a Department of Pharmacy , The Second Xiangya Hospital, Central South University , Changsha , China.
b Institute of Clinical Pharmacy , Central South University , Changsha , China.
Drug Deliv. 2018 Nov;25(1):827-837. doi: 10.1080/10717544.2018.1455763.
Puerarin (PUE) is the most abundant isoflavonoid in kudzu root. It is widely used as a therapeutic agent for the treatment of cardiovascular diseases. However, the short elimination half-life, poor-bioavailability, and acute intravascular hemolysis of PUE are the main obstacles to its widespread clinical applications. Whereas PEG-PE micelles possess the ability to release medicine slowly, enhance the cellular uptake of drugs and improve their biocompatibility. Therefore, it was aim to fabricate puerarin-loaded PEG-PE (PUE@PEG-PE) micelles to improve the pharmaceutical properties of drugs. It can be observed from the TEM images that PUE@PEG-PE micelles appeared obvious core-shell structure and remained well-dispersed without aggregation and adhesion. PUE was successfully embedded in the core of PEG-PE micelles, which was confirmed by FT-IR and H NMR spectra. In vitro studies showed that PUE@PEG-PE micelles exhibited a sustained release behavior in pH 7.4 PBS buffer and decreased hemolysis rate of PUE. Compared with PUE, PUE@PEG-PE micelles showed a 3.2-fold increase in the half-life of PUE and a 1.58-fold increase in bioavailability. In addition, the PUE@PEG-PE micelles exerted enhanced protective effect against isoprenaline-induced H9c2 cells apoptosis compared with PUE, as evident by decreased percentage of Hoechst-positive cells, Caspase 3 activity, Bax expression, and increased Bcl-2 expression. Notably, the PEG-PE micelles exhibited favorable cellular uptake efficiency on H9c2 cells, and this may account for their enhanced anti-apoptotic effect of the incorporated drug. Altogether, the PUE@PEG-PE micelles were not only able to control the drug release but also offered promise to enhance the pharmacokinetic and pharmacodynamic potential of PUE.
葛根素（PUE）是葛根中含量最丰富的异黄酮。它被广泛用作治疗心血管疾病的治疗剂。然而，葛根素半衰期短、生物利用度差和急性血管内溶血是其广泛临床应用的主要障碍。而 PEG-PE 胶束具有缓慢释放药物、增强药物的细胞摄取和提高其生物相容性的能力。因此，目的是制备葛根素负载的 PEG-PE（PUE@PEG-PE）胶束以改善药物的药物特性。可以从 TEM 图像中观察到，PUE@PEG-PE 胶束呈现明显的核壳结构，并且保持良好的分散状态，没有聚集和粘连。PUE 成功地嵌入了 PEG-PE 胶束的核心中，这一点通过 FT-IR 和 H NMR 光谱得到了证实。体外研究表明，PUE@PEG-PE 胶束在 pH7.4 PBS 缓冲液中表现出持续释放行为，并降低了 PUE 的溶血率。与 PUE 相比，PUE@PEG-PE 胶束使 PUE 的半衰期延长了 3.2 倍，生物利用度提高了 1.58 倍。此外，与 PUE 相比，PUE@PEG-PE 胶束对异丙肾上腺素诱导的 H9c2 细胞凋亡表现出增强的保护作用，表现在 Hoechst 阳性细胞的百分比降低、Caspase 3 活性、Bax 表达降低和 Bcl-2 表达增加。值得注意的是，PEG-PE 胶束对 H9c2 细胞具有良好的细胞摄取效率，这可能是其增强了所包含药物的抗凋亡作用的原因。总之，PUE@PEG-PE 胶束不仅能够控制药物释放，而且有望增强 PUE 的药代动力学和药效学潜力。
