Piperlongumine-Eluting Gastrointestinal Stent Using Reactive Oxygen Species-Sensitive Nanofiber Mats for Inhibition of Cholangiocarcinoma Cells

Abstract

Background The aim of this study is to fabricate drug-eluting gastrointestinal (GI) stent using reactive oxygen species (ROS)-sensitive nanofiber mats for treatment of cholangiocarcinoma (CCA) cell. A ROS-producing agent, piperlongumine (PL)-incorporated nanofiber mats were investigated for drug-eluting stent (DES) application. Methods Selenocystamine-conjugated methoxy poly(ethylene glycol) (MePEG) was conjugated with poly(L-lactide) (PLA) to produce block copolymer (LEse block copolymer). Various ratios of poly(ε-caprolactone) (PCL) and LEse block copolymer were dissolved in organic solvent with PL, and then nanofiber mats were fabricated by electro-spinning techniques. Results The higher amount of LEse in the blend of PCL/LEse resulted in the formation of granules while PCL alone showed fine nanofiber structure. Nanofiber mats composed of PCL/LEse polymer blend showed ROS-sensitive drug release, i.e., PL release rate from nanofiber mats was accelerated in the presence of hydrogen peroxide (H 2 O 2 ) while nanofiber mats of PCL alone have small changes in drug release rate, indicating that PL-incorporated nanofiber membranes have ROS responsiveness. PL itself and PL released from nanofiber mats showed almost similar anticancer activity against various CCA cells. Furthermore, PL released from nanofiber mats properly produced ROS generation and induced apoptosis of CCA cells as well as PL itself. In HuCC-T1 cell-bearing mice, PL-incorporated nanofiber mats showed improvement in anticancer activity. Conclusion PL-incorporated ROS-sensitive nanofiber mats were coated onto GI stent and showed improved anticancer activity with ROS responsiveness. We suggested PL-incorporated ROS-sensitive nanofiber mats as a promising candidate for local treatment of CCA cells.

Ciprofloxacin-Releasing ROS-Sensitive Nanoparticles Composed of Poly(Ethylene Glycol)/Poly(D,L-lactide-co-glycolide) for Antibacterial Treatment

“…Based on the fact that oxidative stress is increased in UTIs, we have designed a ROS-sensitive nanoparticulate delivery system of CIP for the treatment of UTI. Since diselenide linkages respond to ROS and can be broken in an oxidative stress environment, diselenide linkages were introduced in the copolymer and ROS-sensitive nanoparticles fabricated [ 30 , 31 ].…”

“…Jang et al, reported that nanofiber mats fabricated from ROS-sensitive polymers such as poly(L-lactide) (PLA)-PEG copolymer having diselenide linkages have sensitivity against H 2 O 2 and then released piperlongumine in a ROS-sensitive manner [ 31 ]. They argued that drug release must be also accelerated by piperlongumine since piperlongumine is a ROS-producing agent.…”

Naturally occurring Piper plant amides potential in agricultural and pharmaceutical industries: perspectives of piperine and piperlongumine

“…Another study confirmed that it takes about 17 weeks to decompose about 10% of the piperlongumine formulation at pH 4 in 25 °C conditions. Finally, piperlongumine formulated into ROS-sensitive nanofibers was found to suppress the growth of cholangiocarcinoma cells [51].…”

Bio-Based Electrospun Fibers for Wound Healing

“…Especially, the stimuli-responsive drug delivery systems are promising materials for generating smart wound dressings. These materials, with the ability to tune drug release in response to stimuli of pH [71][72][73][74], temperature [71,75,76], light irradiation [11,75], electric field [77], and oxygen [11,78] hold remarkable promise for wound healing.…”