title: Hindered disulfide bonds to regulate release rate of model drug from mesoporous silica.
abstract: With the advancement of drug delivery systems based on mesoporous silica nanoparticles (MSNs), a simple and efficient method regulating the drug release kinetics is needed. We developed redox-responsive release systems with three levels of hindrance around the disulfide bond. A model drug (rhodamine B dye) was loaded into MSNs' mesoporous voids. The pore opening was capped with β-cyclodextrin in order to prevent leakage of drug. Indeed, in absence of a reducing agent the systems exhibited little leakage, while the addition of dithiothreitol cleaved the disulfide bonds and enabled the release of cargo. The release rate and the amount of released dye were tuned by the level of hindrance around disulfide bonds, with the increased hindrance causing a decrease in the release rate as well as in the amount of released drug. Thus, we demonstrated the ability of the present mesoporous systems to intrinsically control the release rate and the amount of the released cargo by only minor structural variations. Furthermore, an in vivo experiment on zebrafish confirmed that the present model delivery system is nonteratogenic.
authors.affiliation: National Institute of Chemistry, Hajdrihova ul. 19, SI-1001 Ljubljana, Slovenia.
authors.forename: Peter
authors.initials: P
authors.lastname: Nadrah
authors.forename: Uroš
authors.initials: U
authors.lastname: Maver
authors.forename: Anita
authors.initials: A
authors.lastname: Jemec
authors.forename: Tatjana
authors.initials: T
authors.lastname: Tišler
authors.forename: Marjan
authors.initials: M
authors.lastname: Bele
authors.forename: Goran
authors.initials: G
authors.lastname: Dražić
authors.forename: Mojca
authors.initials: M
authors.lastname: Benčina
authors.forename: Albin
authors.initials: A
authors.lastname: Pintar
authors.forename: Odon
authors.initials: O
authors.lastname: Planinšek
authors.forename: Miran
authors.initials: M
authors.lastname: Gaberšček
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D004625:Embryo, Nonmammalian; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D008956:Models, Chemical; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010084:Oxidation-Reduction; D012235:Rhodamines / Q000737:chemistry / Q000493:pharmacokinetics; D012822:Silicon Dioxide / Q000737:chemistry*; D018675:Toxicity Tests; D015027:Zebrafish; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004220:Disulfides; D004337:Drug Carriers; D005456:Fluorescent Dyes; D012235:Rhodamines; D047392:beta-Cyclodextrins; D012822:Silicon Dioxide; C029773:rhodamine B