Drug and contrast agent delivery into tumor interstitium relies on passive diffusive transport because of poor convection in solid tumors. The size of polymeric nanoparticle therapeutic and diagnostic agents hinders their penetration through tissues and hence can cause inadequate delivery into the interstitium. It is thus vital to characterize the restricted transport of these large particles in order to improve their delivery into tumors. We introduce a simple and reliable method for the measurement of diffusion into tissue-simulating gels utilizing time-resolved MRI. Optimized inversion-recovery and spin-echo imaging sequences validate our methodology and show the consistency between approaches. We measure the diffusion coefficients of different polymer delivery vectors (size range from 10 to 170 nm in diameter) in both agarose and collagen gels with different porosity and internal functionality. Our polymeric nanoparticles include magnetic block polymer particles and clusters that are tailored as drug carriers and sensitive MRI contrast agents, as well as a series of gadolinium-based polymeric theranostic �beacons� that form plasmid-DNA polyplexes for gene delivery and simultaneous in vivo MRItracking of delivery. Diffusion coefficients determined by our method match previous measurements by fluorescence recovery after photobleaching in gels, but allow tracking over macroscopic distances and access to the dynamic time dependence of transport. We will discuss the influence on transport of the size of polymer nanoparticles, the medium tortuosity and porosity, and comparisons with several theoretical models. These results have meaningful implications for designing non-viral polymeric drug and contrast agents for delivery into tumors and tissues, and for enhanced tissue engineering.

Diffusion of nanomedicine into composite hydrogels: Time-resolved microMRI

247th National Meeting (2014)

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