Background: Celecoxib (CXB) has been explored as an anti-inflammatory or chemopreventive
drug for topical treatment of skin diseases and cancer.
Objective: The main aim of this work was to investigate the potential of dimethylsufoxide (DMSO)
and Azone (AZ) as penetration enhancers (P.Es) for topical delivery of CXB.
Method: The in vitro studies, drug release, skin permeability and potential cytotoxicity/genotoxicity
were carried out with formulations containing or not DMSO or AZ (5% and 10%). Skin irritation in
rabbits and topical anti-inflammatory activity in mice were assayed in vivo.
Results: Skin permeation was minimal while higher retention in stratum corneum (SC) and epidermis
plus dermis was found (28.0 and 3-fold respectively) from 10.0% AZ compared to the control indicating
a localized CXB effect. CXB associated to 5% or 10% DMSO has shown high drug permeation
through skin with low retention. Associations of CXB with both enhancers were not cytotoxic or genotoxic,
suggesting safety for cutaneous application. In vivo skin irritation assays of all formulations indicated
mild irritation effects and, thus, possible use for longer periods. In vivo anti-inflammatory tests
showed that ear edema could be inhibited by CXB associated with 5.0% DMSO (53.0%) or 10.0% AZ
(40.0%). These inhibition values were almost 2-fold higher when compared to a commercial formula.
Conclusion: Although DMSO- associated CXB is an efficient edema inhibitor its high skin permeation
suggests risks of systemic effects, whereas association to 10% AZ may improve topical delivery of the
drug with good anti-inflammatory activity and no cytotoxic/genotoxic or significant skin irritation effects.