In situ-forming hydrogels based on the Schiff-base chemistry are promising for drug delivery applications, thanks to their stability under physiological conditions, injectability, self-healing properties, and pH-responsiveness. In this work, two water-soluble poly(ethylene glycol)-based poly(ether urethane)s (PEUs) were engineered. A high-molecular-weight PEU (SHE3350, Mn 24 kDa, D 1.7), bearing primary amino groups along each polymeric chain, was synthesized using N-Boc serinol and subjected to an acidic treatment to expose primary amines (ca. 10^20 units/gSHE3350). In parallel, a low-molecular-weight PEU (AHE1500, Mn 4 kDa, D 1.5) with aldehyde end groups was synthesized by end-capping an isocyanate-terminated prepolymer with 4-hydroxybenzaldehyde, and the aldehyde groups were quantified to be around 10^20 units/gAHE1500. Hydrogels were prepared by simply mixing SHE3350 and AHE1500 aqueous solutions and characterized to assess their physico-chemical and rheological properties. Schiff-base bond formation was proved through carbon-13 and proton solid-state NMR spectroscopies. Rheological characterization confirmed the formation of gels with high resistance to applied strain (ca. 1000%). Hydrogels exhibited high absorption ability (ca. 270% increase in wet weight) in physiological-like conditions (i.e., 37 °C and pH 7.4) up to 27 days. In contact with buffer at pH 5, enhanced fluid absorption was observed until dissolution occurred starting from 13 days due to Schiff-base hydrolysis in acidic conditions. Conversely, gels showed a reduced absorption ability at pH 9 due to shrinkage phenomena. Furthermore, they exhibited high permeability and controlled, sustained, and pH-triggered release of a model molecule (i.e., fluorescein isothiocyanate dextran) for up to 17 days. Lastly, the hydrogels showed easy injectability and self-healing ability.
Schiff-Base Cross-Linked Hydrogels Based on Properly Synthesized Poly(ether urethane)s as Potential Drug Delivery Vehicles in the Biomedical Field: Design and Characterization / Pappalardo, Roberta; Boffito, Monica; Cassino, Claudio; Caccamo, Valeria; Chiono, Valeria; Ciardelli, Gianluca. - In: ACS OMEGA. - ISSN 2470-1343. - ELETTRONICO. - 9:46(2024), pp. 45774-45788. [10.1021/acsomega.4c03157]
Schiff-Base Cross-Linked Hydrogels Based on Properly Synthesized Poly(ether urethane)s as Potential Drug Delivery Vehicles in the Biomedical Field: Design and Characterization
Roberta Pappalardo;Monica Boffito;Valeria Chiono;Gianluca Ciardelli
2024
Abstract
In situ-forming hydrogels based on the Schiff-base chemistry are promising for drug delivery applications, thanks to their stability under physiological conditions, injectability, self-healing properties, and pH-responsiveness. In this work, two water-soluble poly(ethylene glycol)-based poly(ether urethane)s (PEUs) were engineered. A high-molecular-weight PEU (SHE3350, Mn 24 kDa, D 1.7), bearing primary amino groups along each polymeric chain, was synthesized using N-Boc serinol and subjected to an acidic treatment to expose primary amines (ca. 10^20 units/gSHE3350). In parallel, a low-molecular-weight PEU (AHE1500, Mn 4 kDa, D 1.5) with aldehyde end groups was synthesized by end-capping an isocyanate-terminated prepolymer with 4-hydroxybenzaldehyde, and the aldehyde groups were quantified to be around 10^20 units/gAHE1500. Hydrogels were prepared by simply mixing SHE3350 and AHE1500 aqueous solutions and characterized to assess their physico-chemical and rheological properties. Schiff-base bond formation was proved through carbon-13 and proton solid-state NMR spectroscopies. Rheological characterization confirmed the formation of gels with high resistance to applied strain (ca. 1000%). Hydrogels exhibited high absorption ability (ca. 270% increase in wet weight) in physiological-like conditions (i.e., 37 °C and pH 7.4) up to 27 days. In contact with buffer at pH 5, enhanced fluid absorption was observed until dissolution occurred starting from 13 days due to Schiff-base hydrolysis in acidic conditions. Conversely, gels showed a reduced absorption ability at pH 9 due to shrinkage phenomena. Furthermore, they exhibited high permeability and controlled, sustained, and pH-triggered release of a model molecule (i.e., fluorescein isothiocyanate dextran) for up to 17 days. Lastly, the hydrogels showed easy injectability and self-healing ability.File | Dimensione | Formato | |
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https://hdl.handle.net/11583/2995752