ACS Applied Materials & Interfaces
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2026
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IF 7.8
Yanjiao Ding,Daogong Zhang,Jinye Li,Lei Xu,Haibo Wang
Hearing loss is a widespread global disability, commonly treated using dexamethasone (Dex). However, targeted delivery of Dex to the inner ear remains a significant challenge due to the blood-perilymph barrier (BLB), which limits its therapeutic efficacy. In this study, we aimed to develop a strategy to enhance Dex delivery to the inner ear and improve its treatment outcome by the noninvasive intranasal approach. Also, poly(ethylene glycol) (PEG)─liposomal nanoparticles were used as a drug carrier and loaded with Dex (PLN-Dex). For intranasal delivery, a thermosensitive hydrogel was fabricated by methylcellulose. The PLN-Dex nanocomposite was incorporated into the hydrogel to obtain PLN-Dex@Gel. PLN-Dex@Gel could be administrated intranasally and their transport pathway from olfactory mucosa to the cochlea was explored. In vivo magnetic resonance and fluorescence microscopy showed that drugs delivery into the olfactory mucosa reached the inner ear by dispersive transport via the brain. Interestingly, we found that beyond the cochlear duct, the cochlear axis may serve as a crucial pathway for the transportation of drugs from the brain to the inner ear. In guinea pig models of LPS-induced and noise-induced hearing loss, intranasal PLN-Dex@Gel treatment significantly reduced auditory brainstem response thresholds, ameliorated cochlear blood flow, and protected hair cells and synapses. Our findings underscore the potential of intranasal Dex delivery as a noninvasive and effective strategy for treating hearing loss. The target drug delivery to the inner ear, combined with the enhanced formulation of Dex-loaded liposomal hydrogels, offers promising prospects for future research in the treatment of inner ear disorders, with potential for clinical translation. This study expands the understanding of delivery route from nose to inner ear and suggests a method for utilizing intranasal administration as a strategy for treating hearing loss.
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PubMed
高影响因子
Molecular Medicine Reports
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2019
·Vol. 20
·期 1
·401-408
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IF 1.851
Zhigang Nie,Shuang Deng,Lei Zhang,Sen Chen,Qiang Lu,Hao Peng
Osteoblast apoptosis has been identified as an important event in the development of glucocorticoid (GC)‑induced osteoporosis and osteonecrosis of the femoral head. Crocin, a bioactive ingredient of saffron, has been demonstrated to induce antiapoptotic effects on numerous types of cell in vitro; however, the effects of crocin on the dexamethasone (Dex)‑induced apoptosis of osteoblasts remain unclear. In the present study, the protective effects of crocin during Dex‑induced apoptosis of MC3T3‑E1 osteoblasts, and the underlying mechanisms, were investigated. MTT and Annexin V‑FITC/PI flow cytometry assays were performed to evaluate the viability and apoptosis of cells, respectively. The mitochondrial transmembrane potential, reactive oxygen species (ROS), intracellular Ca2+ levels and apoptosis‑associated protein expression were assessed via flow cytometry, fluorescence microscopy and western blotting. It was demonstrated that crocin pretreatment inhibited Dex‑induced apoptosis of osteoblasts in a dose‑dependent manner. Crocin reversed Dex‑induced decreases in the mitochondrial transmembrane potential, and increases in ROS and intracellular Ca2+ levels. Furthermore, crocin upregulated the expression levels of B‑cell lymphoma-2 (Bcl‑2) and mitochondrial cytochrome c (Cyt C), and downregulated those of cleaved caspase‑9, cleaved caspase‑3, Bcl‑2‑associated X protein and cytoplasmic Cyt C. N‑acetylcysteine, a ROS inhibitor, and 1,2‑bis(2‑aminophenoxy)ethane‑N,N,N',N'‑tetraacetic acid, a calcium chelator, attenuated Dex‑induced osteoblast apoptosis, whereas H2O2 and ionomycin, a calcium ionophore that increases intracellular calcium levels, reversed the antiapoptotic effects of crocin on Dex‑treated osteoblasts. These results indicated that crocin may protect osteoblasts from Dex‑induced apoptosis by inhibiting the ROS/Ca2+‑mediated mitochondrial pathway, thus suggesting that crocin has potential value as a treatment for GC‑induced bone diseases.
研究领域:
药理学
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细胞生物学
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骨质疏松症
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骨骼疾病
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PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2023
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IF 5
Xiaolin Li,Xunchan Jiang,Xiaolei Zhou,Yanju Cheng,Feng Cao
Many non-invasive novel nano-formulations were used for delivery from the ocular surface to posterior segment of the eye, while dexamethasone (DEX) ternary cyclodextrin (CD) aggregate suspension eye drops had recently entered phase III clinical trial . In this study, DEX quaternary CD aggregate suspension eye drops containing HPγCD as solubilizing CD, γCD as aggregating CD and poloxamer 407 were developed and easy for large-scale production. The permeability of DEX quaternary CD aggregate (DEX/γCD/HPγCD/P407) eye drops was better than that of DEX ternary CD (DEX/γCD/P407) eye drops in human corneal epithelial cells and human conjunctival epithelial cells. Ocular distribution revealed that the concentrations of DEX in the choroid-retina were still higher than the effective therapeutic concentration within12 h. DEX/γCD/HPγCD/P407 eye drops remained stable for 6 months in long-term testing and accelerated testing. In conclusion, DEX quaternary CD aggregate eye drops offer an efficient strategy for drug delivery from the ocular surface to posterior segment of the eye.
研究领域:
药剂学
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眼科医学
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纳米技术
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DOI
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Hang-yi Hu,Ying-jian Sun,Xiao-feng Yuan,Jiang-fan Han,Tian-tian Liao,Fei-yue Zhang,Jin-dong Mao,Lin Zhang,Wei-liang Ye
Rheumatoid arthritis (RA) is an autoimmune disease that seriously threatens human health and affects the quality of life of patients. At present, pharmacotherapy is still the mainstream treatment for RA, but most methods have shortcomings, such as poor drug targeting, a low effective drug dosage at the inflammatory site, and high systemic toxicity. The combined application of drug-loaded nanobubbles and ultrasound technology provides a new technique for the treatment of RA. Low-intensity focused ultrasound (LIFU) traces the transmission of drug-loaded nanobubbles in the body, and high-intensity focused ultrasound (HIFU) causes the nanobubbles to rupture to release drugs at the inflammatory site, thereby reducing their toxicity to normal tissues. In this study, a drug-loaded nanobubble delivery system (DEXsp@Liposomes/C3F8) with ultrasonic response characteristics was successfully constructed, and its therapeutic effect was evaluated for the treatment of RA in vitro and in vivo. DEXsp@Liposomes/C3F8 + LIFU had good biocompatibility and excellent ultrasound imaging ability. DEXsp@Liposomes/C3F8 +HIFU distinctly increased the cellular uptake of DEXsp and significantly reduced the secretion of related inflammatory factors in RAW264.7 cells. Moreover, DEXsp@Liposomes/C3F8 + HIFU effectively alleviated the symptoms of RA in model rats and significantly improved their exercise capacity. In conclusion, the prepared ultrasound-mediated DEXsp@Liposomes/C3F8 system exhibits good imaging, monitoring and therapeutic effects, and the results of this study provide a new direction for the diagnosis and treatment of RA.
研究领域:
医学
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生物工程
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药理学
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PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2026
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IF 2.5
Jin-Chan Liu,Ren-Ju Yang,Ya-Wen Liu,Fei He
Glucocorticoid-induced skeletal muscle atrophy is characterized by progressive loss of muscle mass and function, yet effective pharmacological interventions remain limited. Prostaglandin E 2 (PGE 2 ) plays an important role in maintaining muscle regeneration, and its degradation is primarily controlled by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Here we investigated whether phillyrin, a natural lignan compound, protects against dexamethasone (DEX)-induced muscle atrophy in mice. Phillyrin treatment significantly attenuated DEX-induced reductions in muscle mass and improved grip strength and motor endurance. Histological analysis showed that phillyrin alleviated myofiber atrophy and preserved mitochondrial ultrastructure. Mechanistically, phillyrin suppressed the upregulation of 15-PGDH and restored intramuscular PGE 2 levels, accompanied by recovery of EP4 signaling. These changes were associated with inhibition of FOXO3a-mediated proteolysis and partial restoration of mTOR and PGC-1α signaling in skeletal muscle. Collectively, these findings indicate that phillyrin protects against glucocorticoid-induced muscle atrophy, potentially through modulation of the 15-PGDH/PGE 2 pathway. These findings suggest that phillyrin may represent a potential therapeutic candidate for the treatment of glucocorticoid-induced skeletal muscle atrophy.
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Chen Rui,Xu Xingjian,Zhu Chuansai,Li Bangliang,Liang Weijia,He Miao,Pan Jinjin,Chen Shengjie,Bao Hongying,Wu Zhenhua,Li Xiang,Guo Qian,Zhou Qiang,He Zuhong,Lin Sen
High-intensity noise exposure induces cochlear injury through mechanical trauma, disruption of ionic homeostasis, and secondary oxidative stress, ultimately leading to noise-induced hearing loss (NIHL). Increasing evidence suggests that oxidative stress not only causes direct cellular damage but also drives pathological remodeling of the cochlear microenvironment by triggering persistent inflammatory activation and disrupting endogenous nitric oxide (NO) biocatalytic regulation. However, current therapeutic strategies based solely on antioxidants or anti-inflammatory agents are insufficient to simultaneously restore inflammatory homeostasis and endogenous catalytic regulation within the injured cochlea. Here, we developed a carrier-free arginine–dexamethasone nanoplatform (AD NPs) through a one-step ultrasound-assisted self-assembly strategy to achieve biocatalytic remodeling of the pathological cochlear microenvironment. By integrating the anti-inflammatory activity of dexamethasone with the physiological substrate function of L-arginine for endothelial nitric oxide synthase (eNOS), AD was designed to coordinately suppress inflammatory signaling while supporting endogenous NO biocatalysis. The resulting nanoparticles exhibited an average diameter of approximately 169.9 nm, a positive surface charge (+ 17.18 mV), sustained drug release with accelerated release under H₂O₂-containing conditions, excellent biocompatibility, and prolonged AD-associated fluorescence in the cochlear region following tympanic bulla administration. In H₂O₂-induced cellular models, AD markedly reduced intracellular reactive oxygen species (ROS) accumulation, inhibited NF-κB signaling activation, promoted macrophage polarization toward a pro-repair phenotype, modulated eNOS/iNOS-associated NO biocatalytic regulation, improved endothelial functional phenotypes, and protected HEI-OC1 cells against oxidative injury. Furthermore, L-NAME markedly attenuated the AD-induced recovery of NO-related fluorescence, supporting the involvement of endogenous NOS activity in this response. In a C57BL/6 mouse model of NIHL, prophylactic administration of AD before noise exposure significantly preserved high-frequency hearing, reduced cochlear hair cell loss, maintained ribbon synapse integrity, and corrected the pathological imbalance between eNOS and iNOS within the stria vascularis. At the mechanistic level, AD remodeled the pathological cochlear microenvironment through coordinated suppression of ROS/NF-κB-mediated inflammatory activation and support of endogenous NO biocatalytic regulation, thereby interrupting the reciprocal amplification between inflammatory dysregulation and vascular-associated dysfunction following acoustic injury. Collectively, this work establishes a carrier-free biocatalytic nanoplatform that harnesses endogenous enzymatic regulation to remodel the pathological cochlear microenvironment. This strategy provides a mechanistic framework for microenvironment-oriented biocatalytic nanomedicine and offers a promising protective approach for preventing or mitigating noise-induced cochlear injury. Graphical Design rationale and biocatalytic protective strategy of the Arg–Dex self-assembled nanoplatform for noise-induced hearing loss.
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高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Yuming Chen,Jiayi Gu,Jian Liu,Ling Tong,Fuxin Shi,Xiaoqin Wang,Xueling Wang,Dehong Yu,Hao Wu
Background: Cisplatin is an extensively used anti-neoplastic agent for the treatment of various solid tumors. However, a high incidence of severe ototoxicity is accompanied by its use in the clinic. Currently, no drugs or therapeutic strategies have been approved for the treatment of cisplatin-induced ototoxicity by the FDA.Purpose: The purpose of this study was to investigate the otoprotective effects of dexamethasone (DEX)-loaded silk-polyethylene hydrogel (DEX-SILK) following round window membrane administration in the cisplatin-induced ototoxicity mouse model.Methods: The morphology, gelation kinetics, viscosity and secondary structure of the DEX-SILK hydrogel were analyzed. DEX concentration in the perilymph was tested at different time points following hydrogel injection on the RWM niche. Cultured cells (HEI-OC1), organ of Corti explants (C57/BL6, P0-2), and cisplatin-induced hearing loss mice model (C57/BL6) were used as in vitro and in vivo models for investigating the otoprotective effects of DEX-SILK hydrogel against cisplatin.Results: Encapsulation of DEX with a loading of 8% (w/v) did not significantly change the silk gelation time, and DEX was evenly distributed in the Silk-PEG hydrogel as visualized by scanning electron microscopy (SEM). The concentration of Silk majorly influenced DEX distribution, morphological characteristics, viscosity, and gelation time. The optimized DEX-SILK hydrogel (8% w/v loading, 15% silk concentration, 10 μl) was administered directly onto the RWM of the guinea pigs. The DEX concentration in the perilymph was maintained above 1 μg/ml for at least 21 days for the DEX-SILK, while it was maintained for less than 6 h in the control sample of free DEX. DEX-SILK (5-60 ng/ml) exhibited significant protective effects against cisplatin-induced cellular ototoxicity and notably reduced the production of reactive oxygen species (ROS). Eventually, pretreatment with DEX-SILK effectively preserved outer hair cells in the cultured organ of Corti explants and demonstrated significant hearing protection at 4, 8, and 16 kHz in the cisplatin-induced hearing loss mice as compared to the effects noted following pretreatment with DEX.Conclusion: These results demonstrated the clinical value of DEX-SILK for the therapy of cisplatin-induced ototoxicity.
研究领域:
药理学
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耳鼻喉科学
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材料科学
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DOI
PubMed
高影响因子
Frontiers in Oncology
·
2020
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IF 4.848
Chen Ying,Li Rui,Zhu Yuqi,Zhong Sixia,Qian Jinjun,Yang Dongqing,Jurczyszyn Artur,Beksac Meral,Gu Chunyan,Yang Ye
The discovery of artemisinin (ART) for malaria treatment won the 2015 Nobel Prize in Medicine, which inspired the rediscovery and development of ART for the treatment of other diseases including cancer. In this study, we investigated the potential therapeutic effect of ART and dihydroartemisinin (DHA) on multiple myeloma (MM) cells including primary MM cells and in 5TMM3VT mouse model. Both in vitro and in vivo experiments showed that DHA might be a more promising anti-MM agent with significantly improved efficacy compared to ART. Mechanistic analyses suggested that DHA activated the mitochondrial apoptotic pathway by interacting with ferrous (Fe2+) ions and oxygen to produce reactive oxygen species (ROS). Intriguingly, DHA could reverse the upregulated expression of B-cell lymphoma 2 (Bcl-2) protein, a typical mitochondrial apoptotic marker, induced by dexamethasone (Dexa) in MM. We further demonstrated that DHA treatment could overcome Dexa resistance and enhance Dexa efficacy in MM. Additionally, DHA combined with Dexa resulted in increased ROS production and cytochrome C translocation from the mitochondria to the cytoplasm, resulting in alterations to the mitochondrial membrane potential and caspase-mediated apoptosis. In summary, our study demonstrated that DHA was superior to ART in MM treatment and overcame Dexa resistance both in vitro and in vivo, providing a promising therapeutic strategy for MM therapy.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Renshu Zhang,Jianhong Zhou,Dan Lin,Yuhan Hu,Bo Jin,Yuqin Wang,Jiaqing Wang,Serhii Vakal,Xingyi Li
Glucocorticoids ( e.g., dexamethasone (Dex)) are the mainstay in the treatment of non-infectious uveitis, but optimal drug delivery system to maximally realize its potent bioactivity is still lacking. In the present study, we rationally designed and screened a dexamethasone-peptide amphiphile (Dex-GGD), which instantly formed a prodrug supramolecular hydrogel in phosphate-buffered saline (PBS, pH = 7.4) without external stimuli for the topical ocular drug delivery. The obtained Dex-GGD hydrogel was thoroughly characterized by rheology, circular dichroism (CD), and transmission electron microscopy (TEM). The results showed that Dex-GGD exhibited a potent in vitro anti-inflammatory capacity in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages with minimal cytotoxicity against L-929 fibroblasts, ARPE-19 cells, and RAW 264.7 macrophages. In a rat model of experimental autoimmune uveitis (EAU), the severity of uveitis was significantly alleviated after the treatment with Dex-GGD hydrogel owing to its potent ability to reduce the influx of inflammatory cells from peripheral blood and suppress the activation of macroglia and microglia in the retina. In contrast to the treatment with an equivalent dose of dexamethasone sodium phosphate (Dexp), the intravitreal injection of Dex-GGD hydrogel hardly induced the apparent ocular side-effects ( e.g. , elevated intraocular pressure or fundus blood vessel tortuosity). As a result, the proposed Dex-GGD prodrug supramolecular hydrogel may be an effective and safe therapeutic option for improving the clinical management of uveitis.
研究领域:
药学
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眼科
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免疫学
·
药物递送系统
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DOI
高影响因子
AAPS PHARMSCITECH
·
2019
·Vol. 20
·期 8
·1-10
·
IF 2.608
Wang Xinxin,Feng Yan,Fu Jijun,Wu Cuishuan,He Bing,Zhang Hua,Wang Xueqing,Dai Wenbing,Sun Yong,Zhang Qiang
Glucocorticoids have been confirmed to be effective in the treatment of a variety of inflammatory diseases. However, their application encounters limitations in terms of tissue distribution and bioavailability in vivo . To address these key issues, we designed and developed a nanopreparation by using egg yolk lecithin/sodium glycocholate (EYL/SGC) and utilize such mixed micelles (MMs) to encapsulate dexamethasone palmitate (DMP) for the treatment of rheumatoid arthritis (RA). The prepared DMP-MMs had an average particle size of 49.18 ± 0.43 nm and were compared with an emulsion-based dexamethasone palmitate. Pharmacokinetic and in vivo fluorescence imaging showed that mixed micelles had higher bioavailability and targeting efficiency in inflammatory sites. An arthritis rat model was established via induction by Complete Freund’s Adjuvant (CFA), followed by the efficacy studies by the observations of paw volume, histology, spleen index, pro-inflammatory cytokines, and CT images. It was confirmed that intravenous injection of DMP-MMs exhibited advantages in alleviating joint inflammation compared with the emulsion system. Composed of pharmaceutical adjuvants only, the nanoscale mixed micelles seem a promising carrier system for the RA treatment with lipophilic drugs.
研究领域:
药剂学
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药理学
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纳米技术
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炎症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
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IF 6.6
Kai Dong,Ying Zhang,Hong Rui Ji,Ze Lin Guan,Dan Yang Wang,Zi Yang Guo,Shu Jing Deng,Bin Yang He,Jian Feng Xing,Cui Yu You
Background The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms.Purpose A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects.Methods Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model.Results The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy.Conclusion The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.
研究领域:
药学
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免疫学
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消化病学
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2023
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IF 5.7
Xiaojing He,Zhining Li,Mengling Ye,Chen Zhao,Siyi Wu,Yi Qin,Youyuan Guo,Lu Zhang,Fei Lin
Introduction: Dexamethasone (DEX), as an important enduring-effect glucocorticoid (GC), holds great promise in the field of lung ischemia-reperfusion injury (LIRI) comprehensive therapy owing to its immunomodulatory properties, such as inducing apoptosis and cell cycle distribution. However, its potent anti-inflammatory application is still restricted because of multiple internal physiologic barriers. Methods: Herein, we developed upconversion nanoparticles (UCNPs) coated with photosensitizer/capping agent/fluorescent probe-modified mesoporous silica (UCNPs@mSiO 2 [DEX]-Py/β-CD/FITC, USDPFs) for precise DEX release synergistic LIRI comprehensive therapy. The UCNPs were designed by covering an inert YOF:Yb shell on the YOF:Yb, Tm core to achieve high-intensity blue and red upconversion emission upon Near-Infrared (NIR) laser irradiation. Results: Under suitable compatibility conditions, the molecular structure of photosensitizer can be damaged along with capping agent shedding, which endowed USDPFs with an outstanding capability to carry out DEX release controlling and fluorescent indicator targeting. Furthermore, the hybrid encapsulating of DEX significantly increased utilization of nano-drugs, improving the water solubility and bioavailability, which was conducive to developing the anti-inflammatory performance of USDPFs in the complex clinical environment. Discussion: The response-controlled release of DEX in the intrapulmonary microenvironment can reduce normal cell damage, which can effectively avoid the side effects of nano-drugs in anti-inflammatory application. Meanwhile, the multi-wavelength of UCNPs endowed nano-drugs with the fluorescence emission imaging capacity in an intrapulmonary microenvironment, providing precise guidance for LIRI.
研究领域:
纳米技术
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药学
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生物医学工程
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药物递送系统
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免疫学
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治疗学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）