Title Study On Synthesis And Properties Of Medical Polymer Materials By High-Gravity Polymerization

Due to the non-toxicity,low side effects,good biocompatibility and biodegradability,polymer nanoparticles have been widely used in controlled release systems,disease diagnosis and precise treatments.The molecular weight of the polymerization products varies significantly with the different reaction conditions,so the composition and structure are difficult to accurately control.For the existing manufacturing technique of medical polymer nanoparticles,the products lack homogeneity and stability.These procedures shows much complexity and difficulty for large-scale production and poor reproducibility.Therefore,it is necessary to develop a feasible and controllable preparation method to synthesize high-quality polymer materials.In this paper,high-gravity technology was used to intensify the molecular mixing and mass transfer for the preparation of three polyacrylates by anionic,condensation and radical polymerizations.The mechanisms of the high-gravity technology intensification for polymerization reactions were discussed,and the operating conditions were optimized.Meanwhile,the relationship between the asprepared polymer structure and properties was investigated.The main research contents and innovations of this paper are as follows:(1)Poly(n-butyl cyanoacrylate)(PBCA)was prepared by high-gravity intensified anionic polymerization.Due to the improved molecular mixing by high-gravity technology,the space steric effect in chain growth step was weakened,and the semi-continuous polymerization process was optimized.The PBCA purity was increased from 93%to 96%and the reaction time was reduced from 12 h to 2 h.The high-gravity technology process shows good reproducibility.The molecular weight distributions of PBCA products are about 1.1.The particle size of PBCA nanoparticles is less than 200 nm,and the particle size distribution is less than 0.1.As-prepared PBCA shows good cytotoxicity and cell uptake capacity.With the increase of the molecular weight of PBCA,the cytotoxicity of PBCA against Hep G2 cells increased firstly and then decreased,and the cell uptake capacity was enhanced.(2)Poly(ethylene glycol)(PEG)-PBCA block polymers were prepared by high-gravity intensified Knoevenagel condensation-Michael addition polymerization.By using high-gravity technology to enhance molecular mixing,the butyl cyanoacetate and formaldehyde as well as the active chains are evenly distributed,and the two monomers can be reacted alternately with the active chain more effectively.The reaction was speeded up,and the reaction time was reduced by 60%compared with the traditional process.At the same time,the enhancement of molecular mixing by high-gravity technology also inhibited the self-polymerization of formaldehyde.The molecular weight distributions of the polymerization products synthesized by high-gravity method are narrow(PDI<1.1),and the particle sizes are less than 300 nm.As-prepared PEG-PBCA shows good cytotoxicity and cell uptake capacity.The cytotoxicity of PEGPBCA increased with the increase of PEG blocks and the decrease of PBCA blocks.As-prepared PEG-PBCA could be effectively absorbed and transfused by blood-brain barrier(BBB)cells,and the short PEG chain and medium length PBCA chain were beneficial to assist Nile red permeating the BBB cells.(3)Poly methacrylates(PMA)were prepared by high-gravity intensified free radical polymerization.With the intensified molecular mixing by highgravity technology,the bimolecular termination was inhibited,increasing the molecular weight.Acute molecular mixing leads to a uniform polymer chain distribution.The supersaturated polymer chains precipitate uniformly and gently,producing more nanoparticle seeds.Thus,the polymer emulsion particle size was reduced to less than 50 nm.As-prepared PMA shows excellent biocompatibility.The cytotoxicity of PMA decreases first and then increases with the increase of molecular weight.The effect of monomer ratio on cytotoxicity is not obvious.(4)A molecular weight prediction model of the high-gravity intensified anionic polymerization reaction was established.Using acetic acid-water-ethyl acetate system,the mass transfer of RPB reactor under different high-gravity level and solvent ratio was measured experimentally.Compared with the experimental results,the error is controlled within 20%.(5)The relationships between the structure of as-prepared acrylate polymers and drug loading and release properties were studied.As-prepared PBCA and PEG-PBCA were used to load hydrophilic drug sorafenib tosylate(SFN)and hydrophobic drug doxorubicin hydrochloride(DOX),respectively.The both drug loading capacity and efficiency of SFN-loaded PBCA increase with the increase of molecular weight of PBCA.The dissolution rate of SFNloaded PBCA increases with the increase of molecular weight.The both drug loading capacity and efficiency of DOX loaded PEG-PBCA increase with the increase of the molecular weight of PBCA blocks,but decrease with the increase of the molecular weight of PEG blocks.The dissolution rate increases with the increase of PEG block molecular weight,and decreases with the increase of PBCA block molecular weight.