(385e) Enhanced Transport of PEG-Based Magnetic Nanocomposites In Artificial Mucus Barriers

Chemotherapy causes many adverse side effects when administered systemically through oral or IV delivery, and therefore, the localization of this therapy will result in improved therapeutic outcomes. Pulmonary administration of chemotherapy has shown enhanced therapeutic response while reducing side effects [1,2], and pulmonary delivery of multifunctional nanoparticles could serve as a multimodal treatment with enhanced patient response. However, the delivery of nanoparticles to mucosal tissue such as the lungs is greatly inhibited by a layer of viscoelastic mucus, and diseased states can enhance the mucus barrier.  In this work, iron oxide core-shell nanocomposites were synthesized, characterized, and investigated in order to determine the effects of heating and surface chemistry on the rate of transport through a PEG-based artificial mucus.  Atom transfer radical polymerization was used to grow PEG-based polymer coatings from iron oxide (Fe₃O₄) cores.  These magnetic cores possess the ability to heat upon exposure to an alternating magnetic field due to Brownian and Neel relaxation processes.  Fourier transform infrared spectroscopy was used to confirm the presence of PEG on the surface of the nanoparticles by examining characteristic peaks in the spectra, and thermogravimetric analysis was used to quantify the amount of PEG attached by calculating mass loss.  Dynamic light scattering was used to determine the average hydrodynamic radius of the nanoparticles.  A PEG-based artificial mucus was synthesized with 95:5 water:macromer ratio by weight, and the transport of nanoparticles into this mesh was studied at room temperature and at an elevated temperature.  Preliminary results indicate that the transport of PEG-coated iron oxide nanoparticles can be increased by heating these particles.

References:

1.         Otterson, G.A., et al., Phase I/II Study of Inhaled Doxorubicin Combined with Platinum-Based Therapy for Advanced Non-Small Cell Lung Cancer. Clinical Cancer Research, 2010. 16(8): p. 2466-2473.

2.         Otterson, G.A., et al., Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs. Clinical Cancer Research, 2007. 13(4): p. 1246-1252.