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.

     

Localization and radiofrequency ablation of slow conducting pathway in left free wall

Objectives To study the Electrophysiologic characteristics and method of radiofrequency ablation in patients with slow conduction in left free wall. Methods When 5 cases induced tachycardia, using VS2 program stimulation terminated the tachycardia to establish that ventricle is the part of reentry circle. Results No retrograde A waves in 4 cases but only 1 case present A wave in terminating tachycardia. The accessory pathways have decreasing conduction in One case. Successful ablation were located in ventricle sides. Conclusions Ventricular sense and S2 program stimulation to terminate tachycardia is a reliable method to different atrial tachycardia . A wave of successful targets ahead of A wave of any coronary sinus leads is 8 -22 ms.     

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.     

Cetuximab conjugated vitamin E TPGS micelles for targeted delivery of docetaxel for treatment of triple negative breast cancers

We developed a system of Cetuximab-conjugated micelles of vitamin E TPGS for targeted delivery of docetaxel as a model anticancer drug for treatment of the triple negative breast cancer (TNBC), which shows no expression of either one of the hormone progesterone receptor (PR), estrogen receptor (ER) and epidermal growth factor receptor 2 (HER2) and is thus more difficult to be treated than the positive breast cancer. Such micelles are of desired particle size, drug loading, drug encapsulation efficiency and drug release profile. Their surface morphology, surface charge and surface chemistry were also characterized. The fibroblast cells (NIH3T3), HER2 overexpressed breast cancer cells (SK-BR-3), ER and PR overexpressed breast cancer cells (MCF7), and TNBC cells of high, moderate and low EGFR expression (MDA MB 468, MDA MB 231 and HCC38) were employed to access in vitro cellular uptake of the coumarin 6 loaded TPGS micelles and cytotoxicity of docetaxel formulated in the micelles. The high IC50 value, which is the drug concentration needed to kill 50% of the cells in a designated period such as 24 h, obtained from Taxotere^® showed that the TNBC cells are indeed more resistant to the free drug than the positive breast cancer cells. However, the therapeutic effects of docetaxel could be greatly enhanced by the formulation of Cetuximab conjugated TPGS micelles, which demonstrated 205.6 and 223.8 fold higher efficiency than Taxotere^® for the MDA MB 468 and MDA MB 231 cell lines respectively.     

Synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) hydrogels grafted with LCST modulated polymers

Two types of thermo-responsive hydrogels arc synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTS) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (poly(IPAAm-(-o-DMAAiii)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37°C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31°C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36°C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.