Transcutaneously refillable nanofluidic implant achieves sustained level of tenofovir diphosphate for HIV pre-exposure prophylaxis

Corrine Ying Xuan Chua, Priya Jain, Andrea Ballerini, Giacomo Bruno, R. Lyle Hood, Manas Gupte, Song Gao, Nicola Di Trani, Antonia Susnjar, Kathryn Shelton, Lane R. Bushman, Marco Folci, Carly S. Filgueira, Mark A. Marzinke, Peter L. Anderson, Ming Hu, Pramod Nehete, Roberto C. Arduino, Jagannadha K. Sastry, Alessandro Grattoni

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) drugs are effective at preventing human immunodeficiency virus (HIV) transmission. However, implementation of PrEP presents significant challenges due to poor user adherence, low accessibility to ARVs and multiple routes of HIV exposure. To address these challenges, we developed the nanochannel delivery implant (NDI), a subcutaneously implantable device for sustained and constant delivery of tenofovir alafenamide (TAF) and emtricitabine (FTC) for HIV PrEP. Unlike existing drug delivery platforms with finite depots, the NDI incorporates ports allowing for transcutaneous refilling upon drug exhaustion. NDI-mediated drug delivery in rhesus macaques resulted in sustained release of both TAF and FTC for 83 days, as indicated by concentrations of TAF, FTC and their respectively metabolites in plasma, PBMCs, rectal mononuclear cells and tissues associated with HIV transmission. Notably, clinically relevant preventative levels of tenofovir diphosphate were achieved as early as 3 days after NDI implantation. We also demonstrated the feasibility of transcutaneous drug refilling to extend the duration of PrEP drug delivery in NHPs. Overall, the NDI represents an innovative strategy for long-term HIV PrEP administration in both developed and developing countries.

Original languageEnglish (US)
Pages (from-to)315-325
Number of pages11
JournalJournal of Controlled Release
Volume286
DOIs
StatePublished - Sep 28 2018

ASJC Scopus subject areas

  • Pharmaceutical Science

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