International Journal of Pharmaceutics, 2016, 511(2):745-756.

Self-emulsifying phospholipid pre-concentrates (SEPPs) for improved oral delivery of the anti-cancer genistein: Development, appraisal and ex-vivo intestinal permeation

Eman M. M. Shehata, Yosra S. R. Elnaggar, Saly Galal, et al

Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt; Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Egypt

Genistein (GEN), a potent anticancer agent, suffers from scanty oral bioavailability due to poor solubility and extensive metabolism. This work endeavored to enhance GEN solubility and intestinal permeability via fabrication of self-emulsifying phospholipid pre-concentrates (SEPPs) using some bioactive surfactants. Moreover, the potential of surfactant-free SEPP to address GEN obstacles was investigated. SEPPs were prepared from Phosal® 53MCT, oil/phosphatidylcholine mixture, alone or with only 30% of different surfactant/co-surfactant mixture (S/CO). In-vitro characterization encompassed globule size analysis, zeta potential (ZP), transmission electron microscopy, and in-vitro release. Ex-vivo intestinal permeation study was performed using non-everted rat intestinal sac technique. Upon aqueous dilution, SEPPs were easily dispersed with spherical globules within a nano-range size (from 165 ± 15 to 425 ± 20 nm) and adequate negative ZP (>−30 mV). SEPPs demonstrated a significant enhancement in GEN release compared to drug suspension without superior effect due to added S/CO. Permeation study revealed that at least 12.13% free GEN was permeated after 120 min from SEPPs compared to only 3.7% from drug suspension. Among different SEPPs, SEPP containing 30% Tween 80/Transcutol HP mixture showed the highest GEN permeation (18.54%). Conclusively, SEPP might be a promising nanocarrier that enhances GEN bioavailability via improving dissolution and inhibition of pre-systemic clearance.

荷兰《国际药剂学杂志》, 2016, 511(2):745-756.

提高抗癌药金雀异黄素口服给药的自乳化磷脂预浓缩物 (SEPPs)︰ 开发、 评价和离体肠道渗透

药剂学系，系药剂，亚历山德里亚大学、 埃及;药学与药品生产，在埃及的亚历山大灯塔大学学院药学部

染料木素（GEN），一种强效的抗癌剂，由于溶解性差和广泛的代谢，口服生物利用度低。这项工作是努力通过使用一些生物活性表面活性剂自乳化磷脂预浓缩物（SEPP）增强GEN溶解度和肠渗透性。此外，研究了无表面活性剂的SEPP解决GEN障碍的潜力。SEPP由单独的或与仅30％的不同表面活性剂/辅助表面活性剂混合物（S / CO）的53MCT，油/磷脂酰胆碱混合物制备。体外表征包括球粒大小分析，ζ电位（ZP），透射电子显微镜和体外释放。使用非外翻大鼠肠囊技术进行离体肠渗透研究。使用非外翻大鼠肠囊技术进行离体肠渗透研究。在水性稀释时，SEPP容易以纳米范围尺寸（从165±15至425±20nm）和足够的负ZP（>-30mV）的球形球分散。与药物悬浮液相比，SEPP显示出GEN释放的显着增强，由于添加的S / CO没有优异的效果。渗透研究显示，在120分钟后从SEPP渗透至少12.13％的游离GEN，相比之下，药物悬浮液仅有3.7％。在不同的SEPP中，含有30％Tween 80 / Transcutol HP混合物的SEPP显示出最高的GEN渗透（18.54％）。最终，SEPP可能是一种有前景的纳米载体，通过改善溶出和抑制前全身清除来增强GEN生物利用度。