基于脂质的复杂注射剂的合理配方和工业制造:里程碑和趋势
Mariana Biscaia-Caleiras1, Nuno A Fonseca2, Ana Sofia Lourenço2
1CNC - Center for Neurosciences and Cell Biology, Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Faculty of Medicine (Polo 1), Rua Larga, 3004-504 Coimbra, Portugal; Bluepharma-Indústria Farmacêutica, S.A., São Martinho do Bispo, 3045-016 Coimbra, Portugal; Univ Coimbra-University of Coimbra, CIBB, Faculty of Pharmacy, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
脂质纳米颗粒正在彻底改变基因治疗的核酸输送,克服稳定性和细胞内运输方面的挑战. 通过设计质量等新的制造方法对于这些复杂的纳米配方的可扩展,稳定和符合监管的生产至关重要.
科学领域:
- 制药科学 制药科学
- 生物技术是生物技术.
- 纳米技术 纳米技术
背景情况:
- 基于脂质的系统是已建立的药物输送工具.
- 脂质纳米颗粒 (LNP) 对核酸输送,包括mRNA显著有前途.
- 基因疗法在药物输送和分子稳定性方面面临着挑战.
研究的目的:
- 探索批准的脂质纳米系统开发中的关键里程碑.
- 为制造复杂的脂质纳米配方提供技术和法规的概述.
- 为解决LNP制造的可扩展性,稳定性,无菌性和监管合规性方面的挑战.
主要方法:
- 目前批准的脂质纳米系统的审查.
- 对设计时质量 (QbD) 原则的分析.
- 探索用于连续制造的过程分析技术 (PAT).
主要成果:
- 林氏基因组是核酸输送的突破性平台,解决了基因治疗的障碍.
- 复杂的多批处理过程阻碍了基于脂质的输送系统的工业制造.
- QbD和PAT对于克服制造业挑战至关重要.
结论:
- 从批量生产过渡到连续制造对于高效的LNP生产至关重要.
- 采用QbD和PAT原则将使可扩展,灵活和合规的制造成为可能.
- 复杂的脂质纳米配方需要进一步开发先进的制造技术.
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