Investigator: Samantha Meenach, University of Rhode Island

Mentor: Geoffrey Bothun, University of Rhode Island

Scientific Theme: Cancer

Abstract: Significant critical barriers in the treatment of lung cancer include the lack of specific therapeutic targeting to cancerous tissue within the lung and the lack of drug penetration into the tumor parenchyma. In addition, limitations in the types of in vitro cell culture models available for the evaluation of lung cancer aerosol-based therapeutics are often limited and not physiologically relevent. The objectives of this project are to develop dry powder nanocomposite systems containing peptide-conjugated nanoparticles loaded with paclitaxel that will be capable of targeting and penetration into non-small cell lung cancer (NSCLC) tumors, and to effectively evaluate these particles using a novel, physiologically-based in vitro cell culture platform. The outcomes of this project will directly improve the health and mortality rates of lung cancer patients through the development of an innovative, targeted drug delivery platform. The specific aims are: 1) To rationally design the characteristics of tumor-penetrating aerosol nanocomposite particles to ensure effective paclitaxel delivery and aerosol properties and to assess their efficacy in the treatment of NSCLC via in vitro analysis using conventional two-dimensional cell culture methods and 2) To develop an in vitro three-dimensional air-interface multicellular spheroid cell culture platform for the evaluation of the aerosol anti-cancer therapeutics. The nanocomposite particle systems will be rationally designed to ensure effective chemotherapeutoc loading and release, tumor cell targeting, aerosol properties, and morphology. The nanoparticles will be formulated via emulsion techniques followed by encapsulation into a lung-friendly excipient via spray drying to produce the final nanocomposite microparticles. The efficacy of the nanocomposite systems will initially be evaluated via a conventional two-dimensional air-interface cell culture method where lung cancer cells will be exposed to the dry powder particles via microparticle insufflation. Air-interface three-dimensional tumor spheroids will be used to evaluate the diffusion and penetration of the nanoparticles into tumor tissue as well as their efficacy. This will allow for an inexpensive, simple assessment of the efficacy of the system, which will result in a more accurate physiological evaluation.

Human Health Relevance: The proposed research is relevant to public health because it will improve the health, morbidity, and mortality of lung cancer patients using a less invasive, safer, more effective inhaler-based therapeutic platform. Cancer patients will be able to inhale particles containing chemotherapeutic directly into their lungs at the site of the tumors, decreasing potential side effects and increasing effectiveness of their treatment.