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Oral Mucosal Permeability and Stability of Transforming Growth Factor Beta-3 In Vitro

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Abstract

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 Kp 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 Kp value was 4.0 ± 0.6 × 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.

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Authors and Affiliations

  1. College of Dentistry, Dows Institute for Dental Research, N419 Dental Science Building, U. Iowa, Iowa City, Iowa, 52242

    Christopher A. Squier, Mary J. Kremer, Arnold Bruskin, Ann Rose & John D. Haley

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  1. Christopher A. Squier
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  2. Mary J. Kremer
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  3. Arnold Bruskin
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  4. Ann Rose
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  5. John D. Haley
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Correspondence to Christopher A. Squier.

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Squier, C.A., Kremer, M.J., Bruskin, A. et al. Oral Mucosal Permeability and Stability of Transforming Growth Factor Beta-3 In Vitro . Pharm Res 16, 1557–1563 (1999). https://doi.org/10.1023/A:1015052520467

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