In situ mucoadhesive hydrogel capturing tripeptide KPV: the anti-inflammatory, antibacterial and repairing effect on chemotherapy-induced oral mucositis
| Autor: | Jiaojiao Yang, Ying-Zheng Zhao, He-Lin Xu, Jianxun Shangguan, Yingying Zhang, Weifeng Shao, Kunjie Ran, Rui Chen, Hanxiao Pan, Gaolong Lin |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
medicine.drug_class
Chemistry technology industry and agriculture Biomedical Engineering Cell migration macromolecular substances Adhesion Tripeptide Pharmacology Matrix (biology) medicine.disease complex mixtures Anti-inflammatory Proinflammatory cytokine Self-healing hydrogels Mucositis medicine General Materials Science |
| Zdroj: | Biomaterials Science. 10:227-242 |
| ISSN: | 2047-4849 2047-4830 |
| DOI: | 10.1039/d1bm01466h |
| Popis: | The self-healing of chemotherapy-induced oral mucositis was difficultly practiced because of both local bacterial infection and severe inflammation. Herein, in situ mucoadhesive hydrogels (PPP_E) was successfully prepared by using temperature-sensitive PLGA-PEG-PLGA (PPP) as matrix and EGCG as adhesion enhancer. Series of PPP_E precursor solution with various EGCG concentration (1%, 2% and 5%) were prepared by fixing the PPP concentration at 25%. EGCG slightly decreased the sol-gel transition temperature and shorten sol-gel transition time of PPP hydrogel. Moreover, the incorporation of EGCG could significantly increase the tissue adhesion properties of PPP hydrogel at 37℃. PPP_2%E displayed the suitable gelation temperature (36.2℃), gelation time (100s) and storage moduli (48Pa). Tripeptide KPV as model drug was easily dissolved in cold PPP_2%E precursor solution to prepare KPV@PPP_2%E hydrogel. The anti-inflammatory activity and promoting cell migration potential of KPV in PPP-2% E hydrogel were well maintained. Moreover, KPV@PPP_2%E exhibited the strong antibacterial efficacy against S. aureus. PPP_2%E precursor solution rapidly transited to hydrogel and adhered to the wound surface for 7 hours when administrated to the gingival mucosa of rats. Treatment with KPV@PPP_2%E hydrogel greatly improved the food intake and body weight recovery of chemotherapy-induced rats with oral mucositis. Moreover, the tissue morphology of the ulcerated gingival after KPV@PPP_E hydrogel was also well repaired via promoting CK10 and PCNA expression. Besides, the inflammatory cytokines including IL-1β and TNF-α were significantly inhibited by KPV@PPP_2%E hydrogel while IL-10 was up-regulated. KPV@PPP_2%E hydrogel also had the anti-bacteria effect on MRSA-infected gingival ulcer wound, which resulted in the obvious inhibition of inflammatory cells infiltration in submucosal tissues. Conclusively, KPV@PPP_E may be a promising practical application for cancer people with chemotherapy-induced oral mucositis. |
| Databáze: | OpenAIRE |
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