Open AccessLong-acting three-drug combination anti-HIV nanoparticles enhance drug exposure in primate plasma and cells within lymph nodes and blood
Author(s) -
Jennifer Freeling,
Josefin Koehn,
Cuiling Shu,
Jianguo Sun,
Rodney J. Y. Ho
Publication year - 2014
Publication title -
aids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.195
H-Index - 216
eISSN - 1473-5571
pISSN - 0269-9370
DOI - 10.1097/qad.0000000000000421
Subject(s) - lopinavir , lymph , ritonavir , drug , pharmacology , medicine , lymphatic system , virology , immunology , viral load , human immunodeficiency virus (hiv) , pathology , antiretroviral therapy
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.