Study Of Synthesis And Micelle Properties Of PH-Responsive Poly(2-Ethyl-2-Oxazoline)-Polylactide Copolymer

The nano drug-loading system of copolymer micelle attracts more research because of its good biocompatibility,small nanometer size,adjustable micelle morphology,excellent drug-loading performance,controllable release rate and easy modification of micellar materials.Cancer is one of the major diseases in current worldwide,and the drugs against solid tumors are mostly hydrophobic chemical structure with poor bioavailability and serious side effects.It is very necessary to deliver them with suitable drug carriers.Therefore,this study aimed to design and synthesize PEOz-PLLA and PEOz-PDLLA copolymer with pH responsiveness,to prepare nano-micelles by self-assembly and explore micellar morphology.And the drug loading performance and release characteristics of micelle carrier need to be evaluated.In addition,the stability and initial degradability of micelles were evaluated.Finally,the comprehensive biocompatibility and safety evaluation was conducted for PEOz-PLA micelles.The main research contents are as follows:1.L-LA and D,L-LA monomers were synthesized by self,and MeOTs initiated EOz monomer to obtain PEOz-OH macroinitiators with different molecular weight by ring-opening synthesis,using it to initiate LA to synthesize PEOz-PLLA and PEOz-PDLLA copolymer via ring-opening polymerization.Adjust the block ratio to synthesize a serise of materials,characterized by ¹H NMR,GPC and DSC,to evaluate the chemical structure,molecular weight and thermal properties of copolymers.2.Self-assembled micelles were prepared by solvent evaporation method.The morphology of PEOz-PLA micelles was investigated by TEM and DLS,and the critical micelle concentration was determined by CMC.Uniform spherical micelles were common in samples,but there were worm-like micelles and long-line micelles in special block ratio samples,and it was rarely found in references of PEOz-PLA.Then,PTX was selected as an anti-tumor model drug,and the drug was loaded by“two-step method”.The LE and LC value of drug-loaded micelles were determined by HPLC to investigate the effect of material changes on drug-loading properties of micelles.The loading efficiency of PTX was up to 90%,and the loading content of that could reach8.2%.Moreover,the drug release properties of micelles were further evaluated from the different perspectives,including length of PLA hydrophobic block,molecular weight of PEOz hydrophilic block,change of pH value,difference of micelle morphology and PEOz-PLLA/PEOz-PDLLA.Taking the pH change factor as an example,the PTX-releasing rate of EOz₂₈L₁₀ micelles during 30 days was 19.4%in pH7.4 PBS,and 29.4%in pH 5.0 PBS.Compared with pH 7.4,the release rate increased significantly at pH 5.0,which reflected the pH responsiveness of the micelle material.3.The stability of PEOz-PLA blank micelles and drug-loaded micelles was evaluated,and the degradation properties of PEOz-PLLA and PEOz-PDLLA micelles were discussed,which was used as the basis for further application research of drug-loaded micelles.4.Comprehensive biocompatibility evaluation of micellar materials,including blood compatibility,cell compatibility and zebrafish embryo toxicity,confirms the safety of micelles in many aspects.In summary,several points about PEOz-PLLA/PEOz-PDLLA micelles were studied in this subject,including various forms of self-assembly,excellent drug-loading performance,stable and slow drug-releasing process,obvious pH-responsive characteristic and good biocompatibility.