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Transcutaneously refillable nanofluidic implant achieves sustained level of tenofovir diphosphate for HIV pre-exposure prophylaxis.
J Control Release. 2018 09 28; 286:315-325.JC

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.

Authors+Show Affiliations

Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.Politecnico di Torino, Turin, Italy.Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA.Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA.Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.Department of Veterinary Sciences, University of Texas MD Anderson Cancer Center, Houston, TX, USA.Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.Departments of Pathology and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA.Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA.Department of Veterinary Sciences, University of Texas MD Anderson Cancer Center, Houston, TX, USA.Division of Infectious Diseases, Department of Internal Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston, TX, USA.Department of Veterinary Sciences, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA; Department of Surgery, Houston Methodist Research Institute (HMRI), Houston, TX, USA; Department of Radiation Oncology, Houston Methodist Research Institute (HMRI), Houston, TX, USA. Electronic address: agrattoni@houstonmethodist.org.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30092254

Citation

Chua, Corrine Ying Xuan, et al. "Transcutaneously Refillable Nanofluidic Implant Achieves Sustained Level of Tenofovir Diphosphate for HIV Pre-exposure Prophylaxis." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 286, 2018, pp. 315-325.
Chua CYX, Jain P, Ballerini A, et al. Transcutaneously refillable nanofluidic implant achieves sustained level of tenofovir diphosphate for HIV pre-exposure prophylaxis. J Control Release. 2018;286:315-325.
Chua, C. Y. X., Jain, P., Ballerini, A., Bruno, G., Hood, R. L., Gupte, M., Gao, S., Di Trani, N., Susnjar, A., Shelton, K., Bushman, L. R., Folci, M., Filgueira, C. S., Marzinke, M. A., Anderson, P. L., Hu, M., Nehete, P., Arduino, R. C., Sastry, J. K., & Grattoni, A. (2018). Transcutaneously refillable nanofluidic implant achieves sustained level of tenofovir diphosphate for HIV pre-exposure prophylaxis. Journal of Controlled Release : Official Journal of the Controlled Release Society, 286, 315-325. https://doi.org/10.1016/j.jconrel.2018.08.010
Chua CYX, et al. Transcutaneously Refillable Nanofluidic Implant Achieves Sustained Level of Tenofovir Diphosphate for HIV Pre-exposure Prophylaxis. J Control Release. 2018 09 28;286:315-325. PubMed PMID: 30092254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcutaneously refillable nanofluidic implant achieves sustained level of tenofovir diphosphate for HIV pre-exposure prophylaxis. AU - Chua,Corrine Ying Xuan, AU - Jain,Priya, AU - Ballerini,Andrea, AU - Bruno,Giacomo, AU - Hood,R Lyle, AU - Gupte,Manas, AU - Gao,Song, AU - Di Trani,Nicola, AU - Susnjar,Antonia, AU - Shelton,Kathryn, AU - Bushman,Lane R, AU - Folci,Marco, AU - Filgueira,Carly S, AU - Marzinke,Mark A, AU - Anderson,Peter L, AU - Hu,Ming, AU - Nehete,Pramod, AU - Arduino,Roberto C, AU - Sastry,Jagannadha K, AU - Grattoni,Alessandro, Y1 - 2018/08/06/ PY - 2018/02/21/received PY - 2018/06/20/revised PY - 2018/08/03/accepted PY - 2018/8/10/pubmed PY - 2019/10/16/medline PY - 2018/8/10/entrez SP - 315 EP - 325 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 286 N2 - 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. SN - 1873-4995 UR - https://www.unboundmedicine.com/medline/citation/30092254/Transcutaneously_refillable_nanofluidic_implant_achieves_sustained_level_of_tenofovir_diphosphate_for_HIV_pre-exposure_prophylaxis L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-3659(18)30471-1 DB - PRIME DP - Unbound Medicine ER -