Imidazolium-based ionic liquid functionalized mesoporous silica nanoparticles as a promising nano-carrier: response surface strategy to investigate and optimize loading and release process for Lapatinib delivery.

Imidazolium-based ionic liquid functionalized PEGylated mesoporous silica nanoparticles MCM-41 (denoted as [ImIL-PEGylated@MCM-41] NPs) is synthesized and evaluated as an efficient and reliable pH-sensitive nano-carrier for controlled release of cationic Lapatinib (Lap) drug. This nano-DDS was fully characterized by dynamic light scattering, scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, N2 adsorption-desorption measurement, and differential scanning calorimeter. Furthermore, the drug loading content and in-vitro drug release profile were studied. The entrapment and loading efficiency of the optimized formulation for Lap were 91 ± 2.0% and 32.21 ± 2.70%, respectively. The results of cytotoxicity assay demonstrated that ImIL-PEG@MCM-41 has no significant toxicity on both cancerous and normal cell lines and the anticancer activity of Lap@ImIL-PEG@MCM-41 was comparable to free drug in case of human breast cells (SKBR3) and human embryonic kidney 293 cells (HEK-293). Meanwhile, three-dimensional (3D) cell culture was performed by multicellular tumor spheroids for understanding of cell response to drugs in physiologically 3D microenvironments. The results of Lap@ImIL-PEG@MCM-41 uptake during 48 hours showed a gradual release of the Lap through the multicellular tumor spheroids. This showed that the pH-responsive controlled release of Lapatinib leads to the satisfactory results in the in vitro breast cancer therapy.