| Hyperbranched polyethyleneimine(HPEI)is a non-toxic polycationic polymer composed of a large number of amino repeating units,its good chemical activity and water solubility make it an excellent parent choice for preparation of amphiphilic polymers.In this article,HPEI was used as the parent,polyethylene glycol monomethyl ether(mPEG),oleic acid(OA)and onitrosuccinate(NBS)were grafted onto it by means of amidation and esterification,then pHstimulating response and photo-stimulation responsive amphiphilic block copolymers with selfassembly function HPEI-OA and mPEG-HPEI-(NBS,OA)were Synthesized,in addition,its application in the field of drug carriers was studied.The specific research contents and results are as follows:(1)The molecular structures of HPEI-OA and mPEG-HPEI-(NBS,OA)were characterized by IR and NMR spectroscopy,the structure of the two derivatives was consistent with the theoretical structure;Moreover,HPEI-OA had good solubility in chloroform and npropanol,while mPEG-HPEI-(NBS,OA)has good solubility in dimethyl sulfoxide and chloroform.(2)The particle size of sample 2(PO2)nanomicelle in polymer HPEI-OA was 84.63±0.45 nm was 84.63±0.45 nm,the Zeta potential was 52.57±1.28 mV,and the CMC was 0.0079mg/mL;Transmission electron microscopy showed that the micelle size was around 80 nm,which was consistent with the particle size measured by 90 Plus Particle Size Analyzer,moreover PO2 nanomicelle showed specific pH responsiveness,and their micelle size increases significantly under strong acid and alkali conditions.The particle size of sample 3(PN3)nanomicelle in polymer mPEG-HPEI-(NBS,OA)was 34.85±0.27 nm,the Zeta potential was 29.88±1.54 mV,and the CMC was 0.0133mg/mL;Transmission electron microscopy showed that the micelle size was around 40 nm,which was consistent with the particle size measured by 90 Plus Particle Size Analyzer,the PN3 nanomicelle showed good light responsiveness,and the particle size of the nanomicelles increased significantly under ultraviolet light.MTT cytotoxicity indicated that both PO2 and PN3 nanomicelles had excellent biocompatibility.(3)The optimum process conditions for the polymer HPEI-OA entrapped kaempferol were: the polymer concentration was 1.208%,the kaempferol concentration was 1.025%,the volume ratio of the organic phase to the aqueous phase was 1:4.32,and the rotation speed was 480 rpm.Under this condition,the theoretical encapsulation efficiency is 91.63%.The particle size of the loaded kaempferol nanomicelle prepared by the dialysis method under the optimal process was 100.47 nm,and the Zeta potential was 51.55 mV;The results of transmission electron microscopy showed that the particle size of the loaded kaempferol nanomicelles was about 110 nm,which was consistent with the particle size measured by 90 Plus.The cumulative drug release rate of kaempferol nanomicelles at pH=8.5,pH=6.5 and pH=5.0 reached 26.41%,23.31% and 25.73%,respectively,and the difference in cumulative drug release rate at the three pHs was small;However,when the pH was adjusted to 9.0 and 4.0,the cumulative drug release rates reached 64.36% and 70.18%,respectively,which was significantly increased compared with the weak acid and weak base conditions.(4)Using mPEG-HPEI-(NBS,OA)as the packaging material,the particle size of the loaded DOX nanomicelle prepared by the dialysis method was 100.47 nm,and the Zeta potential was 51.55 mV;The results of transmission electron microscopy showed that the particle size of the loaded kaempferol nanomicelle was about 60 nm,which was consistent with the particle size measured by 90 Plus.The cumulative drug release rate of the loaded DOX nanomicelle after 72 hours under no light was only 18.55%,however,when irradiated with ultraviolet light(350nm)for 5 min and 10 min respectively,the cumulative drug release rate of the loaded DOX nanomicelle increased significantly,reaching 53.03% and 68.23%;MTT cytotoxicity indicated that the polymer mPEG-HPEI-(NBS,OA)-encapsulated DOX nanomicelle exhibited excellent cell permeability and cytotoxicity. |
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