Department of Materials Science and Engineering, University of Central Florida, Orlando, FL 32816, USA.
Department of Materials Science and Engineering, University of Central Florida, Orlando, FL 32816, USA and NanoScience Technology Center, University of Central Florida, Orlando, FL, USA.
J Mater Chem B. 2019 Nov 7;7(41):6438-6448. doi: 10.1039/c9tb01194c. Epub 2019 Sep 4.
Polyelectrolyte complex (PEC) micelles are formed by mixing a block copolymer composed of a neutral block and a charged block, with an oppositely charged polymer. The micelles formed have a PEC core, capable of encapsulating charged molecules like nucleic acids or proteins, while the neutral block(s) forms the corona that offers protection that can prevent cargo from being degraded under physiological conditions. This work explores using a thermosensitive polymer, poly(N-isopropyl acrylamide) (pNIPAM), as the primary corona-forming block and how that can be leveraged in the context of drug delivery. pNIPAM has a lower critical solubility temperature (LCST), above which a hydrophilic to hydrophobic transition occurs. We are characterizing micelles formed using a diblock copolymer of pNIPAM-b-poly(acrylic acid) with (1) poly(lysine) and (2) poly(ethylene glycol)-b-poly(lysine) using dynamic light scattering, small angle X-ray scattering, absorbance and fluorescence spectroscopy, and transmission electron microscopy. Our results indicate that mixing pNIPAM-b-poly(acrylic acid) and poly(lysine) creates worm-like micelles, while mixing the same diblock with poly(ethylene glycol)-b-poly(lysine) forms spherical micelles. At temperatures above 35 °C, the transition temperature of pNIPAM-b-poly(acrylic acid), the worm-like micelles lose their structure, while the spherical micelles retain their structure, but both aggregate into larger assemblies. Lastly, we evaluate the ability of these micelles to encapsulate and release model charged therapeutics, using a cationic monoion, methylene blue and a cationic polyion, polylysine conjugated rhodamine. We find that methylene blue is not encapsulated by the micelle, and instead exhibits counterion-like behaviour upon polyelectrolyte complex formation. Conversely, fluorescence measurements of rhodamine-labelled polylysine show fluorescence quenching indicating that the polyion is encapsulated. By mixing quenched and unlabelled micelles, we show that both systems are immune to molecular exchange with their environment and instead the cargo remains trapped in the quenched micellar cores. Measurement of the micelle fluorescence above the LCST, decreases indicating no substantial release for either system. However, the increase in micelle quenching above the LCST and its persistence after cooling may offer an additional protective environment for cargo that can be triggered by temperature.
聚电解质复合物（PEC）胶束是由混合由中性嵌段和带电嵌段组成的嵌段共聚物与带相反电荷的聚合物形成的。形成的胶束具有 PEC 核，能够包裹带电荷的分子，如核酸或蛋白质，而中性嵌段形成提供保护的冠，可防止货物在生理条件下降解。这项工作探讨了使用热敏聚合物聚（N-异丙基丙烯酰胺）（pNIPAM）作为主要的冠形成嵌段，以及如何在药物输送的背景下利用它。pNIPAM 具有较低的临界溶解温度（LCST），超过该温度会发生亲水性到疏水性的转变。我们正在使用 pNIPAM-b-聚（丙烯酸）的二嵌段共聚物与（1）聚（赖氨酸）和（2）聚（乙二醇）-b-聚（赖氨酸）形成的胶束进行表征，使用动态光散射、小角 X 射线散射、吸光度和荧光光谱以及透射电子显微镜。我们的结果表明，混合 pNIPAM-b-聚（丙烯酸）和聚（赖氨酸）会形成蠕虫状胶束，而将相同的二嵌段与聚（乙二醇）-b-聚（赖氨酸）混合会形成球形胶束。在温度高于 35°C 时，pNIPAM-b-聚（丙烯酸）的转变温度下，蠕虫状胶束失去结构，而球形胶束保留结构，但两者都聚集形成更大的组装体。最后，我们使用阳离子单离子亚甲蓝和阳离子聚离子聚赖氨酸偶联罗丹明评价这些胶束包封和释放模型带电治疗剂的能力。我们发现亚甲蓝未被胶束包封，而是在形成聚电解质复合物时表现出反离子样行为。相反，罗丹明标记聚赖氨酸的荧光测量显示荧光猝灭，表明聚离子被包封。通过混合猝灭和未标记的胶束，我们表明这两个系统都不受与环境的分子交换的影响，而是货物仍然被困在猝灭的胶束核中。在 LCST 以上测量胶束荧光会降低，表明两种系统都没有实质性释放。然而，LCST 以上的胶束猝灭增加及其冷却后的持续存在可能为货物提供额外的保护性环境，该环境可以通过温度触发。
