Study On Targeted Therapy Of Ibuprofen Manganese Nanocomposite Particles In Inflammatory Diseases

Lactation mastitis,primary dysmenorrhea and endometriosis are common benign diseases in women.These diseases are closely related to inflammation,which seriously affect the quality of life in women around the world.However,traditional medicines are prone to adverse reactions such as gastrointestinal tract,endocrine and metabolic abnormalities.In combination with nanomedicine,it is hopeful to ameliorate inflammation caused by diseases and relieve the symptoms of patients.Objective:To synthesize and characterize nanocomposite particles(IBUMn@Liposome),based on ibuprofen(IBU)and manganese(Mn),and explore the ability to target the inflammatory site and anti-inflammatory effects.Methods:1.Ibuprofen manganese nanocomposite particle(IBU-Mn@Liposome)based on coordination polymers was synthesized by film hydration method,and IBUMn@Liposome was characterized by transmission electron microscope and ZetaSizer potential;2.The vitro biological safety and anti-inflammatory ability were confirmed by MTT and Western blot;3.The targeting capabilities of inflammation of IBU-Mn@Liposome was confirmed by drug biological distribution and fluorescence imaging in vivo.Evaluate the effects of IBU-Mn@liposome anti-inflammatory and antioxidant through H&E staining,photo and ELISA;4.The effect of IBU-Mn@Liposome on primary dysmenorrhea was estimated by biological behavior observation,weight of uterine,area of uterine myometrium and ELISA;5.The targeting capabilities of IBU-Mn@Liposome was confirmed by fluorescence imaging in endometriosis mouse model.Results:1.We successfully synthesized IBU-Mn@Liposome with uniform particle size and good stability in PBS;2.IBU-Mn@Liposome had good biosafety and inhibited the up-regulation of inducible nitric oxide synthase(iNOS)in vitro;3.IBU-Mn@Liposome at the inflammatory site had a stronger fluorescence intensity,and showed a good targeting ability;4.IBU-Mn@Liposome improved the damage in LPS-induced mastitis in mice,and significantly inhibited the up-regulation of IL-12,IL-6,TNF-α and IFN-γ expression levels as well as increased levels of iNOS;5 IBU@Liposome,IBU-Mn@Liposome and dexamethasone(DEX)groups can improve the mammary tissue injury induced by LPS in mouse acute mastitis model,decrease the activity of MPO,the concentration of proinflammatory cytokines and nitric oxide,moreover increase SOD activity.There was no statistical difference in the efficacy between the dexamethasone group and IBUMn@Liposome group;6.IBU-Mn@Liposome reduced the writhing times on oxytocininduced primary dysmenorrhea,but there was no significant difference in the writhing latency.IBU-Mn@Liposome relieved pain primary dysmenorrhea induced by oxytocin in mice,reduced the expression levels of IL-6,IL-1β,TNF-α,IFN-γ in tissues and calcium levels;7.IBU-Mn@Liposome-Cy5.5 had a stronger fluorescence intensity at 24h compared with IBU@Liposome-Cy5.5 and MnC12@Liposome-Cy5.5,suggesting that IBUMn@Liposome had a good targeting ability in endometriosis.Conclusion:IBU-Mn@Liposome was designed and synthesized,which had a good targeting ability to inflammatory lesions.IBU-Mn@Liposome can effectively treat LPSinduced mouse mastitis,reduce oxidative stress in the mammary gland inflammatory site,relieve primary dysmenorrhea caused by oxytocin in mice,and enrich in the endometriosis lesions of the abdominal wall in mice.It provided a new theory,experimental basis and design idea for anti-inflammatory and analgesic therapy in women.