Formulation, antileukemia mechanism, pharmacokinetics, and biodistribution of a novel liposomal emodin.
Emodin is a multifunctional Chinese traditional medicine with poor water solubility. D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a pegylated vitamin E derivate. In this study, a novel liposomal-emodin-conjugating TPGS was formulated and compared with methoxypolyethyleneglycol 2000-derivatized distearoyl-phosphatidylethanolamine (mPEG2000-DSPE) liposomal emodin. TPGS improved the encapsulation efficiency and stability of emodin egg phosphatidylcholine/cholesterol liposomes. A high encapsulation efficiency of 95.2% ± 3.0%, particle size of 121.1 ± 44.9 nm, spherical ultrastructure, and sustained in vitro release of TPGS liposomal emodin were observed; these were similar to mPEG2000-DSPE liposomes. Only the zeta potential of -13.1 ± 2.7 mV was significantly different to that for mPEG2000-DSPE liposomes. Compared to mPEG2000-DSPE liposomes, TPGS liposomes improved the cytotoxicity of emodin on leukemia cells by regulating the protein levels of myeloid cell leukemia 1 (Mcl-1), B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein, which was further enhanced by transferrin. TPGS liposomes prolonged the circulation time of emodin in the blood, with the area under the concentration-time curve (AUC) 1.7 times larger than for free emodin and 0.91 times larger than for mPEG2000-DSPE liposomes. In addition, TPGS liposomes showed higher AUC for emodin in the lung and kidney than for mPEG2000-DSPE liposomes, and both liposomes elevated the amount of emodin in the heart. Overall, TPGS is a pegylated agent that could potentially be used to compose a stable liposomal emodin with enhanced therapeutics.
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, People's Republic of China.
Tiechuang
T
Wang
Xiaodong
X
Yin
Yaping
Y
Lu
Weiguang
W
Shan
Subin
S
Xiong
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004642:Emodin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011897:Random Allocation; D014018:Tissue Distribution; D014168:Transferrin / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
D000970:Antineoplastic Agents; D008081:Liposomes; D010714:Phosphatidylethanolamines; D014168:Transferrin; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D014810:Vitamin E; D011092:Polyethylene Glycols; D004642:Emodin; C014225:tocophersolan