Synthesis And Properties Of Star-shaped Amphiphilic Polyurethanes As Drug Delivery Carriers

Amphiphilic polyurethanes have excellent biocompatibility,biodegradability and feasible molecular tailorability,and they can self-assemble in aqueous solution to form micelles with “core-shell” structure.The hydrophobic core can act as storage for encapsulating water-insoluble drugs,and the hydrophilic shell enables to keep micellar stability.Therefore,amphiphilic polyurethanes have attracted much attention of researchers all over the world in the field of drug delivery carriers.Star-shaped amphiphilic polyurethanes have unique three-dimensional structures and possess many cavities in their micelles,so they will display more excellent properties as drug delivery vehicles.To investiugate the effects of structure and composition of star-shaped amphiphilic polyurethanes on their micellar properties and drug loading properties,a series of amphiphilic polyurethanes with different arm numbers such as two,three and four,different hydrophilic/hydrophobic ratio and different molecular weight were designed and synthesized,using methoxy polyethylene glycol（m PEG）,polycaprolactone-diol（PCL）and hexamethylene diisocyanate（HDI）as materials.Their structure was determined by Fourier transform infrared spectroscopy（FTIR）,proton nuclear magnetic resonance spectroscopy（1H NMR）and so on.The amphiphilic polyurethane could self-assemble in aqueous solution to form micelles with an optimal size（< 200 nm）by solvent evaporation.Their self-assemble behaviors were studied by pyrene fluorescence probe technique and dynamic light scattering（DLS）,the results showed that the micelles formed from four-armed amphiphilic polyurethane had lower critical micelle concentration value and size and that they had excellent stability.The results demonstrated the the hydrophilic segment content and the molecular weight of amphiphilic polyurethane had also effects on the micelle properties when the arm number of polyurethane was unchanged.In addition,selecting indomethacin（IMC）as a model drug,the effect of arm number,hydrophilic/hydrophobic ratio and molecular weight of amphiphilic polyurethane on the drug loading capacity and in vitro drug release properties of their micelles were also reseached by ultraviolet-visible（UV-vis）anlysis.The result of MTT（methylthiazole-tetrazolium）assay experiment showed amphiphilic polyurethanes had almost nontoxic to the growth of Hela cells.To obtain polyurethane micelles with targeting property as drug delivery carriers,Fe₃O₄-modified magnetic amphiphilic polyurethane（MAPU）was successfully synthesized,selecting Fe₃O₄ as magnetic source and amphiphilic polyurethane as framework material.The products were confirmed by Fourier transform infrared spectroscopy（FTIR）and thermogravimetric analyzer（TGA）.The testing results of DLS and vibrating sample magnetometer（VSM）showed that the size of MAPU micelles was less than 45 nm and that the micelles had excellent stability and magnetic responsiveness.In addition,MAPU micelles possessed excellent loading capacity and release-sustained effect for IMC.And the MTT assay experiment indicated that MAPU micelles were almost non-cytotoxicity.