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P407
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Chitosan-P407-PNIPAM hydrogel loaded with AgNPs/lipid complex for antibacterial, inflammation regulation and alveolar bone regeneration in periodontitis treatment

Chengdong Zhang,Yachen Fei,Meng Li,Jing Li,Maomao Tang,Guichun Wang,Jiaxin Li,Yuxiao Wang,Yang Ding,Chengjun Peng,Mengjie Li,Shuangying Gui,Jian Guo

Periodontitis is an oral chronic inflammatory disease induced by pathogenic bacteria. Pathogens continuously activate immune cells to express a large number of pro-inflammatory factors and reactive oxygen species, eventually leading to periodontal tissue damage. Poor eradication of pathogenic bacteria, persistent inflammatory response and impaired periodontal tissue regeneration are the main challenges to control the progression of periodontitis. However, current clinical drug treatment fails to comprehensively address these issues. In this paper, a chitosan-P407-PNIPAM scaffold multi-crosslinked hydrogel (A/CQ-ML@Gel) encapsulating AgNPs and lipid complex (CQ-ML) is developed. This hydrogel shows thermo- and pH-sensitive properties, exhibits excellent injectability, high viscosity and reliable post-injection mechanical strength. A/CQ-ML@Gel possesses a significant antibacterial effect to Porphyromonas gingivalis after implantation, and then by virtue of the programmed release of quercetin microemulsion and caffeic acid phenethyl ester in CQ-ML, exerting excellent inflammation regulation and osteogenic differentiation of periodontal ligament stem cells. Notably, A/CQ-ML@Gel could activate mitophagy through PINK1/Parkin in inflammatory macrophages, thereby inhibiting the production of excess reactive oxygen species, ultimately reprogramming M1/M2 macrophages phenotype for inflammation suppression. In summary, we present an innovative insight into periodontal delivery system for trimodal synergistic therapy strategy in periodontitis.

研究领域: 口腔医学 · 材料科学 · 生物医学工程
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BMC Complementary Medicine and Therapies · 2023 ·Vol. 23 ·期 1 ·1-14 · IF 3.9

Danlou Recipe promotes cholesterol efflux in macrophages RAW264.7 and reverses cholesterol transport in mice with hyperlipidemia induced by P407

Han Wenrun,Zhang Dandan,Zhang Peng,Tao Qianqian,Du Xiaoli,Yu Chunquan,Dong Pengzhi,Zhu Yan

IntroductionLiver X Receptor (LXR) agonists could attenuate the development of atherosclerosis but bring excess lipid accumulation in the liver. Danlou Recipe was believed to be a benefit for improving the lipid profile. Thus, it is unclear whether Danlou Recipe could attenuate hyperlipidemia without excess lipid accumulated in the liver of mice. This study aimed to clarify if Danlou Recipe could alleviate the progression of hyperlipidemia in mice without extra lipids accumulated in the liver.Methods Male murine macrophage RAW264.7 cells and murine peritoneal macrophages were used for the in vitro experiments. Cellular cholesterol efflux was determined using the fluorescent cholesterol labeling method. Those genes involved in lipid metabolism were evaluated by qRT‐PCR and western blotting respectively. In vivo, a mouse model of hyperlipidemia induced by P407 was used to figure out the effect of Danlou Recipe on reverse cholesterol transport (RCT) and hyperlipidemia. Ethanol extract of Danlou tablet (EEDL) was prepared by extracting the whole powder of Danlou Prescription from ethanol, and the chemical composition was analyzed by ultra-performance liquid chromatography (UPLC).Results EEDL inhibits the formation of RAW264.7 macrophage-derived foam cells, and promotes ABCA1/apoA1 conducted cholesterol efflux in RAW264.7 macrophages and mouse peritoneal macrophages. In the P407-induced hyperlipidemia mouse model, oral administration of EEDL can promote RCT in vivo and improve fatty liver induced by a high-fat diet. Consistent with the findings in vitro, EEDL promotes RCT by upregulating the LXR activities.Conclusion Our results demonstrate that EEDL has the potential for targeting RCT/LXR in the treatment of lipid metabolism disorders to be developed as a safe and effective therapy.

研究领域: 药理学 · 心血管疾病 · 脂质代谢
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MATERIALS & DESIGN · 2024 · IF 7.6

Design, fabrication, and in vitro studies of sustained paclitaxel release from 3D-printed TPU/P407 airway stents for treating airway stenosis

Zhining Zhuo,Yuehan Ouyang,Xiyue Zheng,Xiaobang Chen,Zequan Lin,Ruitian Zhu,Lan Lan,Dongyang Qian,Rongrong Li,Jixiang Zhu,Yuanye Dang,Yan Wang,Sida Liao,Xiumei Tian,Fanwen Yang

Airway stenosis, a significant cause of dyspnea, is commonly managed with airway stents. However, conventional stents frequently lead to restenosis. Excessive proliferation of fibroblasts and smooth muscle cells during abnormal repair processes is a key factor in airway restenosis. To address this challenge, a novel drug-loaded airway stent has been designed with personalized tailoring for the patient. This stent features a three-layered structure: an outer layer made from a blend of thermoplastic polyurethane (TPU) and Poloxamer 407 (P407), a drug-loading intermediate layer, and an inner layer made of TPU. This design aims to minimize airway irritation and enable adjustable drug release rates by adjusting the drug carrier and/or the content of P407 in the stent’s outer layer. Drug release profile conforms to the Improved First-Order model. Notably, P407 is released from the stent, serving a dual purpose: it creates micropores to regulate the drug release rate and synergizes with PTX to inhibit the proliferation of fibroblasts. This combination significantly enhances the inhibitory effect on the proliferation of fibroblasts and smooth muscle cells, without adversely affecting airway epithelial cells. This may represent a novel approach to reducing restenosis by addressing a critical complication associated with the use of airway stents.

研究领域: 生物医学工程 · 药学 · 组织工程 · 药物递送系统
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JOURNAL OF DRUG TARGETING · 2026 · IF 4.7

Development of venlafaxine hydrochloride nasal thermosensitive in-situ gel with P407/P188: enhanced bioavailability and antidepressant effects in depressive rats

Yili Wu,Yujia Zhang,Dong Li,Xiangchun Sheng,Xiaofeng Hu,Meihong Ding,Qunxing Wang,Beihua Xu,Ting Zhang,Yiling He,Senlin Shi

Objective To develop and optimise a VEN nasal thermosensitive in-situ gel for reducing the first-pass effect and enhancing bioavailability.Methods High performance liquid chromatography, central composite design-response surface methodology, the membrane-free erosion and the Franz vertical diffusion cell method were used to clarify the optimised formulation. Pharmacokinetic and pharmacodynamic studies evaluated sustained release and efficacy.Results The optimal formulation (32.87-33.17 °C gelation temp) comprised 12.5% w/v VEN, 20.44% w/v poloxamer 407, 0.74% w/v P188, 5% w/v 2-Hydroxypropyl-β-cyclodextrin, 0.5% w/v hydroxypropyl methyl cellulose, 0.12% w/v potassium sorbate, 10% v/v glycerol, and 90% v/v water; it had a good stability and sustained-release effect of VEN and increased bioavailability and reduced O-desmethylvenlafaxine production. It achieved 90% cumulative release at 15h in vitro, and its intranasal Cmax was higher than oral VEN (p < 0.05) without detectable O-desmethylvenlafaxine. Treatment with VEN thermosensitive in-situ gel in a depressive rat model improved the sucrose preference rate in the sucrose preference test and the total distance of movement in the open field test, also significantly increased the level of 5-hydroxytryptamine and norepinephrine in the hippocampus (p < 0.01).Conclusion This innovative P407/P188-based gel enhances VEN bioavailability and antidepressant efficacy via sustained release and brain targeting, providing critical data for nasal formulation development.

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Advanced Science · 2025 · IF 14.1

Evenly Distributed Microporous Structure and E7 Peptide Functionalization Synergistically Accelerate Osteogenesis and Angiogenesis in Engineered Periosteum

Qihong Li,Chen Li,Jun Yan,Chunli Zhang,Yu Jiang,Xiantong Hu,Liwei Han,Li Li,Peng Wang,Lingzhou Zhao,Yantao Zhao

Repairing large bone defects remains a significant clinical challenge. Stem cell is of great importance in bone regeneration, and periosteum is rich in periosteal stem cell, which has a great influence on repairing bone defects. Bioengineered periosteum with excellent biocompatibility and stem cell homing capabilities to promote bone regeneration is of great clinical significance. The E7 peptide (EPLQLKM), which exhibits a specific affinity for mesenchymal stem cells (MSCs), is beneficial for modulating cellular functions. In this study, a unique microporous structured carboxymethyl chitosan/sodium alginate membrane with a proper mass ratio is developed by the addition of Poloxam 407 (P407), which is then functionalized with the E7 affinitive peptide. This membrane, characterized by its microporous structure and E7 peptide functionalization (CSSA/P/E), not only demonstrated favorable mechanical properties, enhanced hydrophilicity, satisfactory biodegradation profile, and excellent biocompatibility, but also synergistically enhanced MSCs recruitment. It is found to promote the proliferation, spreading, and osteogenic differentiation of MSCs in vitro and to accelerate early periosteal regeneration, bone matrix deposition, and vascularization in vivo, leading to effective regeneration of critical-sized bone defects. Overall, this study presents a robust, cell and growth factor-free strategy for bioengineering periosteum, offering a potential solution for the challenging large size bone defects.

CAS / MDL: 9003-11-6
研究领域: 组织工程 · 生物材料 · 再生医学 · 干细胞生物学 · 骨科
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