Preparation Of Drug-Loading Performance Of Polyurethane Nano-Micelles

In the treatment of cancer,most chemotherapeutics have many defects such as poor water solubility,non-targeting,and easy degradation.Polyurethane(PU),as a simple preparation method,easy to "cut",is the first choice for preparing polymer micelles.In this paper,various structures of polyurethane micelles are designed for the controlled release of doxorubicin(DOX).By systematically designing the polyurethane and building the functionality of the micelle system,it has laid the foundation for the development and research of nano-drug carriers.(1)According to the properties of hydrophobic drugs,an amphiphilic linear block polyurethane copolymer m PEG-PU-m PEG was synthesized for DOX delivery.The CMC value of this polyurethane copolymer is 0.8-1.72 mg / L,indicating that m PEG-PU-m PEG can still self-assemble into micelles at low concentrations.The particle size of m PEG-PU-m PEG micelles is 100-170 nm,which is spherical.The drug-loaded micelles at p H 7.4 were significantly inferior to the release effect at p H 5.0.The CCK-8 method was used to test the toxicity of polymer materials and DOX-loaded micelles on Hep G2 cells.It was found that m PEG-PU-m PEG had good biocompatibility,and the inhibition of cells by DOX-loaded micelles increased..At the highest concentration,Hep G2 cells only had a survival rate of 21%.(2)Aiming at the difference in the reduction potential between the normal environment of the human body and the tumor site,by introducing disulfide bonds into the structure,a reduction-responsive amphiphilic block polyurethane copolymer m PEG-PU(SS)-m PEG micelles for delivery of the anticancer drug DOX.Under the condition of p H 5.0 + 10 Mm DTT,the micelles decompose quickly within 24 hours.At the same time,the micelles loaded with DOX had good blood stability,and the micelle structure was still intact after being treated in 50% fetal bovine serum solution for 48 h.At p H 7.4,the release behavior of the drug is simulated,at 48 h,11% of the drug was released.In a simulated tumor cell environment(p H 5.0 + 10 m M DTT),due to the disulfide bond,The fragmentation caused the disintegration of the micelle structure,and the cumulative release reached 62.3% at 48 h.It can be seen that the introduction of disulfide bonds makes the micelles significantly responsive in the reducing environment,effectively promoting the drug release.(3)In order to improve the LC,EE,a reduction-responsive polyurethane copolymer m PEG-PU(SS-COOH)-m PEG containing carboxyl groups was designed and synthesized for the hydrophobic drug DOX.Releasing.This polymer with carboxyl structure can significantly improve the encapsulation efficiency(EE)and drug loading(LC)of micelles.The results of in vitro drug release experiments show that the release of m PEG-PU(SS-COOH)-m PEG-loaded DOX micelles has a good reduction response.The cumulative release was 63.8% at p H 5.0 + 10 m M DTT.The in vitro cytotoxicity test showed that m PEG-PU(SS-COOH)-m PEG itself had low cytotoxicity,while the DOX micelles were more toxic to Hep G2 cells,which significantly inhibited cell proliferation and growth.