Oral mucosal permeability and stability of transforming growth factor beta-3 in vitro

Purpose. To investigate the permeability and localization of topically appl ied I-125-TGF-beta 3 in porcine floor-of-mouth mucosa as a function of conc entration and exposure. Methods. The I-125-TGF-beta 3 diluted in three different vehicles was appli ed to the tissue samples mounted in perfusion cells maintained at 37 degree s C. Flux and K-p values were calculated from the perfusate collected over a 24 hour period. The quantity of I-125-TGF-beta 3 present in the tissue wa s determined by horizontal sectioning and subsequent counting. The stabilit y of I-125-TGF-beta 3 in saliva and in the tissue was analyzed by SDS polya crylamide gradient gel electrophoresis. Results. I-125-TGF-beta 3 was relatively stable in saliva and in the epithe lium; approximately 50% of the total counts in the deeper epithelium were r esident in the 25kDa TGF-beta 3 homodimer. A steady-state flux was reached similar to 6 hours post application and K-p value was 4.0 +/- 0.6 x 10(-6) (mean +/- sem). Penetration of I-125-TGF-beta 3 to the basal cell layer was concentration dependent but reached nanomolar concentrations even after ex tensive surface rinsing, representing over one-thousand fold the IC50 for e pithelial cell cycle arrest. Conclusions. The data suggest that topical application of TGF-beta 3 to the oral mucosa in an appropriate vehicle can provide effective therapeutic de livery to the tissue.