Physicochemical investigations on solid lipid nanoparticles and on oil-loaded solid lipid nanoparticles: a nuclear magnetic resonance and electron spin resonance study.
OBJECTIVE
Recently, colloidal dispersions made of mixtures from solid and liquid lipids have been described to combine controlled-release characteristics with higher drug-loading capacities than solid lipid nanoparticles (SLNs). It has been proposed that these nanostructured lipid carriers (NLCs) are composed of oily droplets that are embedded in a solid lipid matrix. The present work investigates the structure and performance of NLCs.


METHODS
Colloidal lipid dispersions were produced by high-pressure homogenization and characterized by laser diffraction, photon correlation spectroscopy, wide-angle x-ray scattering, and differential scanning calorimetry. Proton nuclear magnetic resonance spectroscopy and electron spin resonance experiments were performed to investigate the mobility of the components and the molecular environment of model drugs. Furthermore, a nitroxide reduction assay with ascorbic acid was conducted to explore the accessibility of the lipid model drug from the outer aqueous phase.


RESULTS
Proton nuclear magnetic resonance spectra clearly demonstrate that NLC nanoparticles differ from nanoemulsions and from SLNs by forming a liquid compartment that is in strong interaction to the solid lipid. The electron spin resonance model drug was found to be accommodated either on the particle surface with close water contact (SLN) or additionally in the oil (NLC). The oil compartment must be localized on the particle surface, because it can be easily reached by ascorbic acid.


CONCLUSIONS
Neither SLN nor NLC lipid nanoparticles showed any advantage with respect to incorporation rate or retarded accessibility to the drug compared with conventional nanoemulsions. The experimental data let us conclude that NLCs are not spherical solid lipid particles with embedded liquid droplets, but they are rather solid platelets with oil present between the solid platelet and the surfactant layer.
Jores
Katja
K
Institute of Pharmacy, Department of Pharmaceutical Technology, Free University of Berlin, Kelchstr. 31, 12169 Berlin, Germany.
Mehnert
Wolfgang
W
Mäder
Karsten
K
D002152:Calorimetry, Differential Scanning; D003102:Colloids; D004337:Drug Carriers; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D036103:Nanotechnology; D010316:Particle Size; D014961:X-Ray Diffraction
D003102:Colloids; D004337:Drug Carriers; D008055:Lipids