In addition to its well-known abortifacient effect, mifepristone (MIF) has been used as an anticancer drug for various cancers in\nmany studies with an in-depth understanding of the mechanism of action. However, application of MIF is limited by its poor water\nsolubility and low oral bioavailability. In this work, we developed a drug delivery system based on chitosan nanoparticles (CNs) to\nimprove its bioavailability and anticancer activity. The MIF-loaded chitosan nanoparticles (MCNs) were prepared by convenient\nionic gelation techniques between chitosan (Cs) and tripolyphosphate (TPP). The preparation conditions, including Cs concentration,\nTPP concentration, Cs/MIF mass ratio, and pH value of the TPP solution, were optimized to gain better encapsulation efficiency\n(EE) and drug loading capacity (DL). MCNs prepared with the optimum conditions resulted in spherical particles with an\naverage size of 200 nm. FTIR and XRD spectra verified that MIF was successfully encapsulated in CNs. The EE and DL of MCNs\ndetermined by HPLC were 86.6% and 43.3%, respectively. The in vitro release kinetics demonstrated that MIF was released from\nCNs in a sustained-release manner. Compared with free MIF, MCNs demonstrated increased anticancer activity in several cancer\ncell lines. Pharmacokinetic studies in male rats that were orally administered MCNs showed a 3.2-fold increase in the area under\nthe curve from 0 to 24 h compared with free MIF. These results demonstrated that MCNs could be developed as a potential delivery\nsystem for MIF to improve its anticancer activity and bioavailability.
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