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Targeting Lung Tumors using a Novel Inhaled Excipient Enhanced Growth Gemcitabine Dry Powder Formulation

Beverlin II B, Hindle M, Longest P, Ferguson M, Kuehl PJ, Lopez A, Montoya D, Anger A, Gordon N.

Respiratory Drug Delivery 2022. Volume , 2022: 123-134.

Abstract:

Lung cancer is the leading cause of cancer mortality with a five-year survival rate of less than 20% following standard of care therapy. Despite the use of aggressive surgery, combination chemotherapy and immunotherapy, a major limitation in the control of primary and metastatic non-small cell pulmonary tumors with the use of the systemic administration of drugs is the low drug concentration in the lungs due to blood volume dilution and metabolism. Preliminary pre-clinical in vivo studies using nebulized chemotherapy drugs have demonstrated efficacy and established the feasibility of delivery via aerosol, but nebulization of toxic drugs has major drawbacks. To address these drawbacks, we are developing a new method of delivering a chemotherapeutic drug via inhalation to reach pulmonary tumors directly to maximize the effectiveness and safety of the aerosol treatment with a fraction of the standard dose. A novel dry powder chemotherapeutic formulation using excipient enhanced growth technology was developed for the treatment of non-small cell lung cancer. In this article we demonstrate (1) formulation and in vitro testing with physicochemical characterization, stability, and performance of a novel dry powder chemotherapeutic aerosol, and (2) in vivo efficacy of the formulation in an orthotopic lung cancer rodent model which was shown to be significantly (P < 0.0001) more efficacious than the standard of care IV formulation, at both matched and half of the IV dose.