Study of a cross-linked hydrogel of Karaya gum and Starch as a controlled drug delivery system

Abstract

A cross-linked hydrogel was synthesized using a hybrid backbone of karaya gum starch and grafted with polyacrylic acid. It showed a maximum swelling ratio (SR) of 30.5?g/g at pH 10 and was explored as an oral drug delivery carrier using paracetamol and aspirin as model drugs. In vitro release experiments revealed that maximum drug release at pH 7.4 in comparison to pH 1.2 (simulated intestinal vs gastric fluid) and neutral medium. The release profiles of these drugs showed no initial burst. It also showed good hemocompatibilty and non-cytotoxicity for its employment as a site specific drug delivery agent.     

Nanocomposites of iridium oxide and conducting polymers as electroactive phases in biological media

Much effort is currently devoted to implementing new materials in electrodes that will be used in the central nervous system, either for functional electrostimulation or for tests on nerve regeneration. Their main aim is to improve the charge capacity of the electrodes, while preventing damaging secondary reactions, such as peroxide formation, occurring while applying the electric field. Thus, hybrids may represent a new generation of materials. Two novel hybrid materials are synthesized using three known biocompatible materials tested in the neural system: polypyrrole (PPy), poly(3,4-ethylenedioxythiophene) (PEDOT) and iridium oxide (IrO₂). In particular, PPy–IrO₂ and PEDOT–IrO₂ hybrid nanocomposite materials are prepared by chemical polymerization in hydrothermal conditions, using IrO₂ as oxidizing agent. The reaction yields a significant ordered new hybrid where the conducting polymer is formed around the IrO₂ nanoparticles, encapsulating them. Scanning electron microscopy and backscattering techniques show the extent of the encapsulation. Both X-ray photoelectron and Fourier transform infrared spectroscopies identify the components of the phases, as well as the absence of impurities. Electrochemical properties of the final phases in powder and pellet form are evaluated by cyclic voltammetry. Biocompatibility is tested with MTT toxicity tests using primary cultures of cortical neurons grown in vitro for 6 and 9 days.     

Designer broad-spectrum polyimidazolium antibiotics

For a myriad of different reasons most antimicrobial peptides (AMPs) have failed to reach clinical application. Different AMPs have different shortcomings including but not limited to toxicity issues, potency, limited spectrum of activity, or reduced activity in situ. We synthesized several cationic peptide mimics, main-chain cationic polyimidazoliums (PIMs), and discovered that, although select PIMs show little acute mammalian cell toxicity, they are potent broad-spectrum antibiotics with activity against even pan-antibiotic-resistant gram-positive and gram-negative bacteria, and mycobacteria. We selected PIM1, a particularly potent PIM, for mechanistic studies. Our experiments indicate PIM1 binds bacterial cell membranes by hydrophobic and electrostatic interactions, enters cells, and ultimately kills bacteria. Unlike cationic AMPs, such as colistin (CST), PIM1 does not permeabilize cell membranes. We show that a membrane electric potential is required for PIM1 activity. In laboratory evolution experiments with the gram-positive Staphylococcus aureus we obtained PIM1-resistant isolates most of which had menaquinone mutations, and we found that a site-directed menaquinone mutation also conferred PIM1 resistance. In similar experiments with the gram-negative pathogen Pseudomonas aeruginosa, PIM1-resistant mutants did not emerge. Although PIM1 was efficacious as a topical agent, intraperitoneal administration of PIM1 in mice showed some toxicity. We synthesized a PIM1 derivative, PIM1D, which is less hydrophobic than PIM1. PIM1D did not show evidence of toxicity but retained antibacterial activity and showed efficacy in murine sepsis infections. Our evidence indicates the PIMs have potential as candidates for development of new drugs for treatment of pan-resistant bacterial infections.

AMPs and AMP mimics have attracted considerable attention as candidates for therapeutic development (1). The basic design elements include a region of charged residues, generally cationic residues, enabling interaction with bacterial cell surfaces, combined with a hydrophobic nature in AMPs (2). Unfortunately, AMPs and related polymers, in general, have one or more issues that limit their use as broad-spectrum antibiotics. Some are quite toxic to human cells, the potency of some is not adequate for human administration, others are sensitive to salt at levels present in human fluids, and some are too difficult and expensive to synthesize (3, 4). One broad-spectrum antimicrobial peptide, CST has seen increased recent use as a last resort antibiotic. CST is believed to kill bacteria by virtue of its ability to disrupt membrane integrity (5). This antibiotic requires intravenous administration and is nephrotoxic (6). The emergence of CST-resistant pathogens has also become a significant problem (7). We are unaware of any new broad-spectrum AMPs that have advanced to clinical trials.Imidazolium (IM) salts are antimicrobials (8), and there is an emerging literature on antimicrobial activity of side-chain and main-chain polyimidazolium (PIM) salts with chemical structures that are in some ways similar to those we describe. Although PIMs are potent antimicrobials, there are biocompatibility problems hindering their development, and some have somewhat limited activity spectra. As with other AMPs, there have been toxicity issues, potency issues, and delivery issues as many have large molecular masses, and there is little known about mammalian cell toxicity or mechanism of action (9–12).Here we show that members of a series of PIMs we designed and synthesized are potent broad-spectrum antibacterial compounds. We selected two for further analysis and showed they retain activity even against pan-antibiotic-resistant bacteria. Unlike CST and many other AMPs, which disrupt bacterial membranes, our model PIM is bactericidal without disrupting bacterial membranes. Our experiments provide insights about mechanism of action, the potential for the emergence of PIM resistance, and indicate PIMs are effective against a model gram-negative and a model gram-positive pathogen in murine infection models.     

Role of polymer–drug conjugates in organ-specific delivery systems

Polymers have been utilized to deliver the drug to targeted site in controlled manner, achieving the high-therapeutic efficacy. Polymeric drug conjugates having variable ligands as attachments have been proved to be biodegradable, stimuli sensitive and targeted systems. Numerous polymeric drug conjugates having linkers degraded by acidity or intracellular enzymes or sensitive to over expressed groups of diseased organ/tissue have been synthesized during last decade to develop targeted delivery systems. Most of these organs have number of receptors attached with different cells such as Kupffer cells of liver have mannose-binding receptors while hepatocytes have asialoglycoprotein receptors on their surface which mainly bind with the galactose derivatives. Such ligands can be used for achieving high targeting and intracellular delivery of the drug. This review presents detailed aspects of receptors found in different cells of specific organ and ligands with binding efficiency to these specific receptors. This review highlights the need of further studies on organ-specific polymer–drug conjugates by providing detailed account of polymeric conjugates synthesized till date having organ-specific targeting.     

Tailor‐Made Antimicrobial/Antiviral Star Polymer via ATRP of Cyclodextrin and Guanidine‐Based Macromonomer

Novel star‐like polymers are prepared via atom transfer radical polymerization (ATRP) of polyhexamethylene guanidine hydrochloride (PHMG) macromonomer and acrylamide (AM) using β‐cyclodextrin (CD) with 8‐active and 5‐active sites as a macroinitiator. The resulting star‐like polymers are characterized by gel permeation chromatography (GPC) and ¹H NMR and are used for deactivating bacteria and viruses. It is found that star polymers with comparable amounts of PHMG possess excellent antimicrobial activity, which, however, strongly depends on the topological structure (i.e., the arm number and the monomer ratio) of the composing copolymers. The in vitro antibacterial activities of the synthesized polymers are investigated against Escherichia coli in terms of the minimum inhibitory concentration (MIC), whereas the antiviral activity of star copolymers is assessed via a plaque assay against non‐enveloped adenovirus (ADV). The results show that the highest antimicrobial activity is achieved by the star‐like copolymer with the monomer ratio of 20:3 (AM:PHGM, mol/mol), while the number of functional arms is fixed at 8. The incorporation of PHMG also renders the star copolymer highly antiviral, thus permitting it to be used as an effective antibacterial/antiviral agent for various applications.

     

Improved Electrical Performance of Poly(3‐hexylthiophene) Induced by Stable Doping with Polymer Dopants

A series of brominated polystyrenes (BPSs) are readily synthesized and blended as polymer dopants with the p‐type semiconducting polymer, poly(3‐hexylthiophene) (P3HT), to improve theirelectrical performance. The obtained P3HT/BPS blend films exhibit increased carrier concentration resulting from doping of P3HT by BPS, which leads to excellent electrical performance, including enhanced hole mobility and conductivity, and the conductivity or mobility increases with the bromination degree of BPS. Compared with conventional small molecular dopants, the polymer dopant, BPS, shows not only excellent doping stability, but also good solution processibility, which makes it a promising materials for fabrication of low cost, flexible, transparent, and high performance solution processable organic electronic devices.

     

多聚物型可吸收冠状动脉支架的研究进展

新一代药物洗脱支架由可吸收多聚物为平台,具有与金属支架相当的的支撑力,以及良好的生物相容性.既可以暂时支撑管壁,抑制早期血栓形成及晚期新生内膜增生,还可作为良好的药物载体实现局部控制释放,达到有效防止支架置入后的血管急性闭塞和降低再狭窄率.     

Folding of a donor-acceptor polyrotaxane by using noncovalent bonding interactions

Mechanically interlocked compounds, such as bistable catenanes and bistable rotaxanes, have been used to bring about actuation in nanoelectromechanical systems (NEMS) and molecular electronic devices (MEDs). The elaboration of the structural features of such rotaxanes into macromolecular materials might allow the utilization of molecular motion to impact their bulk properties. We report here the synthesis and characterization of polymers that contain pi electron-donating 1,5-dioxynaphthalene (DNP) units encircled by cyclobis(paraquat-p-phenylene) (CBPQT(4+)), a pi electron-accepting tetracationic cyclophane, synthesized by using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The polyrotaxanes adopt a well defined "folded" secondary structure by virtue of the judicious design of two DNP-containing monomers with different binding affinities for CBPQT(4+). This efficient approach to the preparation of polyrotaxanes, taken alongside the initial investigations of their chemical properties, sets the stage for the preparation of a previously undescribed class of macromolecular architectures.     

Immunoaffinity Extraction and Alternative Approaches for the Analysis of Toxins in Environmental,Food or Biological Matrices

The evolution of instrumentation in terms of separation and detection allowed a real improvement of the sensitivity and analysis time. However, the analysis of ultra-traces of toxins in complex samples requires often a step of purification and even preconcentration before their chromatographic analysis. Therefore, immunoaffinity sorbents based on specific antibodies thus providing a molecular recognition mechanism appear as powerful tools for the selective extraction of a target molecule and its structural analogs to obtain more reliable and sensitive quantitative analysis in environmental, food or biological matrices. This review focuses on immunosorbents that have proven their efficiency in selectively extracting various types of toxins of various sizes (from small mycotoxins to large proteins) and physicochemical properties. Immunosorbents are now commercially available, and their use has been validated for numerous applications. The wide variety of samples to be analyzed, as well as extraction conditions and their impact on extraction yields, is discussed. In addition, their potential for purification and thus suppression of matrix effects, responsible for quantification problems especially in mass spectrometry, is presented. Due to their similar properties, molecularly imprinted polymers and aptamer-based sorbents that appear to be an interesting alternative to antibodies are also briefly addressed by comparing their potential with that of immunosorbents.