Delivery of retinoic acid to LNCap human prostate cancer cells using solid lipid nanoparticles

Abstract

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.

Characterization of drug delivery vehicles using atomic force microscopy: current status

“…AFM revealed nanoparticles of chitosan containing 2-oxothiazolidine-4-carboxylic acid for ocular delivery to be spherical, of uniform shape and with limited aggregation, supporting SEM investigations [57]. [58]; however, these sizes were smaller than those measured using laser diffraction measurements and this was attributed to sample drying and a slight flattening effect caused by the AFM probe. Interestingly, Cai et al found the mean diameters of polystyrene nanoparticles (for skin penetration) to be significantly less than those obtained from photon correlation spectroscopy (PCS) (36.8 ± 7.3, 56.9 ± 0.7 nm, respectively), although the AFM values were considered to be more accurate due to direct interaction of the materials [59]; SiO2 nanoparticles, however, exhibited no difference in particle diameter when examined by AFM and PCS and this was attributed to variations in surface charge.…”

Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review

“…In vitro cell viability studies revealed that most cell lines can tolerate up to 1 mg/mL of lipid doses of drug-free NLCs [146]. Many studies even provided evidence for adequate cellular tolerability for positively charged lipid-based nanocarriers prepared using cationic surfactants such as cetyltrimethylammonium bromide (CTAB).…”

Co-delivery of Dacarbazine and All-Trans Retinoic Acid (ATRA) Using Lipid Nanoformulations for Synergistic Antitumor Efficacy Against Malignant Melanoma

“…We hypothesized that the combination of two therapeutic components will enhance the antitumor efficacy in melanoma malignancies. It is worth noting that ATRA though exhibits the anticancer properties, did not result in any adverse effect in the systemic environment [23]. As the DBZ is hydrophobic in nature, we have designed lipid nanoformulations that can stably incorporate the hydrophobic drugs in the lipid core and ATRA will be loaded as a structural component of the nanoparticles.…”