Purpose

The aim of this study was to develop liposomes loaded with (-)- epigallocatechin gallate (EGCG) by using the Quality by Design (QbD) approach.

Methods

The risk assessment tools (Ishikawa diagram and Risk Estimation Matrix) highlighted three formulation factors, namely phospholipid concentration, phospholipid to cholesterol molar ratio and EGCG concentration that are likely to influence the critical quality attributes (CQAs) of the EGCG containing liposomes and thus were studied through a D-optimal experimental design.

Results

The results revealed that all three formulation factors presented a great influence on liposomes CQAs. High concentrations of EGCG and cholesterol were observed to increase the encapsulation of EGCG into liposomes at low values of the phospholipid concentration. On the other hand, high concentrations of EGCG increased liposomal size and zeta potential values. The optimal formulation featured an entrapped drug concentration of 221.9 µg/ml, corresponding to an encapsulation efficiency of 69.2%, while the liposomal size was 175.2 nm. The release profile illustrated a prolonged release of EGCG from the optimal formulation on a period of 72 h, with a total percentage released of 56%. The in vitro studies performed on dental follicle (DF) mesenchymal stem cells and periodontal ligament (PDL) mesenchymal stem cells showed that EGCG exert its antioxidant effect on DF but not on PDL.

Conclusion

The application of the QbD concept in the development of EGCG loaded liposomes improved the understanding of the manufacturing process as well as the influence of the formulation factors on the quality attributes of liposomes.

中文翻译：

---

QbD 方法在 EGCG 脂质体制剂开发中的应用

目的

本研究的目的是通过使用质量源于设计 (QbD) 方法开发装载有 (-)- 表没食子儿茶素没食子酸酯 (EGCG) 的脂质体。

方法

风险评估工具（石川图和风险估计矩阵）突出了三个配方因素，即磷脂浓度、磷脂与胆固醇的摩尔比和 EGCG 浓度，它们可能会影响含有脂质体的 EGCG 的关键质量属性 (CQA)，因此进行了研究通过 D 最优实验设计。

结果

结果表明，所有三种配方因素都对脂质体 CQAs 有很大影响。观察到高浓度的 EGCG 和胆固醇会在低磷脂浓度值下增加 EGCG 向脂质体中的包封。另一方面，高浓度的 EGCG 会增加脂质体大小和 zeta 电位值。最佳制剂的包埋药物浓度为 221.9 µg/ml，对应的包封率为 69.2%，而脂质体大小为 175.2 nm。释放曲线表明 EGCG 在 72 小时内从最佳制剂中延长释放，总释放百分比为 56%。

结论

QbD 概念在 EGCG 负载脂质体开发中的应用提高了对制造过程的理解以及配方因素对脂质体质量属性的影响。