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A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis

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Abstract

Purpose

The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by long acting drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP.

Methods

A thin-film polycaprolactone (PCL) membrane controls drug release from a reservoir. To achieve membrane controlled release, TAF requires a formulation excipient such as PEG300 to increase the dissolution rate and reservoir solubility. Short-term In vitro release studies are used to develop an empirical design model, which is applied to the production of in vitro prototype devices demonstrating up to 90-days of linear release and TAF chemical stability.

Results

The size and shape of the TFPD are tunable, achieving release rates ranging from 0.5 to 4.4 mg/day in devices no larger than a contraceptive implant. Based on published data for oral TAF, subcutaneous constant-rate release for HIV PrEP is estimated at <2.8 mg/day. Prototype devices demonstrated linear release at 1.2 mg/day for up to 90 days and at 2.2 mg/day for up to 60 days.

Conclusions

We present a biodegradable TFPD for subcutaneous delivery of TAF for HIV PrEP. The size, shape and release rate of the device are tunable over a >8-fold range.

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Abbreviations

API:

Active pharmaceutical ingredient

ARV:

Antiretroviral

DC:

Direct current

FDC:

Emtricitabine

HPLC:

High performance liquid chromatography

LA-PrEP:

Long acting pre-exposure prophylaxis

PCL:

Polycaprolactone

PDMS:

Polydimethylsiloxane

PEG:

Polyethylene glycol

PrEP:

Pre-exposure prophylaxis

TAF:

Tenofovir alafenamide fumarate

TDF:

Tenofovir disproxil fumarate

TFPD:

Thin film Polycaprolactone device

TFV:

Tenofovir

UV:

Ultraviolet

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Acknowledgments and Disclosures

This research is made possible by the generous support of the American people through the U.S. President’s Emergency Plan for AIDS Relief. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, PEPFAR, or the United States Government.

Tenofovir Alafeinimde Fumarate drug substance and analytical methods were graciously provided by Gilead Sciences, Inc.

Author information

Authors and Affiliations

  1. UC Berkeley-UCSF Graduate Program in Bioengineering, 1700 4th Street Room 204, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA

    Erica Schlesinger & Tejal Desai

  2. Department of Bioengineering and Therapeutic Sciences, 1700 4th Street Room 204, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA

    Daniel Johengen & Tejal Desai

  3. Women’s Global Health Imperative, RTI International, 351 California Street,, San Francisco, California, 94104, USA

    Ellen Luecke & Ariane van der Straten

  4. Emerging Technologies, Research Triangle Institute (RTI) International, Research Triangle Park, North Carolina, 27709, USA

    Ginger Rothrock

  5. University of Pittsburgh Medical School, 204 Craft Ave Rm B-621, Pittsburgh, Pennsylvania, 15213, USA

    Ian McGowan

  6. Center for AIDS Prevention Studies (CAPS), Department of Medicine, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA

    Ariane van der Straten

Authors
  1. Erica Schlesinger
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  2. Daniel Johengen
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  3. Ellen Luecke
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  4. Ginger Rothrock
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  5. Ian McGowan
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  6. Ariane van der Straten
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  7. Tejal Desai
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Corresponding author

Correspondence to Tejal Desai.

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Schlesinger, E., Johengen, D., Luecke, E. et al. A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis. Pharm Res 33, 1649–1656 (2016). https://doi.org/10.1007/s11095-016-1904-6

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  • DOI: https://doi.org/10.1007/s11095-016-1904-6

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