Document Detail


Polymeric nanoparticles containing combination antiretroviral drugs for HIV type 1 treatment.
MedLine Citation:
PMID:  23289671     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Annemarie Shibata; Emily McMullen; Alex Pham; Michael Belshan; Bridget Sanford; You Zhou; Michael Goede; Abhijit A Date; Abjijit A Date; Christopher J Destache
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-01
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  29     ISSN:  1931-8405     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-26     Completed Date:  2013-08-30     Revised Date:  2014-02-06    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  United States    
Other Details:
Languages:  eng     Pagination:  746-54     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / administration & dosage*,  therapeutic use
Benzoxazines / administration & dosage,  therapeutic use
CD4-Positive T-Lymphocytes / metabolism
Cell Line
Cell Survival / drug effects
Drug Therapy, Combination
HIV Infections / drug therapy*
HIV-1 / drug effects*
HeLa Cells / metabolism
Humans
Lactic Acid
Lopinavir / administration & dosage,  therapeutic use
Microscopy, Confocal
Nanoparticles / therapeutic use*
Polyglycolic Acid
Subcellular Fractions / metabolism
U937 Cells / metabolism
Grant Support
ID/Acronym/Agency:
1R15AI076039-01A1/AI/NIAID NIH HHS; 5P20RR016469/RR/NCRR NIH HHS; 5P30RR031151-01/RR/NCRR NIH HHS; 5R01AI080348/AI/NIAID NIH HHS; 8 P30 GM103509-03/GM/NIGMS NIH HHS; 8P20GM103427/GM/NIGMS NIH HHS; P30 GM103509/GM/NIGMS NIH HHS; R01 AI080348/AI/NIAID NIH HHS; R15 AI076039/AI/NIAID NIH HHS; R56 AI095115/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Benzoxazines; 0/polylactic acid-polyglycolic acid copolymer; 2494G1JF75/Lopinavir; 26009-03-0/Polyglycolic Acid; 33X04XA5AT/Lactic Acid; JE6H2O27P8/efavirenz
Comments/Corrections
Erratum In:
AIDS Res Hum Retroviruses. 2013 Jul;29(7):1095
Note: Date, Abjijit A [corrected to Date, Abhijit A]

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