Pharmaceutics
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2025
·Vol. 17
·期 6
·690
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IF 5.5
Yingchao Yang,Jingyi Chen,Shengming Wang,Yaxin Zhu,Yao Wang,Yan Chen,Mingjiang Xia,Ming Yang,Hongliang Yi,Kaiming Su
Objectives: Nasal mucosa wound healing faces challenges such as acidic microenvironments and bacterial proliferation. Persistent mucosal defects predispose to complications such as nasal septal perforation. Conventional drug delivery systems suffer from nonspecific release and short-term efficacy. This study aimed to develop a pH-responsive liposome-hydrogel composite (HYD-Lip/DXMS@HG) to integrate pH-triggered dexamethasone (DXMS) delivery, antifouling properties, and mechanical support for refractory injuries.Methods: The composite combined acylhydrazone-modified liposomes with a hydrogel synthesized from hydroxyethylacrylamide (HEAA) and diethylacrylamide (DEAA). In vitro assays evaluated DXMS release kinetics, RPMI 2650 cell migration/proliferation, and antibacterial properties. In vivo rabbit nasal mucosal injury models assessed healing efficacy via histology analyses. RNA sequencing was performed to identify key signaling pathways.Results: HYD-Lip/DXMS@HG exhibited sustained DXMS release in acidic conditions, accelerating cell migration/proliferation in vitro. In rabbits, the composite reduced TNF-αexpression and CD45+ leukocyte infiltration, while enhancing collagen alignment and epithelial thickness. RNA sequencing identified upregulated ECM receptor interaction, Hippo, TGF-β, and PI3K-Akt pathways, linked to collagen remodeling, anti-apoptosis, and angiogenesis.Conclusions: This multifunctional platform synergizes pH-triggered drug delivery, mechanical support, and antibacterial activity, offering a promising therapeutic strategy for refractory nasal mucosal injuries and postoperative recovery.
研究领域:
药剂学
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生物医学工程
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组织工程
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2024
·
IF 4.5
Shuai Hong,Changxiu Lin,Junsheng Hu,Jingshu Piao,Ming Guan Piao
Nimodipine is the primary clinical drug used to treat cerebral vasospasm following subarachnoid hemorrhage. Currently, tablets have low bioavailability when taken orally, and injections contain ethanol. Therefore, we investigated a new method of nimodipine administration, namely, nasoencephalic administration. Nasal administration of nimodipine was carried out by attaching the cell-penetrating peptide octa-arginine (R8) to liposomes of nimodipine and incorporating it into a temperature-sensitive in situ gel. The prepared liposomes and gels underwent separate evaluations for in vitro characterization. In vitro release exhibited a significant slow-release effect. In vitro toad maxillary cilia model, RPMI 2650 cytotoxicity, and in vivo SD rat pathological histotoxicity experiments showed that all the dosage from the groups had no significant toxicity to toad maxillary cilia, RPMI 2650 cells, and SD rat tissues and organs, and the cilia continued to oscillate up to 694 ± 10.15 min, with the survival rate of the cells being above 85%. A transwell nasal mucosa cell model and an isolated porcine nasal mucosa model were established, and the results showed that the osmolality of the R8-modified nimodipine liposomal gel to nasal mucosal cells and isolated porcine nasal mucosa was 30.41 ± 2.14 and 65.9 ± 7.34 μg/mL, respectively, which was significantly higher than that of the NM-Solution and PEGylated nimodipine liposome gel groups. Animal fluorescence imaging studies revealed that the R8-modified nimodipine liposomal gel displayed increased brain fluorescence intensity compared to the normal liposomal gel. Pharmacokinetic results showed that after transnasal administration, the AUC(0–∞) of the R8-modified nimodipine liposomal gel was 11.662 ± 1.97 μg·mL–1, which was significantly higher than that of the plain nimodipine liposomal gel (5.499 ± 2.89 μg·mL–1). Brain-targeting experiments showed that the brain-targeting efficiencies of the PEGylated nimodipine liposome gel and R8-modified PEGylated nimodipine liposome gels were 20.44 and 33.45, respectively, suggesting that R8/PEG/Lip-NM-TSG significantly increased the brain-targeting of the drug.
研究领域:
药学
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神经学
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药物递送系统
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药理学
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生物技术
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DOI
PubMed
高影响因子
LARYNGOSCOPE
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2022
·
IF 2.97
Tiancong Liu,Yang Sun,Zhaohui Guo,Weiliang Bai
Objectives Allergic rhinitis (AR) is an inflammatory autoimmune disease with disorder of the nasal mucosa. Cadherin 26 (CDH26), an alpha integrin-binding epithelial receptor, is regulated during allergic inflammation. This study aimed to investigate whether CDH26 contributes to the severity of AR. Study design In vivo and in vitro. Methods We investigated the effects of CDH26 knockdown by lentivirus (LV)-mediated shRNA on ovalbumin (OVA)-induced AR mice and IL-13-stimulated human nasal epithelial cells (NECs). Results CDH26 mRNA and protein expression was significantly increased in the nasal mucosa of AR patients and mice. Intranasal instillation of LV-shCDH26 alleviated allergic symptoms and decreased the histological changes of nasal mucosa in AR mice. Furthermore, the serum levels of OVA-specific IgE, IgG, pro-inflammatory factors IL-25, IL-33, and TSLP were decreased in AR mice with CDH26 knockdown. With regard to AR-induced Th2 inflammation, LV-shCDH26 intervention effectively decreased the distribution of CD4 + /GATA3 + Th2 cells, and the mRNA expression of IL-4, IL-5, and IL-13 in the nasal mucosa. CDH26 knockdown down-regulated the expression of β-catenin but not for E-cadherin and ZO-1 in nasal mucosa induced by AR. In vitro, CDH26 knockdown inhibited the protein expression of TSLP, GM-CSF and eotaxin in NECs, and CDH26 overexpression remarkably promoted the production of these inflammatory factors in IL-13-induced NECs. Conclusions CDH26 knockdown attenuates the AR-induced inflammatory response both in vivo and in vitro. Level of Evidence NA Laryngoscope , 2022
研究领域:
免疫学
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分子生物学
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过敏
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呼吸医学
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DOI
PubMed
高影响因子
BMC Oral Health
·
2024
·Vol. 24
·期 1
·1-15
·
IF 2.6
Zou Yin,Mei Xue,Wang Xinhe,Zhang Xuan,Wang Xun,Xiang Wen,Lu Naiyan
Background Effective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels.Methods Primary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration.Results
The addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p < 0.0001), osteocalcin (Ocn, p < 0.0001), type collagen (Col , p < 0.0001), bone morphogenetic protein-2 (Bmp2, p < 0.0001), Smad1 (p = 0.0006), and runt-related transcription factor 2 (Runx2, p < 0.0001) were all significantly upregulated.Conclusion s
EMSCs/BPNs-containing fibrin-KGM hydrogels accelerated the recovery of the alveolar bone defect in rats by effectively up-regulating the expression of osteogenesis-related genes, promoting the formation and mineralisation of bone matrix.
研究领域:
牙科治疗
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组织工程
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干细胞生物学
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材料科学
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生物医学工程
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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）