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Long-acting three-drug combination anti-HIV nanoparticles enhance drug exposure in primate plasma and cells within lymph nodes and blood
Open accessAbstract
Insufficient HIV drug levels in lymph nodes have been linked to viral persistence. To overcome lymphatic drug insufficiency, we developed and evaluated in primates a lipid-drug nanoparticle containing lopinavir, ritonavir, and tenofovir. These nanoparticles produced over 50-fold higher intracellular lopinavir, ritonavir and tenofovir concentrations in lymph nodes compared to free drug. Plasma and intracellular drug levels in blood were enhanced and sustained for 7 days after a single subcutaneous dose, exceeding that achievable with current oral therapy.
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Lipid-based nanoparticles loaded with three to four antiretrovirals including lopinavir, ritonavir and tenofovir enhanced circulation times of the antiretrovirals and increased their uptake into mononuclear cells in peripheral blood and lymph nodes of macaques.
“Nanoencapsulation enhanced circulation times of the antiretrovirals and increased their uptake into the mononuclear cells in peripheral blood and lymph nodes of macaques.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [96]
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References 17 · Cited by 69
Metadata
- Authors
- Freeling, J. P., Koehn, J., Shu, C., Sun, J., & Ho, R. J. Y.
- Affiliations
- University of Washington (US)
- Corresponding author
- Ho, Rodney J.Y.
- Venue
- AIDS
- Published
- 2014-11-13
- Volume
- 28
- Issue
- 17
- Pages
- 2625-2627
- ISSN
- 0269-9370 (ISSN-L)
- PMC
- PMC4376321
- OpenAlex
- W2330655155
- Cited by
- 69
- References
- 17
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 7 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 12 · 2019: 2 · 2018: 11 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 1
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- AIDS (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000423)
- Center for AIDS Research, University of Alabama at Birmingham
- National Institute of Allergy and Infectious Diseases (R01AI077390, AI-077390, R01AI052663)
- National Center for Research Resources (RR00166, RR025014, UL1RR025014, P51RR000166)
- National Center for Advancing Translational Sciences
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- HIV, lopinavir, ritonavir, tenofovir, lymph nodes, intracellular drug concentration, viral persistence, subcutaneous dosing, nonhuman primate model
- MeSH terms
- Tenofovir, Adenine, Animals, Blood Cells, Drug Carriers, Drug Combinations, Lymph Nodes, Macaca nemestrina, Plasma, Anti-HIV Agents, Ritonavir, Nanoparticles, Lopinavir, Organophosphonates
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