(190a) Lung Targeting Hydrogel Microparticles with Embedded Nanoparticles for the Treatment of Lung Cancer

Although only the second most prevalent type of cancer, lung cancer is the most lethal. National Cancer Institute assesses that results of standard treatment are generally poor with only a 15 percent 5-year survival rate for combined cancer stages. Challenges facing the current chemotherapy drugs include, hydrophobicity of therapeutic agents, excessive systemic toxicity in healthy tissues and inability to specifically target lung tumors. The hydrogel-based delivery vehicle described herein aims to overcome these challenges by selectively targeting the lung to deliver hydrophobic, anti-cancer drugs.

The first layer of the delivery system is a poly(ethylene glycol) based gel microparticle (GMP) designed to take advantage of the venous lung filtration pathway and passively accumulate in the lungs after intravenous injection into the body.  The size and modulus of the GMPs affect the targeting, accumulation and clearance from the lungs. The second layer of the delivery system consists of nanoparticles (NP) embedded within the GMP matrix. The NPs are loaded with a camptothecin prodrug designed with a hydrolytically unstable ester linker. As the ester is cleaved, camptothecin is released. This dual-delivery system affords the ability to sustain a high concentration of anti-cancer drugs in the lungs while minimizing the systemic exposure and accordingly reducing the side effects.