, Volume 3, Issue 1-6, pp 65-81
Date: 13 Nov 2012

Apoptosis-induced anticancer effect of transferrin-conjugated solid lipid nanoparticles of curcumin

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Abstract

Broad spectrum therapeutic potential of curcumin is usually hampered by its photodegradation and low bioavailability. Present investigation was designed with an objective to develop transferrin-mediated solid lipid nanoparticles (Tf-C-SLN) resistant to the photostability and capable of enhancing the bioavailability by targeted drug delivery to elicit anticancer activity against SH-SY5Y neuroblastoma cells in vitro. Hot homogenization method was used for the formulation of Tf-C-SLN and evaluated physicochemically using parameters such as, size, zeta potential, entrapment efficiency and photostability, transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), differential scanning colorimetry (DSC), and in vitro release study. In vitro cytotoxicity and apoptosis investigations were performed using microplate analysis and flow cytometry techniques. The physicochemical characterization confirmed the suitability of formulation method and various parameters therein. TEM investigation revealed the spherical morphology while NMR and DSC study confirmed the entrapment of curcumin inside the nanoparticles. The cytotoxicity, reactive oxygen species, and cell uptake were found to be increased considerably with Tf-C-SLN compared with curcumin-solubilized surfactant solution, and curcumin-loaded SLN (C-SLN) suggesting the targeting effect. AnnexinV-FITC/PI double staining, DNA analysis, caspase detection, and reduced mitochondrial potential confirmed the induction of apoptosis with nanoparticle treatment. Enhanced anticancer activity with Tf-C-SLN compared with curcumin-solubilized surfactant solution and C-SLN was observed from flow cytometry investigations with apoptosis being the major underlying mechanism. The in vitro observations of our investigation are very compelling and concrete to advocate the potential of Tf-C-SLN in enhancing the anticancer effect of curcumin against neuroblastoma in vivo and possible clinical applications.