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ACS Appl Mater Interfaces ; 14(1): 236-244, 2022 Jan 12.
Article in English | MEDLINE | ID: mdl-34935360

ABSTRACT

Gelatin is one of the most versatile biopolymers in various biomedical applications. A gelatin derivative gelatin-catechol (Gel-C) was developed in this study to further optimize its chemical and physical properties such as thermal reversibility and injectability. We found that Gel-C remains in a solution state at room temperature, and the temperature-dependent gelation capability of gelatin is well preserved in Gel-C. Its gel-forming temperature decreased to about 10 °C (about 30 °C for gelatin), and a series of gelatin derivatives with different gel-forming temperatures (10-30 °C) were formed by mixing gelatin and Gel-C in different ratios. Additionally, irreversible Gel-C hydrogels could be made without the addition of external stimuli by combining the physical cross-linking of gelatin and the chemical cross-linking of catechol. At the same time, properties of Gel-C hydrogels such as thermal reversibility and injectability could be manipulated by controlling the temperature and pH of the precursor solution. By simulating the formation of an irreversible Gel-C hydrogel in vivo, an in situ gelling system was fabricated by lowering the local temperature of the hydrogel with cold shock, thus realizing targeted and localized molecular delivery with prolonged retention time. This simple system integrated with the temperature responsiveness of gelatin and chemical cross-linking of catechol groups thus provides a promising platform to fabricate an in situ gelling system for drug delivery.


Subject(s)
Catechols/chemistry , Delayed-Action Preparations/chemistry , Gelatin/chemistry , Hydrogels/chemistry , Animals , Catechols/administration & dosage , Catechols/chemical synthesis , Catechols/toxicity , Cell Line , Cold Temperature , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/toxicity , Drug Liberation , Fluorescein-5-isothiocyanate/analogs & derivatives , Fluorescein-5-isothiocyanate/chemistry , Gelatin/administration & dosage , Gelatin/chemical synthesis , Gelatin/toxicity , Hydrogels/administration & dosage , Hydrogels/chemical synthesis , Hydrogels/toxicity , Hydrogen-Ion Concentration , Injections, Subcutaneous , Male , Mice, Nude , Phase Transition/drug effects , Serum Albumin, Bovine/chemistry , Transition Temperature
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