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-β3 in porcine floor-of-mouth mucosa as a function of concentration and exposure. Methods. The ¹²⁵I-TGF-β3 diluted in three different vehicles was applied to the tissue samples mounted in perfusion cells maintained at 37°C. Flux and K(p) values were calculated from the perfusate collected over a 24 hour period. The quantity of ¹²⁵I-TGF-β3 present in the tissue was determined by horizontal sectioning and subsequent counting. The stability of ¹²⁵I-TGF-β3 in saliva and in the tissue was analyzed by SDS polyacrylamide gradient gel electrophoresis. Results. ¹²⁵I-TGF-β3 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-β3 homodimer. A steady-state flux was reached ~6 hours post application and K(p) value was 4.0 ± 0.6 X 10^-6 (mean ± sem). Penetration of ¹²⁵I-TGF-β3 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- β3 to the oral mucosa in an appropriate vehicle can provide effective therapeutic delivery to the tissue.