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

PURPOSE: To investigate the permeability and localization of topically applied 125I-TGF-beta3 in porcine floor-of-mouth mucosa as a function of concentration and exposure.
METHODS: The 125I-TGF-beta3 diluted in three different vehicles was applied to the tissue samples mounted in perfusion cells maintained at 37 degrees C. Flux and Kp values were calculated from the perfusate collected over a 24 hour period. The quantity of 125I-TGF-beta3 present in the tissue was determined by horizontal sectioning and subsequent counting. The stability of 125I-TGF-beta3 in saliva and in the tissue was analyzed by SDS polyacrylamide gradient gel electrophoresis.
RESULTS: 125I-TGF-beta3 was relatively stable in saliva and in the epithelium; approximately 50% of the total counts in the deeper epithelium were resident in the 25kDa TGF-beta3 homodimer. A steady-state flux was reached approximately 6 hours post application and Kp value was 4.0+/-0.6 x 10(-6) (mean +/- sem). Penetration of 125I-TGF-beta3 to the basal cell layer was concentration dependent but reached nanomolar concentrations even after extensive surface rinsing, representing over one-thousand fold the IC50 for epithelial cell cycle arrest.
CONCLUSIONS: The data suggest that topical application of TGF-beta3 to the oral mucosa in an appropriate vehicle can provide effective therapeutic delivery to the tissue.