PEGylated niosomes-mediated drug delivery systems for Paeonol: preparation, pharmacokinetics studies and synergistic anti-tumor effects with 5-FU

• Published in: Journal of liposome research Vol. 27; no. 2; pp. 161 - 170
• Main Authors: He, Rui-Xi, Ye, Xi, Li, Rui, Chen, Wei, Ge, Tao, Huang, Tian-Qing, Nie, Xiang-Jiang, Chen, He-Jun-Tao, Peng, Dai-Yin, Chen, Wei-Dong
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.06.2017
• Subjects: Acetophenones - administration & dosage; Acetophenones - chemistry; Acetophenones - pharmacokinetics; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Screening Assays, Antitumor; Fluorouracil - administration & dosage; Fluorouracil - chemistry; Fluorouracil - pharmacology; Hep G2 Cells; Humans; Liposomes - chemistry; Male; Molecular Structure; Paeonol; PEGylated nonionic surfactant vesicles; pharmacokinetics; Polyethylene Glycols - chemistry; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; synergistic antitumor; Tumor Cells, Cultured; PEGylated nonionic surfactant vesicles; pharmacokinetics; Paeonol; synergistic antitumor
• ISSN: 0898-2104; 1532-2394
• DOI: 10.1080/08982104.2016.1191021

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 (t 1/2 , 87.5 versus 17.0 min) and increased area under the concentration-time curve (AUC 0-t , 38.0 versus 19.48 μg/ml*min) compared to Paeonol solution. Formulated Paeonol had superior cytotoxicity versus the free drug with IC 50 values 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.