Design Of Polyester Materials For Gene Delivery Application

Polyester materials have been widely used as drug and gene delivery system.They show several outstanding advantages such as easy modification,biocompatibility and biodegradability.At present,polymer materials including poly?amino acid?,polyester,glucan,chitosan,etc.as gene carriers exhibit great potential in clinical.Polyester materials are widely used in biomedicine because of their excellent biological loading capability,and commonly used polyesters include poly?lactic acid??PLA?,poly?glycolic acid??PGA?and poly??-caprolactone??PCL?.Currently,most synthetic polyester materials have no post-modification sites.In light of this,a novel polyester was synthesized by polymerizing dimethyl dicarboxylate containing post-modification sites with various types of diols in this paper.The polyesters can be used to co-deliver drug and gene,which overcomes the shortcoming of the traditional polyesters that they only can deliver hydrophobic drugs and unable to co-deliver drugs and genes.It provides a technical reference for the synthesis of new polyester materials and broadens the biological application of polyester materials.Firstly,the side chain dicarbonyl polyester was synthesized by the method of difunctional group polymerization with 1,3-acetone dicarboxylic acid dimethyl ester and 1,6-hexanediol as raw materials.magnetism ¹H-NMR,GPC and hydroxyl value test were used to characterize its structure and molecular weight.The optimal reaction conditions were verified that were 1%catalyst content,feeding ratio of 1:1,reaction temperature in the esterification stage of 100-130?,the polycondensation stage of 130-150?,reaction time of 10 h.The molecular weight of the synthesized polyester material was between 3-8 k.In order to further modify the polyester,the polyester material prepared above was reacted with DPA and then coordinate with Zn²⁺.The optimal reaction conditions were certified by ¹H-NMR characterization that were 5%catalyst content,feeding ratio of 2:1,reaction temperature of 50?,reaction time of 72 h.The target product was successfully synthesized via the reaction between the polyester and DPA,but DPA could not be completely grafted to the polyester side chain.The grafting experiment showed that the maximum grafting rate was about 47%,and the side chain DPA polyester was successfully coordinated with Zn²⁺.Finally,the gene encapsulation ability of the prepared side chain DPA-Zn polyester was explored.The results of agarose gel electrophoresis proved that DNA could be encapsulated.When the charge ratio was greater than 2,the surface charge was positive.The particle size and Zeta potential experiments showed nanoparticles with size in the range of 150-200 nm could be obtained with the increase of the charge ratio.