title: Pharmacokinetics of silybin nanoparticles in mice bearing SKOV-3 human ovarian carcinoma xenocraft.
abstract: The particle fabrication technique was used to fabricate monodisperse size and shape specific poly (lactide-co-glycolide) particles loaded with the silybin. Response surface methodology (RSM) using the central composite rotatable design (CCRD) model was used to optimize formulations of silybin nanoparticles. Further the optimized nanoparticles are characterized for particle size, zeta potential, surface morphology, entrapment efficiency, in-vitro drug release, silybin availability for tumor, plasma, lung, spleen, liver were determined. The significant findings were the optimal formulation of PLGA concentration 10 mg, PVA concentration 2000 and PET width of 6 gave rise to the EE of 88%, mean diameter of 223 nm and zeta potential of 25-mV. Release studies were investigated at pH 1.2 and pH 6.8. It was studied that lower the pH, faster the release of sylibin. The nanoparticles had~15-fold higher plasma exposure as measured by AUC contrasted to pure silybin. The nanoparticles had a 60% increase altogether tumor silybin presentation contrasted with pure silybin. Nanoparticles had higher silybin presentation in the spleen and liver contrasted with pure silybin suspension as expected for a nanoparticle formulation. The lung silybin presentation for the nanoparticle was additionally 2-fold higher than that of the pure silybin suspension. The results of pharmacokinetic parameters and oral bioavailability data exhibited that drug-nanoparticle complex could enhance the oral absorption of silybin and as well as the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.
authors.forename: Xin-Lei
authors.initials: XL
authors.lastname: Guan
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.
authors.forename: Shu-Zhen
authors.initials: SZ
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.
authors.forename: Rui-Jie
authors.initials: RJ
authors.lastname: Hou
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.
authors.forename: Quan-Le
authors.initials: QL
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.
authors.forename: Shan-Lan
authors.initials: SL
authors.lastname: Yin
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, Henan Province, China.
authors.forename: Shi-Jin
authors.initials: SJ
authors.lastname: Wang
keywords: Silybin; nanoparticle; ovarian cancer; pharmacokinetics; response surface methodology