To improve the reliability of in vitro release studies of drug delivery systems, we developed a novel in vitro method for the evaluation of drug release from polymeric micelles in complex biological media. Polymeric micelles based on poly(N-2-hydroxypropyl methacrylamide)-block-poly(N-2-benzoyloxypropyl methacrylamide) (p(HPMAm)-b-p(HPMAm-Bz)) of which 10% of the chains was functionalized with biotin at the p(HPMAm) terminus were prepared using a solvent extraction method. The size of the micelles when loaded with a hydrophobic agent, namely paclitaxel (a clinically used cytostatic drug) or curcumin (a compound with multiple pharmacological activities), was around 65 nm. The biotin decoration allowed the binding of the micelles to streptavidin-coated magnetic beads which occurred within 10 min and reached a binding efficiency of 90 ± 6%. Drug release in different media was studied after the magnetic separation of micelles bound to the streptavidin-coated beads, by determination of the released drug in the media as well as the retained drug in the micellar fraction bound to the beads. The in vitro release of paclitaxel and curcumin at 37 °C in PBS, PBS containing 2% v/v Tween 80, PBS containing 4.5% w/v bovine serum albumin, mouse plasma, and whole mouse blood was highly medium-dependent. In all media studied, paclitaxel showed superior micellar retention compared to curcumin. Importantly, the presence of serum proteins accelerated the release of both paclitaxel and curcumin. The results presented in this study show great potential for predicting drug release from nanomedicines in biological media which in turn is crucial for their further pharmaceutical development.

为了提高药物递送系统体外释放研究的可靠性，我们开发了一种新的体外方法来评估复杂生物介质中聚合物胶束的药物释放。基于聚( N -2-羟丙基甲基丙烯酰胺)-嵌段-聚( N )的聚合物胶束-2-苯甲酰氧基丙基甲基丙烯酰胺) (p(HPMAm)-bp(HPMAm-Bz))，其中 10% 的链在 p(HPMAm) 末端被生物素功能化，采用溶剂萃取法制备。当装载疏水剂，即紫杉醇（一种临床使用的细胞抑制药物）或姜黄素（一种具有多种药理活性的化合物）时，胶束的大小约为 65 nm。生物素装饰允许胶束与链霉亲和素包被的磁珠结合，这在 10 分钟内发生，结合效率达到 90 ± 6%。在对与链霉亲和素包被的珠子结合的胶束进行磁分离后，通过测定介质中释放的药物以及与珠子结合的胶束部分中保留的药物，研究了药物在不同介质中的释放。体外的紫杉醇和姜黄素在 37°C 的 PBS、含有 2% v/v Tween 80 的 PBS、含有 4.5% w / v牛血清白蛋白的 PBS、小鼠血浆和小鼠全血中的释放高度依赖于培养基。在所有研究的介质中，与姜黄素相比，紫杉醇显示出优异的胶束保留。重要的是，血清蛋白的存在加速了紫杉醇和姜黄素的释放。本研究中的结果显示出预测纳米药物在生物介质中的药物释放的巨大潜力，这反过来又对其进一步的药物开发至关重要。