title: Synthesis, characterization, in vitro and in vivo evaluation of PEGylated oridonin conjugates.
abstract: Oridonin (ORI), a diterpenoid compound with promising antitumor activity, was proved to possess potent antileukemia efficacies in vitro and in vivo recently. However, the development and application of ORI was limited by its poor solubility and rapid plasma clearance. The purpose of this study was to solve these problems. PEGylated oridonin linked with succinic acid (SA) as spacer moiety (PEG-SA-ORI conjugate) was synthesized. mPEG amines with four specifications of molecular weight (MW) were utilized. All polymeric conjugates showed satisfactory aqueous solubility and in vitro studies implied that the drug solubility and release features of conjugates were relevant to PEGs. The drug solubility increased more when the MW of PEG was lower, while more significant sustained-release effect was shown with higher PEG MW. Moreover, the release behaviors of conjugates showed a pH-sensitive property. In vivo pharmacokinetic studies demonstrated that the elimination half-life was prolonged in comparison with ORI solution. PEGylation could be a promising method to obtain better efficacy in the field of drug delivery system.
authors: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, PR China.
authors: Jingyi
authors: J
authors: Shen
authors: Dianrui
authors: D
authors: Zhang
authors: Zhongxi
authors: Z
authors: Zhao
authors: Lejiao
authors: L
authors: Jia
authors: Dandan
authors: D
authors: Zheng
authors: Guangpu
authors: G
authors: Liu
authors: Leilei
authors: L
authors: Hao
authors: Qiang
authors: Q
authors: Zhang
authors: Xiaona
authors: X
authors: Tian
authors: Caiyun
authors: C
authors: Li
authors: Hejian
authors: H
authors: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D045786:Diterpenes, Kaurane / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D019802:Succinic Acid / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; C011959:oridonin; D011092:Polyethylene Glycols; D019802:Succinic Acid
keywords: Conjugation; Drug delivery systems; Oridonin; Pharmacokinetics; Poly(ethylene glycol); Synthesis