Amphiphilic Polymers Based On β-cyclodextrin: Synthesis, Characterization And As Drug Delivery Systems

In this work a series of amphiphilic polymers based onβ-CD (β-CD-PLA-mPEG)were synthesized by introducing the methoxyl poly(ethylene glycol)-polylactide(mPEG-PLA)diblock copolymer to the primary hydroxyl group positions onβ-CD.The chemical structures of polymers were characterized by FTIR,~1H NMR and size exclusion chromatograph(SEC).From the results of pyrene fluorescence measurement,it was confirmed that these amphiphilic polymers could self-assemble in aqueous media to form micelles.In addition,the critical micelle concentration(CMC)of the polymers can be regulated from 0.065mg/ml to 0.0032mg/ml by increasing the PLA length to ensure the stability of micelles.Doxorubicin(DOX),as a model drug,was physically loaded into micelles by o/w emulsion method or dialysis method.The effects of methods on drug loading content and entrapment efficiency were investigated.It was found that the drug loading content and entrapment efficiency were both higher when o/w emulsion was employed.For o/w emulsion method,the effects of polymer/drug feed ratio and polymer composition were investigated.The drug loading content was increasing with increasing length of hydrophobic PLA segment.TEM image demonstrated thatβ-CD-PLA-mPEG polymeric micelles were regularly spherical without drug loaded,and when loaded with DOX,they were changed into spindle. The drug loaded micelles size was smaller than that without drug loaded,with the mean diameters of 100～300nm.The in vitro release profiles indicated that DOX-release from micelles was accelerated by decreasing pH,which was quite suited to the physical microenvironment of tumor tissues.In addition,the release rate decreased as increasing length of hydrophobic PLA segment and drug loading content.The MTT assay was used to test cellular cytotoxicity ofβ-CD-PLA-mPEGs in vitro.It showed that the amphiphilic polymer based onβ-CD has good biocompatibility.The cytotoxicity of DOX-loaded micelles compared to that of free DOX was determined by MTT method combined with flow cytometry and confocal laser microscope.It showed that with the growth of hydrophobic chain PLA,the cytotoxicity of drug loaded micelles was enhanced.Compared to free DOX,DOX-loaded micelles showed markedly improved the cytotoxicity to MCF-7/ADR cells,which indicated that it can some extent reverse the drug resistance.These results suggest that the amphiphilic polymers based onβ-CD exhibit potentials as anti-cancer drug delivery system through passive targeting,it is worth in-depth study.