title: Chitosan-based nanoparticles for improved anticancer efficacy and bioavailability of mifepristone.
abstract: In addition to its well-known abortifacient effect, mifepristone (MIF) has been used as an anticancer drug for various cancers in many studies with an in-depth understanding of the mechanism of action. However, application of MIF is limited by its poor water solubility and low oral bioavailability. In this work, we developed a drug delivery system based on chitosan nanoparticles (CNs) to improve its bioavailability and anticancer activity. The MIF-loaded chitosan nanoparticles (MCNs) were prepared by convenient ionic gelation techniques between chitosan (Cs) and tripolyphosphate (TPP). The preparation conditions, including Cs concentration, TPP concentration, Cs/MIF mass ratio, and pH value of the TPP solution, were optimized to gain better encapsulation efficiency (EE) and drug loading capacity (DL). MCNs prepared with the optimum conditions resulted in spherical particles with an average size of 200 nm. FTIR and XRD spectra verified that MIF was successfully encapsulated in CNs. The EE and DL of MCNs determined by HPLC were 86.6% and 43.3%, respectively. The in vitro release kinetics demonstrated that MIF was released from CNs in a sustained-release manner. Compared with free MIF, MCNs demonstrated increased anticancer activity in several cancer cell lines. Pharmacokinetic studies in male rats that were orally administered MCNs showed a 3.2-fold increase in the area under the curve from 0 to 24 h compared with free MIF. These results demonstrated that MCNs could be developed as a potential delivery system for MIF to improve its anticancer activity and bioavailability.
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wu
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Yazhen
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Xiping
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Huang
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Lv
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Chen
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang, 310018, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Liu
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
keywords: anticancer; chitosan; drug delivery; mifepristone; nanoparticles; pharmacokinetics; sustained release