Polymeric nanoparticles containing combination antiretroviral drugs for HIV type 1 treatment
The use of combination antiretroviral nanoparticles (cART NPs) was investigated as a novel treatment approach for the inhibition of HIV-1 replication. We developed nanoparticles of biodegradable polymer, poly-(dl-lactide-co-glycolic acid; PLGA) containing efavirenz (EFV) and boosted lopinavir (lopinavir/ritonavir; LPV/r) by a high-pressure homogenization method. The method resulted in >79% drug entrapment efficiency for each of the three drugs. The average size of cART NPs was 138.3±55.4 nm as measured by dynamic light scanning, confirmed by scanning electron microscopy (SEM) with an average surface charge of -13.7±4.5. Lissamine-rhodamine-labeled fluorescent PLGA NPs exhibited efficient uptake in nonimmune (HeLa cells) and immune (H9 T cells) cells as measured by confocal microscopy. Cells treated with cART NPs resulted in minimal loss of cell viability over 28 days. Subcellular fractionation studies demonstrated that HIV-1-infected H9 monocytic cells treated with cART NPs contained significantly (p<0.05) higher nuclear, cytoskeleton, and membrane antiretroviral drug levels compared to cells treated with drug solutions alone. Finally, cART NPs efficiently inhibited HIV-1 infection and transduction. The IC50 for each of the three drugs in the cART NPs was <31 nM. These experiments demonstrate the efficacy of a novel PLGA NPs formulation for the delivery of cART to inhibit HIV-1 replication.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
AIDS research and human retroviruses - 29(2013), 5 vom: 04. Mai, Seite 746-54 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shibata, Annemarie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.08.2013 Date Revised 21.10.2021 published: Print-Electronic ErratumIn: AIDS Res Hum Retroviruses. 2013 Jul;29(7):1095 Date, Abjijit A [corrected to Date, Abhijit A] Citation Status MEDLINE |
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| doi: |
10.1089/AID.2012.0301 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM223913510 |
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| 500 | |a ErratumIn: AIDS Res Hum Retroviruses. 2013 Jul;29(7):1095 Date, Abjijit A [corrected to Date, Abhijit A] | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The use of combination antiretroviral nanoparticles (cART NPs) was investigated as a novel treatment approach for the inhibition of HIV-1 replication. We developed nanoparticles of biodegradable polymer, poly-(dl-lactide-co-glycolic acid; PLGA) containing efavirenz (EFV) and boosted lopinavir (lopinavir/ritonavir; LPV/r) by a high-pressure homogenization method. The method resulted in >79% drug entrapment efficiency for each of the three drugs. The average size of cART NPs was 138.3±55.4 nm as measured by dynamic light scanning, confirmed by scanning electron microscopy (SEM) with an average surface charge of -13.7±4.5. Lissamine-rhodamine-labeled fluorescent PLGA NPs exhibited efficient uptake in nonimmune (HeLa cells) and immune (H9 T cells) cells as measured by confocal microscopy. Cells treated with cART NPs resulted in minimal loss of cell viability over 28 days. Subcellular fractionation studies demonstrated that HIV-1-infected H9 monocytic cells treated with cART NPs contained significantly (p<0.05) higher nuclear, cytoskeleton, and membrane antiretroviral drug levels compared to cells treated with drug solutions alone. Finally, cART NPs efficiently inhibited HIV-1 infection and transduction. The IC50 for each of the three drugs in the cART NPs was <31 nM. These experiments demonstrate the efficacy of a novel PLGA NPs formulation for the delivery of cART to inhibit HIV-1 replication | ||
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| 700 | 1 | |a Date, Abjijit A |e verfasserin |4 aut | |
| 700 | 1 | |a Destache, Christopher J |e verfasserin |4 aut | |
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