Preparation Of Nanoparticles Loading With Sophocarpine And Its Anti-tumor Effect

Tumor has always been one of the hotspots in nanomedicine research.Although many efforts have been made in modifying nanosystems,due to tumor heterogeneity,tumor-specific targeting remains a problem.The acidification of tumor extracellular matrix provides new ideas for tumor targeted therapy.Sophocarpine has a wide range of pharmacological activities,including inhibition of the central nervous system,antitumor,asthma,analgesic and anti-inflammatory.Sophoraline has strong fat solubility,poor absorption in the body,and low bioavailability,which results in poor efficacy of oral administration,which limits its further development and clinical application.This study intends to combine the advantages of Sophocarpine and solid lipid nanometers to prepare Soppocarpine solid lipid nanoparticles,modify them with drugs to make them targeted,and study their antitumor effects.In this thesis,high performance liquid chromatography(HPLC)was selected for the quantitative detection of Sophocarpine reference substance,and the method was investigated.The results showed that HPLC was used to determine the drug content of Sophocarpine solid lipid nanoparticles.Volume and encapsulation rate,simple method,high sensitivity,precision and recovery meet requirements,good specificity and repeatability.Sophocarpine nanoparticles were prepared by the microemulsion method,using sophocarpine as the model drug,stearic acid as the lipid phase,soybean lecithin as the emulsifier,and poloxamer 188 as the co-emulsifier..Taking the encapsulation efficiency,drug loading and particle size of the nanoparticles as evaluation indexes,the optimal prescription of sophoroline nanoparticles was obtained.The prepared nanoparticles are stored as a lyophilized powder,and the prescription is reproducible.The physicochemical properties of Sophocarpine nanoparticles were characterized,including morphology,particle size and distribution,zeta potential and stability.The Sophocarpine nanoparticles prepared according to the best prescription were observed by transmission electron microscopy,and the morphology of the nanoparticles was round and nonadhesive.The average particle diameter of common locust nanoparticles was 129.8 ± 2.1nm,and the Zeta potential was 20±0.6mv.The PDI was 0.210 ± 0.031.The average particle size of the targeted nanoparticles was 133.6±1.7nm,the zeta potential was-24.9±0.8mv,and the PDI was 0.188±0.015.The change of particle size and the inversion of Zeta potential indicate that CS-SPO-SLN was successfully prepared.The release results showed that after 24 h,the cumulative release of Sophocarpine in p H6.5 and p H7.4 release media was 35% and 13%,respectively and reached 71% in p H5.0 release media.The preliminary stability results show that the prepared nanoparticles have low stability,and it is recommended to make the nanoparticles into a lyop Hilized powder or store them in a low temperature environment.Cell-level studies of nanoparticles include cytotoxicity studies and cell uptake studies.The results showed that the modified targeted nanoparticles had higher toxicity and cell uptake than unmodified ordinary nanoparticles.C57-1 mice were inoculated with axillary tumors derived from Hepa1-6 cells to evaluate the antitumor effect of targeted nanoparticles in vivo.The results showed that polysulfonamide-modified nanoparticles possessed the highest antitumor activity as compared with normal saline.Compared with Free SPO and CS-SPO-SLN groups,the antitumor effect of targeting nanoparticles was most obvious at about 14 days.In this thesis,in vivo imaging technology is used to investigate the drug distribution of nanoparticles in the tissues of heart,liver,spleen,lung,kidney and tumor.