Polymer nanomedicines based on micelle-forming amphiphilic or water-soluble polymer-doxorubicin conjugates: Comparative study of in vitro and in vivo properties related to the polymer carrier structure, composition, and hydrodynamic properties.,Journal of Controlled Release

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Polymer nanomedicines based on micelle-forming amphiphilic or water-soluble polymer-doxorubicin conjugates: Comparative study of in vitro and in vivo properties related to the polymer carrier structure, composition, and hydrodynamic properties.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-03-03 , DOI: 10.1016/j.jconrel.2020.03.002
Alena Braunová ₁ , Petr Chytil ₁ , Richard Laga ₁ , Milada Šírová ₂ , Daniela Machová ₁ , Jozef Parnica ₁ , Blanka Říhová ₂ , Olga Janoušková ₁ , Tomáš Etrych ₁

Affiliation

The study compared the physico-chemical and biological properties of a water-soluble star-like polymer nanomedicine with three micellar nanomedicines formed by self-assembly of amphiphilic copolymers differing in their hydrophobic part (statistical, block and thermosensitive block copolymers). All nanomedicines showed a pH-responsive release of the drug, independent on polymer structure. Significant penetration of all polymer nanomedicines into tumor cells in vitro was demonstrated, where the most pronounced effect was observed for statistical- or diblock copolymer-based micellar systems. Tumor accumulation in vivo was dependent on the stability of the nanomedicines in solution, being the highest for the star-like system, followed by the most stable micellar nanomedicines. The star-like polymer nanomedicine showed a superior therapeutic effect. Since the micellar systems exhibited slightly lower systemic toxicity, they may exhibit the same efficacy as the star-like soluble system when administered at equitoxic doses. In conclusion, treatment efficacy of studied nanomedicines was directly controlled by the drug pharmacokinetics, namely by their ability to circulate in the bloodstream for the time needed for effective accumulation in the tumor due to the enhanced permeability and retention (EPR) effect. Easy and scalable synthesis together with the direct reconstitution possibility for nanomedicine application made these nanomedicines excellent candidates for further clinical evaluation.

中文翻译：

基于形成胶束的两亲性或水溶性聚合物-阿霉素结合物的聚合物纳米药物：体外和体内与聚合物载体结构，组成和流体力学性质相关的性质的比较研究。

该研究将水溶性星状聚合物纳米药物与通过疏水性不同的两亲共聚物的自组装形成的三种胶束纳米药物的物理化学和生物学特性进行了比较（统计，嵌段和热敏嵌段共聚物）。所有纳米药物均显示药物的pH响应释放，而与聚合物结构无关。证明了所有聚合物纳米药物在体外均显着渗透到肿瘤细胞中，其中基于统计学或基于二嵌段共聚物的胶束系统观察到最明显的作用。体内肿瘤的积累取决于溶液中纳米药物的稳定性，对于星形系统来说是最高的，其次是最稳定的胶束纳米药物。星形聚合物纳米药物显示出优异的治疗效果。由于胶束系统表现出稍低的全身毒性，因此当以等毒性剂量给药时，它们可能表现出与星形可溶性系统相同的功效。总之，所研究的纳米药物的治疗功效直接受药物药代动力学的控制，即由于增强的通透性和保留（EPR）效应，它们在血液中循环有效地积累在肿瘤中所需时间的能力。简便，可扩展的合成方法以及直接重组的纳米药物应用可能性使这些纳米药物成为进一步临床评估的极佳候选者。所研究的纳米药物的治疗效果直接受药物药代动力学的控制，即由于增强的通透性和保留（EPR）效应，它们在血液中循环有效地积聚在肿瘤中所需时间的能力。简便，可扩展的合成方法以及直接重组的纳米药物应用可能性使这些纳米药物成为进一步临床评估的极佳候选者。所研究的纳米药物的治疗效果直接受药物药代动力学的控制，即由于增强的通透性和保留（EPR）效应，它们在血液中循环有效地积聚在肿瘤中所需时间的能力。简便，可扩展的合成方法以及直接重组的纳米药物应用可能性使这些纳米药物成为进一步临床评估的极佳候选者。

更新日期：2020-03-03

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