Novel pH-responsive nanovectors for controlled release of ionisable drugs.
Novel pH-responsive nanovectors for controlled release of ionisable drugs.
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用于控制释放可电离药物的新型 pH 响应纳米载体。
DOI：
10.1039/c3tb20360c
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Mastrotto F
中科院分区：
文献类型：
--
作者：
Mastrotto F
提出了一种基于2-（甲基丙烯酰氧基）乙基-3-氯-4-羟基苯甲酸酯（MCH）、功能性pH响应单体和聚（甲氧基-乙二醇）甲基丙烯酸酯（PEGMA）嵌段共聚物的新型"智能"药物纳米载体家族。单体的相对比例的改变允许从胶束（PEGMA11-b-MCH 21）到基于聚合物体（PEGMA11-b-MCH 38）的药物递送纳米载体的容易切换。研究了后者掺入模型抗癌药物-他莫昔芬、紫杉醇和盐酸多柔比星的能力。观察到他莫昔芬的高载药量-高达18 w/w %，他莫昔芬是一种疏水药物，其具有能够与MCH酸性官能团形成离子对的氨基。对未加载的纳米载体进行表征（CAC、DLS和TEM），发现其在生理条件（PBS pH 7.4，37 ° C）下非常稳定，甚至在10%血浆蛋白存在下至少48小时也是如此。由于聚合物/药物离子相互作用的损失，他莫昔芬负载的纳米载体在pH 7.4下显示缓慢的药物释放，并且在暴露于弱酸性环境后显示更快的释放。重要的是，在pH 7.4下，发现负载他莫昔芬的PEGMA11-b-MCH 21胶束对MCF-7细胞的细胞毒性低于游离他莫昔芬，而在更酸性的条件下，在pH 6.8下，观察到相反的行为，胶束纳米载体的细胞毒性增加10倍。在48小时孵育时间实验中发现空纳米载体是无毒的。药代动力学研究证明，在胶束中封装后，他莫昔芬的半衰期增加，清除较慢。这些基于PEGMA-b-MCH的纳米组装体可以代表用于低分子量可电离药物的新的有前途的递送平台。
A family of novel ‘smart’ drug nanovectors based on 2-(methacryloyloxy)ethyl-3-chloro-4-hydroxybenzoate (MCH), a functional pH-responsive monomer, and poly(methoxy-ethylene glycol) methacrylate (PEGMA) block copolymers is presented. Modification of the monomers' relative ratios allowed facile switching from micellar (PEGMA11-b-MCH21) to polymersome-based (PEGMA11-b-MCH38) drug delivery nanocarriers. The ability of the latter to incorporate model anticancer drugs – tamoxifen, paclitaxel and doxorubicin hydrochloride – was investigated. High drug loading – up to 18 w/w% – was observed for tamoxifen, a hydrophobic drug which bears an amino group able to form ion pairs with MCH acidic functionalities. Non-loaded nanovectors were characterized (CAC, DLS and TEM), and were found to be very stable under physiological conditions (PBS pH 7.4, 37 °C), even in the presence of 10% plasma proteins for at least 48 h. Tamoxifen loaded nanocarriers showed slow drug release at pH 7.4 and faster release after exposure to weakly acidic environments, due to the loss of polymer/drug ionic interactions. Importantly, at pH 7.4 tamoxifen-loaded PEGMA11-b-MCH21 micelles were found to be less cytotoxic than free tamoxifen against MCF-7 cells, while under more acidic conditions, at pH 6.8, the opposite behaviour was observed, with a 10-fold increase in cytotoxicity for the micellar nanocarriers. The empty nanocarriers were found to be non-toxic in 48 h incubation time experiments. Pharmacokinetic studies proved the increased half-life and the slower clearance of tamoxifen after encapsulation in the micelles. These PEGMA-b-MCH based nanoassemblies could represent a novel promising delivery platform for low molecular weight ionisable drugs.
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10.8
作者：
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通讯作者：
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