Intratumoral implantable drug delivery system for targeted localized chemotherapy in breast cancer

Abstract

Breast cancer is a significant concern for many women, and local chemotherapy has emerged as a promising approach to address this issue. This study focuses on simulating the performance of chemotherapy using Doxorubicin, Cisplatin, Fluorouracil, and Methotrexate loaded in a dual release implantable system within a mathematical framework. The drugs are loaded in the implant as two forms: as free agents and encapsulated in nanoparticles. The results demonstrate that the elimination rate through blood microvessels and the diffusion mechanism play a crucial role in determining the bioavailability and effective penetration depth of the therapeutic agents. Drugs with high elimination rates, such as Doxorubicin, Cisplatin, and Fluorouracil, exhibit improved penetration depth by approximately 4, 3.75, and 2.25 times when encapsulated in small nanoparticles that release their content in the extracellular space. On the other hand, Methotrexate, with its weak removal rate, maintains a sufficient penetration depth and effective concentration level even as a free drug in the extracellular space. Therefore, encapsulating Methotrexate does not significantly impact on tumor penetration. This study emphasizes the potential of the dual implantable system as an effective approach for chemotherapy, particularly when considering the specific chemotherapy drug and the method of loading the therapeutic agent. The system proves to be particularly beneficial in tumors with low microvascular density. These findings provide valuable insights for future research in the development of local drug delivery systems for breast cancer treatment.