Study On The Treatment Of Ischemic Stroke With Tanshinone ⅡA Nanoagent Based On Polyglutamic Acid As Drug Carrier

Stroke is an important disease endangering human life and health,with high morbidity,disability and fatality rates.So far there is still no brain-protective drug that can be used clinically yet.The inability of drugs to enter the diseased area through the blood-brain barrier(BBB)is an important factor affecting the clinical application of brain-protecting drugs.Therefore,how to make medicine better penetrate the BBB,enhance the concentration of drugs in a targeted manner,and then increase the efficacy of drugs has become a key issue in the treatment of ischemic stroke.In this paper,PLG-G-PEG-MAL nanoparticles were prepared by polyglutamic acid and polyethylene glycol.Tanshinone IIA was coated by hydrophilic and hydrophobic action,and the target group RVG 29 was modified on the surface of the nanocarrier.A compound nanodrug delivery system T-Ts IIA-NPs,which can target the BBB,has good water solubility,stability,immune compatibility and high biosafety,has been constructed.The structure and morphology of PLG-g-PEG-MAL were characterized by UV,IR,~1H NMR,DLS and TEM.TEM results showed that the PLG-g-PEG-MAL nanomaterial synthesized by us was monodispersed and spherical with a particle size of about 4.32±0.99 nm.According to the characteristic absorption peak at 270 nm,Tanshinone IIA was successfully loaded onto nanocarriers by hydrophilic and hydrophobic action,and the encapsulation rate was 88.5%.MTT results showed that PLG-g-PEG-MAL nanoparticles had good safety in mouse adrenal medulla pheochromocytoma PC12 cells.When the dose of PLG-g-PEG-MAL nanoparticles was low than 200μg/m L,it has better cell viability and almost no toxicity was observed.Cell uptake experiments showed that the nanomaterial PLG-g-PEG-MAL could fully enter cells at6 h.A mouse model of cerebral artery ischemia(MCAO)was prepared to assessed the BBB penetration rate and enrichment capacity of T-Ts IIA-NPs composite nanodrug delivery system,as well as the protective status and prognostic treatment effect of nerve injury after stroke.In MCAO mice,the accumulation of T-NPs nanocarrier in the brain was significantly increased compared with other groups.The optimal concentration of tanshinone IIA was 1.25 mg/kg.TTC staining results showed that the infarct area in T-Ts IIA-NPs group was 9.54%lower than that in MCAO group.T-Ts IIA-NPs with brain targeting function could produce certain brain protection function.The nanoparticle drug delivery system based on polyglutamic acid designed in this paper has good biocompatibility and can achieve targeted enrichment of the BBB and raise the permeability of drugs to the BBB,thus enhancing the prognosis and treatment effect of ischemic stroke.This study offers a new method and opinion for the development and clinical transformation of brain protective drugs for the treatment of ischemic stroke.