Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals

优化修饰抗逆转录病毒药物纳米晶体的制备及稳定性

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作者:Tian Zhou, Zhiyi Lin, Pavan Puligujja, Diana Palandri, James Hilaire, Mariluz Araínga, Nathan Smith, Nagsen Gautam, JoEllyn McMillan, Yazen Alnouti, Xinming Liu, Benson Edagwa, Howard E Gendelman

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 &

Conclusion

Direct manufacturing of FA nanoparticles provides a path toward large-scale clinical grade manufacturing of cell-targeted LA-ART.

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.

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