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

被引：67

作者：

Chua, Corrine Ying Xuan ^{[1
]}

Jain, Priya ^{[1
]}

Ballerini, Andrea ^{[1
,2
]}

Bruno, Giacomo ^{[3
]}

Hood, R. Lyle ^{[1
]}

Gupte, Manas ^{[4
]}

Gao, Song ^{[4
]}

Di Trani, Nicola ^{[1
]}

Susnjar, Antonia ^{[1
]}

Shelton, Kathryn ^{[5
]}

Bushman, Lane R. ^{[6
]}

Folci, Marco ^{[1
]}

Filgueira, Carly S. ^{[1
]}

Marzinke, Mark A. ^{[7
,8
]}

Anderson, Peter L. ^{[6
]}

Hu, Ming ^{[4
]}

Nehete, Pramod ^{[5
]}

Arduino, Roberto C. ^{[9
]}

Sastry, Jagannadha K. ^{[5
,10
]}

Grattoni, Alessandro ^{[1
,11
,12
]}

机构：

[1] HMRI, Dept Nanomed, Houston, TX 77030 USA

[2] Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy

[3] Politecn Torino, Turin, Italy

[4] Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Vet Sci, Houston, TX 77030 USA

[6] Univ Colorado, Dept Pharmaceut Sci, Skaggs Sch Pharm & Pharmaceut Sci, Anschutz Med Campus, Aurora, CO USA

[7] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[8] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[9] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Internal Med, Div Infect Dis, Houston, TX 77030 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

[11] HMRI, Dept Surg, Houston, TX 77030 USA

[12] HMRI, Dept Radiat Oncol, Houston, TX 77030 USA

来源：

JOURNAL OF CONTROLLED RELEASE | 2018年 / 286卷

关键词：

ANTIVIRAL ACTIVITY; VAGINAL RING; ALAFENAMIDE; DELIVERY; PREVENTION; MEN; PHARMACOKINETICS; EMTRICITABINE; SAFETY; ORDER;

D O I：

10.1016/j.jconrel.2018.08.010

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：315 / 325

页数：11

共 67 条

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