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Analysis of nanoparticle dispersion, biological interactions and drug incorporation of polyurethane nanocomposite materials

机译:聚氨酯纳米复合材料的纳米颗粒分散,生物相互作用和药物掺入分析

摘要

The use of polymer nanocomposites (NCs) in industrial applications has received growing attention over the past decade due to their improved mechanical properties. However, little work has been reported which analyses the efficacy of NCs in biological applications, including drug delivery systems and implantable materials. This thesis examines the effect of the chemistry of the organic modifier (OM) on the structure and biological performance of poly(ether)urethane NCs (PUNCs) and the influence of the method of drug incorporation on interactions between drug and NC. Organically modified silicates (OMS) were prepared using OMs varying in terminal functionality and alkyl chain length. PUNCs were solvent cast containing 1 and 3wt% OMS and particle dispersion analysed using X-ray diffraction and transmission electron microscopy. Findings revealed that use of an OM with methyl terminal, dodecylamine (12CH3), resulted in superior dispersion of OMS compared with a carboxyl terminated OM, aminododecanoic acid (12COOH), of equivalent alkyl chain length. This is believed to result from increased self interaction of 12COOH compared with 12CH3. Additionally, increased alkyl chain length was shown to improve NC dispersion with a chain length of sixteen units resulting in the optimum dispersion with a partially exfoliated NC structure. Analysis of cellular interactions with the PUNCs revealed a significant difference in both fibroblast and platelet adhesion to NCs incorporating 12CH3 compared with 12COOH. Surface analysis using ToF-SIMS demonstrated the presence of 12CH3 fragments on the NC surface supporting the hypothesis that surface expressed OMs alter cellular interactions with the NC. Altering the alkyl chain length also affected cellular interaction with an alkyl chain length of twelve units or greater, substantially reducing fibroblast adhesion without affecting cell growth inhibition or viability. Incorporation of a model drug, crystal violet, into the PUNCs demonstrated a lower degree of disruption to OMS dispersion when loaded post NC fabrication compared with pre fabrication. This is believed to result from interactions between the drug and NC constituents which also impacted on drug release from the NC system. Results show PUNC properties and biological interactions can be modulated through OM variation and fabrication method, thus showing potential for use in biomedical applications.
机译:由于其改善的机械性能,在过去的十年中,聚合物纳米复合材料(NCs)在工业应用中的使用日益受到关注。然而,很少有报道分析NCs在生物应用中的功效,包括药物输送系统和可植入材料。本文研究了有机改性剂(OM)的化学性质对聚(醚)氨基甲酸乙酯NCs(PUNCs)的结构和生物学性能的影响以及药物掺入方法对药物与NC相互作用的影响。使用末端官能度和烷基链长不同的OM制备有机改性的硅酸盐(OMS)。将PUNCs浇铸成含有1wt%和3wt%的OMS的溶剂,并使用X射线衍射和透射电子显微镜分析颗粒分散度。研究结果表明,与末端为羧基的OM氨基十二烷酸(12COOH)相比,使用带有甲基末端十二烷基胺(12CH3)的OM可以使OMS具有更好的分散性。据信,这是由于12COOH与12CH3的相互作用增加所致。另外,增加的烷基链长显示出改善的NC分散性,链长为16个单元,导致具有部分剥离NC结构的最佳分散性。与PUNCs相互作用的细胞分析表明,与12COOH相比,掺入12CH3的NCs在成纤维细胞和血小板粘附方面均存在显着差异。使用ToF-SIMS进行的表面分析表明,在NC表面上存在12CH3片段,这支持了表面表达的OM改变细胞与NC相互作用的假设。改变烷基链长度也以十二个单元或更大的烷基链长度影响细胞相互作用,从而在不影响细胞生长抑制或生存力的情况下显着降低成纤维细胞粘附。与制造前相比,在NC制造后加载时,将模型药物结晶紫掺入PUNC时,对OMS分散的破坏程度较小。据信这是由于药物和NC成分之间的相互作用所致,而相互作用也影响了NC系统中药物的释放。结果表明,PUNC特性和生物相互作用可以通过OM变化和制造方法进行调节,从而显示出在生物医学应用中的潜力。

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