Department of Pharmacy, University Federico II of Naples, Via Domenico Montesano, 49, 80131 Naples, Italy.
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy.
Int J Pharm. 2020 Oct 15;588:119693. doi: 10.1016/j.ijpharm.2020.119693. Epub 2020 Aug 2.
Hybrid self-assembling nanoparticles (SANPs) have been previously designed as novel drug delivery system that overcomes stability issues following long-term storage and with an easy scale-up. This system has been successfully used to deliver anionic-charged agents, e.g. bisphosphonates, in different types of tumors, such glioblastoma (GBM). Here, SANPs were tested and optimized for the delivery of nucleic acids, in particular of a specific microRNA, e.g. miR603, used for its potential role in controlling the chemoresistance in different forms of cancer, e.g. (GBM). To this aim, SANPs with different lipids were prepared and characterized, in terms of size, polydispersity index, zeta potential, miRNA encapsulation, stability in BSA, serum and hemolytic activity. Then, SANPs were tested in vitro on two different cell lines of GBM. Finally, miRNA biodistribution was tested in vivo in an orthotopic model of GBM. The majority of the formulations showed good technological characteristics and were stable in BSA and serum with a low hemolytic activity. The intracellular uptake studies on GBM cell lines showed that SANPs allow to achieve a higher miRNA delivery compared to others transfection agents, e.g. lipofectamine. Finally, in vivo biodistribution studies in an orthotopic of GBM demonstrated that the optimized SANP formulations, were able to deliver miRNA in different organs, e.g. the brain.
杂化自组装纳米颗粒 (SANP) 以前被设计为一种新的药物传递系统，可克服长期储存后的稳定性问题，并且易于扩大规模。该系统已成功用于递送阴离子带电剂，例如双膦酸盐，用于不同类型的肿瘤，例如神经胶质瘤 (GBM)。在这里，SANP 经过测试和优化，用于递送核酸，特别是特定的 microRNA，例如 miR603，因其在控制不同形式的癌症（例如 GBM）的化学抗性方面的潜在作用而被使用。为此，使用不同的脂质制备和表征了 SANP，从大小、多分散指数、zeta 电位、miRNA 包封、BSA、血清和溶血活性稳定性等方面进行了研究。然后，在两种不同的 GBM 细胞系上进行了体外测试。最后，在 GBM 的原位模型中进行了体内 miRNA 分布测试。大多数制剂表现出良好的技术特性，在 BSA 和血清中稳定，溶血活性低。在 GBM 细胞系上的细胞内摄取研究表明，与其他转染剂（例如脂质体）相比，SANP 允许实现更高的 miRNA 传递。最后，在 GBM 的原位模型中的体内分布研究表明，优化的 SANP 制剂能够将 miRNA 递送到不同的器官，例如大脑。
