Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals

Tian Zhou, Zhiyi Lin, Pavan Puligujja, DIana Palandri, James Hilaire, Mariluz Araínga, Nathan Smith, Nagsen Gautam, JoEllyn M McMillan, Yazen Alnouti, Xinming Liu, Benson J Edagwa, Howard Eliot Gendelman

Research output: Contribution to journalArticle

10 Citations (Scopus)

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. Howard E Gendelman. 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.

Original languageEnglish (US)
Pages (from-to)871-885
Number of pages15
JournalNanomedicine
Volume13
Issue number8
DOIs
StatePublished - Apr 2018

Fingerprint

Folic Acid
Nanoparticles
Nanocrystals
manufacturing
drug
acid
Pharmaceutical Preparations
ligand
Acids
Ligands
Centrifugation
Therapeutics
Poloxamer
efficiency
targeting
purification
Macrophages
Monocytes
Polymers
Hinges

Keywords

  • Cabotegravir
  • Long-acting antiretrovirals
  • Monocyte-derived macrophage
  • Nanocrystals
  • Uptake and release

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

Cite this

Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals. / Zhou, Tian; Lin, Zhiyi; Puligujja, Pavan; Palandri, DIana; Hilaire, James; Araínga, Mariluz; Smith, Nathan; Gautam, Nagsen; McMillan, JoEllyn M; Alnouti, Yazen; Liu, Xinming; Edagwa, Benson J; Gendelman, Howard Eliot.

In: Nanomedicine, Vol. 13, No. 8, 04.2018, p. 871-885.

Research output: Contribution to journalArticle

Zhou, T, Lin, Z, Puligujja, P, Palandri, DI, Hilaire, J, Araínga, M, Smith, N, Gautam, N, McMillan, JM, Alnouti, Y, Liu, X, Edagwa, BJ & Gendelman, HE 2018, 'Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals', Nanomedicine, vol. 13, no. 8, pp. 871-885. https://doi.org/10.2217/nnm-2017-0381
Zhou T, Lin Z, Puligujja P, Palandri DI, Hilaire J, Araínga M et al. Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals. Nanomedicine. 2018 Apr;13(8):871-885. https://doi.org/10.2217/nnm-2017-0381
Zhou, Tian ; Lin, Zhiyi ; Puligujja, Pavan ; Palandri, DIana ; Hilaire, James ; Araínga, Mariluz ; Smith, Nathan ; Gautam, Nagsen ; McMillan, JoEllyn M ; Alnouti, Yazen ; Liu, Xinming ; Edagwa, Benson J ; Gendelman, Howard Eliot. / Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals. In: Nanomedicine. 2018 ; Vol. 13, No. 8. pp. 871-885.
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AU - Araínga, Mariluz

AU - Smith, Nathan

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