title: A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis.
abstract: OBJECTIVE
  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.
authors.affiliation: UC Berkeley-UCSF Graduate Program in Bioengineering, 1700 4th Street Room 204, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Schlesinger
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, 1700 4th Street Room 204, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Johengen
authors.affiliation: Women's Global Health Imperative, RTI International, 351 California Street,, San Francisco, California, 94104, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Luecke
authors.affiliation: Emerging Technologies, Research Triangle Institute (RTI) International, Research Triangle Park, North Carolina, 27709, USA.
authors.forename: Ginger
authors.initials: G
authors.lastname: Rothrock
authors.affiliation: University of Pittsburgh Medical School, 204 Craft Ave Rm B-621, Pittsburgh, Pennsylvania, 15213, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: McGowan
authors.affiliation: Women's Global Health Imperative, RTI International, 351 California Street,, San Francisco, California, 94104, USA.|Center for AIDS Prevention Studies (CAPS), Department of Medicine, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA.
authors.forename: Ariane
authors.initials: A
authors.lastname: van der Straten
authors.affiliation: 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.|Department of Bioengineering and Therapeutic Sciences, 1700 4th Street Room 204, UCSF Mission Bay Campus,, San Francisco, California, 94158, USA. tejal.desai@ucsf.edu.
authors.forename: Tejal
authors.initials: T
authors.lastname: Desai
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000409:Alanine; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D063566:Biodegradable Plastics / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000502:physiology; D005650:Fumarates / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D065129:Pre-Exposure Prophylaxis / Q000379:methods; D012995:Solubility; D000068698:Tenofovir / Q000031:analogs & derivatives
chemical_list: D019380:Anti-HIV Agents; D063566:Biodegradable Plastics; D003692:Delayed-Action Preparations; D005650:Fumarates; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D000068698:Tenofovir; C442442:tenofovir alafenamide; D000225:Adenine; D000409:Alanine
keywords: HIV pre-exposure prophylaxis; antiretroviral; biodegradable implant; membrane controlled release; polycaprolactone; tenofovir alafenamide fumarate