Polymer toxicity

  • 文章类型: Journal Article
    Adagen,腺苷脱氨酶缺乏症的酶替代疗法,是1990年代初批准的第一个蛋白质-聚合物缀合物。在这一监管批准之后,许多聚合物药物和聚合物纳米颗粒已经进入市场作为先进或下一代聚合物为基础的治疗,而其他许多人目前已经进行了临床试验。与治疗部分缀合的聚合物提供了几个优点,比如增强药物的溶解,控释,降低免疫原性,延长循环。本综述旨在强调治疗有效的聚合物-药物缀合物(PDC)设计中的考虑因素,包括接头化学的选择。制定PDC的潜在合成策略已经随着不同类型的PDC的最新进展进行了讨论,即,聚合物-小分子量药物偶联物,聚合物-蛋白质结合物,和刺激响应性PDC,正在进行临床/临床前调查。已经解决了阻碍PDC临床转化为改善疾病状况的有效治疗方案的当前障碍和调节障碍。
    Adagen, an enzyme replacement treatment for adenosine deaminase deficiency, was the first protein-polymer conjugate to be approved in early 1990 s. Post this regulatory approval, numerous polymeric drugs and polymeric nanoparticles have entered the market as advanced or next-generation polymer-based therapeutics, while many others have currently been tested clinically. The polymer conjugation to therapeutic moiety offers several advantages, like enhanced solubilization of drug, controlled release, reduced immunogenicity, and prolonged circulation. The present review intends to highlight considerations in the design of therapeutically effective polymer-drug conjugates (PDCs), including the choice of linker chemistry. The potential synthetic strategies to formulate PDCs have been discussed along with recent advancements in the different types of PDCs, i.e., polymer-small molecular weight drug conjugates, polymer-protein conjugates, and stimuli-responsive PDCs, which are under clinical/preclinical investigation. Current impediments and regulatory hurdles hindering the clinical translation of PDC into effective therapeutic regimens for the amelioration of disease conditions have been addressed.
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  • 文章类型: Journal Article
    Plastics in marine environments vary in their physical and chemical properties, influencing their risk to biota once ingested. Manta rays are large filter-feeders that ingest plastics. To assess this risk, we characterized the plastics in a critical feeding habitat off Nusa Penida, Indonesia. We examined the color and polymer composition of sampled small-sized plastics (<30 mm). Plastics were mostly secondary microplastics and transparent (46%), white/off-white (24%), and blue/green (22%). Fourier transform infrared spectroscopy of plastics grouped according to type (films, fragments, foam, or lines) and color indicated that most plastics were polyethylene (PE) or polypropylene (PP) (99%), with the remainder polystyrene and polyester. Visual characterization aligned with single polymer composition in seven out of ten groups. Although PE and PP have relatively low toxicity compared to other plastics, their composing monomers and associated pollutants and microbes are of concern to manta rays and other marine biota.
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  • 文章类型: Journal Article
    The nanosized (∼10nm in 0.01M PBS and 210nm in water) star-shaped polymethacrylates with various content of pendant carboxyl groups were characterized via basic physicochemical and biological properties toward their use as drug carriers for intravenous administration. The carboxyl groups in polymer were employed to conjugate fluorescein (FA) or doxorubicin (DOX) via amide bond formation. In case of DOX, the conjugation efficiency was higher (4.0-16.0%) than of FA conjugation (1.5-4.5%) for corresponding copolymers. The solubility of conjugates strongly depended on the type of attached compound, that is free carriers and their FA conjugates were water-soluble, whereas DOX conjugates were insoluble in water. Cytotoxicity tests performed on model fibroblast and epithelial cell lines showed that negatively charged copolymers (ZP ranged from -75 to -25mV) were slightly toxic for normal cells (NHDF) and non-toxic for cancer cell lines (HCT-116 and MCF-7/R). The copolymer dose equal to 125μg/mL resulted in cell viability 118% towards NHDF and 90% for HCT116 cells. The internalization of a representative polymer-fluorescein conjugate by HCT-116 and its accumulation in cytoplasm was proven via fluorescence microscopy. MMA/MAA stars showed no adverse effect on HCT-116 cells, hence fluorescein-tagged polymers might be applied as fluorescence probes for in vitro imaging, whereas doxorubicin-tagged polymers might be developed as a new polymeric drug carriers.
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  • 文章类型: Journal Article
    Neutral Methacrylate Copolymer is a fully polymerised copolymer used in the pharmaceutical industry to permit pH-independent delayed release of active ingredients from oral dosage forms. This function has potential use with food supplements and this article describes available information on the safety of the substance. Oral administration of radiolabelled copolymer to rats resulted in the detection of chemically unchanged copolymer in the faeces, with negligible absorption. Safety studies revealed no adverse toxicity following repeated administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity occurred at up to 2000 mg/kg bw/d in rats or rabbits. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential. An ADI value of 20 mg/kg bw was concluded from two alternative approaches. Daily exposure from use in dietary supplements is estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There would therefore appear to be no safety concerns under the intended conditions of use. The information provided is intended to support an evaluation that the substance may be \"generally recognized as safe\" (GRAS).
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