Development of novel S PC-3 gefitinib lipid nanoparticles for effective drug delivery in breast cancer. Tissue distribution studies and cell cytotoxicity analysis

Abstract

ObjectiveThe present work was aimed to develop gefitinib solid lipid nanoparticles (GFT-SLN) using novel lipids (Lipoid S PC-3) and to analyse its cell cytotoxicity and tissue distribution efficacy. MethodsGFT SLNs were prepared by a modified hot homogenization method using a variable concentration of lipid (Lipoid S PC-3) and poloxamer 407. GFT SLNs were characterised for physicochemical properties, in vitro drug release, cell cytotoxicity (MCF-7 cell lines), in vivo tissue distribution studies and stability analysis. ResultsThe mean particle size of SLNs was between 178 ± 10 to 348 ± 15 nm. A higher EE (>92%) and negative zeta potential (mV) was observed in all SLNs. FTIR and DSC data exhibit no possible interaction between the drug and excipients. PXRD reveal the amorphous nature of SLNs. SEM images show SLNs were of nanosize (<178.73 ± 10.66 nm) and spherical in shape. The in vitro release of SLNs showed an initial burst release (25%) within 2 h followed by a sustained release (>90%) during 72 h. Kinetic analysis of GFT SLNs fits best to the Higuchi model (R2 = 0.935). In vitro cytotoxicity of SLN demonstrated higher antitumour activity (cell viability >65%) in comparison to free drug (p < 0.05). In vivo tissue distribution studies show higher drug concentration in the liver (28,930 ± 91 ng), followed by kidneys (22,284 ± 1626 ng) and less in the brain (7042 ± 62 ng) (p < 0.05). GFT SLN was stable at 40 ± 2 °C/75 ± 5% RH and refrigerated temperature (4 ± 2 °C) during 3 months. ConclusionGFT SLNs developed using novel lipoid S PC-3 lipid offer higher antitumour efficacy and better drug distribution in tissues.