Design and evaluation of pH-sensitive liposomes constructed by poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate for doxorubicin delivery

摘要: In this study, a novel material, poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate (PEtOz-CHEMS), was synthesized to construct pH-sensitive liposomes. The structure of PEtOz-CHEMS confirmed by thin-layer chromatography, Fourier transform infrared spectroscopy, and (1)H NMR. Anticancer fluorescent drug doxorubicin (DOX) encapsulated into the Compared with conventional liposomes (CL), CHEMS modified (CH-L) PEGylated (PEG-L), PEtOzylated (PEtOz-L) showed an acidic pH-induced increase in particle size. At pH 6.4, heme release PEtOz-L group close that positive control group, whereas CL, CH-L PEG-L negative group. vitro studies demonstrated DOX released from pH-dependent manner, (CL-DOX), loaded (CH-DOX-L) (PEG-DOX-L) had no pronounced differences under each medium. cellular uptake assays PEtOz-DOX-L indicated significant fluorescence intensity at 6.4 compared 7.4. CL-DOX, CH-DOX-L PEG-DOX-L did not achieve any obvious diversity different conditions. Confocal laser scanning microscopy images can fuse endosomal membrane conditions endosome, cytoplasm, then gather nucleus. Therefore, PEtOz help "endosomal escape". cytotoxicity experiment results on A375 cells resulted lower cell viability than low These confirm pH-responsive promising material for intracellular targeted delivery system might be used overcoming "PEG dilemma".