Optimization of preparation and antitumor activity of PEGylated dendrimer loaded cabazitaxel
Objective To prepare PEGylated dendrimer delivery micelles(mPEG-PAMAM)with high efficiency delivery of cabazitaxel(CTX),and optimize its formulation and preparation.Methods mPEG-PAMAM micelles were obtained by the Michael addition reaction of polyamide-amine dendrimer(PAMAM)with PEG.After the drug loading by nanoprecipitation method,the structure of mPEG-PAMAM was identified by IR and 1H NMR.The morphology,particle size and potential of the drug-loaded micelles were observed by transmission electron microscope and dynamic light scattering,and the drug loading and encapsulation efficiency were determined by HPLC.The cytotoxicity was determined by MTT assay and the cellular uptake of drug-loaded micelles by confocal microscopy.The mouse tumor model was established by injecting RM-1 prostate cancer cells at the animal level to determine the overall tumor inhibition ability.Results mPEG-PAMAM@CTX micelles had regular sphere with an average particle size of(162.8±0.7)nm,drug loading of 6.58%,and encapsulation efficiency of 61.12%.The drug release reached 86.8%within 48 h.mPEG-PAMAM@CTX had good cell uptake and effectively killed tumor cells.In the in vivo animal models,CTX mainly enriched in the tumor site through in vivo circulation,indicating efficient delivery of CTX to RM-1 tumor tissue by mPEG-PAMAM micelles,with the tumor inhibition rate of 68.97%.Conclusion The mPEG-PAMAM@CTX micellar prepared in this study can effectively improve the solubility of CTX and enhance tumor inhibiton,which provides new ideas for the development of drug delivery with poor solubility.
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