In-vivo studies of targeted and localized cancer drug release from microporous poly-di-methyl-siloxane (PDMS) devices for the treatment of triple negative breast cancer.

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 fabricated implantable drug-loaded microporous poly-di-methyl-siloxane (PDMS) devices for the delivery of targeted therapeutic agents [Luteinizing Hormone-Releasing Hormone conjugated paclitaxel (PTX-LHRH) and Luteinizing Hormone-Releasing Hormone conjugated prodigiosin (PG-LHRH)] for the treatment and possible prevention of triple-negative cancer recurrence. In vitro assessment using the Alamar blue assay demonstrated a significant reduction (p < 0.05) in percentage of cell growth in a time-dependent manner in the groups treated with PG, PG-LHRH, PTX, and PTX-LHRH. 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 but partially removed, and the device implanted. Mice were observed for tumor regrowth and organ toxicity. The animal study revealed that there was no tumor regrowth, six weeks post-treatment, when the LHRH targeted drugs (LHRH-PTX and LHRH-PGS) were used for the treatment. The possible cytotoxic effects of the released drugs on the liver, kidney, and lung are assessed using quantitative biochemical assay from blood samples of the treatment groups. Ex vivo histopathological results from organ tissues showed that the targeted cancer drugs released from the implantable drug-loaded device did not induce any adverse effect on the liver, kidneys, or lungs, based on the results of qualitative toxicity studies. The implications of the results are discussed for the targeted and localized treatment of triple negative breast cancer.

Prodigiosin-loaded electrospun nanofibers scaffold for localized treatment of triple negative breast cancer.

Hybrid composite nanofibers, with the potential to enhance cell adhesion while improving sustained drug release profiles, were fabricated by the blend electrospinning of poly(d,l-lactic-co-glycolic acid) (PLGA), gelatin, pluronic F127 and prodigiosin (PG). Scanning Electron Microscopy (SEM) images of the nanofibers revealed diameters of 1.031 ±â€¯0.851 µm and 1.349 ±â€¯1.264 µm, corresponding to PLGA/Ge-PG and PLGA/Ge-F127/Ge, respectively. The Young's moduli were also determined to be 1.446 ±â€¯0.496 kPa and 1.290 ±â€¯0.617 kPa, while the ultimate tensile strengths were 0.440 ±â€¯0.117 kPa and 0.185 ±â€¯0.480 kPa for PLGA/Ge-PG and PLGA/Ge-F127/Ge, respectively. In-vitro drug release profiles showed initial (burst) release for a period of 1 h to be 26.000 ±â€¯0.004% and 16.000 ±â€¯0.015% for PLGA/Ge and PLGA/Ge-F127 nanofibers, respectively. This was followed by 12 h of sustained release, and subsequent slow sustained release of PG from the composite nanofibers. The cumulative release of PG (for three days) was determined to be 82.0 ±â€¯0.1% for PLGA/Ge and 49.7 ±â€¯0.1% for PLGA/Ge-F127 nanofibers. The release exponents (n) show that both nanofibers exhibit diffusion-controlled release by non-Fickian (zeroth order) and quasi-Fickian diffusion in the initial and sustained release regimes, respectively. The suitability of the composite nanofibers for supporting cell proliferation and viability, as well as improving sustained release of the drug were explored. The in-vitro effects of cancer drug (PG) release were also studied on breast cancer cell lines (MCF-7 and MDA-MB-231 cells). The implications of the results are discussed for the potential applications of drug-nanofiber scaffolds as capsules for localized delivery of chemotherapeutic drugs for the treatment of triple negative breast cancer.