期刊
NANOMEDICINE
卷 13, 期 8, 页码 871-885出版社
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2017-0381
关键词
cabotegravir; long-acting antiretrovirals; monocyte-derived macrophage; nanocrystals; uptake and release
资金
- National Institutes of Health [AG043540, DA028555, NS036126, NS034239, MH064570, NS043985, MH062261]
- Carol Swarts Emerging Neuroscience Fund
- Nebraska Research Initiative
- ViiV Healthcare
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. [GRAPHICS] .
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