Medicina Oral Patologia Oral y Cirugia Bucal
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2025
·Vol. 30
·期 5
·e657
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IF 2.1
Jing-jing Zeng,Zeng-lin Tan,Ke Zhang,Qian-nian Han,Shi-ning Ou,Ze-kai Wang,Jian-wei Liu,Fang-yan Wang,Ying-peng Huang,Lin-feng Wu
Background Chemotherapy-induced oral mucositis (OM) is a common complication of cancer treatment that significantly impacts patients' quality of life. Butyrate, a short-chain fatty acid, has been shown to inhibit inflammation and mitigate intestinal mucosal damage. How, its effect in treating OM remains unclear. Material and Methods OM model in mice pretreated with 5-FU solution was established by injecting 20% acetic acid into oral mucosa. Sodium butyrate was given for treatment. H&E staining was used to observe histopathological changes, and qRT-PCR to assess inflammatory factor level changes in ulcer tissues after treatment. Also, qRT-PCR and immunofluorescence staining were used to evaluate the expression and distribution of tight junction protein in ulcer tissues. Results Sodium butyrate treatment improved the weight loss in mice caused by OM and promoted the repair of oral mucosa in a time-dependent manner. In addition, sodium butyrate significantly inhibited the mRNA levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-18 (IL-18) in the ulcer tissue. Moreover, sodium butyrate promoted the mRNA and protein expressions of tight junction protein-1 (ZO-1) and Claudin-1 in the epithelial cells of the ulcer tissue. Conclusions Butyrate promotes OM healing by reducing inflammation and increasing the expression of tight junction proteins in ulcer tissues. Key words: Butyrate, chemotherapy, oral mucositis, inflammation, tight junction proteins.
研究领域:
肿瘤学
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免疫学
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分子生物学
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口腔医学
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药理学
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DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-12
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IF 3.9
Sun Honglan,Yang Chao,Yin Xiaoyunqing,Chen Shizhao,Huang Yuqi,Kuang Huifang,Luo Wen
The chronic illness known as oral submucous fibrosis (OSF) results in tissue fibrosis, precancerous lesions, and scarring. It usually manifests itself in the buccal mucosa. It frequently occurs in the buccal mucosa. Von Hippel-Lindau (VHL) is an essential component of E3 ubiquitin ligase complex. The loss of VHL led to reduced fibrotic responses, accompanied by ameliorated fiber deposition. However, the precise impact of VHL on OSF is yet unclear. OSF tissues and normal mucosal tissues were applied to analyze the distinct expression of VHL and histone deacetylase 6 (HDAC6). Oral fibroblasts were treated to arecoline to simulate OSF in vitro, and molecular biological experiments were conducted to identify the role of VHL in buccal mucosa fibroblasts (BMFs). VHL was downregulated and HDAC6 was upregulated in OSF tissues and BMFs. Overexpression of VHL inhibited fibrosis in arecoline-treated BMFs. VHL inhibits the level of HDAC6 by inducing the ubiquitination of HDAC6. Knockdown of HDAC6 reduces the fibrogenic ability of BMFs. Furthermore, overexpression of HDAC6 contributes to the activation of NF-κB signaling in BMFs. HDAC6 selective inhibitor ACY-1215 inhibited the NF-κB signaling pathway. VHL attenuated arecoline-induced OSF by inhibiting the ubiquitination of HDAC6 and blocking NF-κB pathway. As a result, our study offers new perspectives into the discovery of novel tactics that can be employed against OSF.
研究领域:
医学
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分子生物学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2024
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IF 18.5
Hengjie Zhang,Jianhua Zhang,Tianyou Wang,Haotian Li,Rong Zhang,Xianchun Chen,Zhipeng Gu,Yiwen Li
Although bio-adhesives have achieved many progresses, creating robust bio-glues that could withstand the complex physiological microenvironment remains a significant challenge such as limited bioadhesion strength and stability, as well as slow adhesion speed caused by pH, enzymes, salt, and bacteria. Herein, a series of strong bio-glues are successfully fabricated using a polyphenol–acrylamide–ruthenium crosslinking (PARC) reaction under visible light irradiation, involving acrylamides radical polymerization, polyphenols (extracts) coupling reaction, and ruthenium-mediated photochemistry. The resulting bio-glues underwent rapid sol–gel transition and exhibited adhesive properties within a short of time (≈5 s), which could quickly bond to various bio-tissues. Moreover, these bioadhesives demonstrate high adhesion strength and stability with mucosal tissue in the oral environment, effectively promoting rat and pig oral mucosal wound healing. It is anticipated that this class of visible light-responsive polyphenolic bio-glues could serve as a robust tool for addressing oral mucosal defects in the clinic, offering a promising alternative to traditional treatments for oral mucosal disorders.
研究领域:
生物材料学
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医学工程
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组织修复
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DOI
高影响因子
POWDER TECHNOLOGY
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2017
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IF 2.942
Wang-Zhan Jiang,Yang Cai,Hao-Ying Li
The main issues attracting substantial consideration when delivering drugs to the oromucosa include the enhancement of mucoadhesion of drug formulations in order to elongate their residence time on the site of delivery and the sustained release of drug from the formulations following deposition. In this study, the mucoadhesive biopolymers of chitosan and its derivatives, including high molecular weight , low molecular weight, and carboxylic derivative, were employed as the excipients to prepare spray-dried microspheres for the oromucosal drug (e.g. benzydamine hydrochloride, BZH) delivery with the aim to enhance the delivery efficiency. All chitosan-modified spray-dried powders showed the size < 10 μm with greater surface roughness , moisture content < 10% w/w, and improved flowability . The addition of chitosan in the formulations can tremendously extend the duration of drug release. More importantly, the mucoadhesive interaction of chitosan-modified microparticles was strongly enhanced, and it can be further improved as the augmentation of chitosan contents in the formulations. Our data clearly demonstrate that the inclusion of chitosan in spray-dried microspheres elongates the duration of drug release and also enhance the mucoadhesive interaction force of microspheres to the mucosal membrane, which may be of benefit in the treatment of local conditions.
研究领域:
药剂学
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生物材料
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药物递送
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DOI
高影响因子
Pharmaceutics
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2023
·Vol. 15
·期 3
·758
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IF 5.4
Tingfeng Xu,Huijie Li,Yi Xia,Sheng Ding,Qingliang Yang,Gensheng Yang
As an oral mucosal drug delivery system, oral films have been of wide concern in recent years because of their advantages such as rapid absorption, being easy to swallow and avoiding the first-pass effect common for mucoadhesive oral films. However, the currently utilized manufacturing approaches including solvent casting have many limitations, such as solvent residue and difficulties in drying, and are not suitable for personalized customization. To solve these problems, the present study utilizes liquid crystal display (LCD), a photopolymerization-based 3D printing technique, to fabricate mucoadhesive films for oral mucosal drug delivery. The designed printing formulation includes PEGDA as the printing resin, TPO as the photoinitiator, tartrazine as the photoabsorber, PEG 300 as the additive and HPMC as the bioadhesive material. The influence of printing formulation and printing parameters on the printing formability of the oral films were elucidated in depth, and the results suggested that PEG 300 in the formulation not only provided the necessary flexibility of the printed oral films, but also improved drug release rate due to its role as pore former in the produced films. The presence of HPMC could greatly improve the adhesiveness of the 3D-printed oral films, but excessive HPMC increased the viscosity of the printing resin solution, which could strongly hinder the photo-crosslinking reaction and reduce printability. Based on the optimized printing formulation and printing parameters, the bilayer oral films containing a backing layer and an adhesive layer were successfully printed with stable dimensions, adequate mechanical properties, strong adhesion ability, desirable drug release and efficient in vivo therapeutic efficacy. All these results indicated that an LCD-based 3D printing technique is a promising alternative to precisely fabricate oral films for personalized medicine.Keywords:3D printing;oral films;liquid crystal display;bilayer films;oral mucosal drug delivery
研究领域:
药剂学
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生物医学工程
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2025
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IF 6.5
Xiangjuan Wei,Mengyuan Wang,Xiaocong Dong,Yichen He,Wenbin Nan,Shenglu Ji,Mengyuan Zhao,Haodang Chang,Hongliang Wei,Dan Ding,Hongli Chen
Background Oral mucositis (OM) is a common acute side effect among patients undergoing chemotherapy and/or radiotherapy, with complex pathogenesis and limited current treatment efficacy. Rabdosia rubescens, a traditional Chinese herb, contains oridonin (ORI) with antibacterial and anti - inflammatory properties. However, ORI’s poor solubility and low bioavailability hamper its clinical use. Medicinal plant - derived exosome - like nanovesicles (ENs) are emerging as a promising drug delivery system for wound repair. This study aimed to develop a novel therapeutic approach.Methods We fabricated internally-externally homologous drug-loaded exosome-like nanovesicles (ORI/ENs) derived from Rabdosia rubescens and encapsulated them in a semi-interpenetrating network hydrogel system (ORI/ENs/Gel) to repair chemoradiotherapy-induced OM. The morphology, biocompatibility, and antibacterial properties were evaluated. Moreover, the proliferative and migratory capacity were measured using L929 cells. In addition, the pro-healing effects and the underlying molecular mechanisms of ORI/ENs/Gel were assessed in vivo.Results ENs were extracted and purified from Rabdosia rubescens by sequential ultra-centrifugations. The encapsulation efficiency (EE) and loading capacity (LC) of ORI in ORI/ENs were 76.4 ± 3.2% and 9.21 ± 0.45%, respectively, suggesting that ENs had a high loading efficiency for homologous drug ORI. The evaluation of toxicity and antibacterial effects has been proven that ORI/ENs has biocompatibility and antibacterial properties. In vivo, ORI/ENs/Gel promoted collagen deposition, targeted NLRP3 to reduce inflammation, and accelerated OM wound healing.Conclusion The hydrogel composite incorporating internally-externally homologous drug-loaded ENs offers the potential to provide targeted therapy, improve bioavailability, and promote efficient healing of the OM.
研究领域:
药学
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生物医学工程
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yingying Wu,Lei Jiang,Kesang Li,Jialin Liu,Ping Chen,Jianfen Xu,Jiantao Zhang
Chemoradiotherapy-induced oral mucositis (CIOM), characterized by high incidence and delayed healing, severely impairs patient recovery and quality of life. Current treatments face challenges due to poor wet adhesion, dynamic oral environments, and lack of multiple active substances for mucosal repair. This situation makes an urgent need for therapeutic platforms that combine robust mucosal adhesion with multifunctionality. In this study, a crosslinked hyaluronic acid based hydrogel (PHB) embedded with core-shell microgels was developed. Core-shell microgels were fabricated to encapsulate growth factor (core) and lidocaine (shell), enabling spatiotemporal drug release. The hydrogel exhibited superior mucosal adhesion, with a displacement of only 5.5 mm after 24 h on an inclined agar plate containing mucin, attributed to hydrogen bonding between hydroxyl groups of PHB and mucin. The bacteriostasis experiment results show that PHB has excellent antibacterial properties against E. coli and S. aureus , which can help to prevent the growth of oral bacteria and promote wound healing. Furthermore, sustained release of EGF and lidocaine from the PHB hydrogel was maintained for 24 h, aligning with the time window required for oral mucosal repair.. In vivo studies demonstrated PHB hydrogels accelerated mucosal proliferation and remodeling in CIOM in golden hamsters. This study presents a combined drug hydrogel system addressing CIOM's multifactorial pathology. The PHB platform synergizes prolonged wet adhesion, antibacterial action, analgesia, and tissue regeneration, offering a clinically solution for oral mucosal repair.
研究领域:
生物医学工程
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口腔医学
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药剂学
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组织工程
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黏膜修复学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2025
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IF 5.5
Yi Yu,Mingjin Zhang,Jing Li,Zhengyuan Liu,Liang Lyu,Yujia Xiao,Gengchen Yang,Jiayi Liu,Qirui Wang,Xiaoyang Ding,Ting Zhang,Yuguang Wang,Xing Wang,Tingting Yu,Dawei Liu
Diabetes mellitus is a global health threat, with chronic wounds, including oral mucosal wounds, being a severe complication. These wounds are characterized by delayed healing and increased inflammation due to hyperglycemia, affecting patients’ quality of life. Current treatments for oral mucosal wounds cannot offer sustained management of these injuries in diabetic patients. Here, a glucose/ROS dual-responsive hydrogel incorporating sitagliptin was developed for the treatment of diabetic oral mucosal wounds. After chemical modification of tetra-armed poly(ethylene glycol) succinimidyl glutarate (tetra-PEG-SG) by dopamine (DA) and tetra-armed poly(ethylene glycol) amine (tetra-PEG-NH2) by phenylboronic acid (PBA), the resulting hydrogel was capable of rapid gelation, robust tissue adhesion, self-healing, antioxidant capacity, and dual response to glucose and reactive oxygen species (ROS), enabling the feasible injection and stable adherence in the moist oral environment while ensuring sustained therapeutic sitagliptin release. In vivo experiments on oral mucosal defects in diabetic mice revealed that the sitagliptin-loaded hydrogel could effectively reduce inflammation and promote wound healing. Collectively, this finding identifies a potential wound dressing as a therapeutic strategy for diabetic oral mucosal wounds.
研究领域:
生物材料学
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药剂学
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糖尿病治疗
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伤口愈合
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产品关联
DOI
PubMed
高影响因子
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
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2020
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IF 2.802
Qiyu Liu,Zhe Yang,Ning Ma,Weixing Wang,Yangqun Li
This study aimed to investigate the long-term scar hypertrophy in the rabbit transplanted oral mucosa and scrotal skin with changed matrix environment, as well as the scar location expression, quantitative analysis of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) and biomechanical changes in the transplanted tissues. The split-thickness skin grafts were collected from the oral mucosas and scrotal skins of 30 male rabbits, and prepared into reelpipes for autologous transplantation into the rabbit back muscular tissues. Samples were collected to carry out elastic tensile mechanical detection and histological observation. The maximum longitudinal tensile displacement of scrotal skin before 8 weeks of transplantation was greater than that after 8 weeks of transplantation (P < 0.05). The expression intensities of MMP-2 and TIMP-2 in the oral mucosa and in scrotal skin at 2 W time point were higher than those at T o time point (P < 0.05). The expression quantities of TIMP-2 in oral mucosa and scrotal skin during 8–24 W were higher than those of MMP-2 (P < 0.05). At 8 W time point, the TIMP-2/MMP-2 ratio in scrotal skin was higher than that in oral mucosa (P < 0.05). MMP-2 and TIMP-2 expression in normal oral mucosa and scrotal skin is weak, but their expression is remarkably up-regulated after 2 weeks of transplantation, revealing that scar formation was related to the high expression of MMP-2 and TIMP-2. At the 8th–24th weeks, the AOD values of TIMP-2 in oral mucosa and scrotal skin are apparently higher than those of MMP-2; moreover, the TIMP-2/MMP-2 ratio in scrotal skin at the 8th week was higher than that in oral mucosa, which can well explain the earlier scar formation in scrotal skin than in oral mucosa, and it also suggests that the different expression levels between TIMP-2 and MMP-2 may account for the important cause of scar formation.
研究领域:
生物医学工程
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组织工程
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伤口愈合
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
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2022
·
IF 0
Xin-Jiao Li,Yao Li,Yang Meng,Xing-Qun Pu,Jia-Wang Qin,Rui Xie,Wei Wang,Zhuang Liu,Lu Jiang,Xiao-Jie Ju,Liang-Yin Chu
A composite microneedle patch (MN patch) is developed for oral transmucosal administration. To improve the oral transmucosal drug delivery efficiency, the composite MN patch is designed to consist of an array of 100 dissolvable microneedles (MNs) with drug-loaded tips and a backing layer. The MNs are composed of two parts, the hyaluronic acid (HA) tip part and the polyvinylpyrrolidone (PVP) base part. Due to the small size and sufficient mechanical strength , the HA-PVP MNs can painlessly penetrate the oral mucosa barrier and deliver drugs directly to the basal layer or submucosa. Betamethasone sodium phosphate (BSP), as the model drug, is concentrated in the HA tip parts to avoid the drug waste caused by mucosa elasticity. Considering the special moist environment and saliva flow in the mouth, a double-layer backing layer composed of a poly(vinyl alcohol) (PVA) adhesive layer and an ethyl cellulose (EC) waterproof layer is designed and constructed, which could reduce the saliva flow effects. The in vitro and in vivo results demonstrate that the MN patch could achieve rapid and efficient BSP release in oral mucosa due to the rapid dissolution of HA. The proposed MN patch provides a novel strategy for the therapy of oral mucosal diseases.
研究领域:
药剂学
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生物材料学
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口腔医学
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DOI
PubMed
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Yanxuan Xiao,Caiyong Song,Hongping Ye,Dan Li,Jiayi Shi,Xiaoke Huang,Qianming Chen,Rui Liu
Radiation-induced oral mucositis (RIOM) is a common complication among patients undergoing radiotherapy. Ionizing radiation (IR) has been shown to induce the excessive production of reactive oxygen species (ROS) and ferroptosis, both of which play critical roles in the development of RIOM. This study fabricates a novel detachable dissolvable microneedle patch DC@MNs for the therapy of RIOM. The nano-enzyme Ceria nanoparticles (Ceria NPs) at the top of needle tips can scavenge ROS and enhance penetration capability of DC@MNs. Additionally, the microneedles (MNs) incorporate deferoxamine (DFO), a known ferroptosis inhibitor, to form a combined therapeutic strategy for RIOM. Cell viability assays demonstrate that the combination of DFO and Ceria NPs effectively mitigates IR-induced cell death. Furthermore, in vivo studies using rat RIOM models further confirm that DC@MNs can penetrate the mucosal epithelium, thereby facilitating drug delivery. Finally, measurement of intracellular ROS, lipid peroxidation, and ferrous ion levels reveals that the DC@MNs protect oral mucosal cell through ROS scavenging and ferroptosis inhibition. This study provides a novel radiation protection strategy and highlights its potential applicability in drug delivery to oral mucosal for patients receiving radiotherapy.
研究领域:
肿瘤学
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放射治疗
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药物递送系统
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纳米技术
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产品关联
DOI
高影响因子
DRUG DELIVERY
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2020
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IF 4.902
Yuqi Yang,Yiyue Guo,You Xu,Yingying Meng,Xing Zhang,Xuejun Xia,YuLing Liu
Deformable nanovesicles (DNVs) have been used in the buccal delivery of biomacromolecules due to their ability to enhance drug penetration. However, no breakthroughs have been made until now due to limited understanding of the factors affecting in vivo buccal delivery. In this study, we designed a series of DNVs, based on an insulin–phospholipid complex (IPC-DNVs), to investigate the influence of drug dose, buccal administration methods, and key quality characteristics of IPC-DNVs for buccal delivery. IPC-DNVs showed a non-linear dose–response relationship between 8 and 12 IU. There was no significant effect of drug delivery site (sublingual mucosa/buccal mucosa) or ligation time (15 or 30 min) on buccal absorption of IPC-DNVs. However, the area above the curve of reduction in blood glucose level overtime (AAC0–6h) for oral mucosa administration was significantly higher than that for buccal mucosa administration. Increasing the drug concentration in IPC-DNVs led to a decrease in AAC0–6h. This might be due to local leakage of DNVs, while squeezing through biological barriers with high concentration of insulin, thus hindering the subsequent delivery of DNVs. IPC-DNVs, measuring 80–220 nm in size, did not significantly affect AAC0–6h. However, when the size was increased to approximately 400 nm, AAC0–6h decreased, thus suggesting that IPC-DNVs with reasonable size were more effective. Additionally, increased deformability of IPC-DNVs might cause drugs to leak easily, thus reducing the promoting effect of buccal absorption. Our results clarified the effect of characteristics of IPC-DNVs on buccal delivery in vivo and provided meaningful support for the design of dosage form of DNVs.
研究领域:
药剂学
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生物医学工程
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药物传递系统
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）