Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
J Control Release. 2021 Jan 10;329:1037-1045. doi: 10.1016/j.jconrel.2020.10.032. Epub 2020 Oct 17.
Safe and efficient gene therapy for the treatment of Duchenne muscular dystrophy (DMD), a genetic disorder, is required. For this, the muscle-targeting delivery system of genes and nucleic acids is ideal. In this study, we focused on the A2G80 peptide, which has an affinity for α-dystroglycan expressed on muscle cell membranes, as a muscle targeted nanocarrier for DMD and developed A2G80-modified liposomes. We also prepared A2G80-modified liposomes coated with long- and short-chain PEG, called A2G80-LSP-Lip, to improve the blood circulation of liposomes using microfluidics. The liposomes had a particle size of approximately 80 nm. A2G80-LSP-Lip showed an affinity for the muscle tissue section of mice by overlay assay. When the liposomes were administered to DMD model mice (mdx mice) via the tail vein, A2G80-LSP-Lip accumulated efficiently in muscle tissue compared to control liposomes. These results suggest that A2G80-LSP-Lip can function as a muscle-targeting liposome for DMD via systemic administration, and may be a useful tool for DMD treatment.
需要安全有效的基因治疗方法来治疗杜氏肌营养不良症（DMD），一种遗传性疾病。为此，基因和核酸的肌肉靶向递送系统是理想的选择。在这项研究中，我们专注于 A2G80 肽，它与肌肉细胞膜上表达的α-肌聚糖有亲和力，作为 DMD 的肌肉靶向纳米载体，并开发了 A2G80 修饰的脂质体。我们还使用微流控技术制备了 A2G80 修饰的长链和短链聚乙二醇（PEG）包被的脂质体，称为 A2G80-LSP-Lip，以提高脂质体的血液循环。脂质体的粒径约为 80nm。A2G80-LSP-Lip 通过覆盖测定法显示出对小鼠肌肉组织切片的亲和力。当脂质体通过尾静脉给药给 DMD 模型小鼠（mdx 小鼠）时，与对照脂质体相比，A2G80-LSP-Lip 能够更有效地在肌肉组织中积累。这些结果表明，A2G80-LSP-Lip 可以通过全身给药作为 DMD 的肌肉靶向脂质体发挥作用，并且可能是 DMD 治疗的有用工具。
