Selection of topically applied non-steroidal anti-inflammatory drugs for oral cancer chemoprevention

TY - JOUR

T1 - Selection of topically applied non-steroidal anti-inflammatory drugs for oral cancer chemoprevention

AU - Sood, Sandeep

AU - Shiff, Steven J.

AU - Yang, Chung S.

AU - Chen, Xiaoxin

N1 - Funding Information: Supported by NIH grant CA101235.

PY - 2005/7

Y1 - 2005/7

N2 - Topical delivery of non-steroidal anti-inflammatory drugs through the oral mucosa has been used for oral cancer chemoprevention. Local permeation of these agents has been one of the major concerns. Here we propose an approach to predict the permeability of topically applied agents for oral cancer chemoprevention. In theory, the total flux through the oral mucosa (J max) can be estimated by adding the transcellular flux (J TC) and the paracellular flux (JPC). To target the Cox-2 enzyme in oral epithelial cells, it is desirable to maximize the theoretical activity index, the ratio of JTC and IC50 of a Cox-2 inhibitor (JTC/IC50-Cox-2). Among the 12 commonly used NSAIDs, celecoxib, nimesulide and ibuprofen had the highest values and may be the agents of choice to target Cox-2 in oral epithelial cells through topical application. Based on these calculations, a long-term chemopreventive experiment using celecoxib (3% or 6%) through topical application was performed in a DMBA induced hamster oral cancer model. Both 3% and 6% reduced the incidence of squamous cell carcinoma at the post-initiation stage.

AB - Topical delivery of non-steroidal anti-inflammatory drugs through the oral mucosa has been used for oral cancer chemoprevention. Local permeation of these agents has been one of the major concerns. Here we propose an approach to predict the permeability of topically applied agents for oral cancer chemoprevention. In theory, the total flux through the oral mucosa (J max) can be estimated by adding the transcellular flux (J TC) and the paracellular flux (JPC). To target the Cox-2 enzyme in oral epithelial cells, it is desirable to maximize the theoretical activity index, the ratio of JTC and IC50 of a Cox-2 inhibitor (JTC/IC50-Cox-2). Among the 12 commonly used NSAIDs, celecoxib, nimesulide and ibuprofen had the highest values and may be the agents of choice to target Cox-2 in oral epithelial cells through topical application. Based on these calculations, a long-term chemopreventive experiment using celecoxib (3% or 6%) through topical application was performed in a DMBA induced hamster oral cancer model. Both 3% and 6% reduced the incidence of squamous cell carcinoma at the post-initiation stage.

KW - NSAIDs

KW - Oral cancer

UR - http://www.scopus.com/inward/record.url?scp=20444506460&partnerID=8YFLogxK

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U2 - 10.1016/j.oraloncology.2005.01.003

DO - 10.1016/j.oraloncology.2005.01.003

M3 - Review article

C2 - 15975519

SN - 1368-8375

VL - 41

SP - 562

EP - 567

JO - Oral Oncology

JF - Oral Oncology

IS - 6

ER -