Erica Schlesinger1, Daniel Johengen2, Ellen Luecke3, Ginger Rothrock4, Ian McGowan5, Ariane van der Straten3,6, Tejal Desai7,8. 1. UC Berkeley-UCSF Graduate Program in Bioengineering, 1700 4th Street Room 204, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA. 2. Department of Bioengineering and Therapeutic Sciences, 1700 4th Street Room 204, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA. 3. Women's Global Health Imperative, RTI International, 351 California Street,, San Francisco, California, 94104, USA. 4. Emerging Technologies, Research Triangle Institute (RTI) International, Research Triangle Park, North Carolina, 27709, USA. 5. University of Pittsburgh Medical School, 204 Craft Ave Rm B-621, Pittsburgh, Pennsylvania, 15213, USA. 6. Center for AIDS Prevention Studies (CAPS), Department of Medicine, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA. 7. UC Berkeley-UCSF Graduate Program in Bioengineering, 1700 4th Street Room 204, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA. tejal.desai@ucsf.edu. 8. Department of Bioengineering and Therapeutic Sciences, 1700 4th Street Room 204, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA. tejal.desai@ucsf.edu.
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.
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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