Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareily Road, Lucknow, India.
Drug Deliv Transl Res. 2022 Dec;12(12):3047-3062. doi: 10.1007/s13346-022-01169-8. Epub 2022 Apr 30.
Limited targeted therapies are available for triple-negative breast cancer (TNBC). Thus, the current research focused on developing a targeted protein nanoparticle for TNBC. First, the doxorubicin hydrochloride (Dox)-loaded genipin-crosslinked whey protein nanoparticles (WD) were prepared and optimised by the QbD method using BBD. The hydrodynamic diameter of WD was found to be 364.38 ± 49.23 nm, zeta potential -27.59 ± 1.038 mV, entrapment 63.03 ± 3.625% and Dox loading was found to be 1.419 ± 0.422%. The drug recovery after 18 months of storage was 69%. Then, it was incubated with NAC to obtain modified WD (CyWD). WD followed first-order release kinetics, whereas CyWD followed the Higuchi model. Hemagglutination and hemolysis were not found qualitatively in WD and CyWD. Upon injecting the nanoformulations to 4T1-induced mice, the highest efficacy was found to be in CyWD followed by WD and Dox injection. Upon histopathological observance, it was found that the CyWD group gave the most significant damage to the 4T1 tumour tissue. Thus, NAC-modified protein nanoparticles carrying chemotherapeutic agents can be an excellent targeted therapeutic system against TNBC.
针对三阴性乳腺癌（TNBC），目前仅有有限的靶向治疗方法。因此，目前的研究集中在开发针对 TNBC 的靶向蛋白纳米颗粒。首先，采用 QbD 方法，利用 BBD 制备并优化了盐酸多柔比星（Dox）负载的京尼平交联乳清蛋白纳米粒（WD）。WD 的水动力学直径为 364.38±49.23nm，zeta 电位为-27.59±1.038mV，包封率为 63.03±3.625%，Dox 载药量为 1.419±0.422%。储存 18 个月后，药物回收率为 69%。然后，将其与 NAC 孵育得到改性 WD（CyWD）。WD 遵循一级释放动力学，而 CyWD 遵循 Higuchi 模型。WD 和 CyWD 在定性上均未发现血凝和溶血。将纳米制剂注射到 4T1 诱导的小鼠中后，发现 CyWD 的疗效最高，其次是 WD 和 Dox 注射。通过组织病理学观察，发现 CyWD 组对 4T1 肿瘤组织的损伤最大。因此，载有化疗药物的 NAC 修饰蛋白纳米粒可以成为针对 TNBC 的优秀靶向治疗系统。
