The Synthesis Stimuli-responsive Polycarbonate And Its Applications For Drug Delivery

Functional polycarbonate was widely applied in biomedical field.The properties and structures of polycarbonates could be easily adjusted and optimized by functionalization.To achieve it,the modification of side chains in polycarbonate was significant importrant.Various functional groups were attached to the polycarbonate backbone to construct the desired multi-functional polycarbonates.Firstly,a series of novel thermoresponsive copolycarbonates were constructed by cyclic trimethylene carbonate(MTC)monomers bearing oligo ethylene glycol(OEG)and with thioether or/and sulphone linkages.They were initiated by 1,4-benzenedim ethanol with N-(3,5-trifluoromethyl)phenyl-N'-cyclohexylthiourea(TU)1,8-diazabicyclo[5,4,0]undec-7-ene)(DBU)as the organic catalyst.The lower critical solution temperature(LCST)properities of the polycarbonates with thioether or sulphone linkage were studied and discussed in regard to molecular weight,salt concentration and polymer concentration.By using monomers of different OEG chain lengths and thioether and/or sulphone linkages,theLCSTs of biodegradable and thermoresponsive polycarbonate copolymers can be easily tunedwithin a wide temperature window from 15 C to 46 C(3 g/L in aqueous solution).In addition,block polycarbonates with two tunable LCSTs were further synthesized and investigated.Results showed that LCST1 was constructed by polycarbonate with hydrophobic thioether linkage,while the LCST2 was achieved by polycarbonate containing hydrophilic sulphone linkage.Then,we design a novel triple-stimuli-sensitivegraft copolymer assembly which responds to the changes in temperature,reducing agent and light.The graft copolymer consists of thermo-responsive tetraethyleneglycolylpoly(trimethylene carbonate)(P(MTC-4EG))as backbone and light-sensitive poly(2-nitrobenzyl methacrylate)(PNBM)as side chain linked by an intervening disulfide bond.In aqueous solution,the polymer can self-assemble into micelle with thermo-sensitive shell(P(MTC-4EG)),light-sensitive core(PNBM)and disulfide linker.The assemblies in response to stimuli were revealed by dynamic light scatting(DLS)and transmission electron microscopy(TEM).The drug release behaviors of Nile Red(NR)loaded carriers were also valued with stimuli from temperature,reducing agent and lightThrough modifications of side chains,the multi-functional biodegradable polycarbonate which could meet the actual demands were constructed.We believed that these novel polycarbonates could show great potential in biomedical field.