pH-responsive poly(4-hydroxybenzoyl methacrylates) - design and engineering of intelligent drug delivery nanovectors
pH-responsive poly(4-hydroxybenzoyl methacrylates) - design and engineering of intelligent drug delivery nanovectors
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DOI：
10.1039/c3py00496a
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发表时间：
2013-01-01
影响因子：
4.6
通讯作者：
Mantovani, Giuseppe
中科院分区：
文献类型：
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作者：
Mastrotto, Francesca;Salmaso, Stefano;Mantovani, Giuseppe
在这项研究中，一类新的pH值响应性聚合物的基础上，新的取代苯酚单体。芳香环上吸电子基团的明智选择允许调节它们的pK（a）和疏水性。使用聚[2-（（甲基丙烯酰氧基）乙基-3-氯-4-羟基苯甲酸酯）-r-（甲基丙烯酸甘油酯）]（聚（MCH-r-GMA））的初步实验表明，MCH重复单元的pK（a）在6.5-7范围内，这为其在药物递送纳米载体组装中的应用开辟了道路。这些pH响应性材料的不寻常之处在于，与经常用于此目的的基于有机胺的系统不同，它们在碱性水性条件下具有亲水性行为，而它们在酸化时变得疏水。聚（MCH-b-PEGMA（475））可以通过简单地改变其嵌段组分的亲水：疏水平衡而容易地组装在稳定的胶束或聚合物囊泡纳米载体中。有趣的是，发现聚（MCH-b-PEGMA（475））纳米聚集体的尺寸具有强烈的pH依赖性，从pH 7.4的32 nm到pH 5.5的120 nm。初步的药物包埋实验显示，他莫昔芬模型疏水性药物的载量高达17- 19%w/w，而正如预期的，大量的亲水性盐酸阿霉素（14%w/w）可以掺入聚合物囊泡聚（MCH-b-PEGMA（475））纳米载体中。
In this study a novel class of pH-responsive polymers based on new substituted phenol monomers is presented. A judicious choice of the electron-withdrawing groups on the aromatic ring allowed modulation of both their pK(a) and hydrophobicity. Preliminary experiments using poly[2-((methacryloyloxy) ethyl-3-chloro-4-hydroxybenzoate)-r-(glycerol methacrylate)], poly(MCH-r-GMA), showed that the pK(a) of the MCH repeating units is in the 6.5-7 range, which opened the way for their application in the assembly of drug-delivery nanocarriers. These pH-responsive materials are unusual in that, unlike the systems based on organic amine frequently employed for this purpose, they possess hydrophilic behaviour in basic aqueous conditions, whilst they become hydrophobic upon acidification. Poly(MCH-b-PEGMA(475)) could be easily assembled in either stable micellar or polymersome nanocarriers by simply modifying the hydrophilic : hydrophobic balance of their block components. Interestingly, the size of poly(MCH-b-PEGMA(475)) nanoaggregates was found to be strongly pH-dependent, going from 32 nm at pH 7.4 to 120 nm at pH 5.5. Preliminary drug entrapment experiments showed a loading of tamoxifen model hydrophobic drug as high as 17-19% w/w, whilst as expected a significant amount of hydrophilic doxorubicin hydrochloride, 14% w/w, could be incorporated in polymersome poly(MCH-b-PEGMA(475)) nanocarriers.