Rustad Eirik A L, von Hofsten Susannah, Kumar Robin, Lænsman Eirik A, Berge Gerd, Škalko-Basnet Nataša
Drug Transport and Delivery Research Group, Department of Pharmacy, UiT The Arctic University of Norway, 9019 Tromsø, Norway.
Tumor Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, 9019 Tromsø, Norway.
Pharmaceutics. 2022 May 25;14(6):1125. doi: 10.3390/pharmaceutics14061125.
Nanomedicine has been, to a certain degree, a success story in the development of superior anticancer therapies. However, there are tumors that remain a huge challenge for nanoformulations, for instance, brain tumors such as glioblastoma, the most common and aggressive brain tumor. To utilize the fact that such tumors are characterized by an acidic extracellular environment, we selected pH-responsive liposomes as a potential drug delivery system for superior delivery to GBM. Liposomes comprising PEGylated lipid of two chain lengths with encapsulated fluorescent marker calcein were characterized and challenged against non-PEGylated vesicles. The in vitro calcein release from three liposomal formulations (<200 nm), namely non-PEGylated (pH-Lip) and PEGylated, pH-Lip−PEG750, and pH-Lip−PEG2000, was followed at three pH conditions to prove the pH-responsiveness. The intracellular delivery of a liposomally encapsulated marker was determined in GL261 glioblastoma cell lines in vitro using both flow cytometry and confocal microscopy. The inclusion of PEG2000 within liposomal formulation resulted in reduced in vitro pH-responsiveness compared to pH-Lip and pH-Lip750. All three pH-responsive liposomal formulations improved intracellular uptake in GL261 cells compared to non-pH-responsive liposomes, with negligible differences regarding PEG length. The proposed formulations should be further evaluated in glioblastoma models.
在开发卓越的抗癌疗法方面，纳米医学在一定程度上取得了成功。然而，仍有一些肿瘤对纳米制剂构成巨大挑战，例如脑肿瘤，如胶质母细胞瘤，这是最常见且侵袭性最强的脑肿瘤。为利用此类肿瘤细胞外环境呈酸性这一特点，我们选择了pH响应型脂质体作为一种潜在的药物递送系统，以实现对胶质母细胞瘤的高效递送。对包含两种链长的聚乙二醇化脂质且包裹有荧光标记物钙黄绿素的脂质体进行了表征，并与未聚乙二醇化的囊泡进行了对比。在三种pH条件下监测了三种脂质体制剂（<200 nm），即未聚乙二醇化的（pH-Lip）、聚乙二醇化的pH-Lip−PEG750和pH-Lip−PEG2000中钙黄绿素的体外释放情况，以证明其pH响应性。使用流式细胞术和共聚焦显微镜在体外GL261胶质母细胞瘤细胞系中测定了脂质体包裹标记物的细胞内递送情况。与pH-Lip和pH-Lip750相比，脂质体制剂中加入PEG2000导致体外pH响应性降低。与非pH响应性脂质体相比，所有三种pH响应型脂质体制剂均提高了GL261细胞的细胞内摄取，聚乙二醇长度方面的差异可忽略不计。所提出的制剂应在胶质母细胞瘤模型中进一步评估。
