| Objective: To research a new method and new idea for drugs of Alzheimer's disease through brain targeted drug delivery system (BTDDS). Alzheimer's disease is also called senile dementia. It happens in old age earlier stage and gerontic and it is a kind of primary degenerative cerebral disease, referring to one kind of high-grade persistence nerve function activity hindering disease. It's appearances are thought, remembrance, analytical judgement, vision appreciation of spatial dimension and emotion obstacles under the circumstances of not being conscious disturbance. It is investigated that the average life of senile dementia patient is 5.5 years, and senile dementia has become "the fourth killer" for old people's health after the cardiovascular disease, cerebrovascular disease and cancer. Now there are many drugs for curing it in domestic. But Piracetam (PA) that cures senile dementia is the most typical medicine. It can effectively improve the patient's memory impairment and emotional obstacles and activate, protect and repair the brain cells. And it also improves brain function of a comprehensive range of pharmacological, physiological effects and has advantages such as low toxicity,high safety and so on.With biodegradable type material glycerin monostearate as a carrier, sel-ect piracetam as a model drug, using modified emulsion solvent evaporationmethod to prepare solid lipid nanoparticles (SLN) of piracetam. We carried out on the appearance of solid lipid nanoparticles morphology, particle size,particle size distribution studies; A high performance liquid chromatography method was built to examine content of Piracetam, by the properties and m-ethods of vali-dation studies to determine the feasibility of the method andconducted piracet-am solid lipid nanoparticles encapsulation efficiency, drug loading in vitro rele-ase rate, stability and other experimental studies; Solid lipid nanoparticles of piracetam in tissues of mice in vivo tissue distribution have been studied to conduct a preliminary exploration of its targeting an effort to Alzheimer's disease forbreaking through the limitations of drug the-rapy for brain targeting admini-stration.Methods:The method of emulsion w/o/w multiple emulsion-solvent diffusion technique was employed to prepare PA-SLN. According different variables, the orthogonal experiment was designed to seek best prescription and preparation process. Use transmission electronic microscope (TEM) to observe the appearance of solid lipid nanoparticles and use SAS software to conduct statistical analysis of normal size and particle size distribution, surface Zeta potential was determined by surface potential analyzer; In vitro release of PA from solid lipid nanoparticles was performed by dialysis film method. The tissue distribution in mice of the PA-SLN and PA injection were invest-tigated.Results: The optimal formulation was obtained by orthogonal experimenttal design method, with the entrapment efficiency of PA-SLN as the criterion, and the type and amount of lipid material, the amount of lecithin emulsifier, surfactantdosage, time and intensity of ultrasonic emulsification, emulsion temperature as influence factors.PA-SLN was prepared by optimal for-mulation, it was semi-transparent milky appearance uniform dispersion and in the transmission electron microscope it showed a large number of uniform, spherical particles, with an average particle size of 100.06±8.2nm.HPLC method was established as the quality controlled standard, there was a good linearity of the drug concentration within the range of 25.4～815.5μg·mL-1 .The linear equation was A=11.555C+316.22(r=0.9999),The average recovery was more than 100.21% and the RSD were less than 1%.The incorporation efficiency were 56.06%.The in vitro release behavior of PA-SLN could be described by Ritger-Peppas eduation and could be expressed by the following equation lnQ=0.4076lnt+2.864(r=0.9978).HPLC method was established to investigate the drug distribution in mice. The recovery of drug in tissues of mice was more than 90% and the RSD was less than 4%. The linear equation was:y=32.618x+390.96,r=0.9948 ( brain ); y=27.826x+180.85,r=0.9981(heart) ; y=22.446x+637.52,r=0.9943 ( liver );y=25.945x+198.43,r=0.9951(spleen);y=21.273x+174, r= 0.9989(lung);y=21.625x+221.02,r=0.9944(kidney);y=22.398x+136.89,r=0.9967(stomach)。There was a good linearity within the rage of 0.5～32.0μg·mL-1.The minimum that could be detected was 0.05μg·mL-1, which can content the desire of analysis for biological detection.After mice tail vein injection of piracetam injection and solid lipid nanoparticles suspension, one part was phagocytosised by reticuloendothelial system and another part cut through the blood-brain barrier into the brain. With the commercially available piracetam injection compared with carriers of solid lipid nanoparticles, the latter increased the concentration of drug in the brain and reduces the concentration in the stomach.Conclusion: PA has remarkable effects in curing of Alzheimer's disease, but it has some disadvantages such as the body extensive distribution and some side effects. In addition to nausea, abdominal pain and other gastrointestinal side effects, the liver function is also slightly damaged. After PA be-ing made of solid lipid nanoparticles, the drug can effectively transport, concentration in the brain lesions, reduce the frequency and dosage of medicine, improve therapeutic index and reduce toxicity. In vitro dissolution study showed that PA-SLN has a significant delayed release; tissue distribution studies in mice Results show that PA-SLN had increased role of the brain targeted, compared to the injection. The content of piracetam has decreased in varying degrees in the heart, liver, stomach, lung, kidney and other tissues. The purpose and requirements.of experimental design had elementary achieved.
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