title: PEGylated niosomes-mediated drug delivery systems for Paeonol: preparation, pharmacokinetics studies and synergistic anti-tumor effects with 5-FU.
abstract: This work describes the preparation of a PEGylated niosomes-mediated drug delivery systems for Paeonol, thereby improving the bioavailability and chemical stability of Paeonol, prolonging its cellular uptake and enhancing its synergistic anti-cancer effects with 5-Fu. PEGylated niosomes, which are prepared from biocompatible nonionic surfactant of Spans 60 and cholesterol, and modified with PEG-SA. Pae-PEG-NISVs were evaluated in vitro and in vivo. The cytotoxicity of Pae-PEG-NISVs was investigated against HepG2 cells. Fluorescence microscope was used to detect the apoptotic morphological changes. Growth inhibition assays were carried out to investigate whether Pae-PEG-NISVs could enhance the antiproliferative effects of Pae co-treated with 5-FU on HepG2 cells. The optimized Pae-PEG-NISVs had mean diameters of approximately 166 nm and entrapment efficiency (EE) of 61.8%. Furthermore, the in vitro release study of Paeonol from PEGylated niosomes exhibited a relatively prolonged release profile for 12 h. Pharmacokinetic studies in rats after i.v. injection showed that Pae-PEG-NISVs had increased elimination half-lives (t1/2, 87.5 versus 17.0 min) and increased area under the concentration-time curve (AUC0-t, 38.0 versus 19.48 μg/ml*min) compared to Paeonol solution. Formulated Paeonol had superior cytotoxicity versus the free drug with IC50values of 22.47 and 85.16 μg/mL at 24 h on HepG2 cells, respectively, and we found that low concentration of Pae-PEG-NISVs and 5-Fu in conjunction had obviously synergistic effect. Our results indicate that the PEG-NISVs system has the potential to serve as an efficient carrier for Paeonol by effectively solubilizing, stabilizing and delivering the drug to the cancer cells.
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: Rui-Xi
authors.initials: RX
authors.lastname: He
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Ye
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ge
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: Tian-Qing
authors.initials: TQ
authors.lastname: Huang
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: Xiang-Jiang
authors.initials: XJ
authors.lastname: Nie
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: He-Jun-Tao
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: Dai-Yin
authors.initials: DY
authors.lastname: Peng
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , Anhui , PR China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Chen
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008297:Male; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D008081:Liposomes; C013638:paeonol; D011092:Polyethylene Glycols; D005472:Fluorouracil
keywords: PEGylated nonionic surfactant vesicles; Paeonol; pharmacokinetics; synergistic antitumor