Synthesis And Property Of Carbonate Liquid Crystalline Materials Based On Cholesteryl Group

The amphiphilic polymers can be used to prepare nanomaterials with ordered structure and different morphologies,and are widely used in the field of biomedicine.Aliphatic polycarbonates have good biodegradability,biocompatibility,and non-toxicity,and importantly,their physical,chemical and biological properties can be adjusted by introducing side chain functional groups,so as to better adapt to the needs for the adhesion or growth of the cells or tissues.And the aliphatic polycarbonates can be used to construct the hydrophobic segments of amphiphilic block copolymers.The cholesterol is an important structural component of the mammalian membranes and has a highly hydrophobic backbone.Introducing the cholesterol into the polymers not only can increase the biocompatibility of the polymers,but also can form the liquid crystallines(LCs)with the ordered arrangement to provide a driving force for polymer self-assembly,and to respond to external stimuli such as temperature,stress,light,electricity,and magnetism.The amphiphilic polymers functionalized with cholesterol have become an important part of self-assembly research,and they exhibit excellent biocompatibility as drug nanocarriers,which can achieve passive targeting and result in significant anti-cancer effects.At present,there are few reports on the study of aliphatic polycarbonate functionalized with cholesterol,especially the cholesterol is introduced in the side chain.In this paper,novel cholesteryl-based LC compounds,cyclic carbonate LC monomers,and amphiphilic polycarbonate LC copolymers were designed and synthesized.The obtained monomers can be used to synthesize novel aliphatic polycarbonates or other block copolymer materials,while the obtained copolymers can be used to construct functional drug nanocarrier with stimuli response.The main contents and results are as follows.In chapter 2,four LC intermediate compounds(C1-C4)and four cyclic carbonate LC monomers(M1-M4)based on cholesteryl groups were synthesized.The structures were characterized by FT-IR and 1H NMR,and the LC properties were characterized with POM,XRD and DSC,and the effect of the flexible spacer length on the properties was explored,which indicated that the obtained compounds all conformed to the molecular designs.C1-C4 all showed enantiotropic mesophase,and the length of the flexible spacer had a certain effect on the mesophase and the molecular arrangement.Furthermore,with the number of flexible methylene groups increased,the melting point(Tm),the transition temperature between different mesophase,and the clearing temperature(Ti)of the LC intermediate compounds showed a decreasing trend,and the overall LC mesophase range was narrowed.M1-M4 were all enantiotropic mesophase,and exhibited the focal conic texture of a SmA phase and an interdigitated molecular arrangement.In addition,except M1,the glass transition temperature(Tg)and Ti of the M2-M4 exhibited a decreasing tendency as the number of flexible methylene groups increased in the even,and the mesophase temperature range became narrower.In chapter 3,amphiphilic polycarbonate LC copolymers functionalized with cholesterol[mPEG43-b-P(MCC-Cn)51(n=1-4)]and amphiphilic copolymers with cholesterol and carboxyl(Pn)were synthesized,which were different in the length of the flexible spacer connecting the main chain and side chain,and the graft ratio of the side chain LC groups.The structures and properties were characterized by FT-IR,1H NMR,GPC,POM,XRD,DSC and TGA,and the relationship between the structure and performance was discussed systematically.The results are as follows:for the copolymers mPEG43-b-P(MCC-Cn)51,the copolymer had no LC property when n=1,while the other three copolymers all showed enantiotropic mesophase of a SmA phase and an interdigitated molecular arrangement.Moreover,as the flexible spacer numbers increased,the Tg of the copolymers decreased and Ti increased,so that the range of the LC mesophase was widened.For the copolymers Pn,only P3 exhibited LC property.And as the flexible spacer numbers increased,the Tg showed a decreasing tendency.Compared with the corresponding copolymers of mPEG43-b-P(MCC-Cn)51 series,the Pn copolymers showed lower Tg for the lower graft ratio of side chain LC groups.The TGA results indicated that,the introduction of the side chain cholesteryl LC groups could greatly improve the thermal stability of the copolymers.In chapter 4,the self-assembly behavior,in vitro drug release behavior using doxorubicin as drug model and cytotoxicity assay research based on functionalized polycarbonate LC copolymers Pn were studied.The results showed that:(a)The size and morphology of the copolymer self-assembly aggregates could be controlled by changing selective solvent,copolymer concentration in solution,pH value,temperature and the copolymer structure.And the introduction of LC groups to the copolymer could effectively improve the stability of the self-assembly aggregates.(b)The drug loading and encapsulation efficiency of the copolymer could be effectively increased by selecting proper solvent such as tetrahydrofuran,weak acidic or neutral condition,and endowing the copolymer with LC property.The weak acid condition and elevated temperature would accelerate the drug release rate of the drug-loaded micelles.And with the condition of pH=5.4 and temperature 37℃,the DOX cumulative release of P3 drug-loaded micelles could reach 85%after 24 hours.Therefore,the copolymer drug-loaded micelles could achieve a pH-triggered rapid drug release under weakly acidic conditions of the tumor cells.(c)The copolymer P3 was not cytotoxic to normal or cancer cells.Moreover,P3 drug-loaded micelles could enter cells through endocytosis,and effectively deliver the drug into tumor cells to produce obvious anti-tumor effects.Chapter 5 summarized the above works,and the further developments and potential applications of the functionalized polycarbonate LC copolymers were discussed.