Reactive Oxygen Species (ROS), while biologically necessary at homeostatic levels, can lead to severe impairments when in excess, such as during uncontrolled inflammation. ROS can be scavenged with i.e. sulfur (-II)-based polymers, that can be formulated as nano-objects (high density of active groups per mass), water soluble/dispersible polymers, patches for dermal application or microcapsules. Poly(propylene sulfide) (PPS) has been found to be responsive to hypochlorite, hydroxyl radicals and hydrogen peroxide, while poly(thioacetal) (PTA) reacts quickly also with superoxide anions. Thus, their combination into copolymers with various primary structures (multi-block, statistical, alternating) and compositions (repartition of sulfur-containing groups between thioethers and thioacetals) allows a simultaneous and efficient scavenging of a wide range of the ROS spectrum, translatable to intra or extracellular removal according to the administration route. Herein we present a synthetic strategy reaching number average molecular weights up to 20 kDa, based on a combination of anionic ring opening and step-growth polymerizations. Copolymerization between polymers (each with a typical distribution of molecular weights) implicated several challenges due to solubility, reduced chain reactivity and stoichiometric control. The resulting copolymers were then formulated as nanoemulsions able to stoichiometrically reduce ROS levels in an aqueous environment, while their hydrolysis allowed a fine tuning of the hydrophilic-lipophilic balance yielding amphiphilic, functionalizable materials that were enclosed into biocompatible microcapsules for macrophage targeting. Finally, copolymers end-capped with acrylates were used to produce stable, cross-linked nanoparticles that showed a reduced scavenging activity of ROS compared to that of nanodroplets. All copolymers were also prepared as high internal phase emulsions that were cross-linked resulting in highly porous materials (foams).
Macromolecular and colloidal systems for responsive release in anti-inflammatory therapies
CORADELLO, GIULIA
2024-03-26
Abstract
Reactive Oxygen Species (ROS), while biologically necessary at homeostatic levels, can lead to severe impairments when in excess, such as during uncontrolled inflammation. ROS can be scavenged with i.e. sulfur (-II)-based polymers, that can be formulated as nano-objects (high density of active groups per mass), water soluble/dispersible polymers, patches for dermal application or microcapsules. Poly(propylene sulfide) (PPS) has been found to be responsive to hypochlorite, hydroxyl radicals and hydrogen peroxide, while poly(thioacetal) (PTA) reacts quickly also with superoxide anions. Thus, their combination into copolymers with various primary structures (multi-block, statistical, alternating) and compositions (repartition of sulfur-containing groups between thioethers and thioacetals) allows a simultaneous and efficient scavenging of a wide range of the ROS spectrum, translatable to intra or extracellular removal according to the administration route. Herein we present a synthetic strategy reaching number average molecular weights up to 20 kDa, based on a combination of anionic ring opening and step-growth polymerizations. Copolymerization between polymers (each with a typical distribution of molecular weights) implicated several challenges due to solubility, reduced chain reactivity and stoichiometric control. The resulting copolymers were then formulated as nanoemulsions able to stoichiometrically reduce ROS levels in an aqueous environment, while their hydrolysis allowed a fine tuning of the hydrophilic-lipophilic balance yielding amphiphilic, functionalizable materials that were enclosed into biocompatible microcapsules for macrophage targeting. Finally, copolymers end-capped with acrylates were used to produce stable, cross-linked nanoparticles that showed a reduced scavenging activity of ROS compared to that of nanodroplets. All copolymers were also prepared as high internal phase emulsions that were cross-linked resulting in highly porous materials (foams).File | Dimensione | Formato | |
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phdunige_4963927_1.pdf
embargo fino al 26/03/2025
Descrizione: Pages 0:209; cover, table of contents, abbreviation list, abstract, declaration and copyright statement, general introduction and state of the art, aims and objectives, results and discussion section 1
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phdunige_4963927_2.pdf
embargo fino al 26/03/2025
Descrizione: Pages 210:375; results and discussion section 2:5, conclusions and outlook, acknowledgements, list of publications
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15.65 MB
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