title: A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine.
abstract: BACKGROUND
  There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. This study describes an innovative barrier contraceptive device--based on the SILCS diaphragm--that also provides long-term controlled release of the lead candidate anti-HIV microbicide dapivirine.
  
  
  METHODS
  Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded with a nonmedicated silicone elastomer sheath were fabricated by injection molding processes. In vitro release testing, thermal analysis and mechanical characterization were performed on the devices.
  
  
  RESULTS
  A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine provided continuous and controlled release of dapivirine over a 6-month period, with a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the new diaphragm were closely matched to the SILCS diaphragm.
  
  
  CONCLUSIONS
  The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. In discontinuous clinical use, release of dapivirine may be readily extended over 1 or more years.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Major
authors.forename: Peter
authors.initials: P
authors.lastname: Boyd
authors.forename: Maggie
authors.initials: M
authors.lastname: Kilbourne-Brook
authors.forename: Gene
authors.initials: G
authors.lastname: Saxon
authors.forename: Jessica
authors.initials: J
authors.lastname: Cohen
authors.forename: R Karl
authors.initials: RK
authors.lastname: Malcolm
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D003080:Cold Temperature / Q000009:adverse effects; D003274:Contraceptive Devices, Female; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission; D054303:HIV Reverse Transcriptase / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D007700:Kinetics; D008422:Materials Testing; D055595:Mechanical Phenomena; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D012995:Solubility
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D011743:Pyrimidines; D054303:HIV Reverse Transcriptase; C481671:Dapivirine