Preparation And Application Of Dextran-based Responsive Drug Carrier

Nature occurring polymeric materials are cheap and easy to obtain.There nontoxic materials have a very broad prospect application in biomedicine.Because of its’ degradability and biocompatibility,as a natural high molecular polysaccharide,dextran is widely used as a drug delivery carrier and it has remarkable effects in drug controlled release and tumor treatment.Meanwhile,the dextran molecule contains a large amount of hydroxyl groups,which can be easily modified.Considering these advantages,we designed a serial of dextran based drug delivery systems to facilitate a more versatile drug delivery strategy by simple chemical modification of carrier materials,and achieved high-efficiency drug controlled release and efficacy.We proved a new strategy for designing drug delivery systems.First,the dextran-based temperature-sensitive hydrogels drug delivery system for delivering the anticancer drug doxorubicin was designed.To obtain the gelling agents,cyanodextran and aldehyde-dextran were prepared.The methylene group attached to the cyano group and the aldehyde group on dextran were cross-linked in 1:1 molar ratio reation to form dextran-based hydrogels.MTT assay showed no significant toxicity of the hedrogel.The hydrogel has excellent mechanical properties,good temperature sensitivity,and is capable of slowly releasing the entrapped doxorubicin.Second,we designed a p H-responsive nanoparticle drug delivery system that binds the anticancer drug camptothecin(CPT)with dextran as a canrrier.In this system,we uses phosgene to modify the phenylboronic acid group(4-hydroxymethylbenzeneboronic acid)onto the drug molecule(camptothecin),and then use the phenylboronic acid group to react with the diol to modify the drug molecule.The drug-loaded dextran molecule(Dex-CPT)was self-assembled into nanoparticles in PBS,and producing Dex-CPT nanomedicine.The borate ester bonds cleaved within the tumor microenvironment(p H<6.8),resulting in cleavage of the nanoparticles and releasing a camptothecin drug to induce apoptosis in cancer cells.Based on this system,we designed a p H-responsive nanoparticle drug delivery system that uses dextran as a carrier to bind the anti-inflammatory drug ibuprofen.In this system,the 4-hydroxymethylbenzeneboronic acid pinacol ester was attached to the drug ibuprofen molecule.The phenylboronic acid groups were recovered by deprotected reaction,and subsequently reacted with the diol to form the modified ibuprofen.The drug molecules were loaded onto the dextran,and eventually self-assembled into nanoparticles in PBS.The borate bond cleaved in an acidic environment at the inflammatory tissue,causing the cleavage of the nanoparticles to release anti-inflammatory drugs.