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; Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Egypt.
Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Behira, Egypt.
Colloids Surf B Biointerfaces. 2018 Sep 1;169:183-194. doi: 10.1016/j.colsurfb.2018.05.008. Epub 2018 May 15.
The self-tumor targeting polymers, lactoferrin (LF) and hyaluronic acid (HA) were utilized to develop layer-by-layer (LbL) lipid nanoparticles (NPs) for dual delivery of berberine (BER) and rapamycin (RAP) to lung cancer. To control its release from the NPs, BER was hydrophobically ion paired with SLS prior to incorporation into NPs. Spherical HA/LF-LbL-RAP-BER/SLS-NPs 250.5 nm in diameter, with a surface charge of -18.5 mV were successfully elaborated. The NPs exhibited sequential release pattern with faster release of BER followed by controlled release of RAP which enables sensitization of lung tumor cells to the anti-cancer action of RAP. LbL coating of the NPs was found to enhance the drug cytotoxicity against A549 lung cancer cells as augmented by remarkable increase in their cellular internalization through CD44 receptors overexpressed by tumor cells. In vivo studies in lung cancer bearing mice have revealed the superior therapeutic activity of LbL-RAP-BER/SLS-NPs over the free drugs as demonstrated by 88.09% reduction in the average number of microscopic lung foci and 3.1-fold reduction of the angiogenic factor VEGF level compared to positive control. Overall, the developed HA/LF-LbL-coated lipid NPs could be potential carriers for targeted co-delivery of BER and RAP to lung cancer cells.
利用具有自主靶向肿瘤能力的聚合物乳铁蛋白（LF）和透明质酸（HA），开发了层层（LbL）脂质纳米粒（NPs），用于双重递送至肺癌的小檗碱（BER）和雷帕霉素（RAP）。为了控制 NPs 中药物的释放，BER 与 SLS 疏水离子配对，然后再将其包埋入 NPs 中。成功制备了直径为 250.5nm、表面电荷为-18.5mV 的球形 HA/LF-LbL-RAP-BER/SLS-NPs。NPs 表现出顺序释放模式，BER 快速释放，随后 RAP 受控释放，从而使肺癌细胞对 RAP 的抗癌作用敏感。研究发现，NPs 的 LbL 涂层能够增强药物对 A549 肺癌细胞的细胞毒性，这是通过肿瘤细胞过度表达的 CD44 受体显著增加细胞内化而实现的。在荷肺癌小鼠的体内研究中，与游离药物相比，LbL-RAP-BER/SLS-NPs 具有更好的治疗效果，表现为平均肺灶数减少了 88.09%，血管生成因子 VEGF 水平降低了 3.1 倍，优于阳性对照。总的来说，开发的 HA/LF-LbL 涂层脂质 NPs 可能是靶向递送至肺癌细胞的 BER 和 RAP 共递送的潜在载体。
