, Rachel P. O.


    The goals of our studies have been the use of renewable raw materials in the preparation of polymeric materials with diversified properties. In this context, lignosulfonate, which is produced in large scale around the world, but not widely used in the production of polymeric materials, was used to replace phenol and polyols in the preparation of phenolic- (Ligno-PH) and polyurethane-type (Ligno-PU) polymers, respectively. These polymers were used to prepare composites reinforced with sisal lignocellulosic fibers. The use of lignosulfonate in the formulation of both types of polymers was beneficial, because in general composites with improved properties, specially impact strength, were obtained. Composites were also prepared from the so called "biopolyethylene" (HDPE), curaua lignocellulosic fiber, and castor oil (CO). All composites HDBPE/CO/Fiber exhibited higher impact strength, when compared to those of the corresponding HDBPE/Fiber. These results, combined with others (eg SEM images of the fractured surfaces) indicated that, in addition to acting as a plasticizer, this oil may have acted as a compatibilizer of the hydrophilic fiber with the hydrophobic polymer. The set of results indicated that (i) mats with nano (diameter ≤ 100nm) and/or ultrafine (submicron scale) fibers were produced, (ii) hybrid fibers were produced (bio-based mats composites), (iii) cellulosic pulp (CP) and/or lignin (Lig) can be combined with PET matrices to control properties such as stiffness and hydrophilicity of the respective mats. Materials with diversified properties were prepared from high content of renewable raw materials, thus fulfilling the proposed targets.