Novel cationic SLN containing a synthesized single-tailed lipid as a modifier for gene delivery.

Cationic solid lipid nanoparticles (SLN) can bind DNA directly via ionic interaction and mediate in vitro gene transfection. However, toxicity is still an obstacle, which is strongly dependent on the cationic lipid used. In the present study, a novel single-tailed cationic lipid, 6-lauroxyhexyl lysinate (LHLN), was synthesized and used as a modifier to prepare stable SLN-DNA complexes by a nanoprecipitation method. The commonly used cationic lipid cetyltrimethylammonium bromide (CTAB) modified SLN-DNA formulation served as a contrast. These two formulations were characterized and compared in terms of morphology, particle size, surface charge, DNA binding capacity, release profile, cytotoxicity, and transfection efficiency. The LHLN SLN-DNA complexes had a similar spherical morphology, a relatively narrow particle size distribution and a more remarkable DNA loading capability compared to the CTAB ones. Most importantly, LHLN modified SLN had a higher gene transfection efficiency than the naked DNA and CTAB ones, which was approximately equal to that of Lipofectamine-DNA complexes, and a lower cytotoxicity compared with CTAB-SLN and Lipofectamine 2000. Thus, the novel cationic SLN can achieve efficient transfection of plasmid DNA, and to some extent reduce the cytotoxicity, which might overcome some drawbacks of the conventional cationic nanocarriers in vivo and may become a promising non-viral gene therapy vector.

Injectable actarit-loaded solid lipid nanoparticles as passive targeting therapeutic agents for rheumatoid arthritis.

This work systematically studied the intravenous injection formulation of solid lipid nanoparticles (SLNs) loaded with actarit, a poor water soluble anti-rheumatic drug. The goal of this study was to design passive targeting nanoparticles which could improve therapeutic efficacy and reduce side-effects such as nephrotoxicity and gastrointestinal disorders commonly associated with oral formulations of actarit. Based on the optimized results of single-factor and orthogonal design, actarit-loaded SLNs were prepared by a modified solvent diffusion-evaporation method. The formulated SLNs were found to be relatively uniform in size (241+/-23 nm) with a negative zeta potential (-17.14+/-1.6 mV). The average drug entrapment efficiency and loading were (50.87+/-0.25)% and (8.48+/-0.14)%, respectively. The actarit-loaded SLNs exhibited a longer mean retention time in vivo (t(1/2(beta)), 9.373 h; MRT, 13.53 h) compared with the actarit 50% propylene glycol solution (t(1/2(ke)), 0.917 h; MRT, 1.323 h) after intravenous injection to New Zealand rabbits. The area under curve of plasma concentration-time (AUC) of actarit-loaded SLNs was 1.88 times greater than that of the actarit in 50% propylene glycol solution. The overall targeting efficiency (TE(C)) of the actarit-loaded SLNs was enhanced from 6.31% to 16.29% in spleen while the renal distribution of actarit was significantly reduced as compared to that of the actarit solution after intravenous administration to mice. These results indicated that injectable actarit-loaded solid lipid nanoparticles were promising passive targeting therapeutic agents for rheumatoid arthritis.

Anionic solid lipid nanoparticles supported on protamine/DNA complexes.

The objective of this study was to design novel anionic ternary nanoparticles for gene delivery. These ternary nanoparticles were equipped with protamine/DNA binary complexes (150-200 nm) as the support, and the anionic formation was achieved by absorption of anionic solid lipid nanoparticles (≤20 nm) onto the surface of the binary complexes. The small solid lipid nanoparticles (SLNs) were prepared by a modified film dispersion-ultrasonication method, and adsorption of the anionic SLNs onto the binary complexes was typically carried out in water via electrostatic interaction. The formulated ternary nanoparticles were found to be relatively uniform in size (257.7 ± 10.6 nm) with a 'bumpy' surface, and the surface charge inversion from 19.28 ± 1.14 mV to -17.16 ± 1.92 mV could be considered as evidence of the formation of the ternary nanoparticles. The fluorescence intensity measurements from three batches of the ternary nanoparticles gave a mean adsorption efficiency of 96.75 ± 1.13%. Circular dichroism spectra analysis showed that the protamine/DNA complexes had been coated by small SLNs, and that the anionic ternary nanoparticles formed did not disturb the construction of the binary complexes. SYBR Green I analysis suggested that the ternary nanoparticles could protect the DNA from nuclease degradation, and cell viability assay results showed that they exhibit lower cytotoxicity to A549 cells compared with the binary complexes and lipofectamine. The transfection efficiency of the ternary nanoparticles was better than that of naked DNA and the binary complexes, and almost equal to that of lipofectamine/DNA complexes, as revealed by inversion fluorescence microscope observation. These results indicated that the anionic ternary nanoparticles could facilitate gene transfer in cultured cells, and might alleviate the drawbacks of the conventional cationic vector/DNA complexes for gene delivery in vivo.