Synthesis And Application Of Zwitterionic Dextran Derivative

Drug nanocarriers are expected to be internalized by tumor cells to achieve more effective therapeutic response.Polysaccharide derivatives are typical drug nanocarriers which are nontoxic and biodegradable.However,as is the case for all drug delivery systems,polysaccharide derivatives have to face the issue of protein fouling which can be recognized and phagocytosed by immune cells.In this paper,we present the design and synthesis of two types polymers:carboxybetaine-modified dextran-polycaprolactone(Dex-CB-PCL)copolymers with PCL polymerization degree of 17 and 36 respectively,and carboxybetaine-modified dextran-curcumin(Dex-CB-Cur)polymers.After being synthesized,the copolymers were characterized by ~1H NMR spectrum and FTIR spectrum.Moreover,the critical micelle concentration of each copolymer was determined using pyrene as a fluorescence probe.The result shows that the more hydrophobic micelle has lower critical micelle concentration.Further,the Dex-CB-PCL copolymers with different PCL polymerization degree were utilized as doxorubicin(DOX)nanocarriers,with the objective to circumvent the issue of protein fouling.Results showed that Dex-CB-PCL micelles could wrap and load DOX molecules efficiently in certain concentration of DOX solution.Also,the DOX-loaded micelles exhibited better cumulative release at the pH value of 5.2 than at the physiological pH of 7.4,which indicated potential applications in killing tumor cells while minimizing the toxicity to normal tissues.Additionally,antifouling properties of carboxybetaine functionalized dextran micelles were much better than that of unmodified dextran in phosphate buffered saline buffer(pH=7.4)for fibrinogen and lysozyme as tested by isothermal titration microcalorimetry.Finally,cytotoxicity tests using Hela cells showed that Dex-CB-PCL and DOX-loaded micelles exhibited great biocompatibility.All the above observations lead us to believe that Dex-CB-PCL micelles are potentially drug carriers for the treatment of human cancerous tumors.