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Lung cancers and pulmonary infections are important causes of morbidity and mortality. Despite the availability of better chemotherapeutic agents, treatment failures are common. In the search for more effective drugs for the treatment of these diseases, my laboratory has utilized compounds that have proven effective, but that suffer from solubility, toxicity, and/or pulmonary localization (targeting) problems. Reformulating these drugs in liposomes or nanoparticles and directly targeting the lungs by aerosol administration, we have been able to achieve lung concentrations that are 10- to 100-fold higher than administering these drugs by more conventional routes. Thus, this drug delivery system may increase local efftiveness while decreasing system toxicity, creating a larger therapeutic window. We have used this approach to treat pulmonary, as well as systemic, disease in both humans an animal models of influenza and respiratory syncytial virus infections, in fungal infections and in immune mediated disease.

Currently, a major forus of the laboratory is the treatment of both lung and systemic cancers. Using topoisomerase I inhibitors formulated in liposomes, we have shown that aerosol delivery of these drugs effectively reduces tumor growth rates. We have extended these studies into human clinical trials. We believe that this ability to target the lungs has many applications for the treatment of human diseases.

Recent Publications (PubMed)

Knight, V., N.V. Koshkina, J.C. Waldrep, B.C. Giovanella and B.E. Gilbert. 1999. Anti-cancer effect of 9-nitrocamptothecin liposome aerosol on human cancer xenografts in nude mice. Cancer Chemother. Pharmacol. 44:177-186.

Parthasarathy, R., B. Gilbert and K. Mehta. 1999. Aerosol delivery of liposomal all-trans-retinoid acid to the lungs. Cancer Chemother. Pharmacol. 43:277-283.

Wyde, P.R., D.K. Moore-Poveda, E. DeClercq, J. Neyts, A. Matsuda, N. Minakawa, E. Guzman and B.E. Gilbert. 2000. Use of cotton rats to evaluate the efficacy of antivirals in the treatment of measles virus infections. Antimicrob. Agents Chemother. 44:1146-1152.

Gautam, A., J. C. Waldrep, C. L. Densmore, N. Koshkina, S. Melton, L. Roberts, B. Gilbert and V. Knight. 2002. Growth inhibition of established B16-F10 lung metastases by sequential aerosol delivery of p53 gene and 9-nitrocamptothecin. Gene Therapy 9: 353-357.

Lawson, K.A., K. Anderson, M. Menchaca, J. Atkinson, L. Sun, V. Knight, B.E. Gilbert, C. Conti, B.G. Sanders and K. Kline. 2003. Novel vitamin E analogue decreases syngeneic mouse mammary tumor burden and reduces lung metastasis. Mol. Cancer Therap. 2:437-444.