Zwitterionic Modified Starch Derivatives,Preparation And Application In Drug Delivery And Implants

Starch,a food source polysaccharide,has the advantage of low price and excellent biocompatibility.In this study,we have studied the potential applications of the zwitterionic based starch derivatives.Two parts were included in this study.The first part: Preparation of starch based micelle with the modification of zwitterionic which has the ability of longer circulation time in vivo.The second part: Preparation of starch based hydrogels with the function of anti-nonspecific protein adsorption,which has the ability of avoiding the formation of fibrous capsule.Recently,most of the nanocarriers for the in vivo drug delivery focused on the local microenvironment of the lesion site and precise structural nanoparticles.However,the basic questions is the amounts of protein which is prone to adsorb onto the nanoparticles.Then,the nanoparticles would be recognized by the macrophage and cleared by the body immune system,resulting in the failure of drug delivery.It has been reported that once the ordinary micelles were injected into blood,they would be cleared in less than three hours.Therefore,the “stealth” plays an important role for the long circulation drug delivery.In the first part of our studies,the zwitterionic(SB)was incorporated into the starch(ST)by the ether bond firstly.Then,the octyl(OC)was grafted onto the starch by the ester bond.The targeted bi-modified starch derivatives(SB-ST-OC)was successfully synthesized and used for the preparation of micelles.The zwitterionic segments on the surface of micelles exhibited excellent anti protein and had lower activation of macrophages,which can be call “stealth micelle”.Based on the results in vitro,the micelles were used for the pharmacokinetic study.Compared to the ordinary micelles without zwitterionic modification,the SB-ST-OC micelles can prolong the half-time,extend the residence time and improve the drug bioavailability significantly.The implant materials,such as the scaffold and hydrogel,would be wrapped by the fibroblast due to the body immune system,which is impermeable to the nutrients and metabolites,leading to the implant failure.The first step of the immune reaction was the protein adsorption.The reject reaction could be minimized if the implant had the ability of anti-protein.In the second part of our study,based the natural polysaccharide starch,the zwitterionic SBMA as the monomer was incorporated into the main chain of starch by atom transfer radical polymerization.The target product ST-g-PSBMA was successfully synthesized.By adjusting the substitute of Br and the degree of polymerization,a series of copolymers STDS-g-PSBMAn were synthesized.The copolymer can change the states among precipitate-hydrogel-solution phage according to the different salt concentration.The polymer can self-assemble into physical hydrogel by the electrostatic interactions in saline.The hydrogel exhibited excellent protein resistance and anti-cell adhesive properties.The physical hydrogel was formed by the electrostatic interactions which could lead to the collapse of the hydrogel if they were dissociated by the salt solution.Additionally,the starch could be degraded in vivo,which could also avoid the harm to our body causing by the surgical removal of non-degradable material.