Characterization of a Reservoir-Style Implant for Sustained Release of Tenofovir Alafenamide (TAF) for HIV Pre-Exposure Prophylaxis (PrEP)
Long-acting (LA) HIV pre-exposure prophylaxis (PrEP) offers the potential to improve adherence by lowering the burden of daily or on-demand regimens of antiretroviral (ARV) drugs. This paper details the fabrication and in vitro performance of a subcutaneous and trocar-compatible implant for the LA d...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/7/315 |
| _version_ | 1811306197009039360 |
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| author | Leah M. Johnson Sai Archana Krovi Linying Li Natalie Girouard Zach R. Demkovich Daniel Myers Ben Creelman Ariane van der Straten |
| author_facet | Leah M. Johnson Sai Archana Krovi Linying Li Natalie Girouard Zach R. Demkovich Daniel Myers Ben Creelman Ariane van der Straten |
| author_sort | Leah M. Johnson |
| collection | DOAJ |
| description | Long-acting (LA) HIV pre-exposure prophylaxis (PrEP) offers the potential to improve adherence by lowering the burden of daily or on-demand regimens of antiretroviral (ARV) drugs. This paper details the fabrication and in vitro performance of a subcutaneous and trocar-compatible implant for the LA delivery of tenofovir alafenamide (TAF). The reservoir-style implant comprises an extruded tube of a biodegradable polymer, poly(ε-caprolactone) (PCL), filled with a formulation of TAF and castor oil excipient. Parameters that affect the daily release rates of TAF are described, including the surface area of the implant, the thickness of the PCL tube walls (between 45 and 200 µm), and the properties of the PCL (e.g., crystallinity). In vitro studies show a linear relationship between daily release rates and surface area, demonstrating a membrane-controlled release mechanism from extruded PCL tubes. Release rates of TAF from the implant are inversely proportional to the wall thickness, with release rates between approximately 0.91 and 0.15 mg/day for 45 and 200 µm, respectively. The sustained release of TAF at 0.28 ± 0.06 mg/day over the course of 180 days in vitro was achieved. Progress in the development of this implant platform addresses the need for new biomedical approaches to the LA delivery of ARV drugs. |
| first_indexed | 2024-04-13T08:40:08Z |
| format | Article |
| id | doaj.art-883073d8b1b24b6a82e05b259999c461 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-13T08:40:08Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-883073d8b1b24b6a82e05b259999c4612022-12-22T02:53:56ZengMDPI AGPharmaceutics1999-49232019-07-0111731510.3390/pharmaceutics11070315pharmaceutics11070315Characterization of a Reservoir-Style Implant for Sustained Release of Tenofovir Alafenamide (TAF) for HIV Pre-Exposure Prophylaxis (PrEP)Leah M. Johnson0Sai Archana Krovi1Linying Li2Natalie Girouard3Zach R. Demkovich4Daniel Myers5Ben Creelman6Ariane van der Straten7Engineered Systems, RTI International, 3040 E. Cornwallis Road, Research Triangle Park, NC 27709, USAEngineered Systems, RTI International, 3040 E. Cornwallis Road, Research Triangle Park, NC 27709, USAEngineered Systems, RTI International, 3040 E. Cornwallis Road, Research Triangle Park, NC 27709, USAEngineered Systems, RTI International, 3040 E. Cornwallis Road, Research Triangle Park, NC 27709, USAWomen’s Global Health Imperative, RTI International, 351 California Street, Suite 500, San Francisco, CA 94104, USAPATH, 2201 Westlake Ave, Suite 200, Seattle, WA 98121, USAPATH, 2201 Westlake Ave, Suite 200, Seattle, WA 98121, USAWomen’s Global Health Imperative, RTI International, 351 California Street, Suite 500, San Francisco, CA 94104, USALong-acting (LA) HIV pre-exposure prophylaxis (PrEP) offers the potential to improve adherence by lowering the burden of daily or on-demand regimens of antiretroviral (ARV) drugs. This paper details the fabrication and in vitro performance of a subcutaneous and trocar-compatible implant for the LA delivery of tenofovir alafenamide (TAF). The reservoir-style implant comprises an extruded tube of a biodegradable polymer, poly(ε-caprolactone) (PCL), filled with a formulation of TAF and castor oil excipient. Parameters that affect the daily release rates of TAF are described, including the surface area of the implant, the thickness of the PCL tube walls (between 45 and 200 µm), and the properties of the PCL (e.g., crystallinity). In vitro studies show a linear relationship between daily release rates and surface area, demonstrating a membrane-controlled release mechanism from extruded PCL tubes. Release rates of TAF from the implant are inversely proportional to the wall thickness, with release rates between approximately 0.91 and 0.15 mg/day for 45 and 200 µm, respectively. The sustained release of TAF at 0.28 ± 0.06 mg/day over the course of 180 days in vitro was achieved. Progress in the development of this implant platform addresses the need for new biomedical approaches to the LA delivery of ARV drugs.https://www.mdpi.com/1999-4923/11/7/315poly(ε-caprolactone) (PCL)tenofovir alafenamide (TAF)pre-exposure prophylaxis (PrEP)long-acting drug delivery systemsimplant |
| spellingShingle | Leah M. Johnson Sai Archana Krovi Linying Li Natalie Girouard Zach R. Demkovich Daniel Myers Ben Creelman Ariane van der Straten Characterization of a Reservoir-Style Implant for Sustained Release of Tenofovir Alafenamide (TAF) for HIV Pre-Exposure Prophylaxis (PrEP) Pharmaceutics poly(ε-caprolactone) (PCL) tenofovir alafenamide (TAF) pre-exposure prophylaxis (PrEP) long-acting drug delivery systems implant |
| title | Characterization of a Reservoir-Style Implant for Sustained Release of Tenofovir Alafenamide (TAF) for HIV Pre-Exposure Prophylaxis (PrEP) |
| title_full | Characterization of a Reservoir-Style Implant for Sustained Release of Tenofovir Alafenamide (TAF) for HIV Pre-Exposure Prophylaxis (PrEP) |
| title_fullStr | Characterization of a Reservoir-Style Implant for Sustained Release of Tenofovir Alafenamide (TAF) for HIV Pre-Exposure Prophylaxis (PrEP) |
| title_full_unstemmed | Characterization of a Reservoir-Style Implant for Sustained Release of Tenofovir Alafenamide (TAF) for HIV Pre-Exposure Prophylaxis (PrEP) |
| title_short | Characterization of a Reservoir-Style Implant for Sustained Release of Tenofovir Alafenamide (TAF) for HIV Pre-Exposure Prophylaxis (PrEP) |
| title_sort | characterization of a reservoir style implant for sustained release of tenofovir alafenamide taf for hiv pre exposure prophylaxis prep |
| topic | poly(ε-caprolactone) (PCL) tenofovir alafenamide (TAF) pre-exposure prophylaxis (PrEP) long-acting drug delivery systems implant |
| url | https://www.mdpi.com/1999-4923/11/7/315 |
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