Surface-Modified Diatom Nanoparticles for Targeted Naproxen Delivery and Toxicity Assessment Using Zebrafish Embryo Model

This study focuses on enhancing the targeting efficiency of surface-modified diatom nanoparticles (DNPs) as carriers for naproxen. Diatom nanoparticles fabricated from diatomaceous earth using hot alcoholic acid treatments followed by calcination and surface functionalization with 3-aminopropyltriethoxysilane (APTE). DNPs and APTES-DNPs were characterized by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and thermogravimetric differential thermal analysis (TGDTA). APTES-DNPs exhibited small, polyshaped particles with a high naproxen loading content (23.47 ± 0.41%) and encapsulation efficiency (84.84 ± 1.2%). FTIR and XRD confirmed the presence of amine groups and crystallinity, while EDX and TGDTA analysis indicated the presence of essential elements and endothermic properties at 381°C for DNPs and 293°C for APTES-DNPs. In-vitro drug release studies revealed sustained naproxen release for 87.6% (± 5.6) over 300 minutes at pH 7.4, with release kinetics best fitting the First order model (R²=0.9464) and Hixson-Crowell model (R²=0.9550). Zebrafish embryo toxicity assays assessed hatching rate, mortality, and malformation at 12, 24, 48, 72, and 96 post-fertilization hours (pfh) by DNPs and APTES-DNPs. LC ₅₀ values calculated by probit analysis along with 95% confidence limits, were 125.24 mg/L for DNPs and 453.00 mg/L for APTES-DNPs. APTES-DNPs caused a more reduction in hatching rates and mortality percentage compared to unmodified DNPs, reflecting higher bioavailability and cellular uptake. Overall, the findings suggest that surface-functionalized diatom nanoparticles are promising, pH-sensitive, cost-effective, and eco-friendly drug delivery systems. They offer potential for targeted delivery of Naproxen and may be further explored for acute gastroenteritis.