Influence of molar mass, dispersity, and type and location of hydrophobic side chain moieties on the critical micellar concentration and stability of amphiphilic HPMA-based polymer drug carriers
Influence of molar mass, dispersity, and type and location of hydrophobic side chain moieties on the critical micellar concentration and stability of amphiphilic HPMA-based polymer drug carriers
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DOI：
10.1007/s00396-017-4027-7
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发表时间：
2017-08-01
影响因子：
2.4
通讯作者：
Papadakis, Christine M.
中科院分区：
文献类型：
--
作者：
Filippov, Sergey K.;Vishnevetskaya, Natalya S.;Papadakis, Christine M.
在本文中，我们解决了这样一个问题：如果成功给药所需的所有关键参数都已经预设，那么临床相关的药物递送载体的临界胶束浓度（cmc）值可以在多大程度上变化？为此，详细研究了基于胆固醇侧基的N-（2-羟丙基）甲基丙烯酰胺（HPMA）的两亲性聚合物载体的cmc值，这些载体在摩尔质量、分散性、结构（统计与二嵌段共聚物）和间隔结构等各种参数上的差异。因此，我们选择生理条件（pH为7.4的磷酸盐缓冲盐水），并使用荧光相关光谱研究聚合物浓度对胶束形成的影响。此外，通过pH可切割的腙键将胆固醇部分连接到HPMA骨架上的缀合物在pH 7.4下的长期稳定性随时间的变化进行了研究，发现纳米颗粒在几周内会改变大小。当pH值从7.4变化到5.0（典型的肿瘤细胞）后，纳米颗粒在最初的几个小时内生长，然后收缩。对于基于hma的聚合物，无论其结构、多分散性和间隔结构如何，cmc值与疏水性基团的含量之间存在弱相关性。cmc值与分散度之间有更强的相关性。这一发现可以用位于高摩尔质量分数的HPMA共聚物上的疏水性基团的绝对数量较高来解释，这引发了胶束的形成。
In the present paper, we address the question to which extent the critical micellar concentration (cmc) value can be varied for clinically related drug delivery carriers if all crucial parameters needed for successful drug delivery are already preset. For this purpose, the cmc values of an amphiphilic polymer carrier based on N-(2-hydroxypropyl) methacrylamide (HPMA) with cholesterol side groups, differing in a variety of parameters, such as molar mass, dispersity, architecture (statistical vs. diblock copolymer), and spacer structure, were studied in detail. At this, we chose physiological conditions (phosphate buffered saline at pH 7.4) and investigated the formation of micelles using fluorescence correlation spectroscopy in dependence on polymer concentration. Moreover, conjugates where the cholesterol moieties are attached to the HPMA backbone by a pH-cleavable hydrazone bond were investigated in dependence on time with respect to their long-term stability at pH 7.4, and it was found that the nanoparticles change size in the course of a few weeks. After a pH change from 7.4 to 5.0 (typical for tumor cells), the nanoparticles grow during the first few hours, then shrink. A weak correlation between the cmc value and the content of the hydrophobic group was found for HPMA-based polymers, regardless their architecture, polydispersity, and spacer structure. A much stronger correlation was observed between the cmc value and the dispersity. This finding could be explained by the higher absolute number of hydrophobic groups located on the higher molar mass fractions of the HPMA copolymers, which initiate the micelle formation.