Liu Huanhuan, Chen Hong, Cao Fuhu, Peng Daiyin, Chen Weidong, Zhang Chuanling
The College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
Anhui Province Key Laboratory of Advanced Catalytic Materials and Reaction Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei 230009, China.
Polymers (Basel). 2019 May 7;11(5):820. doi: 10.3390/polym11050820.
Gambogenic acid (GNA) has been demonstrated with outstanding antitumor activity as a potential antitumor drug in recent years. However, the low solubility and deficient bioavailability of GNA seriously hinder its practical application in the clinic area. In this study, a novel amphiphilic block copolymer, poly (acrylic acid)--polycaprolactone (PAA--PCL) is prepared and assembled into pH-responsive polymeric micelles (PMs) as one mold of drug delivery system (DDS) with unique properties. Relevant investigation on PMs exhibits excellent carrying potential and pH-dependent release performance for GNA. The drug loading capacity (DLC) and drug loading efficiency (DLE) for GNA-loaded PMs can be achieved as high as 15.20 ± 0.07% and 83.67 ± 0.49%, respectively. The in vitro experiments indicate that the GNA releasing time, cytotoxicity, and cellular uptake are significantly enhanced. Especially, the peak concentration (Cmax) and area under the curve (AUC) are promoted sharply in the GNA-loaded PMs concentration-time curve. This study not only provides a novel way to widen the application of anticancer GNA in the future, but also extends the potential of stimuli-responsive copolymers to biomedical applications.
藤黄酸（GNA）近年来已被证明作为一种潜在的抗肿瘤药物具有出色的抗肿瘤活性。然而，GNA的低溶解度和不足的生物利用度严重阻碍了其在临床领域的实际应用。在本研究中，制备了一种新型两亲性嵌段共聚物聚（丙烯酸）-聚己内酯（PAA-PCL），并将其组装成pH响应性聚合物胶束（PMs），作为一种具有独特性质的药物递送系统（DDS）。对PMs的相关研究表明其对GNA具有出色的载药潜力和pH依赖性释放性能。载GNA的PMs的载药量（DLC）和载药效率（DLE）分别可高达15.20±0.07%和83.67±0.49%。体外实验表明，GNA的释放时间、细胞毒性和细胞摄取均显著增强。特别是，在载GNA的PMs浓度-时间曲线中，峰浓度（Cmax）和曲线下面积（AUC）急剧升高。本研究不仅为未来拓宽抗癌GNA的应用提供了一种新方法，还扩展了刺激响应性共聚物在生物医学应用方面的潜力。
