Synthesis Of Reversible Crosslinked Polyesters And Application In Drug/Gene Carriers

Biodegradable polymer materials,which can be absorbed by the body or discharged out of the body after hydrolysis or enzymatic hydrolysis,have good biological compatibility,non-toxic and no side effects.The polymer with outstanding degradation performance,is widely used in biomedical fields such as drug carrier,healing materials,absorption type sutures,adhesive and tissue defect repair materials.Polyester polymers,in particular,play a crucial role in the development of Drug Delivery systems.In recent years,gene therapy has played an increasingly important role in the intervention and treatment of a variety of genetic diseases.By expressing exogenous proteins,inhibiting the induction of certain genes or editing adverse genomic mutations,gene therapy can effectively regulate cell function and response.However,most nucleic acid drugs are susceptible to the enzymatic hydrolysis of nucleases.Usually,appropriate gene carriers are needed to deliver nucleic acid substances to the needed cells of the human body in order to exert the maximum therapeutic effect.However,traditional polyester materials do not have modification sites and cannot encapsulate genes.Therefore,two kinds of polyester materials with multiple modification sites were designed and synthesized in this project in view of the limitation of lack of functionalization of synthetic polyester materials at present,and they were modified by post-functionalization to make them have the function of gene delivery.The amphiphilic materials were prepared and self-assembled in water to form a core-shell micelle structure to realize the co-encapsulation of hydrophobic drugs and genes,providing new ideas and new methods for the synthesis of new biomedical polyester materials and the application of drug gene delivery.The general content of the study is as follows:Firstly,1,4-butylene glycol or 2-methylene-1,3-propanediol and 1,3-acetone dimethyl dicarboxylic acid as raw material,tetrabutyl titanate as catalyst,the polyesters with carbonyl and double bond on the main chain were synthesized by the method of melting transesterification.Best reaction conditions were explored.The molecular structure,molecular weight and its distribution Polymers were characterized by using ~1H-NMR and GPC.Secondly,functional groups including dimethylpyridinamine(DPA),2-aminoethanethiol,and PEG were modified onto the main chain of polyester by the post-modification methods including amino-ketone reaction,thiol-ene photocatalytic Click reaction,esterification reaction,and metal coordination reaction.As a result,reversible crosslinking amphiphilic polyester P2DOPs Zn was obtained.Finally,the performance of the polyester materials were tested and characterized by agarose coagulation electrophoresis and dynamic light scattering method,evaluating the performance of self-assembly in water and the ability to encapsulate hydrophobic drugs and genes.It is proved that the prepared amphiphilic polyester materials can form stable micelle particles by self-assembly in water.It has REDOX responsiveness and stability and have the ability to encapsulate hydrophobic drugs and DNA.