Development and characterization of a long-acting nanoformulated abacavir prodrug

Dhirender Singh; Jo Ellyn McMillan; James Hilaire; Nagsen Gautam; Diana Palandri; Yazen Alnouti; Howard E. Gendelman; Benson Edagwa

doi:10.2217/nnm-2016-0164

Development and characterization of a long-acting nanoformulated abacavir prodrug

Dhirender Singh, Jo Ellyn McMillan, James Hilaire, Nagsen Gautam, Diana Palandri, Yazen Alnouti, Howard E. Gendelman, Benson Edagwa

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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 language	English (US)
Pages (from-to)	1913-1927
Number of pages	15
Journal	Nanomedicine
Volume	11
Issue number	15
DOIs	https://doi.org/10.2217/nnm-2016-0164
State	Published - Aug 2016

Keywords

abacavir prodrug
antiretroviral therapy
monocyte-macrophages
nanoformulated antiretrovirals
pharmacokinetics

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
General Materials Science
Development

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title = "Development and characterization of a long-acting nanoformulated abacavir prodrug",

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.",

keywords = "abacavir prodrug, antiretroviral therapy, monocyte-macrophages, nanoformulated antiretrovirals, pharmacokinetics",

author = "Dhirender Singh and McMillan, {Jo Ellyn} and James Hilaire and Nagsen Gautam and Diana Palandri and Yazen Alnouti and Gendelman, {Howard E.} and Benson Edagwa",

note = "Publisher Copyright: {\textcopyright} 2016 Future Medicine Ltd.",

year = "2016",

month = aug,

doi = "10.2217/nnm-2016-0164",

language = "English (US)",

volume = "11",

pages = "1913--1927",

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AU - Singh, Dhirender

AU - McMillan, Jo Ellyn

AU - Hilaire, James

AU - Gautam, Nagsen

AU - Palandri, Diana

AU - Alnouti, Yazen

AU - Gendelman, Howard E.

AU - Edagwa, Benson

PY - 2016/8

Y1 - 2016/8

N2 - 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.

AB - 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.

KW - abacavir prodrug

KW - antiretroviral therapy

KW - monocyte-macrophages

KW - nanoformulated antiretrovirals

KW - pharmacokinetics

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Development and characterization of a long-acting nanoformulated abacavir prodrug

Abstract

Keywords

ASJC Scopus subject areas

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