Targeting lung cancer by identifying genes associated with resistance and developing lipid based nanodispersions for the inhalation delivery of therapeutic payloads
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Kuzmov, Andriy. Targeting lung cancer by identifying genes associated with resistance and developing lipid based nanodispersions for the inhalation delivery of therapeutic payloads. Retrieved from https://doi.org/doi:10.7282/t3-g68c-5n68
TitleTargeting lung cancer by identifying genes associated with resistance and developing lipid based nanodispersions for the inhalation delivery of therapeutic payloads
DescriptionThe efficacy of cancer chemotherapy is limited by the development of resistance and intolerable side effects to conventional chemotherapeutic agents. To help overcome these barriers and improve the treatment of lung cancer, we propose the use of local inhalation delivery of chemotherapeutic drugs in combination of siRNA targeting pump and non-pump cellular resistance mechanism. To deliver the poorly soluble small molecule drug paclitaxel in combination with siRNA, we propose the use of a cationic lipid nanodispersion that can deliver the both therapeutic entities at the same time. To increase the targeting of the drug to cancer cells, LHRH peptide is attached to the delivery system. To reduce the particle size, improve the stability of the formulation, and improve its biocompatibility, we evaluate the effect of formulation buffer, solid lipids, and surfactant blends on the characteristics of the lipid dispersions. We report the formulation of gefitinib in the optimized lipid nanodispersions. To investigate the role of the PI3K/AKT pathway in the pathogenesis of cancer and development of resistance, we describe the evaluation of the gene expression of three cell lines with varying sensitivities to the EGFR inhibitor gefitinib.