Alhakamy Nabil A, A Fahmy Usama, Badr-Eldin Shaimaa M, Ahmed Osama A A, Asfour Hani Z, Aldawsari Hibah M, Algandaby Mardi M, Eid Basma G, Abdel-Naim Ashraf B, Awan Zuhier A, K Alruwaili Nabil, Mohamed Amir I
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Pharmaceutics. 2020 Apr 11;12(4):346. doi: 10.3390/pharmaceutics12040346.
Icariin (ICA) is a flavonol glycoside that has pleiotropic pharmacological actions. It has cytotoxic effects against ovarian cancer cells and increases their chemosensitivity to chemotherapeutic drugs. Phytosomes are identified for their potential in drug delivery of cytotoxic agents. Thus, the purpose of this study was to determine the potential enhancement of ICA cytotoxicity activity in OVCAR-3 ovarian cancer cells via its formulation in phytosomes. ICA-phytosomal formulation was optimized using a Box-Behnken design. Particle size, shape, and in vitro drug release were used to characterize the optimized formula. The optimized formulation exhibited enhanced in vitro drug release. ICA-phytosomes exhibited enhanced cytotoxicity against ovarian cancer cells. Cell cycle analysis indicated accumulation of cells challenged with ICA-phytosomes in G2/M and pre-G1 phases. Staining of cells with annexin V indicated significant elevation of percentage cells with early and late apoptosis as well as total cell death. In addition, the formulation significantly disturbed mitochondrial membrane potential and cellular content of caspase 3. In addition, intracellular release of reactive oxygen species (ROS) was enhanced by ICA-phytosomes. In conclusion, phytosome formulation of ICA significantly potentiates its cytotoxic activities against OVCAR-3 cells. This is mediated, at least partly, by enhanced ICA cellular permeation, apoptosis, and ROS.
淫羊藿苷（ICA）是一种具有多种药理作用的黄酮醇苷。它对卵巢癌细胞具有细胞毒性作用，并增加其对化疗药物的化学敏感性。植物药脂质体因其在细胞毒性药物递送方面的潜力而被认可。因此，本研究的目的是通过将ICA制成植物药脂质体来确定其对OVCAR-3卵巢癌细胞细胞毒性活性的潜在增强作用。采用Box-Behnken设计对ICA-植物药脂质体制剂进行优化。通过粒径、形状和体外药物释放来表征优化后的配方。优化后的制剂表现出增强的体外药物释放。ICA-植物药脂质体对卵巢癌细胞表现出增强的细胞毒性。细胞周期分析表明，用ICA-植物药脂质体处理的细胞在G2/M期和G1期前积累。用膜联蛋白V对细胞进行染色表明，早期和晚期凋亡细胞以及总细胞死亡的百分比显著升高。此外，该制剂显著扰乱线粒体膜电位和细胞内半胱天冬酶3的含量。此外，ICA-植物药脂质体增强了活性氧（ROS）的细胞内释放。总之，ICA的植物药脂质体制剂显著增强了其对OVCAR-3细胞的细胞毒性活性。这至少部分是由ICA细胞渗透、凋亡和ROS增强介导的。
