title: A smart hydrogel-based time bomb triggers drug release mediated by pH-jump reaction.
abstract: We demonstrate a timed explosive drug release from smart pH-responsive hydrogels by utilizing a phototriggered spatial pH-jump reaction. A photoinitiated proton-releasing reaction ofo-nitrobenzaldehyde (o-NBA) was integrated into poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) (P(NIPAAm-co-CIPAAm)) hydrogels.o-NBA-hydrogels demonstrated the rapid release of protons upon UV irradiation, allowing the pH inside the gel to decrease to below the pKavalue of P(NIPAAm-co-CIPAAm). The generated protons diffused gradually toward the non-illuminated area, and the diffusion kinetics could be controlled by adjusting the UV irradiation time and intensity. After irradiation, we observed the enhanced release of entrapped L-3,4-dihydroxyphenylalanine (DOPA) from the gels, which was driven by the dissociation of DOPA from CIPAAm. Local UV irradiation also triggered the release of DOPA from the non-illuminated area in the gel via the diffusion of protons. Conventional systems can activate only the illuminated region, and their response is discontinuous when the light is turned off. The ability of the proposed pH-jump system to permit gradual activation via proton diffusion may be beneficial for the design of predictive and programmable devices for drug delivery.
authors.affiliation: Department of Materials Engineering, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan; Biomaterials Unit, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.
authors.forename: Prapatsorn
authors.initials: P
authors.lastname: Techawanitchai
authors.affiliation: Biomaterials Unit, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.
authors.forename: Naokazu
authors.initials: N
authors.lastname: Idota
authors.affiliation: Biomaterials Unit, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Uto
authors.affiliation: Biomaterials Unit, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ebara
authors.affiliation: Department of Materials Engineering, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan; Biomaterials Unit, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Aoyagi
keywords: pH-jump reaction; pH-responsive hydrogels; photoacid generators (PAGs); smart polymers; time bomb