Abstract

Nanoparticle drug delivery better targets neoplastic lesions than free drugs and thus has emerged as safer form of cancer therapy. Nanoparticle design variables are important determinants of efficacy as they influence the drug biodistribution and pharmacokinetics. Previously, we determined optimal designs through mechanistic modeling and optimization. However, the numerical nature of the tumor model and numerous candidate nanoparticle designs hinder hypothesis generation and treatment personalization. In this paper, we utilize the parallel coordinates technique to visualize high-dimensional optimal solutions and extract correlations between nanoparticle design and treatment outcomes. We found that at optimality, two major design variables are dependent, and thus the optimization problem can be reduced. In addition, we obtained an analytical relationship between optimal nanoparticle sizes and optimal distribution, which could facilitate the utilization of tumors models in preclincal studies. Our approach has simplified the results of the previously integrated modeling and optimization framework developed for nanotherapy and enhanced the interpretation and utilization of findings. Integrated mathematical frameworks are increasing in the medical field, and our method can be applied outside nanotherapy to facilitate clinical translation of computational methods.

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