Kraft John C, Freeling Jennifer P, Wang Ziyao, Ho Rodney J Y
Department of Pharmaceutics, University of Washington, Seattle, Washington.
J Pharm Sci. 2014 Jan;103(1):29-52. doi: 10.1002/jps.23773. Epub 2013 Nov 25.
Liposomes are spherical-enclosed membrane vesicles mainly constructed with lipids. Lipid nanoparticles are loaded with therapeutics and may not contain an enclosed bilayer. The majority of those clinically approved have diameters of 50-300 nm. The growing interest in nanomedicine has fueled lipid-drug and lipid-protein studies, which provide a foundation for developing lipid particles that improve drug potency and reduce off-target effects. Integrating advances in lipid membrane research has enabled therapeutic development. At present, about 600 clinical trials involve lipid particle drug delivery systems. Greater understanding of pharmacokinetics, biodistribution, and disposition of lipid-drug particles facilitated particle surface hydration technology (with polyethylene glycol) to reduce rapid clearance and provide sufficient blood circulation time for drug to reach target tissues and cells. Surface hydration enabled the liposome-encapsulated cancer drug doxorubicin (Doxil) to gain clinical approval in 1995. Fifteen lipidic therapeutics are now clinically approved. Although much research involves attaching lipid particles to ligands selective for occult cells and tissues, preparation procedures are often complex and pose scale-up challenges. With emerging knowledge in drug target and lipid-drug distribution in the body, a systems approach that integrates knowledge to design and scale lipid-drug particles may further advance translation of these systems to improve therapeutic safety and efficacy.
脂质体是主要由脂质构成的球形封闭膜泡。脂质纳米颗粒负载有治疗剂,可能不包含封闭的双层结构。大多数已获临床批准的脂质纳米颗粒直径为50 - 300纳米。对纳米医学日益增长的兴趣推动了脂质 - 药物和脂质 - 蛋白质研究,为开发提高药物效力并减少脱靶效应的脂质颗粒奠定了基础。整合脂质膜研究的进展推动了治疗学的发展。目前,约600项临床试验涉及脂质颗粒药物递送系统。对脂质 - 药物颗粒的药代动力学、生物分布和处置的更深入了解促进了颗粒表面水合技术(使用聚乙二醇)的发展,以减少快速清除并为药物到达靶组织和细胞提供足够的血液循环时间。表面水合使得脂质体包裹的癌症药物阿霉素(多柔比星脂质体)在1995年获得临床批准。目前有15种脂质治疗剂已获临床批准。尽管许多研究涉及将脂质颗粒与对隐匿细胞和组织具有选择性的配体连接,但制备程序通常很复杂,并且存在扩大规模的挑战。随着对药物靶点和体内脂质 - 药物分布的新知识不断涌现,一种整合知识以设计和扩大脂质 - 药物颗粒规模的系统方法可能会进一步推动这些系统的转化,以提高治疗安全性和疗效。