Enzymatic triggered release of an HIV-1 entry inhibitor from prostate specific antigen degradable microparticles

Int J Pharm. 2011 Jul 15;413(1-2):10-18. doi: 10.1016/j.ijpharm.2011.04.004. Epub 2011 Apr 12.


This paper describes the design, construction and characterization of the first anti-HIV drug delivery system that is triggered to release its contents in the presence of human semen. Microgel particles were synthesized with a crosslinker containing a peptide substrate for the seminal serine protease prostate specific antigen (PSA) and were loaded with the HIV-1 entry inhibitor sodium poly(styrene-4-sulfonate) (pSS). The particles were composed of N-2-hydroxyproplymethacrylamide and bis-methacrylamide functionalized peptides based on the PSA substrates GISSFYSSK and GISSQYSSK. Exposure to human seminal plasma (HSP) degraded the microgel network and triggered the release of the entrapped antiviral polymer. Particles with the crosslinker composed of the substrate GISSFYSSK showed 17 times faster degradation in seminal plasma than that of the crosslinker composed of GISSQYSSK. The microgel particles containing 1 mol% GISSFYSSK peptide crosslinker showed complete degradation in 30 h in the presence of HSP at 37°C and pSS released from the microgels within 30 min reached a concentration of 10 μg/mL, equivalent to the published IC(90) for pSS. The released pSS inactivated HIV-1 in the presence of HSP. The solid phase synthesis of the crosslinkers, preparation of the particles by inverse microemulsion polymerization, HSP-triggered release of pSS and inactivation of HIV-1 studies are described.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Linking Reagents / chemical synthesis
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Carriers / pharmacokinetics
  • Drug Compounding
  • Drug Delivery Systems*
  • Excipients / chemistry
  • Fluorescein-5-isothiocyanate / chemistry
  • Fluorescein-5-isothiocyanate / metabolism
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Gels / chemistry
  • HIV Fusion Inhibitors / chemistry*
  • HIV Fusion Inhibitors / metabolism
  • HIV Fusion Inhibitors / pharmacokinetics
  • HIV Infections / prevention & control
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Male
  • Particle Size
  • Peptides / chemistry
  • Polystyrenes / chemistry
  • Polystyrenes / metabolism
  • Polystyrenes / pharmacology
  • Prostate-Specific Antigen / chemistry*
  • Prostate-Specific Antigen / metabolism
  • Prostate-Specific Antigen / pharmacokinetics
  • Semen / metabolism


  • Cross-Linking Reagents
  • Drug Carriers
  • Excipients
  • Gels
  • HIV Fusion Inhibitors
  • Peptides
  • Polystyrenes
  • polystyrene sulfonic acid
  • Prostate-Specific Antigen
  • Fluorescein-5-isothiocyanate