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Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals.


ABSTRACT: 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.

SUBMITTER: Zhou T 

PROVIDER: S-EPMC5992566 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals.

Zhou Tian T   Lin Zhiyi Z   Puligujja Pavan P   Palandri Diana D   Hilaire James J   Araínga Mariluz M   Smith Nathan N   Gautam Nagsen N   McMillan JoEllyn J   Alnouti Yazen Y   Liu Xinming X   Edagwa Benson B   Gendelman Howard E HE  

Nanomedicine (London, England) 20180319 8


<h4>Aim</h4>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.<h4>Materials & methods</h4>Ligand-decorated nanoparticle manufacturi  ...[more]

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