Preparation Of Amphiphilic Polyphosphazene Self-assembly And Drug Release Behavior In Vitro

Traditional drug carrier materials have high toxicity and poor solubility.The ideal drug carrier must have good stability,biocompatibility,and specific part targeting capabilities,which is a severe challenge to traditional drug carrier materials.Therefore,the synthesis of amphipathic polyphosphazene drug carriers is of great significance.The amphiphilic polymer nanomicelle is a novel drug carrier.The hydrophilic segment and the hydrophobic segment in the structure form a hydrophilic shell hydrophobic inner shell as a hydrophobic drug container in the aqueous solution,with fewer side effects,increasing Solubility.It self-assembles in aqueous solution to form nanocapsules or nanomicelles.The surface of nanoparticles is modified with polyethylene glycol to prolong the circulation time in vivo.During the long cycle,it is enriched at the tumor site by EPR effect,releasing the drug.By embedding the drug in a physically loaded drug method,the drug can be quickly released in the acidic environment of the tumor.(1)Design and synthesis of amphiphilic polyphosphazene drug carriers with different hydrophilic and hydrophobic ratios:Polyethylene glycol monomethyl ether(MPEG)and GlyPheLeuGlyPheLeu-OEt hexapeptides as raw materials,synthesized by polynuclear substitution reaction with polyphosphazene as backbone Polyethylene glycol monomethyl ether is a hydrophilic segment,and the peptide is a hydrophobic segment of an amphiphilic graft polyphosphazene copolymer.The amphipathic polyphosphazene drug carrier with different pro-hydrophobic ratios was synthesized and its structure was characterized.The micelle behavior in water was studied and the structure of micelles was confirmed.The fluorescence probe method was used to measure MPEG/NP/HP-2.The critical micelle concentration(CMC)of MPEG/NP/HP-3,MPEG/NP/HP-4,MPEG/NP/HP-5,and MPEG/NP/HP-6 in water is proportional to the hydrophilic side The increase of the critical micelle concentration increases in turn;the DFS determination of the hydrodynamic diameters indicates that the particle size also gradually increases with the increase of the MPEG content.Atomic force microscope observation of the self-assembly spherical micelles.(2)Three amphiphilic grafted polyphosphazene embedding drugs with a high proportion of hydrophilic moieties were used to determine drug loading and entrapment efficiency.The drug loadings were 23%,19.12%,and 17.95%,respectively.It is 71.05%,47.81%and 44.88%.Three drug-loaded micelles were measured for CMC and DLS in water to observe the morphology of the hydrodynamic diameter and AFM.After loading the drug,the amphiphilic grafted polyphosphazene particle size was about 200 nm,and the self-assembly was spherical bundle.The cumulative release of amphiphilic grafted polyphosphazene at different pH values after 72 hours of drug loading was determined to be 23.55%and 22.56%at pH 7.4,19.17%,14.98%,14.07%and pH=6.8,respectively.20.21%,when the medium pH=5 was 55.4%,55.09%,52.32%.