Anti-breast Cancer Effect Of Ivermectin Nanoparticles Modified By TPGS

Breast cancer has become the world’s most common cancer.Chemotherapeutic drugs are the main treatment methods for breast cancer in clinic,but their accuracy,efficiency and safety need to be further improved.Nanodrug delivery technology has developed rapidly in recent years because it can improve the targeting and uptake of chemotherapy drugs by tumor cells and reduce their toxic and side effects.To screen out drugs with anti-tumor activity from existing clinical drugs and solve the limitations of their application by preparing nanoparticles to enhance their efficacy,we can provide more drug choices for clinical anti-breast cancer treatment.Ivermectin is a common anti-parasitic drug.Previous studies have shown that it also has a good therapeutic effect on breast cancer and can resist drug resistance.However,the low solubility of Ivermectin can not meet the blood concentration requirements of intravenous administration.TPGS,as a classical hydrophobic nano-carrier,can overcome multidrug resistance,and has been widely used.Using TPGS to deliver Ivermectin to prepare nanomaterials can not only effectively improve the dispersion of Ivermectin in aqueous solution,but also achieve effective enrichment in tumor area,providing more choices for clinical application of anti-breast cancer drugs.In this paper,TPGS-Iver NPs was successfully synthesized by nano precipitation method,and its particle size was determined by particle size meter and scanning electron microscope to be about 130 nm.The potentiometer measured its potential as negative.The particle size was about 130 nm after intermittent determination within 1 month.The solubility comparison experiment shows that the solubility is improved greatly.The content of Ivermectin in nanoparticles was determined by HPLC.We evaluated the uptake and cytotoxicity of nanomaterials in tumor cells using multiple breast cancer cell lines as models.Fluorescence assay results showed that tumor cells had better uptake of TPGS-Ce6 NPs.MTT assay and LDH release assay showed that TPGS-Iver NPs had a good anti-tumor effect.Clonal formation assay showed that TPGS-Iver NPs could inhibit the proliferation of tumor cells.Apoptosis experiments showed that the nanoparticles could significantly induce cell apoptosis.These results all proved that TPGS-Iver NPs has good antitumor effect.We used the 4T1 xenograft tumor-bearing mice as animal models.The absorption of TPGS-Ce6 NPs in was measured,suggesting that the absorption effect was good;the tumor inhibition rate of TPGS-Iver NPs is better than the control group,slightly better than Paclitaxel Liposome for Injection;at the same time,there was no significant difference in body weight of mice and no obvious abnormality was found in H＆E staining of heart,liver,spleen,lung and kidney sections,indicating high safety of nano-preparation.In conclusion,TPGS-Iver NPs prepared by nano precipitation method has a moderate particle size,good uniformity,and high stability.In vitro experiments,TPGS-Iver NPs showed good uptake and cytotoxicity,with the highest apoptosis level.In vivo experiments,the nanoparticles showed better tumor aggregation effect,and the tumor inhibition experiment showed better tumor inhibition effect and slightly better tumor inhibition effect than the simple force.TPGS-Iver NPs solve the problem of poor solubility of Ivermectin original drug,and at the same time makes it have a good tumor targeting effect.It has a good tumor inhibition effect in vivo and in vitro experiments,and has a good safety,which is expected to provide a candidate drug for anti-breast cancer treatment.