Synthesis And Micellar Bhaviors Of Dehydroabietic Poly [Ethylene Glycol] Dynamic Polymer Based On Acylhydrazone Bond

Dynamic polymers are polymers having dynamic covalent bonds,which can respond to external stimulations（such as pH,temperature,light,etc.）to achieve the reversible formation or fragmentation of bonds.Acylhydrazone bond is one of the dynamic covalent bonds,and it has pH responsiveness.In this thesis,four kinds of dehydroabietic poly（ethylene glycol）dynamic polymers based on acylhydrazone bond were designed and synthesized using dehydroabietic acid（DHA）,poly（ethylene glycol）（PEG）or poly（ethylene glycol）monomethyl ether（mPEG）as main raw materials.Then,the micellar and drug release behaviors were characterized and tested.The main research results were as follows:1.Dehydroabietic acid（DHA）was separated and purified from disproportionated rosin,and the dehydroabietic acylhydrazine（DHA-NHNH₂）was synthesized via the reactions of DHA with SOCl₂ and hydrazine hydrate（NH₂NH₂·H₂O）in turn.Four poly（ethylene glycol）containing aldehyde end group were synthesized by the reactions of mPEG（M_n=1000,1900）and PEG（M_n=1000,2000）with 4-carboxybenzaldehyde,respectively.Then,four kinds of dehydroabietic poly（ethylene glycol）dynamic polymers(mPEG₁₀₀₀-DHA,mPEG₁₉₀₀-DHA,DHA-PEG₁₀₀₀-DHA and DHA-PEG₂₀₀₀-DHA)based on acylhydrazone bond were prepared by the addition-elimination reaction of DHA-NHNH₂ with four poly（ethylene glycol）containing aldehyde end group,respectively.The reaction conditions were explored and optimized,and the target products were confirmed by ¹H NMR and FT-IR.2.The dynamic polymer micelles of resulting four dehydroabietic poly（ethylene glycol）were prepared by dialysis with DMF as solvent.The morphology and particle size of the micelles were determined by transmission electron microscopy（TEM）and dynamic light scattering（DLS）.The CMC（critical micelle concentration）of micelles was determined by UV-visible spectrophotometer,and the pH responsiveness of micelles was investigated.The results showed that the foure kinds of polymer micelles were spherical with small particle size ranging from 46 nm to 82 nm.The CMC values of the four polymer micelles ranged from 0.0031 to 0.0055 g/L,and increased in the order of DHA-PEG₁₀₀₀-DHA,DHA-PEG₂₀₀₀-DHA,mPEG₁₀₀₀-DHA and mPEG₁₉₀₀-DHA,which indicated that CMC was related to the ratio of hydrophilic and hydrophobic chain segments of the polymers,and CMC decreased with the increase of hydrophobic DHA percent.The particle size of the micelles increased with the decrease of pH value of the solution;when pH=2.0,the solution of DHA-PEG₁₀₀₀-DHA micelles became cloudy,indicating that the hydrolyzation of acylhydrazone bond resulted in the production of DHA-NHNH₂,which showed that the micelles had good pH responsiveness.3.The DOX-loaded dynamic polymer micelles of dehydroabietic poly（ethylene glycol）were prepared by dialysis with DMSO as solvent.The drug encapsulation rate and drug loading capacity of the drug-loaded micelles were determined by UV-visible spectrophostometer;the cumulative DOX release rate of the drug-loaded micelles in a buffer medium with pH=5.0 was investigated within 48 h.The results showed that the particle sizes of the prepared micelles ranged from 73 nm to 96 nm,which was slightly larger than that of the blank micelles.The encapsulation rate and loading capacity of mPEG₁₀₀₀-DHA,DHA-PEG₁₀₀₀-DHA,mPEG₁₉₀₀-DHA and DHA-PEG₂₀₀₀-DHA were 32.9%and6.6%,11.9%and 2.4%,37.6%and 7.5%,14.3%and 2.9%,respectively;the cumulative DOX release rate of the drug-loaded micelles reached to 33.9%,54.5%,30.6%and 49.5%at 48 h,respectively,which indicated that dehydroabietic poly（ethylene glycol）dynamic polymer has obvious drug-release behaviors.For mPEG-DHA or DHA-PEG-DHA,the cumulative DOX release rate was slightly higher when the molecular weight of PEG was smaller;the cumulative DOX release rate of DHA-PEG-DHA polymer micelles was faster than that of mPEG-DHA.The dynamic polymer of dehydroabietic poly（ethylene glycol）based on acylhydrazone bond possesses biocompatibility,pH responsiceness,and drug release behaviors,and therefore has potential application in the fields of the sustained release of drugs and pesticides.