Study On The Thermo-sensitive Polyaminoacids By Photo-crosslinking For Drug Loading

Drugs used in the chemotherapy treatment of cancer are lack of targeting,and have heavy toxic side effects.Nanocarriers can solve above problems to a large extent because of their passive targeting and sustained release properties.However,the drug carriers have the disadvantages of poor targeting and low cumulative release at the tumor site.Therefore,according to the high temperature and weak acid environment of tumor tissue,nano-micelle carriers and nanogel carriers with dual response to temperature and pH were designed.Compared with traditional nanocarriers,it has stronger targeting and higher cumulative release.Firstly,the micelles which are responsive to pH and temperature were prepared.Polyisopropylacrylamide-b-poly?L-glutamic acids??PNIPAM-b-PLGA?were made by atom transfer radical polymerization and ring-opening polymerization using a multi-functional initiator,and then polyethylene glycol monomethyl ether(mPEG₁₁₃-OH)was used to modify a carboxyl group of PLGA to synthesize the amphiphilic block polymers,polyisopropylacrylamide-b-poly?L-glutamic acids?/polyethylene glycol monomethyl ether(PNIPAM-b-PLGA/mPEG₁₁₃).The compositions and molecular weights of the block polymers were characterized by nuclear magnetic resonance,infrared spectrum and gel permeation chromatography.What'more,the lowest critical dissolution temperature of the block polymers was 38?,which is closer to the temperature of the tumor site.The polymers which can self-assemble into spherical nano-micelles with core-shell structure in aqueous solution could load doxorubicin?DOX?effectively and achieve sustained release.The release behavior of DOX in vitro were affected by temperature and pH.Under the stimulation of high temperature and low pH,the cumulative release of DOX is higher.Secondly,in order to improve the stability,drug loading and encapsulation efficiency of nanocarriers,nanogels which are responsive to temperature and pH were made.Polyisopropylacrylamide-b-poly?L-glutamic acids??PNIPAM-b-PLGA?were modified with 3-phenylacrylic alcohol?CA?to prepare PNIPAM-b-P?LGA/CLG?.In addition,mPEG₁₁₃-b-P?LGA/CLG?were obtained by ring-opening polymerization of BLG-NCAs initiated by macromolecular initiator NH₂-mPEG₁₁₃,and then modified by CA.Finally,the mixed solution of two kinds of polymers was irradiated by ultraviolet light of 254 nm,and then the nanogels were successfully received by the polymerization of 3-phenylacr-ylonitrile.It is noteworthy that the photocrosslinking process does not require chemical agents and it is environmentally friendly.The morphology of the nanogels were spherical,and the particle sizes were about 40⁶0 nm,which also exhibited dual response to temperature and pH.The nanogels can load DOX effectively and release slowly.The cumulative release of DOX is higher under the stimulation of high temperature and low pH,and the stability,durg loading and encapsulation efficiency are higher than micelles.