ISSN:
1573-904X
Keywords:
transforming growth factor
;
permeability
;
chemotherapy
;
oral mucosa
;
mucositis and pharmacokinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015052520467
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