Asfour Hani Z, Alhakamy Nabil A, Fahmy Usama A, Ahmed Osama A A, Rizg Waleed Y, Felimban Raed I, Abdel-Naim Ashraf B, Abourehab Mohammad A S, Mansouri Rasha A, Omar Ulfat M, Badr-Eldin Shaimaa M
Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Pharmaceutics. 2022 Jun 16;14(6):1279. doi: 10.3390/pharmaceutics14061279.
Icariin (ICA), a main active compound of the Epimedium genus, is used as an aphrodisiac in traditional Chinese herbal medicine. Despite its therapeutic efficacy, ICA displays reduced oral absorption, and therefore, low bioavailability hindered its clinical application. Implementing nanotechnology in the field of formulation has been a focus to improve the efficacy of ICA. In this regard, polymeric nanoparticles find a potential application as drug delivery systems. A nanosphere formula was designed, aiming to improve the drug's efficacy. The proposed ICA nanosphere formula (tocozeinolate) was optimized using D-optimal response surface design. The concentrations of ICA (X), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS, X), zein (X), and sodium deoxycholate (SDC, X) expressed as percentages were investigated as quantitative independent variables. As per the experimental design, 23 formulations were developed, which were investigated for particle size (PS, nm), zeta potential (ZP, mV), and entrapment efficiency (EE, %) as response parameters. Numerical optimization and desirability approach were employed to predict the optimized variable levels that, upon combination, could result in minimized size and maximized zeta potential and ICA entrapment. The optimized ICA-tocozeinolate nanospheres showed a particle size of 224.45 nm, zeta potential of 0.961 mV, and drug entrapment of 65.29% that coincide well with the predicted values. The optimized ICA-tocozeinolate nanospheres were evaluated for sexual behavior in Wistar male rats compared to raw ICA at equivalent doses (20 mg/kg). In vivo assessment results showed significant sexual behavior enhancement by the optimized formulation, as evidenced by decreased average time of both mount latency (ML) and ejaculation latency (EL) to almost half those of raw ICA. Additionally, intromission latency (IL) time was reduced by 41% compared to the raw ICA. These results highlighted the potential of the proposed ICA-tocozeinolate nanospheres as a promising platform for improving the delivery and efficacy of therapeutic agents.
淫羊藿苷（ICA）是淫羊藿属的主要活性化合物，在传统中药中用作壮阳药。尽管ICA具有治疗功效，但其口服吸收减少，因此，低生物利用度阻碍了其临床应用。在制剂领域应用纳米技术一直是提高ICA疗效的重点。在这方面，聚合物纳米颗粒作为药物递送系统具有潜在应用。设计了一种纳米球配方，旨在提高药物疗效。使用D-最优响应面设计对所提出的ICA纳米球配方（生育三烯酚）进行优化。将以百分比表示的ICA浓度（X1）、聚乙二醇1000维生素E琥珀酸酯（TPGS，X2）、玉米醇溶蛋白（X3）和脱氧胆酸钠（SDC，X4）作为定量自变量进行研究。根据实验设计，制备了23种制剂，并将粒径（PS，nm）、zeta电位（ZP，mV）和包封率（EE，%）作为响应参数进行研究。采用数值优化和可取性方法预测优化后的变量水平，这些变量组合后可使粒径最小化、zeta电位最大化和ICA包封率最大化。优化后的ICA-生育三烯酚纳米球粒径为224.45 nm，zeta电位为0.961 mV，药物包封率为65.29%，与预测值吻合良好。将优化后的ICA-生育三烯酚纳米球与等效剂量（20 mg/kg）的原料药ICA相比，在Wistar雄性大鼠中进行性行为评估。体内评估结果显示，优化后的制剂显著增强了性行为，表现为爬跨潜伏期（ML）和射精潜伏期（EL）的平均时间均降至原料药ICA的近一半。此外，插入潜伏期（IL）时间比原料药ICA减少了41%。这些结果突出了所提出的ICA-生育三烯酚纳米球作为改善治疗药物递送和疗效的有前景平台的潜力。
