Targeted and Localized Cancer Drug Release Kinetics from Microporous Poly-di-methyl-siloxane (PDMS) Devices: in-vivo Studies for the Treatment of Triple Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) treatment is challenging and frequently characterized by an aggressive phenotype and low prognosis in comparison to other subtypes. This paper presents an implantable microporous poly-di-methyl-siloxane device for the delivery of targeted therapeutic agents (LHRH-paclitaxel and LHRH-prodigiosin) for the treatment and possible prevention of triple-negative cancer recurrence. The possible cytotoxic effects of the drugs on liver, kidney, and lung tissues are also assessed. Drug-loaded implantable microporous poly-di-methyl-siloxane (PDMS) devices were fabricated. Subcutaneous triple-negative xenograft breast tumors were then induced in athymic female nude mice that were four weeks old. Two weeks later, the tumors were surgically removed, and the device implanted. Mice were observed for tumor regrowth and organ toxicity. In addition, the cytotoxic response was assessed in vitro using the Alamar blue assay. The animal study revealed that there was no tumor regrowth, six weeks post-treatment, when the LHRH targeted drugs (LHRH-paclitaxel and LHRH-prodigiosin) were used for the treatment. It was also noted that the targeted cancer drugs did not induce any adverse effect on the liver, kidneys, or lungs, based on the results of the quantitative and qualitative toxicity studies. Furthermore, the outcomes of the in vitro assessment demonstrated a significant reduction (P < 0.05) in percentage cell growth inhibition in a time-dependent manner in the groups treated with PG, PG-LHRH, PTX, and PTX-LHRH. The implications of the results are discussed for the targeted and localized treatment of triple negative breast cancer.