Synthesis of non-ionic and enzyme-responsive bolaamphiphiles for drug delivery applications
Synthesis of non-ionic and enzyme-responsive bolaamphiphiles for drug delivery applications
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DOI：
10.1016/j.eurpolymj.2018.10.007
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发表时间：
2018-12-01
影响因子：
6
通讯作者：
Sharma, Sunil K.
中科院分区：
文献类型：
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作者：
Prasad, Suchita;Achazi, Katharina;Sharma, Sunil K.
纳米级药物递送系统是由具有生物相容性和生物可降解性的分子设计而成的，这些分子具有易于经受外部刺激的官能团，已经成为一种有前途的方法，以规避与疏水药物伴随的药物作用放大相关的陷阱。鉴于纳米结构的优势，同时也为了寻找具有生物医学应用前景的两亲分子，我们利用固定化酶（脂肪酶），通过化学-酶促方法合成了一种能够自组装成酶响应性超分子结构的新型两亲体系（Novozym 435），并使用生物相容性起始材料，即对羟基苯甲酸、单甲氧基聚乙二醇（mPEG）和甘油。所得到的bola两亲物的聚集行为进行了研究，使用临界聚集浓度和动态光散射测量，进一步补充低温透射电子显微镜研究。所开发的两亲物使得模型疏水药物和染料，例如尼罗红、尼莫地平和姜黄素在水溶液中的有效增溶。此外，结果表明，一个微妙的两亲性系统的结构调制改变了客体分子的输运行为。使用水解酶（南极假丝酵母脂肪酶）对合成的bola两亲物的酶响应行为的研究揭示了基于酰胺的纳米载体在与酶孵育时分解并释放包封的货物。3-（4，5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑鎓（MTS）测定揭示了bola两亲物在测试浓度下的可忽略的细胞毒性，表明它们在开发用于生物医学应用的纳米载体中的相关性。
Nanoscale drug delivery systems devised from biocompatible and biodegradable molecules with functional groups which are readily amenable to external stimuli, have become a promising approach to circumvent the pitfalls associated with the hydrophobic drugs concomitant with the amplification of drugs' action. Taking the cognizance of advantages offered by nanostructures and also in search of amphiphiles with intended biomedical applications, a novel and elite family of amphiphilic system that can self-assemble into enzyme-responsive supramolecular architectures has been synthesized via a chemo-enzymatic approach using an immobilized enzyme (lipase) from Candida antarctica (Novozym 435) and employing biocompatible starting materials, i.e. p-hydroxybenzoic acid, monomethoxypolyethyleneglycol (mPEG), and glycerol. The aggregation behavior of the resulting bolaamphiphiles have been studied using critical aggregation concentration and dynamic light scattering measurements, further supplemented by cryogenic transmission electron microscopic studies. The developed amphiphiles render efficient solubilization of model hydrophobic drugs and dyes, e.g. Nile red, nimodipine, and curcumin in aqueous solution. Moreover, the results demonstrate that a subtle structural modulation of the amphiphilic system alters the transportation behavior of the guest molecule. The investigation of the enzyme-responsive behavior of the synthesized bolaamphiphiles using a hydrolase enzyme, Candida antarctica lipase reveals that amide based nanocarriers disassemble and release the encapsulated cargo on incubation with the enzyme. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay unravels negligible cytotoxicity of the bolaamphiphiles at the tested concentrations, indicating their relevance in the development of nanocarriers for biomedical applications.