title: Biodegradable self-assembled MPEG-PCL micelles for hydrophobic oridonin delivery in vitro.
abstract: The great potential of oridonin (ORI) for clinical application in cancer therapy is greatly limited due to its poor water-solubility. The purpose of this study was to increase the water solubility of oridonin using monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (MPEG-PCL) as drug carrier. The ORI-loaded MPEG-PCL micelles were prepared by thin film hydration method. The obtained ORI-micelles could be lyophilized into powder form, which could be re-dissolved in water to form homogeneous solution. This study showed that ORI was successfully incorporated in the core-shell structure of MPEG-PCL micelles and maintained its anticancer activity. The average particle size was 25.55 +/- 0.10 nm and the mean zeta potential was -4.71 +/- 0.05 mV. The actual drug loading and encapsulation efficiency were 7.99 +/- 0.03% and 99.51 +/- 0.34%, respectively. ORI could be released from MPEG-PCL micelles in a sustained manner in vitro. The permeation profiles of ORI from ORI-micelles and ORI water saturated solution through excised mouse skin demonstrated that ORI-micelles showed much better transdermal penetration performance than ORI water saturated solution. The prepared ORI-micelles have great potential for both direct intravascular administration and being further developed as a transdermal drug delivery system in cancer chemotherapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Bingxin
authors.initials: B
authors.lastname: Xue
authors.forename: Yingjing
authors.initials: Y
authors.lastname: Wang
authors.forename: XiaoHai
authors.initials: X
authors.lastname: Tang
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Yujun
authors.initials: Y
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.forename: Chunjie
authors.initials: C
authors.lastname: Wu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Qian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D012995:Solubility; D014867:Water
chemical_list: D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D014867:Water; C011959:oridonin; D011092:Polyethylene Glycols