N-(2-Hydroxypropyl)methacrylamide-Based Linear, Diblock, and Starlike Polymer Drug Carriers: Advanced Process for Their Simple Production,Biomacromolecules

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N-(2-Hydroxypropyl)methacrylamide-Based Linear, Diblock, and Starlike Polymer Drug Carriers: Advanced Process for Their Simple Production
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-09-05 00:00:00 , DOI: 10.1021/acs.biomac.8b00973
Eva Koziolová , Libor Kostka , Lenka Kotrchová , Vladimír Šubr , Rafal Konefal , Benjamin Nottelet ₁ , Tomáš Etrych

Affiliation

We developed a new simplified method for the synthesis of well-defined linear, diblock, or starlike N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer drug carriers using controlled reversible addition–fragmentation chain transfer polymerization. The prepared monodispersed polymers are after the drug attachment intended for enhanced anticancer therapy. This new approach significantly reduces the number of required synthetic steps and minimizes the consumption of organic solvents during the synthesis. As a result, highly defined linear, diblock, and starlike copolymers designed for pH-triggered drug activation/release in tumor tissue were formed in sufficient amounts for further physicochemical and biological studies. Within the synthesis, we also developed a new procedure for the selective deprotection of tert-butoxycarbonyl hydrazide and amine groups on hydrophilic HPMA copolymers, including the one-pot removal of polymer end groups. We studied and described in detail the kinetics and efficacy of the deprotection reaction. We believe the simplified synthetic approach facilitates the preparation of polymer conjugates bound by the pH-sensitive hydrazone bond and their application in tumor treatment.

中文翻译：

基于N-（2-羟丙基）甲基丙烯酰胺的线性，二嵌段和星形聚合物药物载体：简单生产的先进工艺

我们开发了一种新的简化方法，该方法使用可控的可逆加成-断裂链转移聚合反应来合成定义明确的线性，二嵌段或星形N-（2-羟丙基）甲基丙烯酰胺（HPMA）基聚合物药物载体。制备的单分散聚合物在用于增强抗癌治疗的药物附着之后。这种新方法大大减少了所需的合成步骤，并最大程度地减少了合成过程中有机溶剂的消耗。结果，形成了足够量的高度定义的线性，二嵌段和星形共聚物，其设计用于在肿瘤组织中进行pH触发的药物活化/释放，以用于进一步的物理化学和生物学研究。在合成过程中，我们还开发了一种新的程序，用于选择性脱保护亲水HPMA共聚物上的叔丁氧羰基酰肼和胺基团，包括一锅法除去聚合物端基。我们研究并详细描述了脱保护反应的动力学和功效。我们认为，简化的合成方法有助于通过pH敏感键结合的聚合物共轭物的制备及其在肿瘤治疗中的应用。

更新日期：2018-09-05

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