Translational Pharmaceutics Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Hyderabad, Pilani, India.
Nanomedicine and Bioengineering Research Laboratory, Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, India.
AAPS PharmSciTech. 2024 May 6;25(5):97. doi: 10.1208/s12249-024-02806-w.
Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal types of cancer with high mortality/incidence. Considering the crucial role of vascular endothelial growth factor (VEGF) in PDAC progression, its inhibition can be a viable strategy for the treatment. Pazopanib, a second-generation VEGF inhibitor, is approved for the treatment of various oncological conditions. However, due to associated limitations like low oral bioavailability (14-39%), high inter/intra-subject variability, stability issues, etc., high doses (800 mg) are required, which further lead to non-specific toxicities and also contribute toward cancer resistance. Thus, to overcome these challenges, pazopanib-loaded PEGylated nanoliposomes were developed and evaluated against pancreatic cancer cell lines. The nanoliposomes were prepared by thin-film hydration method, followed by characterization and stability studies. This QbD-enabled process design successfully led to the development of a suitable pazopanib liposomal formulation with desirable properties. The % entrapment of PZP-loaded non-PEGylated and PEGylated nanoliposomes was found to be 75.2% and 84.9%, respectively, whereas their particle size was found to be 129.7 nm and 182.0 nm, respectively. The developed liposomal formulations exhibited a prolonged release and showed desirable physicochemical properties. Furthermore, these liposomal formulations were also assessed for in vitro cell lines, such as cell cytotoxicity assay and cell uptake. These studies confirm the effectiveness of developed liposomal formulations against pancreatic cancer cell lines. The outcomes of this work provide encouraging results and a way forward to thoroughly investigate its potential for PDAC treatment.
胰腺导管腺癌 (PDAC) 是一种高致命性癌症，死亡率/发病率很高。考虑到血管内皮生长因子 (VEGF) 在 PDAC 进展中的关键作用，抑制其活性可能是一种可行的治疗策略。帕唑帕尼是一种第二代 VEGF 抑制剂，已被批准用于治疗各种肿瘤疾病。然而，由于其存在口服生物利用度低（14-39%）、个体内/间变异性高、稳定性问题等限制，需要使用高剂量（800mg），这会导致非特异性毒性，并导致癌症耐药性。因此，为了克服这些挑战，开发了载帕唑帕尼的 PEG 化纳米脂质体，并对胰腺癌细胞系进行了评估。纳米脂质体通过薄膜水化法制备，然后进行特性和稳定性研究。这种基于 QbD 的工艺设计成功地开发出了一种具有理想特性的合适的载帕唑帕尼脂质体制剂。载有 PZP 的非 PEG 化和 PEG 化纳米脂质体的包封率分别为 75.2%和 84.9%，而它们的粒径分别为 129.7nm 和 182.0nm。所开发的脂质体制剂表现出延长的释放，并表现出理想的物理化学性质。此外，还对这些脂质体制剂进行了体外细胞系评估，如细胞细胞毒性测定和细胞摄取。这些研究证实了开发的脂质体制剂对胰腺癌细胞系的有效性。这项工作的结果提供了令人鼓舞的结果，并为进一步研究其在 PDAC 治疗中的潜力提供了方向。
