Institutional members access full text with Ovid®

Share this article on:

Tenofovir alafenamide and elvitegravir loaded nanoparticles for long-acting prevention of HIV-1 vaginal transmission

Mandal, Subhra; Prathipati, Pavan K.; Kang, Guobin; Zhou, You; Yuan, Zhe; Fan, Wenjin; Li, Qingsheng; Destache, Christopher J.

doi: 10.1097/QAD.0000000000001349
Basic Science

Objective: This report presents tenofovir (TFV) alafenamide (TAF) and elvitegravir (EVG) fabricated into nanoparticles for subcutaneous delivery as prevention strategy.

Design: Prospective prevention study in humanized bone marrow–liver–thymus (hu-BLT) mice.

Methods: Using an oil-in-water emulsion solvent evaporation technique, TAF + EVG drugs were entrapped together into nanoparticles containing poly(lactic-co-glycolic acid). In-vitro prophylaxis studies (90% inhibition concentration) compared nanoparticles with drugs in solution. Hu-BLT (n = 5/group) mice were given 200 mg/kg subcutaneous, and vaginally challenged with HIV-1 [5 × 105 tissue culture infectious dose for 50% of cells cultures (TCID50)] 4 and 14 days post-nanoparticle administration (post-nanoparticle injection). Control mice (n = 5) were challenged at 4 days. Weekly plasma viral load was performed using RT-PCR. Hu-BLT mice were sacrificed and lymph nodes were harvested for HIV-1 viral RNA detection by in-situ hybridization. In parallel, CD34+ humanized mice (3/time point) compared TFV and EVG drug levels in vaginal tissues from nanoparticles and solution. TFV and EVG were analyzed from tissue using liquid chromatograph-tandem mass spectrometry (LC-MS/MS).

Results: TAF + EVG nanoparticles were less than 200 nm in size. In-vitro prophylaxis indicates TAF + EVG nanoparticles 90% inhibition concentration was 0.002 μg/ml and TAF + EVG solution was 0.78 μg/ml. TAF + EVG nanoparticles demonstrated detectable drugs for 14 days and 72 h for solution, respectively. All hu-BLT control mice became infected within 14 days after HIV-1 challenge. In contrast, hu-BLT mice that received nanoparticles and challenged at 4 days post-nanoparticle injection, 100% were uninfected, and 60% challenged at 14 days post-nanoparticle injection were uninfected (P = 0.007; Mantel–Cox test). In-situ hybridization confirmed these results.

Conclusion: This proof-of-concept study demonstrated sustained protection for TAF + EVG nanoparticles in a hu-BLT mouse model of HIV vaginal transmission.

aSchool of Pharmacy & Health Professions, Creighton University, Omaha

bNebraska Center for Virology and School of Biological Sciences

cNebraska Center for Virology and Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.

Correspondence to Christopher J. Destache, Pharm. D., Professor of Pharmacy Practice and Infectious Diseases, School of Pharmacy & Health Professions, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA. Tel: +1 402 280 4744; e-mail:

Received 25 August, 2016

Revised 7 November, 2016

Accepted 14 November, 2016

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

Copyright © 2017 Wolters Kluwer Health, Inc.