Transvaginal diffusion of synthetic peptides

Topical microbicide peptides are being developed to combat the transfer of HIV, but little is known about the permeation of these compounds through vaginal epithelium. The object of the present study is to investigate the in vitro permeation of synthetic transport peptides through vaginal mucosa. The permeation kinetics of three FITC (fluorescein isothiocyanate)-labelled peptides MEA-5 (Mw = 2911.4 Da), MDY-19 (Mw = 2409.5 Da) and PCI (Mw = 2325 Da) across human vaginal mucosa was studied by means of a continuous flow-through diffusion system. Permeability studies were conducted at concentrations of 1 mM, 0.75 mM and 0.5 mM in PBS buffer at 37 C and 20 C, respectively, and over a time period of 24 h, using fluorospectrophotometry as detection method. Effects of a surfactant on MDY-19 permeation and de-epithelialisation of the vaginal mucosa were also studied. Statistical tests used included an ANOVA and Duncan's multiple range test to establish steady state diffusion kinetics. All three peptides readily penetrate vaginal mucosa. Microbicides may be coupled to MDY-19 and PCI to be transported transmucosally. Although increased size of the peptide/microbicides complex may decrease mucosal permeability, this could possibly be overcome by the addition of a permeation enhancer, e.g. a surfactant. Removal of the vaginal epithelium increased the flux rates of the peptides across the mucosa and may have implications for a more rapid uptake of these and other microbicides in vivo. Concentration- and temperature-dependency of peptide flux rates must be taken into consideration when performing in vitro permeability studies.