In recent years, Cycloxygenase (COX)-2 has emerged as a therapeutic target for the prevention and treatment of various types of cancers.
However, celecoxib, a potent COX-2 inhibitor has been shown to induce heart attacks and strokes in the Phase III cancer studies which was primarily attributed to the high oral dose of celecoxib (400 mg, twice daily) employed in these studies. Inhalation drug delivery represents a novel and potential delivery route for the treatment of lung cancer.
Researchers from Florida A&M University, College of Pharmacy, demonstrated that aerosolized celecoxib at a much lower therapeutic dose than oral celecoxib shows significant inhibition of tumor progression in orthotopic NSCLC xenograft model. The study published in Sep 2006 issue of Pharmaceutical Research demonstrated superior efficacy of inhaled celecoxib as compared to conventional oral route of administration (Lead author: Dr. Suniket Fulzele).
Dr. Fulzele optimized the celecoxib aerosol performance and its delivery to tumor bearing mice. There are very few techniques that are available to study aerosol performance in animals. This is particularly complicated by the fact that rodents (rats/mice) have extremely small tidal volumes and unlike humans they breathe only by nose. Study of the efficacy of inhaled products in tumor bearing animals is also impaired by the differences in breathing pattern due to presence of tumors in the lungs. Dr. Fulzele and his colleagues formulated and effectively delivered celecoxib via aerosolization to treat orthotopic lung tumors in combination with intravenous docetaxel. Aerosolized celecoxib at a significantly lower therapeutic dose (4.56 mg/kg/day) demonstrated comparable anti-tumor efficacy to orally administered celecoxib (150 mg/kg/day).
The researchers demonstrated their experiments in mouse model of lung cancer. Mice treated with celecoxib (aerosol/oral) + docetaxel showed significant reduction in lung weight and tumor area as compared to celecoxib or docetaxel treatments. Combination of aerosol/oral celecoxib with docetaxel produced significant anti-tumor effect mediated via reduced prostaglandin E 2 (PGE2), IL-8 and Factor VIII levels and increased apoptosis mediated via Fas pathway.