Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab-160062, India.
Drug Deliv Transl Res. 2024 Feb;14(2):510-523. doi: 10.1007/s13346-023-01415-7. Epub 2023 Aug 21.
Breast cancer is challenging to treat accompanied with poor clinical outcomes. Paclitaxel (PTX) is a first-line chemotherapeutic agent, but possesses limitations due to side effects, high dose, non-specific tissue distribution, and drug resistance. An epigenetic modulator, vorinostat (VOR) is known to enhance PTX efficacy and therefore to resolve the issues of conventional PTX formulations, we designed PTX- and VOR-bound albumin nanoparticles (PTX-VOR-BSA-NPs) using antisolvent precipitation technique where albumin is used as a carrier and a targeting agent. The PTX-VOR-BSA-NPs were of 140 nm size, polydispersity index around 0.18, and about 78% and 68% of entrapment efficiency for PTX and VOR, respectively. A bi-pattern release of both PTX and VOR was observed from PTX-VOR-BSA-NPs with a burst release for 2 h succeeded by sustained release until 24 h. A significantly lower %cell viability was observed in MCF-7 cell lines, while efficient cellular drug uptake was found in MDA-MB-231 cells. Furthermore, a greater apoptotic index was found compared to free PTX and VOR because of the synergistic activity of these drugs. The PTX-VOR-BSA-NPs also showcased superior pharmacokinetic profile and noteworthy reduction in the tumor volume compared to Intaxel in 4T1 cell line-induced breast tumor model. Further, the NPs showed similar levels of toxicity biomarkers as that of control. Overall, the developed PTX-VOR-BSA-NPs were found to have less toxicity and more effectiveness compared to the marketed formulation, thus affirming the generation of a potent as well as and safe product.
乳腺癌的治疗具有挑战性，临床疗效较差。紫杉醇（PTX）是一种一线化疗药物，但由于副作用、高剂量、非特异性组织分布和耐药性等问题，其应用受到限制。表观遗传调节剂伏立诺他（VOR）可增强 PTX 的疗效，因此为了解决传统 PTX 制剂的问题，我们采用抗溶剂沉淀技术设计了 PTX 和 VOR 结合的白蛋白纳米粒（PTX-VOR-BSA-NPs），其中白蛋白被用作载体和靶向剂。PTX-VOR-BSA-NPs 的粒径为 140nm，多分散指数约为 0.18，PTX 和 VOR 的包封效率分别约为 78%和 68%。从 PTX-VOR-BSA-NPs 中观察到 PTX 和 VOR 的双模式释放，前 2 小时有突释，随后持续释放至 24 小时。在 MCF-7 细胞系中观察到细胞存活率显著降低，而在 MDA-MB-231 细胞中发现了有效的细胞内药物摄取。此外，与游离 PTX 和 VOR 相比，由于这些药物的协同作用，发现凋亡指数更高。与 Intaxel 相比，PTX-VOR-BSA-NPs 在 4T1 细胞系诱导的乳腺癌模型中还表现出更好的药代动力学特征和肿瘤体积显著减少。此外，纳米粒的毒性生物标志物水平与对照组相似。总的来说，与市售制剂相比，开发的 PTX-VOR-BSA-NPs 具有较低的毒性和更高的疗效，这证实了该产品具有更强的疗效和安全性。
