Study On The Preparation Of Sanguinarine Microspheres And In Vivo Distribution In Mice

As a natural potential broad-spectrum anti-tumor alkaloid drug,sanguinarine can inhibit the expansion of tumor cell lines and promote apoptosis.There is a remarkable therapeutic effect in lung cancer,which can effectively inhibit the proliferation and metastasis of lung cancer cells,but the sanguinarine can cause some damage to the liver and heart.Therefore,in this study,chitosan was used as the carrier material to prepare the sanguinarine into microspheres by emulsifying cross-linking method.The recipe technology,preparation,in vitro release and in vivo tissue distribution of sanguinarine microspheres were studied and evaluated respectively,so that they could achieve lung targeting.In this experiment,ultraviolet spectrophotometry was established for the determination of drug loading and capability of sanguinarine microspheres.HPLC method was used to determine the stability,extracorporeal release and distribution of mouse tissues.Methodological studies show that the analytical methods are accurate and reproducible which can meet the requirements of sample analysis,provide a reliable analytical method for the recipe design,preparation evaluation and tissue distribution of sanguinarine microspheres.The sanguinarine microspheres were prepared by emulsified cross-linking.the amount of chitosan,emulsifier and the rotational speed were selected as the influence factors by single factor experiment.the particle size was the response value,and the preparation process of sanguinarine chitosan microspheres was optimized by using the star point design test.The optimal recipe:emulsification time 90 min,crosslinking time 3.5 h,chitosan dosage 0.07 g,acetic acid concentration 2%,hemagnitine consumption 0.06 g,water-oil ratio 3:10,emulsifier content1.82 g,crosslinking agent dosage 0.25 ml,temperature 40?,rotational speed 500 r/min.The average drug loading of microspheres was 4.49±0.93%.The encapsulation efficiency was54.64±0.39%.And the particle size was 8.14±0.13?m.The results show that the optimal formulation can produce sanguinarine microspheres with suitable particle size and have good reproducibility.The appearance morphology,particle size distribution and extracorporeal release were studied and evaluated by optical microscope,scanning electron microscope and laser particle size meter.The sanguinarine microspheres have round appearance,no adhesion and good dispersion.The average particle size is 8.14?m,and the particle size distribution is 2-20?m.When released in vitro,the sanguinarine raw material was basically released completely in4 h in pH7.4 phosphate buffer solution.But the microspheres were released 75%in 24 h,indicating that the sanguinarine microspheres could achieve the slow release effect.The stability results showed that the microspheres had good stability in the low-temperature dry environment.By studying the physical and chemical properties of sanguinarine microspheres,the preparation quality can be effectively controlled.The content of sanguinarine in different tissues were determined by intravenous injection of sanguinarine solution and microsphere suspension in mice.the experimental results show that compared with sanguinarine injection,the drug concentration in the microsphere group increased significantly in the lungs,re?ce?T~ce 5.62,3.33 and 50.18%,respectively.The results showed that the sanguinarine microspheres could change the distribution of drugs in tissues and organs,and had obvious lung targeting.