优化修饰抗逆转录病毒药物纳米晶体制备和稳定性。

AIM: While the therapeutic potential for current long-acting (LA) antiretroviral therapy (ART) is undeniable, ligand-decorated nanoformulated LA-ART could optimize drug delivery to viral reservoirs. The development of decorated ART hinges, however, on formulation processes and manufacture efficiencies. To this end, we compared manufacture and purification techniques for ligand-decorated antiretroviral drug nanocrystals. MATERIALS & METHODS: Ligand-decorated nanoparticle manufacturing was tested using folic acid (FA) nanoformulated cabotegravir. RESULTS: Direct manufacturing of FA-cabotegravir resulted in stable particles with high drug loading and monocyte-macrophage targeting. A one step 'direct' scheme proved superior over differential centrifugation or tangential flow filtration facilitating particle stability and preparation simplicity and efficiency. CONCLUSION: Direct manufacturing of FA nanoparticles provides a path toward large-scale clinical grade manufacturing of cell-targeted LA-ART.

目的：虽然目前长效（LA）抗逆转录病毒疗法（ART）的治疗潜力不可否认，但配体修饰的纳米制剂 LA-ART 可以优化药物向病毒储存库的输送。然而，配体修饰的 ART 的发展取决于制剂工艺和制造效率。为此，我们比较了配体修饰抗逆转录病毒药物纳米晶体的制造和纯化技术。

材料与方法：使用叶酸（FA）纳米制剂卡博特韦测试了配体修饰纳米颗粒的制造。

结果：FA-卡博特韦的直接制造可得到具有高载药量和单核细胞-巨噬细胞靶向性的稳定颗粒。一步“直接”方案优于差速离心或切向流过滤，有利于颗粒稳定性以及制剂的简单和高效制备。

结论：FA 纳米颗粒的直接制造为大规模临床级靶向细胞的 LA-ART 的制造提供了一条途径。