Molecular Design,Synthesis And Drug Release Of Thermo-sensitive Polyureas

Thermo-sensitive polymer is an intelligent polymer that responds to temperature stimuli.Thermo-sensitive polymer has aroused the widespread concern in drug releasing,immune analysis,tissue engineering,biological monitoring and other fields.For this reason,the design and synthesis of the polymer with biocompatibility and thermo-sensitivity has become one of the hot spots in today’s polymer science.This article mainly includes the molecular design,synthesis and properties of thermo-sensitive polyurea,and its research on drug release.It is divided into four parts.A series of new polyurea materials were prepared by hydrogenation transfer addition reaction with 5 kinds of diamine and L-lysine ethyl diisocyanate（LDI）as monomers.The structure of the polyurea material was characterized by FTIR,NMR and GPC.The relationship between the structure of the polyurea material and its properties was revealed by XRD,contact angle and FTIR.It is found that,due to the steric hindrance of two methyl groups,poly（L-lysine ethyl ester diisocyanate-co-N,N’-dimethylcyclohexane-1,2-diamine）（PLI-N）is able to generate more hydrogen bonds with water,promoting PLI-N with the most hydrophobic groups to be soluble in water and exhibiting thermo-sensitive properties.The effects of reaction time,temperature and solvent on the polymerization were examined,and the best polymerization conditions were also obtainedOf the 5 homopolymers,only PLI-N shows good temperature sensitivity behavior,and its lower critical solution temperature（LCST）is 10℃,and the LCST value decreases with the increase of molecular weight.In the copolymerization of N,N’-dimethylcyclohexane-1,2-diamine（NMC）and other four kinds of diamines,the LCST of the polyurea material can be controlled near room temperature or body temperature.The results of He La cytotoxicity test based on MTT method showed that the cell viability was higher than 87%in the DMSO/H₂O solution of 0.2-125μg/mL polyurea material,that is,there was no obvious cytotoxicity of the polyurea.The nanoparticles with core-shelled structure were prepared by the thermo-sensitivity of polyurea and hydrophobicity of paclitaxel（PTX）.The PTX loaded particles were characterized by laser particle size and scanning electron microscope（SEM）.The experimental results show that the particle size of the polyurea-PTX drug-loaded particles is 199 nm,achieving sustained release of PTX in vitro,which lays a theoretical foundation for its practical application in the field of biomedicine.Using LDI,NMC and cystamine as comonomers,by changing the feeding ratio of NMC to cystamine in copolymerization,the poly（L-lysine ethyl ester diisocyanate-co-N,N’-dimethylcyclohexane-1,2-diamine-co-cystamine）（CPLI-N-Y）with different S-S bond content on the main chain was successfully prepared.The UV-vis spectrum data shows that when cystamine structure unit is 12%and 24%on the CPLI-N-Y chain,CPLI-N-Y shows thermo-sensitivity,and the LCST is 35℃and 38℃respectively.In addition,the core-shelled structure particles with diameter of 320 nanometer were obtained by dialysis.With the characteristic reaction of the chain-breaking agent L-glutathione（GSH）and the S-S bond on the CPLI-N-Y backbone,the novel polyurea material with thermo-sensitive properties and a cleavable group S-S bond is expected to achieve effective controlled release of curcumin.A series of polyurea materials containing piperazine structure in the main chain were successfully prepared by the hydrogen transfer addition reaction of five piperazine and its derivatives with LDI.The infrared spectrum and nuclear magnetic resonance spectroscopy confirmed the chemical structure of polyurea materials.It was found that the polyurea formed by cis-2,6-dimethylpiperazine and LDI has a thermo-sensitivity with an LCST of 14°C.The other four polyureas containing the piperazine structure have no thermo-sensitive properties,the reason is the strong hydrogen bonding between the macromolecular chains prevents the formation of hydrogen bond with water.This polyurea material containing piperazine structure has potential application in biomedical fields such as antibacterial properties.