Oral ulcers, prevalent lesions of the oral mucosa, often stem from trauma, viral infections, and autoimmune diseases, necessitating effective treatment strategies to address both their physical and psychological impacts. Current treatments are often limited by issues such as poor adhesion and rapid dilution within the dynamic oral environment. To overcome these challenges, we have explored the application of thermosensitive hydrogels, specifically aqueous solutions of poly(ethylene glycol)–poly(trimethylene carbonate) (PEG–PTMC) copolymers. These copolymers are noted for their biocompatibility and temperature-responsive phase transition properties. We engineered a thermosensitive drug delivery system by fine-tuning the molecular weight and segment lengths of PEG–PTMC, which gels near 32 °C and precipitates at 37 °C. Utilizing the slight temperature differential between the oral mucosa and ambient air, the system forms a Janus structure with distinct gel and precipitate layers, ensuring sustained drug release and enhanced tissue adhesion. This innovative formulation not only acts as a protective, drug-laden dressing that promotes healing but is also designed for ease of use, allowing for self-administration. This study presents a significant advancement in the treatment of oral ulcers, offering a promising solution through the in situ formation of a bilayered, drug-loaded dressing, leveraging the unique properties of thermosensitive hydrogels.
Yuandou Wang,Laishun Xi,Baogang Zhang,Qingzhen Zhu,Feng Su,Katarzyna Jelonek,Arkadiusz Orchel,Janusz Kasperczyk,Suming Li
PTMC-PEG-PTMC triblock copolymers were prepared by ring-opening polymerization of trimethylene carbonate (TMC) in the presence of dihydroxylated poly(ethylene glycol) (PEG) with Mn of 6000 and 10,000 as macro-initiator. The copolymers with different PTMC block Lengths and the two PEGs were end functionalized with acryloyl chloride. The resulting diacrylated PEG-PTMC-DA and PEG-DA were characterized by using NMR, GPC and DSC. The degree of substitution of end groups varied from 50.0 to 65.1%. Hydrogels were prepared by photo-crosslinking PEG-PTMC-DA and PEG-DA in aqueous solution using a water soluble photo-initiator under visible light irradiation. The effects of PTMC and PEG block lengths and degree of substitution on the swelling and weight loss of hydrogels were determined. Higher degree of substitution leads to higher crosslinking density, and thus to lower degree of swelling and weight loss. Similarly, higher PTMC block length also leads to lower degree of swelling and weight loss. Freeze dried hydrogels exhibit a highly porous structure with pore sizes from 20 to 100 µm. The biocompatibility of hydrogels was evaluated by MTT assay, hemolysis test, and dynamic clotting time measurements. Results show that the various hydrogels present outstanding cyto- and hemo-compatibility. Doxorubicin was taken as a model drug to evaluate the potential of PEG-PTMC-DA and PEG-DA hydrogels as drug carrier. An initial burst release was observed in all cases, followed by slower release up to more than 90%. The release rate is strongly dependent on the degree of swelling. The higher the degree of swelling, the faster the release rate. Finally, the effect of drug loaded hydrogels on SKBR-3 tumor cells was evaluated in comparison with free drug. Similar cyto-toxicity was obtained for drug loaded hydrogels and free drug at comparable drug concentrations. Therefore, injectable PEG-PTMC-DA hydrogels with outstanding biocompatibility and drug release properties could be most promising as bioresorbable carrier of hydrophilic drugs.
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