Development and characterization of a long-acting nanoformulated abacavir prodrug

Dhirender Singh, JoEllyn M McMillan, James Hilaire, Nagsen Gautam, Diana Palandri, Yazen Alnouti, Howard Eliot Gendelman, Benson J Edagwa

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Aim: A myristoylated abacavir (ABC) prodrug was synthesized to extend drug half-life and bioavailability. Methods: Myristoylated ABC (MABC) was made by esterifying myristic acid to the drug's 5-hydroxy-cyclopentene group. Chemical composition, antiretroviral activity, cell uptake and retention and cellular trafficking of free MABC and poloxamer nanoformulations of MABC were assessed by proton nuclear magnetic resonance and tested in human monocyte-derived macrophages. Pharmacokinetics of ABC and nanoformulated MABC were evaluated after intramuscular injection into mice. Results: MABC antiretroviral activity in monocyte-derived macrophages was comparable to native drug. Encasement of MABC into poloxamer nanoparticles extended drug bioavailability for 2 weeks. Conclusion: MABC synthesis and encasement in polymeric nanoformulations improved intracellular drug accumulation and demonstrate translational potential as part of a long-acting antiretroviral regimen.

Original languageEnglish (US)
Pages (from-to)1913-1927
Number of pages15
JournalNanomedicine
Volume11
Issue number15
DOIs
StatePublished - Aug 2016

Fingerprint

Macrophages
Prodrugs
drug
Nuclear magnetic resonance
Pharmacokinetics
Poloxamer
Pharmaceutical Preparations
Biological Availability
bioavailability
Nanoparticles
Acids
Cyclopentanes
Chemical analysis
trafficking
Intramuscular Injections
Myristic Acid
half life
Half-Life
nuclear magnetic resonance
Protons

Keywords

  • abacavir prodrug
  • antiretroviral therapy
  • monocyte-macrophages
  • nanoformulated antiretrovirals
  • pharmacokinetics

ASJC Scopus subject areas

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

Cite this

Development and characterization of a long-acting nanoformulated abacavir prodrug. / Singh, Dhirender; McMillan, JoEllyn M; Hilaire, James; Gautam, Nagsen; Palandri, Diana; Alnouti, Yazen; Gendelman, Howard Eliot; Edagwa, Benson J.

In: Nanomedicine, Vol. 11, No. 15, 08.2016, p. 1913-1927.

Research output: Contribution to journalArticle

Singh, Dhirender ; McMillan, JoEllyn M ; Hilaire, James ; Gautam, Nagsen ; Palandri, Diana ; Alnouti, Yazen ; Gendelman, Howard Eliot ; Edagwa, Benson J. / Development and characterization of a long-acting nanoformulated abacavir prodrug. In: Nanomedicine. 2016 ; Vol. 11, No. 15. pp. 1913-1927.
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AU - Palandri, Diana

AU - Alnouti, Yazen

AU - Gendelman, Howard Eliot

AU - Edagwa, Benson J

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