POx as an Alternative to PEG? A Hydrodynamic and Light Scattering Study,Macromolecules

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POx as an Alternative to PEG? A Hydrodynamic and Light Scattering Study
Macromolecules ( IF 5.1 ) Pub Date : 2018-02-22 00:00:00 , DOI: 10.1021/acs.macromol.7b02665
Mandy Grube _{1,

2} , Meike N. Leiske _{1,

2} , Ulrich S. Schubert _{1,

2} , Ivo Nischang _{1,

2}

Affiliation

Poly(ethylene glycol)s (PEG) are widely and intensely used in the pharmaceutical industry and biomedical applications, and due to this fact, antibodies have recently been reported. Poly(2-oxazoline)s (POx) are promising candidates for potential replacement of PEG in related applications, and as such, their hydrodynamic properties and characteristics derived from light scattering experiments are important to reconcile their behavior in solution. In this study, we have investigated the molecular hydrodynamic characteristics of poly(2-methyl-2-oxazoline)s and poly(2-ethyl-2-oxazoline)s in the pharmaceutical molar mass range as base candidates for such applications, prepared by cationic ring-opening polymerization in a microwave reactor. A combined viscometry and sedimentation–diffusion analysis by using sedimentation velocity experiments in an analytical ultracentrifuge includes (i) the study of intrinsic viscosities, (ii) sedimentation coefficients, and (iii) derived translational diffusion coefficients. These characteristics are then interrelated through hydrodynamic invariants that showed consistency between all these hydrodynamic parameters and, consequently, adequate values of derived absolute molar masses. The established scaling relationships of POx could as well be related quantitatively to that of pharmaceutical PEG from a recent study. Complementary, the molar masses were estimated by asymmetrical flow field-flow fractionation (AF4) and size exclusion chromatography (SEC) in conjunction with multiangle laser light scattering (MALLS). Thus, the obtained results of molar masses show an overarching good correlation to that of the hydrodynamic analysis utilizing the ultracentrifuge and viscometry. However, we demonstrate as well that AF4-/SEC-MALLS experiments of macromolecules below 10 000 g mol^–1 may provide erroneous information on their molar mass, identified and discussed by the hydrodynamic invariant concept interrelating three independent experimental approaches on the same sample, i.e., (i) intrinsic viscosities, (ii) intrinsic sedimentation coefficients, and (iii) molar masses from light scattering. Our results open the gate for the replacement of pharmaceutical PEG by POx on a physicochemical basis with key first-principles hydrodynamic parameters of interest, all associated with values of the molar mass.

中文翻译：

POx替代PEG？水动力和光散射研究

聚（乙二醇）（PEG）在制药工业和生物医学应用中被广泛和广泛地使用，并且由于这个事实，最近已经报道了抗体。聚（2-恶唑啉）（POx）是有望在相关应用中替代PEG的有前途的候选物，因此，它们的流体力学性质和源自光散射实验的特性对于调和它们在溶液中的行为很重要。在这项研究中，我们研究了在药物摩尔质量范围内的聚（2-甲基-2-恶唑啉）s和聚（2-乙基-2-恶唑啉）s的分子流体力学特性，作为此类应用的基础候选物，通过微波反应器中的阳离子开环聚合。在分析型超速离心机中使用沉降速度实验进行的粘度测定和沉降扩散分析相结合，包括（i）特性粘度的研究，（ii）沉降系数和（iii）导出的平移扩散系数。然后通过流体动力学不变量将这些特性相互关联，该变量显示所有这些流体力学参数之间的一致性，因此，得出的绝对摩尔质量也应具有足够的值。从最近的一项研究中，POx的确定比例关系也可能与药用PEG的比例关系定量相关。补充地，摩尔质量通过不对称流场流分馏法（AF4）和尺寸排阻色谱法（SEC）结合多角度激光散射（MALLS）进行估算。因此，摩尔质量的获得的结果与利用超速离心机和粘度计进行的流体力学分析显示出总体良好的相关性。但是，我们也证明了低于4万克分子的大分子AF4- / SEC-MALLS实验^–1可能会提供有关其摩尔质量的错误信息，这些信息是通过流体动力学不变性概念进行识别和讨论的，该概念将在同一样品上的三种独立实验方法相互关联，即（i）固有粘度，（ii）固有沉降系数和（iii）摩尔质量从光散射。我们的结果为在物理化学基础上用感兴趣的关键第一原理流体力学参数（均与摩尔质量值相关）的POx替代药物PEG开辟了大门。

更新日期：2018-02-22

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