Elucidating the Molecular Interactions of Encapsulated Doxorubicin within a Nonionic, Thermoresponsive Polyester Coacervate,ACS Applied Bio Materials

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Elucidating the Molecular Interactions of Encapsulated Doxorubicin within a Nonionic, Thermoresponsive Polyester Coacervate
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-06-22 , DOI: 10.1021/acsabm.0c00507
Mangaldeep Kundu ₁ , Daniel L Morris ₂ , Megan A Cruz ₁ , Toshikazu Miyoshi ₁ , Thomas C Leeper ₃ , Abraham Joy ₁

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Thermoresponsive polymers that display a lower critical solution temperature (LCST) are attractive drug delivery systems (DDSs) due to their potential to encapsulate and release therapeutics in a sustained manner as a function of temperature input. To attain the full potential of such DDSs, methods that illustrate the details of drug–polymer interactions are necessary. Here, we synthesized a nonionic, coacervate-forming, thermoresponsive polyester to encapsulate doxorubicin (Dox) and used solution state NMR spectroscopy and fluorescence microscopy techniques to probe the interactions between the polymer and Dox at the molecular level. The incomplete dehydration provides a matrix for encapsulation of sensitive therapeutics and preserving their activity, while the low hysteresis property of the polyester provides rapid transition from soluble to coacervate phase. Saturation transfer difference (STD) NMR revealed the Dox–polymer interactions within the coacervates. ¹H–¹H nuclear Overhauser effect spectroscopy (NOESY) cross-peak differences of Dox confirmed the Dox–polymer interactions. Diffusion-ordered spectroscopy (DOSY) revealed the slower diffusion rate of Dox in the presence of polyester coacervates. These studies illustrate how the state of the polyester (below and above LCST) affects the polyester–Dox interactions and offers details of the specific functional groups involved in these interactions. Our results provide a framework for future investigations aimed at characterizing fundamental interactions in polymer-based DDSs.

中文翻译：

阐明非离子、热响应性聚酯凝聚层中包封多柔比星的分子相互作用

显示较低临界溶液温度 (LCST) 的热响应聚合物是有吸引力的药物递送系统 (DDS)，因为它们具有作为温度输入函数以持续方式封装和释放治疗剂的潜力。为了充分发挥此类 DDS 的潜力，有必要使用说明药物-聚合物相互作用细节的方法。在这里，我们合成了一种非离子、形成凝聚层的热响应聚酯来封装阿霉素 (Dox)，并使用溶液状态 NMR 光谱和荧光显微镜技术在分子水平上探测聚合物和 Dox 之间的相互作用。不完全脱水为封装敏感治疗剂并保持其活性提供了基质，而聚酯的低滞后特性提供了从可溶相到凝聚相的快速转变。饱和转移差 (STD) NMR 揭示了凝聚层内的 Dox-聚合物相互作用。^{Dox 的1} H – ¹ H 核 Overhauser 效应光谱 (NOESY) 交叉峰差异证实了 Dox-聚合物相互作用。扩散有序光谱 (DOSY) 揭示了在聚酯凝聚层存在的情况下，Dox 的扩散速率较慢。这些研究说明了聚酯的状态（低于和高于 LCST）如何影响聚酯-Dox 相互作用，并提供了参与这些相互作用的特定官能团的详细信息。我们的结果为未来的研究提供了一个框架，旨在描述基于聚合物的 DDS 中的基本相互作用。

更新日期：2020-07-20

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