在临床治疗强度下开发和描述稳定的glatiramer乙酸/oligonucleotide复合体的冷化配方
Huan Gong1, Xi Luan1, J Daniel Griffin2
1Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047, United States.
International journal of pharmaceutics
|February 9, 2026
概括
格拉提拉默酸盐 (GA) 和细胞因子-瓜寡氧核酸 (CpG ODN) 形成用于癌症治疗的纳米粒子. 微流体生产和特异性缓冲器提高了纳米粒子的稳定性和可复制性,用于临床应用.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
- 制药配方 制药配方 制药配方
背景情况:
- 格拉提拉乙酸 (GA) 电静态复合与细胞因子-瓜因因 oligodeoxynucleotides (CpG ODN) 形成阴离子纳米粒子,在注射部位定位免疫刺激剂.
- 之前的研究表明GA-CpG纳米颗粒保留了抗瘤活性,同时减少了全身不良事件.
- 复制性生产,使用和储存稳定性方面的挑战阻碍了聚-寡核酸复合物的临床转化.
研究的目的:
- 系统地研究微流体混合用于可复制的GA-CpG纳米粒子的生产.
- 选缓冲系统以获得最佳的合稳定性和CpG功效.
- 开发使用冷保护剂的稳定配方,以改善储存.
主要方法:
- 利用微流体混合用于纳米粒子生产和动态光散射用于尺寸分析.
- 选了各种缓冲系统,重点关注pH和离子类型,以评估体稳定性和CpG功效.
- 用不同的冷保护剂 (HP-β-CD,三) 评估冷解和冷干燥的稳定性.
主要成果:
- 与传统方法相比,微流体处理产生了明显更小和更均的GA-CpG纳米粒子.
- 氨基酸缓冲器,特别是谷氨酸,显示出优越的颗粒稳定性比普通的肠道缓冲器.
- 使用5%HP-β-CD或三糖的配方在加速储存6个月后保持颗粒大小 (<127 nm).
结论:
- 微流体混合为生产稳定的GA-CpG纳米粒子提供了一种可重复的方法.
- 特定的缓冲系统和冷保护剂对于提高这些纳米药物的稳定性至关重要.
- 优化的配方显示出改善使用和长期储存的前景,促进临床转化.
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