Using Aerosolized Tumor-Penetrating Nanocomposite Microparticles for the Local Treatment of Lung Cancer

The second leading cause of death in the world is cancer. Within the United States, lung and bronchus cancers are the leading causes of cancer-related deaths with an estimated 158,040 deaths expected in 2015. Additionally, only 17.4% of lung cancer patients survive five years after being diagnosed with lung or bronchus cancer.

The objective of this research was to synthesize and characterize a nanocomposite microparticle (nCmP) system to be used for the local treatment of lung cancer. This system involved a dry powder aerosol containing paclitaxel-loaded tumor-penetrating peptide-conjugated nanoparticles that were encapsulated into microparticles via spray drying. By using nanoparticle therapeutics, the delivery of paclitaxel (PTX) directly to the tumor site can be achieved, circumventing the adverse side effects seen with systemic delivery. The polymer used to create the nanoparticles was acetalated dextran (Ac-Dex). The nanoparticles were characterized for their size, surface charge, and polydisperisty via dynamic light scattering, and drug encapsulation efficiency via high-performance liquid chromatography (HPLC). The tumor-penetrating peptide iRGD was conjugated via oxime bonding between the aldehyde groups on Ac-Dex and the alkoxyamine groups on iRGD. iRGD is used to target αv integrins overexpressed on tumors while simultaneously increasing the tumor tissue penetrating capability of the nanoparticles. Once conjugated, the nanoparticles were suspended in a solution of mannitol and spray-dried into microparticles. The resulting nCmP were then characterized for their water content using Karl Fischer titration and their aerodynamic properties using a Next Generation Impactor.

SEM indicated the presence of nanoparticles encapsulated into microparticles in the proper size range for lung deposition, and HPLC verified the presence of PTX inside the nanoparticles. Further cell viability studies will be conducted to understand how nCmP interact with cancer cells and how iRGD enhances the penetrating capabilities of nanoparticles into cancerous cells and tissues. Results have shown the efficacy of nCmP as a potential therapeutic for lung cancer.