Bioactive Materials
·
2022
·
IF 16.874
Mengna Li,Jing-Wei Xu,Jiayong Li,Wei Wang,Chenqi Luo,Haijie Han,Zhi-Kang Xu,Ke Yao
Postoperative endophthalmitis (POE) has been the most threatening complication after cataract surgery, which perhaps can be solved by the antibiotic-loaded intraocular lens (IOL). However, most drug-loaded IOLs demonstrate insufficient drug quantity, short release time, increased implantation-related difficulties or other noticeable drawbacks. To prevent POE and to address these deficiencies, a drug-loaded copolymer IOL, prepared from poly (urethane acrylate) prepolymer, isobornyl methacrylate (IBOMA), N-vinyl-2-pyrrolidone (NVP), Irgacure 819, RUVA-93, and gatifloxacin (GAT), was rapidly fabricated via photocuring and by using a 3D-printed mold. This composite displayed an outstanding and controllable GAT release behavior in vitro , a high light transmittance, and a moderate refractive index. Also, it demonstrated improved strain stress and elongation compared with the reference commercial acrylic IOL material. In vivo tests demonstrated satisfying released drug concentration at the early treatment stage. In vitro and in vivo studies further confirmed the remarkable bacterial inhibition and prevention of POE by the proposed IOL, which also displayed good biocompatibility. These findings suggested that the GAT-loaded IOL could be a promising implant to prevent and cure POE, also the proposed methods could inspire more designs for various medical applications.
研究领域:
眼科
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Zunzhen Ming,Lin Han,Huanhuan Zhu,Meiyu Bao,Qiangyuan Fan,Shaobo Xue,Kesheng Wang,Yue Zhang,Meiling Lu,Chongshun Xu,Qi Wu,Tingting Li,Fenyong Sun
Bacterial endophthalmitis is a serious ocular infection and frequently results in vision loss or even blindness. Most of the present treatment methods are mainly embodied in strengthening the bactericidal effect, whereas the bacteria induced vigorous host immune response often leads to irreversible damage to eye tissue. Herein, we report an injectable hydrogel to treat endophthalmitis by killing invading bacteria and regulating ocular immunity. The designed hydrogel was formed by dynamic coordination crosslinking of sulfhydryl modified gelatin and silver ion while embedding the anti-CXCL1 antibody evenly. The injectable hydrogel can not only kill bacteria by releasing silver ions with its degradation, but also alleviate the bacteria-triggered excessive immune response via releasing anti-CXCL1 antibody to neutralize chemokine CXCL1, thus avoiding the host inflammatory response mediated bystander damage. Both in vitro and in vivo experiments showed that it has excellent ability against bacteria and immunomodulatory performance, preserving more integral retinal architecture and promoting visual recovery. This work may open up new avenues for combining antibacterial and immunotherapy in infectious endophthalmitis.
研究领域:
眼科学
·
免疫学
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药学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
RESEARCH IN MICROBIOLOGY
·
2025
·
IF 3.4
Ping Lu,Juan Xue,Xuemeng Ji
Klebsiella pneumoniae is a major cause of endogenous endophthalmitis, a rapidly progressing intraocular infection associated with severe inflammation and vision loss. The vitreous body presents a hypoxic and iron-restricted environment, yet the bacterial metabolic adaptations that enable persistence in this niche remain largely unknown. Here, we show that K. pneumoniae undergoes metabolic reprogramming to facilitate intraocular survival, characterized by enhanced glycolysis and siderophore-mediated iron acquisition. Proteomic profiling under vitreous-mimicking conditions revealed significant upregulation of PfkA, PykF, and EntB. Targeted deletion of these genes impaired bacterial growth under hypoxia and iron limitation, and significantly reduced intraocular colonization, proinflammatory cytokine production, and visual impairment in a murine model. Double mutants lacking both glycolytic and iron acquisition pathways were nearly avirulent. Correspondingly, infected eyes exhibited lower levels of lactate and iron, reflecting reduced bacterial metabolic activity. These findings establish glycolysis and iron acquisition as critical determinants of K. pneumoniae virulence in the eye and provide insight into the metabolic strategies underpinning bacterial persistence in nutrient-limited host environments.
研究领域:
微生物学
·
免疫学
·
眼科学
·
代谢
·
发病机制
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yijing Li,Dan Lin,Jinrun Chen,Wenqiao Zhang,Huanting Jin,Shuqi Feng,Huanyu Mao,Jiabei Hou,Xingyi Li,Yuqin Wang,Jianhong Zhou
Autoimmune uveitis (AU) remains a leading cause of visual impairment and blindness worldwide, necessitating efficient and innovative therapeutic strategies to overcome the limitations of current clinical interventions. Capitalizing on the significant elevation of alkaline phosphatase (ALP) levels in intraocular tissues (vitreous humor, retina) during AU pathogenesis, we rationally designed an ALP-responsive self-delivering dexamethasone sodium phosphate (DexP) hydrogel using an ionic cross-linking approach. This DexP hydrogel serves as a sustained-release depot for adalimumab (ADA), enabling synergetic AU therapy through a simple combination of aqueous DexP and ADA solutions with calcium chloride under mild conditions, which facilitates controlled release of both therapeutics in an ALP-responsive manner. Importantly, in vivo experiments demonstrated that a single intravitreal (IVT) injection of ADA@DexP hydrogel significantly attenuated autoimmune intraocular inflammation by effectively inhibiting inflammatory cell infiltration, suppressing pro-inflammatory cytokines (IL-17 A, IL-1β, TNF-α), and preserving blood-retinal barrier (BRB) integrity. Furthermore, the intravitreal administration of ADA@DexP hydrogel exhibited excellent intraocular biocompatibility and a safety profile. Overall, this carrier-free ADA@DexP hydrogel represents a promising alternative strategy for AU therapy, particularly given that both DexP and ADA are FDA-approved clinical agents.
研究领域:
生物材料
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药物递送
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免疫治疗
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眼科
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2021
·
IF 10.041
Qianni Wu,Dong Liu,Wan Chen,Hui Chen,Cheng Yang,Xiangling Li,Chengduan Yang,Haotian Lin,Shuyi Chen,Ning Hu,Weirong Chen,Xi Xie
While intraocular lens (IOL) implantation is the only effective treatment for vision restoration in cataract patients, it is always suffering from the related complications after surgery. A leading post-implantation complication, posterior capsule opacification (PCO), is induced by the adhesion and proliferation of residual lens epithelial cells (LECs) on the IOL surface and posterior capsule. In recent years, various surface modified IOLs have been developed to reduce the incidence of PCO, however, these IOLs are rarely resistant to biofouling while maintaining close contact with the posterior capsule. This study reports a complex surface-functionalized hydrophobic acrylic IOL, namely (NT+LLL)-IOL, which can effectively prevent intraocular inflammation and the development of PCO. The surface of the hydrophobic IOL was functionalized with nanotopography and covalently conjugated with “liquid-like” polydimethylsiloxane brush. The (NT+LLL)-IOL was capable of inhibiting intraocular inflammatory responses triggered by bioadhesion and preventing residual LECs migration-induced PCO. Furthermore, the (NT+LLL)-IOL possessed advantages of optical transparency, excellent biocompatibility, and mechanical robustness despite the liquid-like layer coating. After in vivo implantation for 60 days, the (NT+LLL)-IOL could maintain optical properties by inhibiting intraocular inflammation, fibrous LEC proliferation, and further PCO occurrence, in contrast to the pristine IOLs which were prone to induce PCO after implantation. This technology provides a promising opportunity to develop an implantable IOL with reduced risks of post-operative complications and thus greatly beneficial for cataract patients.
研究领域:
眼科
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生物材料
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Xue Wu,Lianyi Yang,Qing Chen,Ruijin Ran,Jun Cao,Ming Zhang
Experimental autoimmune uveitis (EAU) is a widely used model for noninfectious uveitis (NIU), a sight-threatening autoimmune ocular disease. Although glucocorticoids remain the first-line therapy, their short half-life and frequent administration increase the risk of systemic and ocular side effects. Here, we report the development of microenvironment-responsive hydrogels with drug-loaded microspheres for sustained dexamethasone acetate release: dexamethasone acetateloaded microspheres (DAMS) and polyethylene glycol (PEG) hydrogel-encapsulated microspheres (DAMS@Gel). Poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated and subsequently embedded in pH-responsive and injectable hydrogel formed via Schiff base crosslinking. The materials were then thoroughly characterized.In vitro, both DAMS and DAMS@Gel showed excellent biocompatibility with retinal pigment epithelial (ARPE-19) cells, as confirmed by reactive oxygen species (ROS), apoptosis, cell cycle, and cytotoxicity assays. In vivo safety was verified through subconjunctival injection in rabbits. In the rat EAU model, intravitreal administration of DAMS and DAMS@Gel significantly alleviated ocular inflammation, as evidenced by ocular inflammatory symptom observations, fundus imaging, histopathological examination, and decreased glial activation. This study demonstrated that the DAMS and DAMS@Gel drug delivery systems were successfully established and exhibited sustained release properties and stable characteristics. In vitro and in vivo assays indicated that the biological materials had excellent biocompatibility. In addition, both of DAMS and DAMS@Gel exerted therapeutic effects on EAU model rats, and intraocular inflammation was markedly reduced. This research may provide a theoretical foundation for the treatment of uveitis with DAMS and DAMS@Gel.
✓ 已验证
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2022
·Vol. 10
·期 6
·
IF 9.043
Jun Ren,Menghuan Yu,Wenjin Gao,Chuanfan Ding,Shengjie Li,Shaoning Yu,Wenjun Cao
Prompt clinical diagnosis and antimicrobial therapy are key to managing infective endophthalmitis. The small volume of aqueous humor, low bacterial counts, and empirical medication by physicians make existing diagnostic methods time-consuming and imprecise. Here, we investigated the feasibility of combining Fc-containing mannose-binding lectin-coated Fe3O4 (Fc-MBL@Fe3O4) enrichment with matrix-assisted laser desorption–ionization time of flight mass spectrometry (MALDI-TOF MS) profiling to identify pathogens in aqueous humor. Aqueous humor aspirated from freshly enucleated porcine eyes was treated with different inocula of Staphylococcus aureus, Staphylococcus epidermidis, and Klebsiella pneumoniae. We performed identification directly in aqueous humor samples and after short-term culture of micro-LB broth. Aqueous humor endophthalmitis samples were enriched with Fc-MBL@Fe3O4 and analyzed using MALDI-TOF MS. The identification time and minimum bacterial concentration required for identification were determined. The enrichment efficiency of Fc-MBL@Fe3O4 for different bacteria was greater than (87.5 ± 5.0)%. The objects of direct identification include live bacteria and bacteria treated with antibiotics, which can be completed within 1.5 h. The minimum number of bacteria needed for positive identification was 2.20 × 106 CFU. For micro-LB broth culture, the identification of bacteria can be completed within 6.5 to 9.5 h for aqueous humor samples with an initial bacterial count of tens to hundreds.IMPORTANCE Fc-MBL@Fe3O4 capture not only live bacteria in aqueous humor but also bacteria inactivated by antibiotics. Fc-MBL@Fe3O4 combined with micro-LB broth culture significantly reduced the turnaround time (TAT) by more than half a day by shortening the time required for bacterial identification. Our findings demonstrate that combining Fc-MBL@Fe3O4 enrichment with MALDI-TOF MS identification is a fast, sensitive, and efficient analytical method with great potential for identifying pathogens in aqueous humor samples.
研究领域:
临床微生物学
·
质谱分析
·
眼科
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2021
·
IF 6.988
Yang Xiang,Rongrong Jin,Ying Zhang,Kaijun Li,Gongyan Liu,Xu Song,Yunbing Wang,Yu Nie
Hydrophobic acrylic intraocular lenses (IOLs) are widely used in cataract treatment for posterior capsule opacification (PCO) prophylaxis. However, undesired glistening and postoperative endophthalmitis are two major potential risks. Hence, a series of poly(2-phenoxyethyl methacrylate-co-2-phenoxyethyl acrylate-co-2-ethylhexyl methacrylate) (PPPE) acrylic IOL materials were synthesized for “glistening-free” optimization. The selected PPPE with 2% 2-ethylhexyl methacrylate showed excellent optical, foldable, and thermomechanical properties. The anterior surface of PPPE was coated with polydopamine followed by gentamycin conjugation (PDA/GS). It inhibited bacterial adhesion by 74% and decreased the biofilm thickness by 87%. In inflammatory mimicking conditions, bacterial proliferation was restrained, with acidic-dependent GS release behavior. The surface of PPPE toward the posterior capsule remained hydrophobic. It was conducive to human lens epithelial cell adhesion, collagen IV and fibronectin adsorption, and the following “sealed sandwich structure” formation. In summary, the PPPE with a dual-side heterogeneous surface displayed good application prospects in postoperative endophthalmitis and PCO prevention.
研究领域:
眼科
·
生物材料
·
材料科学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Hui Shi,Shuo Huai,Huiling Wei,Ying Xu,Lei Lei,Hao Chen,Xingyi Li,Huixiang Ma
Intraocular inflammation seriously impairs vision, and the effectiveness of intraocular drug delivery is hampered by various physiological barriers, such as the corneal barrier. In this paper, we present a simple approach to fabricating a dissolvable hybrid microneedles (MNs) patch for the efficient delivery of curcumin to treat intraocular inflammatory disorders. Water-insoluble curcumin was first encapsulated into polymeric micelles with high anti-inflammatory capacities, and then were combined with hyaluronic acid (HA) to create a dissolvable hybrid MNs patch using a simple micromolding method. Curcumin was amorphously dispersed within the MNs patch as indicated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analyses. According to an in vitro drug release study, the proposed MNs patch provided sustainable drug release over 8 h. Following its in vivo topical application, the MNs patch demonstrated an extended pre-corneal retention time over 3.5 h and exhibited great ocular biocompatibility . Additionally, such MNs patch could reversibly penetrate the corneal epithelium, generating an array of microchannels on the corneal surface, thereby increasing ocular bioavailability. Of greater significance, the use of MNs patch demonstrated the improved therapeutic effectiveness in treating endotoxin-induced uveitis (EIU) in a rabbit model compared to curcumin eye drops via a significant reduction in the infiltration of inflammatory cells such as CD45 + leukocytes and CD68 + macrophages. Overall, the topical application of the MNs patch as an efficient ocular drug delivery system could potentially serve as a promising approach for treating different types of intraocular disorders.
研究领域:
药学
·
生物医学工程
·
眼科
·
药物递送系统
✓ 已验证
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）