Kester Mark, Bassler Jocelyn, Fox Todd E, Carter Carly J, Davidson Jeff A, Parette Mylisa R
Biol Chem. 2015 Jun;396(6-7):737-47. doi: 10.1515/hsz-2015-0129.
Despite the therapeutic potential of sphingolipids, the ability to develop this class of compounds as active pharmaceutical ingredients has been hampered by issues of solubility and delivery. Beyond these technical hurdles, significant challenges in completing the necessary preclinical studies to support regulatory review are necessary for commercialization. This review seeks to identify the obstacles and potential solutions in the translation of a novel liposomal technology from the academic bench to investigational new drug (IND) stage by discussing the preclinical development of the Ceramide NanoLiposome (CNL), which is currently being developed as an anticancer drug for the initial indication of hepatocellular carcinoma (HCC).
尽管鞘脂具有治疗潜力，但将这类化合物开发成活性药物成分的能力受到了溶解性和递送问题的阻碍。除了这些技术障碍外，要完成支持监管审查所需的临床前研究还面临重大挑战，这对于商业化来说是必要的。本综述旨在通过讨论神经酰胺纳米脂质体（CNL）的临床前开发，来确定将一种新型脂质体技术从学术实验室转化为研究性新药（IND）阶段的障碍和潜在解决方案，CNL目前正作为一种抗癌药物进行开发，其初始适应症为肝细胞癌（HCC）。
