To characterize a drug-combination nanoparticle (DcNP) containing water-insoluble lopinavir (LPV) and efavirenz (EFV), and water-soluble tenofovir (TFV), for its potential as a long-acting combination HIV treatment.Design:
Three HIV drugs (LPV, EFV, TFV) with well established efficacy and safety were coformulated into a single DcNP suspension. Two macaques were administered one subcutaneous injection and drug concentrations in plasma and mononuclear cells (in peripheral blood and lymph nodes) were analyzed over 2 weeks. Pharmacokinetic parameters and cell-to-plasma relationships of LPV, EFV, and TFV were determined.Results:
This three-in-one nanoformulation provided extended concentrations of all drugs in lymph node cells that were 57- to 228-fold higher than those in plasma. Levels of all three drugs in peripheral blood mononuclear cells persisted for 2 weeks at levels equal to or higher than those in plasma.Conclusion:
With long-acting characteristics and higher drug penetration/persistence in cells, this three-in-one DcNP may enhance therapeutic efficacy of these well studied HIV drugs due to colocalization and targeting of this three-drug combination to HIV host cells.