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

Cancer Nanotechnology

Original Paper

Anant R. Paradkar¹  Jukka Mönkkönen²  Kakasaheb R. Mahadik³  Rohit S. Mulik⁴  Risto O. Juvonen⁵ 

[1] Centre for Pharmaceutical Engineering Science, University of Bradford, BD7 1DP, Bradford, UK;Department of Biopharmacy, School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland;Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth University, Erandwane, 411038, Pune, India;Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth University, Erandwane, 411038, Pune, India;Department of Biopharmacy, School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland;Department of Toxicology, School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland;Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, 75390, Dallas, TX, USA;Department of Toxicology, School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland;

关键词: Curcumin;    Solid lipid nanoparticles;    Neuroblastoma;    Flow cytometry;    Apoptosis;   

DOI  :  10.1007/s12645-012-0031-2

 received in 2012-09-24, accepted in 2012-10-16,  发布年份 2012

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Springer-Verlag Wien 2012