Radiolabeled 5-Fluorouracil-Loaded Solid Lipid Nanoparticles: A Potential Platform for Colorectal Cancer Imaging

Radiolabeled 5-fluorouracil (5-FU)-loaded solid lipid nanoparticles (SLNs) were successfully developed using high shear homogenization and ultrasonication techniques. The SLNs were characterized for particle size, polydispersity index, and zeta potential. The formulations exhibited a mean particle size below 150 nm with narrow size distribution and negative surface charge, indicating good colloidal stability. The radiolabeling of SLNs with technetium-99m ([^99mTc]-Tc) was performed using stannous chloride as the reducing agent, achieving a high radiolabeling efficiency (>90%). The <i>in vitro</i> radiochemical stability of [^99mTc]-Tc-5-FU-SLNs was confirmed in saline, serum, and cell culture medium, where the radiochemical purity remained above 90% for up to 6 h. Partition coefficient studies demonstrated that the radiolabeled formulations exhibited hydrophilic characteristics, supporting their potential for systemic circulation with reduced nonspecific tissue uptake. Cellular binding studies using the HT-29 human colorectal adenocarcinoma cell line revealed that [^99mTc]-Tc-5-FU-SLNs demonstrated strong and sustained cell association over time, significantly higher than free [^99mTc]-Tc-5-FU and negative controls. The SLN formulations were found to be biocompatible, showing no adverse effects on cell morphology during the incubation period. These findings indicate that radiolabeled 5-FU-loaded SLNs represent a promising platform for potential use in targeted colorectal cancer imaging, pending further <i>in vivo</i> validation.