Elzoghby Ahmed O, Mostafa Shaimaa K, Helmy Maged W, ElDemellawy Maha A, Sheweita Salah A
Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
Pharm Res. 2017 Sep;34(9):1956-1969. doi: 10.1007/s11095-017-2207-2. Epub 2017 Jun 22.
In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB).
Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer.
Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core. Moreover, phospholipid coating provided protection for cationic PRM-NCs against interaction with RBCs and serum proteins enabling their systemic administration. Pharmacokinetic analysis demonstrated prolonged circulation and delayed clearance of both drugs after intravenous administration into rats. The superior anti-tumor efficacy of multi-reservoir NCs was manifested as powerful cytotoxicity against MCF-7 breast cancer cells and marked reduction in the mammary tumor volume in Ehrlich ascites bearing mice compared with free LTZ-CXB combination. Moreover, the NCs induced apoptotic caspase activation and marked inhibition of aromatase expression and angiogenic marker, VEGF as well as inhibition of both NFκB and TNFα.
Multi-reservoir phospholipid shell coating PRM-NCs could serve as a promising nanocarrier for parenteral combined delivery of LTZ and CXB.
在当前工作中，我们提出了一种用于来曲唑（LTZ）和塞来昔布（CXB）的联合递送纳米平台。
通过将鱼精蛋白纳米胶囊（PRM-NCs）包裹在药物-磷脂复合双层中，开发了多储库纳米载体。
磷脂双层中纳米胶囊的包封通过尺寸从109.7 nm增加到179.8 nm以及表面电荷从+19.0 mV降低到+7.78 mV得以证实。多隔室核壳结构实现了塞来昔布的双相释放，最初由与磷脂壳的络合诱导快速释放，随后从油性核心实现延长释放。此外，磷脂涂层为阳离子PRM-NCs提供了保护，使其免受与红细胞和血清蛋白的相互作用，从而能够进行全身给药。药代动力学分析表明，静脉注射到大鼠体内后，两种药物的循环时间延长，清除延迟。与游离LTZ-CXB组合相比，多储库纳米胶囊具有卓越的抗肿瘤功效，表现为对MCF-7乳腺癌细胞具有强大的细胞毒性，以及在携带艾氏腹水瘤的小鼠中乳腺肿瘤体积显著减小。此外，纳米胶囊诱导凋亡半胱天冬酶激活，并显著抑制芳香化酶表达和血管生成标志物VEGF，以及抑制NFκB和TNFα。
多储库磷脂壳包被的PRM-NCs可作为一种有前景的纳米载体，用于来曲唑和塞来昔布的肠胃外联合递送。
