title: PEGylated long circulating nanostructured lipid carriers for Amoitone B: preparation, cytotoxicity and intracellular uptake.
abstract: Amoitone B is a newly synthesized derivative of antitumor drug cytosporone B, which exhibits excellent anticancer activity in vivo. Nevertheless, the water-insolubility and short biological half-life limit its further development. In the present study, polyethylene glycol-modified, Amoitone B-loaded long circulating nanostructured lipid carriers (AmB-PEG-NLC) were prepared by the emulsion-evaporation and low temperature-solidification method. The in vitro antitumor activity and intracellular uptake of AmB-PEG-NLC in the human colon cancer SW620 cells and liver cancer HepG2 cells were evaluated in detail. MTT assay was employed to investigate the inhibition effect on cellular viability. Propidium iodide and DAPI staining were performed to visually examine the fluorescent morphology changes of the cells incubated with AmB-PEG-NLC. Flow cytometry was utilized to determine the influence of AmB-PEG-NLC on apoptosis of SW620. The intracellular uptake was observed by rhodamine B, a fluorescent maker. Cytotoxicity assay, observation of morphological changes and apoptosis examination revealed that AmB-PEG-NLC could markedly enhance the cytotoxicity of AmB against cancer cell compared to AmB solution and AmB-NLC. An increased uptake of PEG-NLC was obtained compared with NLC in SW620 cells, which might attribute to the effect of PEG. Based on these results, AmB-PEG-NLC could be a promising delivery system for AmB with effective cancer therapy.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Luan
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Medicine and Nursing, Dezhou University, Dezhou 253023, China.
authors.forename: Lianjun
authors.initials: L
authors.lastname: Chu
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China. Electronic address: professorgxzhai@126.com.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D004337:Drug Carriers / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D010648:Phenylacetates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010648:Phenylacetates; C576231:n-amyl 2-(3,5-dihydroxy-2-(1-nonanoyl)phenyl)acetate; D011092:Polyethylene Glycols
keywords: Amoitone B; Apoptosis; Intracellular uptake; Nanostructured lipid carriers; PEG