Towards Optimal Design of Cancer Nanomedicines: Multi-stage Nanoparticles for the Treatment of Solid Tumors
Economides, E. A.
Baish, J. W.
Jain, R. K.
SourceAnnals of Biomedical Engineering
Google Scholar check
MetadataShow full item record
Conventional drug delivery systems for solid tumors are composed of a nano-carrier that releases its therapeutic load. These two-stage nanoparticles utilize the enhanced permeability and retention (EPR) effect to enable preferential delivery to tumor tissue. However, the size-dependency of the EPR, the limited penetration of nanoparticles into the tumor as well as the rapid binding of the particles or the released cytotoxic agents to cancer cells and stromal components inhibit the uniform distribution of the drug and the efficacy of the treatment. Here, we employ mathematical modeling to study the effect of particle size, drug release rate and binding affinity on the distribution and efficacy of nanoparticles to derive optimal design rules. Furthermore, we introduce a new multi-stage delivery system. The system consists of a 20-nm primary nanoparticle, which releases 5-nm secondary particles, which in turn release the chemotherapeutic drug. We found that tuning the drug release kinetics and binding affinities leads to improved delivery of the drug. Our results also indicate that multi-stage nanoparticles are superior over two-stage nano-carriers provided they have a faster drug release rate and for high binding affinity drugs. Furthermore, our results suggest that smaller nanoparticles achieve better treatment outcome. © 2015, Biomedical Engineering Society.
Showing items related by title, author, creator and subject.
Energy-based model reduction methodology for automated modeling Louca, Loucas S.; Stein, J. L.; Hulbert, G. M. (2010)In recent years, algorithms have been developed to help automate the production of dynamic system models. Part of this effort has been the development of algorithms that use modeling metrics for generating minimum complexity ...
A review of proper modeling techniques Ersal, T.; Fathy, H. K.; Rideout, D. G.; Louca, Loucas S.; Stein, J. L. (2008)A dynamic system model is proper for a particular application if it achieves the accuracy required by the application with minimal complexity. Because model complexity often-but not always-correlates inversely with simulation ...
A model accuracy and validation algorithm Sendur, P.; Stein, J. L.; Peng, H.; Louca, Loucas S. (American Society of Mechanical Engineers (ASME), 2002)Dynamic models of physical systems with physically meaningful states and parameters have become increasingly important, for design, control and even procurement decisions. The successful use of models in these contexts ...