期刊
AIDS
卷 32, 期 17, 页码 2463-2467出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000001969
关键词
drug combination nanoparticles; efavirenz; HIV drug exposure; HIV treatment; long-acting; lopinavir; targeted drug delivery; tenofovir
资金
- NIH [UM1AI120176, P51OD010425, AI27757, UL1 TR00231, T32-GM007750, TL1-TR000422]
Objective: 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. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
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