Main-chain polyacetal conjugates with HIF-1 inhibitors: temperature-responsive, pH-degradable drug delivery vehicles†,Journal of Materials Chemistry B

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Main-chain polyacetal conjugates with HIF-1 inhibitors: temperature-responsive, pH-degradable drug delivery vehicles†
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2018-01-08 00:00:00 , DOI: 10.1039/c7tb01417a
Sanjoy Samanta _{1,

2,

3,

4} , Chathuranga C. De Silva _{1,

2,

3,

4} , Porakrit Leophairatana _{1,

2,

3,

4} , Jeffrey T. Koberstein _{1,

2,

3,

4}

Affiliation

Main-chain polymer–drug conjugates are prepared from polyacetals (PA) and three hydrophobic diol-based HIF-1 inhibitors. The new conjugates are temperature-responsive with lower critical solution temperature (LCST) behavior and are intrinsically pH-degradable. While soluble in plasma at room temperature, they lose solubility above a target temperature that can be adjusted to virtually any temperature of physicological interest, providing mechanisms for site-specific delivery by active thermal targeting or temperature-induced gelation. The reverse phase transition temperature can be precisely tuned by proper choice of four structural variables that characterize the amphiphilic diol and divinyl ether monomers used in the synthesis, or by adjusting the content of drug incorporated within the polymer. These main-chain PA–drug conjugates also allow for site-specific controlled release as they degrade in acidic microenvironments such as tumors. The degradation rates increase with decreasing pH, degradation products are neutral, and pristine drug is released, without any remnants of the conjugation chemistry.

中文翻译：

具有HIF-1抑制剂的主链聚缩醛共轭物：温度响应型，pH可降解的药物递送载体†

主链聚合物-药物偶联物是由聚缩醛（PA）和三种基于疏水二醇的HIF-1抑制剂制备的。新的结合物具有温度响应性，且临界溶液温度（LCST）较低，并且具有内在的pH降解能力。尽管它们在室温下可溶于血浆，但在高于目标温度（可调节至几乎任何生理学温度）的温度下失去溶解度，从而提供了通过主动热靶向或温度诱导的胶凝作用进行位点特异性递送的机制。逆相变温度可通过表征在合成中使用两亲性二醇和二乙烯基醚单体四个结构变量适当选择被精确地调谐，或通过调节聚合物中的掺入的药物的含量。这些主链PA药物偶联物还可以在酸性微环境（例如肿瘤）中降解，从而实现特定位置的控制释放。降解速率随pH降低而增加，降解产物呈中性，并且释放出原始药物，而没有任何共轭化学残留物。

更新日期：2018-01-08

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