Gao Yuan, Wen Tianjiao, Shan Bin, Meng Meng, Bai Jing, Tian Wei, Li Congxin
Department of Pharmacy, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, Hebei, China.
Department of Pharmacy, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
Sci Rep. 2025 May 7;15(1):15940. doi: 10.1038/s41598-025-00855-0.
This study aimed to prepare mitoxantrone thermosensitive liposome (MTX-TSL) to enhance the targeting capability of liposomes and thus improve the therapeutic effect of the drug on prostate cancer. MTX-TSL were prepared using the thin-film hydration method. A single-factor experiment was conducted to optimize the formulation process, and the liposome quality was assessed alongside short-term stability testing. The in vitro efficacy of MTX-TSL was evaluated using RM-1 prostate cancer cell inhibition assays. In vivo experiments were conducted on BDF1 mice inoculated with RM-1 cells to assess the tissue distribution and anticancer activity of MTX-TSL. Quality assessments of MTX-TSL revealed a pH of 6.53 ± 0.02, osmotic pressure of 309 ± 3 mOsmol/Kg, particle size of 100.10 ± 1.50 nm, and encapsulation efficiency of 98.41% ± 0.23%. Stability tests showed no major quality changes for liposome suspensions stored at 2-8 °C for 2 months. In vitro release studies showed that MTX-TSL exhibited good thermosensitive properties. Experiments performed on BDF1 mice indicated that initiating hyperthermia before drug administration was beneficial for drug accumulation in tumor tissue and that MTX-TSL outperformed free drugs in suppressing tumor growth when combined with appropriate hyperthermia. MTX-TSL can effectively inhibit tumor growth while increasing the drug's therapeutic index.
本研究旨在制备米托蒽醌热敏脂质体(MTX - TSL),以增强脂质体的靶向能力,从而提高药物对前列腺癌的治疗效果。采用薄膜水化法制备MTX - TSL。进行单因素实验以优化制剂工艺,并同时评估脂质体质量和短期稳定性。使用RM - 1前列腺癌细胞抑制试验评估MTX - TSL的体外疗效。对接种RM - 1细胞的BDF1小鼠进行体内实验,以评估MTX - TSL的组织分布和抗癌活性。MTX - TSL的质量评估显示,其pH值为6.53±0.02,渗透压为309±3 mOsmol/Kg,粒径为100.10±1.50 nm,包封率为98.41%±0.23%。稳定性测试表明,脂质体悬浮液在2 - 8°C下储存2个月,质量无重大变化。体外释放研究表明,MTX - TSL表现出良好的热敏特性。对BDF1小鼠进行的实验表明,给药前启动热疗有利于药物在肿瘤组织中的蓄积,并且当与适当的热疗相结合时,MTX - TSL在抑制肿瘤生长方面优于游离药物。MTX - TSL可以有效抑制肿瘤生长,同时提高药物的治疗指数。