| Salvia miltiorrhiza is the dried roots and rhizomes of Salvia miltiorrhiza Bge in the labiatae family.It has the functions of removing blood stasis and pain,promoting blood circulation and clearing the heart and removing annoyance.Salvianolic acid B is the most active phenolic acid compound among the water-soluble substances of Salvia miltiorrhiza,accounting for more than 50% of the water-soluble active ingredients.It can dilate coronary arteries,anti-platelet aggregation,inhibit thrombosis and protect nerve cells from brain injury.However,due to the presence of the blood-brain barrier,the distribution half-life and elimination half-life of salvianolic acid B solution for injection in the human body are very short,the distribution volume is large,the clearance rate is high and the average residence time is very short,so it affects its development of.Polybutyl cyanoacrylate is a commonly used nanomaterial with good degradability,biocompatibility and blood-brain barrier penetration.It is easy to achieve targeted drug delivery through chemical or physical modification.It is one of the hot spots of drug delivery system research.Borneol is a valuable traditional Chinese medicine.Traditional Chinese medicine believes that it has the functions of refreshing and invigorating the brain,aroma and so on.It is often used in the prevention and treatment of cardiovascular and cerebrovascular diseases.Studies have shown that borneol can promote transdermal absorption and increase the permeability of the blood-brain barrier.Therefore,in this paper,polybutyl cyanoacrylate was used as a carrier,modified with borneol,salvianolic acid B was prepared into nanoparticles,and brain targeted research was carried out.In this paper,the encapsulation rate and drug loading are used as the evaluation indicators,and the preparation process and formulation factors of the nanoparticles were selected.Then,the orthogonal test was used to determine the optimal formulation of the nanoparticles and verify the optimal formulation.The optimal formulation process was to weigh 15 mg of Sal B and poloxamer 188 150 mg in 10 m L of distilled water to dissolve it by ultrasonication,adjusted its p H to 2.0 with 0.1 mol/L HCl,dissolved 2.0 mg borneol and 1.2% n-butyl cyanoacrylate with an appropriate amount of acetone and added it dropwise to the above solution,magnetically stir at 25℃ 600 r/min for 2 h,then adjusted its p H to 7.0 with 0.1 mol/L Na OH,stir for 0.5 h and pass 0.45 μm filter membrane.Pharmacological evaluation was performed on the best formulation obtained.The transmission electron microscope observed that the appearance was round and spherical,and good dispersion;the average particle size was122.8 nm,PDI was 0.164 and the Zeta potential was-4.98 m V,p H is about 7.14 and it is stable when left at room temperature for about 60 days;the encapsulation rate is 91.92%,and the drug loading is 11.49%.The results of in vitro release test showed that the cumulative release rate of 12 hours reached about 77%,which has a slow-release effect,and the in vitro drug release conforms to the Weibull equation.A tissue distribution test was carried out on mice to study their targeting.The experimental results showed that compared with the reference preparation,the concentration of the nano-preparation group in the mouse brain increased significantly,and the peak concentration was 3.95 times that of the control group,which had a certain brain targeting.The salvianolic acid B polymer nanoparticles prepared according to the optimal formulation increase the concentration of the drug in the brain and enhance the brain targeting of the drug.The results of this study can provide a theoretical basis and reference basis for the development of salvianolic acid B brain-targeted new formulations. |
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