A dynamic thermo-responsive drug delivery concept using poly(2-oxazoline) copolymers conjugated with a hydrophobic drug is presented. The novel strategy entails the synthesis of copolymers comprising 2-n-propyl-2-oxazoline and 2-methoxycarbonylpropyl-2-oxazoline to which the drug, benazepril is conjugated via an ester linkage. The polymer without drug is non-toxic and has a cloud point temperature in aqueous conditions around 50 °C meaning that it is soluble at body temperature. Yet, when conjugated with the drug, the cloud point temperature decreases to in between 0 and 30 °C, depending on the quantity of drug coupled to the polymer. Conversely, as the drug is cleaved via ester hydrolysis, the cloud point temperature shifts to higher temperature and the polymer becomes soluble. This shift in cloud point temperature from above to below body temperature upon modification of the polymer with the drug benazepril is hypothesized to make it suitable as an injectable soluble polymer–drug conjugate that forms an insoluble depot to slowly release the pristine drug followed by redissolution of the drug-free polymer.

中文翻译：

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基于聚（2-恶唑啉）共聚物的动态浊点温度的药物-聚合物共轭物

提出了使用与疏水性药物共轭的聚（2-恶唑啉）共聚物的动态热响应药物递送概念。该新策略需要合成包含2-正丙基-2-恶唑啉和2-甲氧基羰基丙基-2-恶唑啉的共聚物，药物贝那普利通过酯键与之结合。没有药物的聚合物是无毒的，在约50°C的水性条件下具有浊点温度，这意味着它在体温下可溶。然而，当与药物结合时，浊点温度会降低到0到30°C之间，这取决于与聚合物偶联的药物量。相反，当药物通过酯水解时，浊点温度转移到更高的温度，聚合物变得可溶。据推测，用贝那普利对聚合物进行改性后，浊点温度从高于体温转变为低于体温，使其适合用作可注射的可溶性聚合物-药物共轭物，形成不溶性贮库，以缓慢释放原始药物，然后重新溶解无毒品的聚合物。