Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals
| Autor: | Yazen Alnouti, Howard E. Gendelman, Tian Zhou, James R. Hilaire, Zhiyi Lin, JoEllyn M McMillan, Diana L. Palandri, Nathan Smith, Xin Ming Liu, Pavan Puligujja, Benson J Edagwa, Mariluz Araínga, Nagsen Gautam |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug Materials science Pyridones media_common.quotation_subject Biomedical Engineering Medicine (miscellaneous) Nanoparticle HIV Infections Bioengineering Antiretroviral drug Nanotechnology 02 engineering and technology Development Mice 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems Folic Acid Cabotegravir nanocrystals Animals Humans Tissue Distribution General Materials Science media_common monocyte-derived macrophage Macrophages cabotegravir 021001 nanoscience & nanotechnology Antiretroviral therapy uptake and release Disease Models Animal 030104 developmental biology Anti-Retroviral Agents Nanocrystal chemistry Folic acid Drug delivery HIV-1 Nanoparticles long-acting antiretrovirals 0210 nano-technology Research Article |
| Zdroj: | Nanomedicine |
| ISSN: | 1748-6963 1743-5889 |
| Popis: | 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. Lay abstract Folic acid (FA) decoration on the surface of nanocrystals can be achieved by mixing FA conjugated poloxamer 407 (FA-P407) and native P407 in varied ratios followed by size reduction by homogenization and differential centrifugation or tangential flow filtration to remove excess unbound polymers. The optimized manufacturing scheme is by direct homogenization with predetermined quantity of FA conjugated P407. Direct manufacturing method yields stable homogenous nanoparticles with high drug loading. |
| Databáze: | OpenAIRE |
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