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用于生物医学应用的两亲性菊粉-D-α-生育酚琥珀酸酯(INVITE)生物缀合物。

Amphiphilic inulin-D-α-tocopherol succinate (INVITE) bioconjugates for biomedical applications.

机构信息

Department of Pharmacy, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy.

Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.

出版信息

Carbohydr Polym. 2014 Mar 15;103:46-54. doi: 10.1016/j.carbpol.2013.11.056. Epub 2013 Dec 12.

Abstract

Herein is reported the synthesis and characterization of innovative inulin (INU)-vitamin E succinate (VITE) bioconjugates (INVITE). The obtained amphiphilic INU-based polymers, self-assembling in nanostructures, have been thought as new drug delivery systems (DDS) for the therapy of urinary tract infections (UTI). The synthesis of INVITE bioconjugates was carried out in bulk, without isolation of intermediate products, to reduce the amount of solvents used in the purification steps and to prevent possible VITE oxidation during work up. Six different INVITE conjugates (INVITE 1-6) have been synthesized by varying both the relative amount of VITE with respect to INU repetitive units and the reaction temperature. Afterwards, the ability of the new conjugates to form micelle systems, by applying two different established methods for critical aggregation concentration (CAC) evaluation, has been verified. Both methods produced similar CAC values ranging from 2.5 × 10(-3)mM to 2.4 × 10(-2)mM in agreement with the different degrees of derivatization shown by the INVITE 1-6 conjugates. The mean diameter of prepared INVITE micelles, resulted in the range 24-60 nm. The size of the obtained INVITE micelles did not change as measured at different time points up to 12 days, so confirming their stability upon storage.

摘要

本文报道了创新的菊粉(INU)-维生素 E 琥珀酸酯(VITE)生物缀合物(INVITE)的合成与表征。所得到的两亲性 INU 基聚合物,自组装成纳米结构,被认为是治疗尿路感染(UTI)的新型药物传递系统(DDS)。INVITE 生物缀合物的合成是在本体中进行的,无需分离中间产物,以减少纯化步骤中使用的溶剂量,并防止在处理过程中可能发生的 VITE 氧化。通过改变 VITE 与 INU 重复单元的相对量和反应温度,合成了六种不同的 INVITE 缀合物(INVITE 1-6)。随后,通过应用两种不同的建立方法来验证新缀合物形成胶束系统的能力,用于评估临界聚集浓度(CAC)。两种方法都产生了相似的 CAC 值,范围从 2.5×10(-3)mM 到 2.4×10(-2)mM,与 INVITE 1-6 缀合物表现出的不同程度的衍生化一致。制备的 INVITE 胶束的平均直径在 24-60nm 范围内。在 12 天内的不同时间点测量时,获得的 INVITE 胶束的大小没有变化,因此证实了它们在储存时的稳定性。

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