Development of a shape‐controlled H₂S delivery system using epoxide‐functional nanoparticles

Abstract

Hydrogen sulfide (H2S), an endogenous modulator of signaling processes, has potential as a therapeutic drug or in combination drug therapies. Due to its broad biological impacts and malodorous nature, there is considerable interest in vehicles capable of delivering H2S in a controlled manner. Herein, we report postpolymerization modification of polymers incorporating glycidyl methacrylate (GMA) units to form thiol‐triggered macromolecular H2S donors. By combining this approach with polymerization‐induced self‐assembly, this methodology allows the facile preparation of polymeric nanoparticulate donors with either spherical or worm‐like morphology. The thiol‐reactive epoxide functional groups in poly(GMA) were chemically transformed into acyl‐protected perthiol groups using a three‐step procedure throughout which both morphologies remained intact. The H2S releasing properties were subsequently studied, with both spherical and worm‐like nanoparticulate donors shown to successfully release H2S in the presence of the model thiol, l‐cysteine. In addition, the donor polymers were shown to effectively increase H2S inside cells, upon exposure to biologically relevant endogenous thiol levels. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1982–1993

Synthesis and Evaluation of Multifunctional Anionic Initiators Based on n‐BuLi and Meta‐Diisopropenyl Benzene

“…Multifunctional anionic and organometallic initiators used in the polymerization of vinyl compounds or dienes can be synthesized by reacting an organolithium with unsaturated aromatic compounds. Many authors [2,[8][9][10] showed, however, that these reactions might lead to the formation of insoluble compounds, when performed in non-polar media, such as cyclohexane, due to association, oligomerization and formation of aggregates. [5] However, certain additives, such as tertiary amines, can prevent the formation of insoluble crosslinked compounds.…”

“…[7] The synthesis of bifunctional initiators is often performed by reacting diolefins with n-BuLi in non-polar solvents, such as cyclohexane. However, this technique does not necessarily result in soluble bifunctional initiators with well defined molecular architecture, [8][9][10] also generating initiator fractions that contain more than two active centers and allowing for undesired diolefin oligomerization. [11] Besides, the possible reincorporation of unsaturated chains and chain agglomeration can lead to formation of insoluble fractions that are very poorly reactive.…”

Intelligent polymeric hydrogen sulfide delivery systems for therapeutic applications

“…Though lots of small molecular H 2 S donors have been developed, they usually unable to meet the requirements of in vivo applications, since the stability, water solubility, stimuli-responsive property, and toxicity of donors themselves or their byproducts are difficult to regulate at the small molecule level [ 27 ]. With the purpose to overcome these limits, various biocompatible polymers are utilized to establish H 2 S delivery systems, mainly by physically encapsulating or chemically conjugating H 2 S donors with polymeric carriers such as micelles [ 28 , 29 ], liposomes [ 30 ], nanoparticles [ 31 ], nanofibers [ 32 ], or hydrogels [ 33 ]. The main advantage of these polymeric H 2 S delivery systems is that the H 2 S releasing behaviors including releasing dosage, releasing kinetics, as well as releasing locations are effectively regulated and the biocompatibility is significantly improved without drastically changing the chemical properties of the loaded H 2 S donors.…”

An Exciting Time for Polymer Chemists in Australia

“…A novel monomer, 2,2,2‐trifluoroethylamide l ‐arginine methacrylamide, was prepared and copolymerised to yield amphiphilic block copolymers, which can self‐assemble in water to yield micelles. Quinn, Davis, and co‐workers have utilised polymer nanoparticles for the delivery of hydrogen sulphide. The authors report a post‐modification approach utilising glycidyl functionalities as targets to form macromolecular hydrogen sulphide donors.…”