Preparation And Properties Of Liposomal Nanomaterials With Selective Targeting Of Organs

Traditional drug delivery systems often lead to strong toxic side effects and poor therapeutic efficacy due to their nonspecific biodistribution.At present,the core goal of nanomedicine targeted drug delivery system is to increase the concentration of the target site,while reducing the distribution of the non-targeted site of the drug to improve the efficacy and reduce the biological toxicity and side effects.Liposome is widely used in the field of nano medicine as a kind of carrer material with good biocompatibility and can modify target groups.In this study,we first synthesized choline polymer(P1)and introduced it into liposomes as a charge-regulating molecule,and successfully prepared choline modified liposome nanoparticles(NP1).After injecting into mice by caudal vein,rapid specific enrichment in liver was achieved compared with unmodified lipid nanoparticles.On this basis,cholinine-modified liposomes(NP1/Cur)loaded with curcumin were prepared successfully for the treatment of hepatic fibrosis in mouse models.After treatment,the symptoms of liver fibrosis were effectively improved,which confirmed that the lipid nanocarriers designed and synthesized by us have good drug encapsulation and delivery capabilities.The Blood Brain Barrier can protect the brain by blocking the entry of most foreign substances.Therefore,crossing the blood brain barrier is a prerequisite and crucial condition for the therapeutic effect of drugs in the treatment of central nervous system(CNS)diseases.In this thesis,we investigate the effect of surface graft targeting groups on the biodistribution of liposomes.Based on the surface modification of polyethylene glycol(PEG),the lipid nanomaterial introduced the targeting peptide-T7 targeting transferrin receptors on cerebral vascular endothelial cells,and obtained the ability to cross the blood-brain barrier,paving the way for the subsequent treatment of mouse brain edema model by loading drugs.In this thesis,we describe in detail the regulation of the distribution of nanoparticles in vivo by changing the surface charge of liposome nanoparticles and surface grafting targeting peptides,with the expectation of specific enrichment in liver and brain.The preliminary exploration of the relationship between the surface properties of nanoparticles and biological tissues will provide new ideas and new possible ways for researchers to study the relationship between nanoparticles and biological distribution in the future.