TY - JOUR
T1 - Delivery of retinoic acid to LNCap human prostate cancer cells using solid lipid nanoparticles
AU - Akanda, Mushfiq H.
AU - Rai, Rajeev
AU - Slipper, Ian J.
AU - Chowdhry, Babur Z.
AU - Lamprou, Dimitrios
AU - Getti, Giulia
AU - Douroumis, Dennis
PY - 2015/9/30
Y1 - 2015/9/30
N2 - In this study retinoic acid (RTA) loaded solid lipid nanoparticles (SLNs) were optimized by tuning the process parameters (pressure/temperature) and using different lipids to develop nanodispersions with enhanced anticancer activity. The RTA-SLN dispersions were produced by high-pressure homogenization and characterized in terms of particle size, zeta potential, drug entrapment efficiency, stability, transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and in vitro drug release. Thermal and X-ray analysis showed the RTA to be in the amorphous state, whilst microscopic images revealed a spherical shape and uniform particle size distribution of the nanoparticles. Anticancer efficiency was evaluated by incubating RTA-SLNs with human prostate cancer (LNCap) cells, which demonstrated reduced cell viability with increased drug concentrations (9.53% at 200 ug/ml) while blank SLNs displayed negligible cytotoxicity. The cellular uptake of SLN showed localization within the cytoplasm of cells and flow cytometry analysis indicated an increase in the fraction of cells expressing early apoptotic markers, suggesting that the RTA loaded SLNs are able to induce apoptosis in LNCap cells. The RTA-SLN dispersions have the potential to be used for prostate anticancer treatment.
AB - In this study retinoic acid (RTA) loaded solid lipid nanoparticles (SLNs) were optimized by tuning the process parameters (pressure/temperature) and using different lipids to develop nanodispersions with enhanced anticancer activity. The RTA-SLN dispersions were produced by high-pressure homogenization and characterized in terms of particle size, zeta potential, drug entrapment efficiency, stability, transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and in vitro drug release. Thermal and X-ray analysis showed the RTA to be in the amorphous state, whilst microscopic images revealed a spherical shape and uniform particle size distribution of the nanoparticles. Anticancer efficiency was evaluated by incubating RTA-SLNs with human prostate cancer (LNCap) cells, which demonstrated reduced cell viability with increased drug concentrations (9.53% at 200 ug/ml) while blank SLNs displayed negligible cytotoxicity. The cellular uptake of SLN showed localization within the cytoplasm of cells and flow cytometry analysis indicated an increase in the fraction of cells expressing early apoptotic markers, suggesting that the RTA loaded SLNs are able to induce apoptosis in LNCap cells. The RTA-SLN dispersions have the potential to be used for prostate anticancer treatment.
KW - retinoic acid
KW - solid lipid nanoparticles
KW - cytotoxicity
KW - prostate cancer
KW - flow cytometry
UR - http://www.sciencedirect.com/science/article/pii/S0378517315300612
U2 - 10.1016/j.ijpharm.2015.07.042
DO - 10.1016/j.ijpharm.2015.07.042
M3 - Article
SN - 0378-5173
VL - 493
SP - 161
EP - 171
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -
