Cytotoxic effects of gemcitabine-loaded solid lipid nanoparticles in pancreatic cancer cells

Abstract

This study investigated the cytotoxic effects of gemcitabine-loaded solid lipid nanoparticle (Gem-SLN) on the patient-derived primary pancreatic cancer cell lines (PPCL-46) and MiaPaCa-2 pancreatic cancer cells. Different SLN formulations were prepared from glyceryl monostearate (GMS), polysorbate 80 (Tween® 80) and poloxamer 188 (Pol 188) as surfactants using a cold homogenization method. Gem-SLN was characterized for particle size and charge distribution, entrapment efficiency and loading capacity. Fourier Transform Infra-Red (FTIR) spectroscopy was used to verify Gem and SLN interaction while differential scanning calorimetry (DSC) was used to acquire thermodynamic information on Gem-SLN. Cytotoxicity studies was conducted on PPCL-46 cells and Mia-PaCa-2 cells. Among the different Gem-SLN formulations prepared, Gem-SLN15 was selected based on entrapment efficiency (EE) of Gem, loading efficiency of Gem, cytotoxicity and rate of Gem release. Cytotoxic effect of Gem-SLN15-treated PPCL-46 culture (IC50 (2D) = 27 ± 5 μM; IC50 (3D) = 66 ± 2 μM) was remarkably higher than gemcitabine hydrochloride (GemHCl)-treated PPCL-46 culture (IC50 (2D) = 126 ± 3 μM; IC50 (3D) = 241 ± 3 μM). Similar trend of higher Gem-SLN15 inhibition in MiaPaCa-2 culture was found (IC50 (2D) = 56 ± 16 μM; IC50 (3D) = 127 ± 4 μM) compared with GemHCl-treated Mia-PaCa-2 culture (IC50 (2D) = 188 ± 46 μM; IC50 (3D) = 254 ± 52 μM). Overall, Gem-SLN15 proved to be more effective against PPCL_46 and Mia-PaCa-2 cells than GemHCl treated PPCL-46 and Mia-PaCa-2 cancer cells.