Chemotherapy is often limited by its systemic toxicity and lack of specificity, necessitating the development of targeted drug delivery systems that can enhance therapeutic efficacy while minimizing adverse effects. Addressing this, our study aimed to synthesize and characterize 5-Fluorouracil loaded calcium carbonate nanoparticles derived from cockle shells. The research aimed at increasing site-specific drug release and reducing cytotoxicity. The nanoparticles were prepared using a simple co-precipitation method, ensuring eco-friendliness and cost-effectiveness. The encapsulation of 5-FU was confirmed by transmission electron microscopy (TEM), which revealed an increase in nanoparticle size from 19.2 ± 2.284 nm for the unloaded ones to 34.8 ± 4.066 nm for the 5-FU-loaded CaCO3 NPs. In vitro release studies demonstrated a pH-sensitive release profile, with more rapid drug release at pH 4.8 compared to pH 7.3. Biocompatibility assays on the HS-27 human skin fibroblast cell line indicated high cell viability, with over 90% maintained even at high nanoparticle concentrations (1000 µg/mL). In addition, cytotoxicity assays on the SW480 (primary colon cancer) and SW620 (metastatic colon cancer) cell lines showed a dose-dependent decrease in cell viability and demonstrated a more controlled and sustained release compared to free 5-FU, resulting in higher cell viability at all time points and concentra-tions. The 5-FU-loaded CaCO3 NPs significantly reduced the immediate cytotoxic effects observed with free 5-FU while effectively targeting cancer cells. These findings suggest that the 5-FU-CaCO3 NPs offer a promising alternative to conventional chemotherapy, providing targeted drug delivery with the potential for reduced systemic toxicity and enhanced therapeutic efficacy.
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