Investigation Of β-cyclodextrin Polymers For Solubilization And Targeted Delivery Of Docetaxel

Cancer is one of the major diseases worldwide,and chemotherapy is a common method of cancer treatment.However,most of the existing chemotherapeutic drugs have problems such as poor targeting,large toxic and side effects,low water solubility,and storage intolerance,which limit their clinical applications.As an emerging drug delivery carrier,the cyclodextrin supramolecular drug delivery system exhibits the characteristics of easy preparation,good solubilization effect,and high biological safety,and has broad application prospects in biomedicine.The internal hydrophobic cavity of cyclodextrin can form complexes with guest molecules(small molecules,linear or branched polymers,etc.)in aqueous solution or solid state to carry out drug entrapment and functionalization.Based on these,this paper selects β-cyclodextrin polymer as the carrier,and uses the hostguest interaction between the cyclodextrin and the drug and the hydrophobic interaction between the drug molecules to form nanoparticles.The lyophilized powder of self-assembled nanoparticles(SSNP)containing docetaxel(DTX)coated with β-cyclodextrin polymer was prepared,and the selective killing ability of the targeted nanoparticles on cancer cells was investigated.Specifically completed the following two aspects of research work:1.Based on the host guest interaction between β-cyclodextrin polymer and drug DTX,a simple self-assembly strategy was used to encapsulate drug DTX,and a kind of self-assembly nanoparticles was prepared,its cytotoxicity to tumor cells was investigated.The results show that:(1)Among the six β-cyclodextrin polymers synthesized in this article,the linear β-cyclodextrin polymer(β-CDP-JS2)with a molecular weight of about 73 k has the best solubilization effect on DTX: 40 mg/m L β-CDP-JS2 aqueous solution can dissolve 6 mg/m L DTX,and the solution remains stable within 8 hours after being lyophilized and reconstituted;(2)The carrier β-CDP-JS2 has good biocompatibility,when the concentration reaches 2.5 m M(2.6 mg/m L),the cell survival rate is still above 89%;(3)The use of the carrier β-CDP-JS2 did not reduce the cytotoxicity of docetaxel.2.After the successful preparation of cyclodextrin polymer(β-CDP-JS2)loaded DTX selfassembled nanoparticles,in order to provide targeting effect for SSNP,the host guest interaction between adamantane which modified on aptamers and cyclodextrin polymer was used to connect the targeted molecule(AS1411)to SSNP.The effects of two different synthesis methods on the properties of the nanoparticles were investigated: after SSNP was prepared,aptamer was directly added to prepare freeze-dried powder(one-step method);first prepare the lyophilized powder of SSNP,and then add aptamer for targeting after reconstitution(two-step method).The results showed that:(1)the self-assembled nanoparticles lyophilized powders prepared by these two methods had good stability,remained in the particle state within 8 hours,and the encapsulated DTX did not leak;(2)The targeted self-assembled nanoparticles prepared by these two methods showed selective binding and killing effects on target cells.