Research and Early Development, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
Pharma Technical Development Europe Analytics, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.
J Pharm Biomed Anal. 2021 Jan 5;192:113642. doi: 10.1016/j.jpba.2020.113642. Epub 2020 Sep 19.
Lipid nanoparticles, especially liposomes and lipid/nucleic acid complexed nanoparticles have shown great success in the pharmaceutical industry. Their success is attributed to stable drug loading, extended pharmacokinetics, reduced off-target side effects, and enhanced delivery efficiency to disease targets with formidable blood-brain or plasma membrane barriers. Therefore, they offer promising formulation options for drugs limited by low therapeutic indexes in traditional dosage forms and current "undruggable" targets. Recent development of siRNA, antisense oligonucleotide, or the CRISPR complex-loaded lipid nanoparticles and liposomal vaccines also shed light on their potential in enabling versatile formulation platforms for new pharmaceutical modalities. Analytical characterization of these nanoparticles is critical to drug design, formulation development, understanding in vivo performance, as well as quality control. The multi-lipid excipients, unique core-bilayer structure, and nanoscale size all underscore their complicated critical quality attributes, including lipid species, drug encapsulation efficiency, nanoparticle characteristics, product stability, and drug release. To address these challenges and facilitate future applications of lipid nanoparticles in drug development, we summarize available analytical approaches for physicochemical characterizations of lipid nanoparticle-based pharmaceutical modalities. Furthermore, we compare advantages and challenges of different techniques, and highlight the promise of new strategies for automated high-throughput screening and future development.
脂质纳米颗粒，特别是脂质体和脂质/核酸复合纳米颗粒，在制药行业取得了巨大的成功。它们的成功归因于稳定的药物负载、延长的药代动力学、减少脱靶副作用以及增强对具有坚固血脑或质膜屏障的疾病靶点的递药效率。因此，它们为传统剂型中治疗指数低的药物和当前“不可成药”的靶点提供了有前景的制剂选择。最近载有 siRNA、反义寡核苷酸或 CRISPR 复合物的脂质纳米颗粒和脂质体疫苗的发展也表明了它们在为新型药物制剂平台提供多功能制剂方面的潜力。这些纳米颗粒的分析表征对于药物设计、制剂开发、体内性能的理解以及质量控制至关重要。多脂质赋形剂、独特的核-双层结构和纳米级尺寸都突出了其复杂的关键质量属性，包括脂质种类、药物包封效率、纳米颗粒特性、产品稳定性和药物释放。为了应对这些挑战并促进脂质纳米颗粒在药物开发中的未来应用，我们总结了基于脂质纳米颗粒的药物制剂物理化学特性的现有分析方法。此外，我们比较了不同技术的优缺点，并强调了新策略在自动化高通量筛选和未来发展方面的前景。
