Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy.
Department of Pharmacy, University Federico II of Naples, Via Domenico Montesano, 49, 80131 Naples, Italy.
Int J Mol Sci. 2022 May 5;23(9):5138. doi: 10.3390/ijms23095138.
Self-assembling nanoparticles (SANPs) promise an effective delivery of bisphosphonates or microRNAs in the treatment of glioblastoma (GBM) and are obtained through the sequential mixing of four components immediately before use. The self-assembling approach facilitates technology transfer, but the complexity of the SANP preparation protocol raises significant concerns in the clinical setting due to the high risk of human errors during the procedure. In this work, it was hypothesized that the SANP preparation protocol could be simplified by using freeze-dried formulations. An in-depth thermodynamic study was conducted on solutions of different cryoprotectants, namely sucrose, mannitol and trehalose, to test their ability to stabilize the produced SANPs. In addition, the ability of SANPs to deliver drugs after lyophilization was assessed on selected formulations encapsulating zoledronic acid in vitro in the T98G GBM cell line and in vivo in an orthotopic mouse model. Results showed that, after lyophilization optimization, freeze-dried SANPs encapsulating zoledronic acid could retain their delivery ability, showing a significant inhibition of T98G cell growth both in vitro and in vivo. Overall, these results suggest that freeze-drying may help boost the industrial development of SANPs for the delivery of drugs to the brain.
自组装纳米颗粒 (SANP) 有望有效递送至神经胶质瘤 (GBM) 的双磷酸盐或 microRNAs，并通过在使用前立即顺序混合四种成分来获得。自组装方法便于技术转让，但由于在该过程中人为错误的风险很高，SANP 制备方案的复杂性在临床环境中引起了重大关注。在这项工作中，假设通过使用冻干制剂可以简化 SANP 制备方案。对不同冷冻保护剂（即蔗糖、甘露醇和海藻糖）的溶液进行了深入的热力学研究，以测试它们稳定所产生 SANP 的能力。此外，还评估了冻干后 SANPs 对选定制剂的药物递送能力，这些制剂体外在 T98G GBM 细胞系中封装唑来膦酸，体内在原位小鼠模型中封装唑来膦酸。结果表明，经过冻干优化后，冻干的封装唑来膦酸的 SANP 能够保留其递药能力，在体外和体内均显著抑制 T98G 细胞生长。总体而言，这些结果表明，冻干可能有助于促进 SANP 用于向大脑递药的工业发展。
