Improved anti-tumor efficacy and pharmacokinetics of bufalin via PEGylated liposomes

Jia-ni YUAN＊,Xuan-xuan ZHOU＊,Wei CAO,Lin-lin BI,Yi-fang ZHANG,Qian YANG,Si-wang WANG

(1.Department of Natural Medicine&Institute of Materia Medica,School of Pharmacy,The Fourth ilitary Medical University,Xi′an,China;2.Shaanxi Pharmaceutical Development Center,Xi′an,China)

T1-39

Improved anti-tumor efficacy and pharmacokinetics of bufalin via PEGylated liposomes

Jia-ni YUAN1＊,Xuan-xuan ZHOU1＊,Wei CAO1,Lin-lin BI1,Yi-fang ZHANG2,Qian YANG1,Si-wang WANG1

(1.Department of Natural Medicine&Institute of Materia Medica,School of Pharmacy,The Fourth ilitary Medical University,Xi′an,China;2.Shaanxi Pharmaceutical Development Center,Xi′an,China)

OBJECTIVETo determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODSBufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method.The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique.The direct imaging of morphology of liposomes was charactered by transmission electron microscope.The content of bufalin in liposomes was analysed by HPLC method.The entrapment eff i ciency and the particle size was applied to assess the stability profile,after storage at 4℃on day 0,7,15,30 and 90.The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃.In-vitro cytotoxicity studies were carried out using MTT〔3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide〕assay on several kinds of tumor cell lines including SW620,PC-3,MDA-MB-231,A549,U251,U87 and HepG2.In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method.RESULTSTheir mean particle sizes were 127.6 nm and 155.0 nm,mean zeta potentials were 2.24 mV and-18.5 mV,entrapment efficiencies were 76.31%and 78.40%,respectively.In-vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes.The cytotoxicity of blank liposomes has been found within acceptable range,whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity.In-vivo pharmacokinetics indicated that bufalinloaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats.CONCLUSIONThe results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.

bufalin;PEGylated liposome;high pressure homogenization;pharmacokinetics

＊Co-first author.

The Project Supported by Overall Innovation Plan Projects of Science and Technology of Shaanxi Province in China(2015KTZDSF02-01-02)

Qian YANG,E-mail:12154521@qq.com,Tel:(029)84773265;Si-wang WANG,E-mail:wangsiw@fmmu.edu.cn,Tel:(029)84772519,Fax:(029)83224790