The Preparation And Properties Research Of Drug Loaded Solid Lipid Nanoparticles

Solid lipid nanoparticles(SLN), the new type of submicron particulate drug carrier, are composed of physiological, biodegradable lipid compounds. Combining advantages of the traditional systems such as emulsions, liposomes and polymeric nanoparticles, but avoiding some of their major disadvantages, SLN represent an alternative carrier system to traditional colloidal carriers. SLN can improve the stability of drug, release drug continually and slowly and enhance the bioavailability of the drug.The main goal of this paper was to study the preparation method and drug entrapment mechanism of drug loaded SLN and to investigate the physical-chemical characteristics, drug pharmacokinetics, as well as toxicity of them. Three types of drug different in water-solubility were loaded in solid lipid nanoparticles and the stealth SLN was prepared by PEG modification.Two step research had been done toward to the preparation method. First, with the criterion of average size and stability, the test of single factor were performed to obtain the method and ordinarily process; then based on the test of single factor, the formulation and the preparation technics of SLN were optimized by the orthogonal design.The nanoparticle's quality evaluating system was also build up. The morphology of SLN was examined by transmission electron microscope. The size of SLN was determined by Photon Correlation Spectroscopy method. The encapsulation ratio of SLN was determined by gel filtration column chromatography. The dialytic method was used to study drug release action of SLN in vitro. The toxicity effects were observed by MTT assay.The results showed that the podophyllotoxin-SLN were uniform spheres. Its size was 52.9nm and the encapsulation ratio was 78.3%. The podophyllotoxin-SLN had the continually and slowly release ability in vitro and the MTT assay proved the low toxicity and good cell restrain ability. The size and encapsulation ratio of the caffeic acid-SLN was 60.2nm and 35.3%. Trp/βCD-SLN's size and encapsulation ratio was 61.6nm and 43.4%. And finally three conclusions can be summarized as follows. 1. Emulsion evaporation-solidification at low temperature is a perfect preparation method of Solid lipid nanoparticles, its preparation mechanism fit the lipophilic drug. And toward to the hydrophilic drug, the method ofβcd inclusion can be successfully used.2. The stealth solid lipid nanoparticles has the better performance compared with the non-stealth solid lipid nanoparticles due to its samller average size and better release ability in vitro. But its encapsulation ratio is a bit lower because the stealth agent can partly improve the solubility of drug in the water phase.3. The drug loaded solid lipid nanoparticles is a biodegradable, safety drug carrier system, which can improve the stability, enhance the bioavailability and reduce the toxicity of drug.