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In Vitro and In Vivo Evaluation of DMSO and Azone as Penetration Enhancers for Cutaneous Application of Celecoxib

[ Vol. 14 , Issue. 7 ]

Author(s):

Thassia D´Arc Senna, Hilton Antonio Mata dos Santos, Daniel Mabundu Kibwila, Alvaro Costa Leitao, Alexandre dos Santos Pyrrho, Marcelo de Padula, Elaine Cruz Rosas, Tatiana Almeida Padua, Marilisa Guimaraes Lara and Maria Bernadete Riemma Pierre*   Pages 992 - 1004 ( 13 )

Abstract:


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.

Keywords:

Anti-inflammatory activity, azone, celecoxib, cutaneous permeability, dimethylsulfoxide, glycerol, topical application.

Affiliation:

School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, Applied Pharmacology Laboratory, Fiocruz, Rua Sizenando Nabuco no 100, Rio de Janeiro, RJ, Applied Pharmacology Laboratory, Fiocruz, Rua Sizenando Nabuco no 100, Rio de Janeiro, RJ, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Av. do Cafe, s/n, 14040-160, Ribeirao Preto, SP, School of Pharmacy, Federal University of Rio de Janeiro- Av. Carlos Chagas Filho, 373, 21.941.590, Rio de Janeiro

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