Science Advances
·
2025
·Vol. 11
·期 10
·
IF 12.5
Chuhan Wang,Xiaobing Liu,Wenyan Lv,Xiao Kuang,Feng Wu,Xianqun Fan,Yan Pang
Topical drug delivery on ocular surface always suffers from frequent administration and low bioavailability due to short drug residence. Despite advances of different adhesive ophthalmic drugs in extending release, cornea and eyelid nonselective adhesion inevitably causes ocular discomfort and even damage. Here, we describe in situ formation of an adhesive lubricative Janus nanocoating (ALJN) to enable long-lasting comfort drug delivery. By iron complexation, an asymmetric ALJN is formed on ocular surface via facile sequential instillation. The adhesive polyphenol inner layer binding with ocular surface enables drug loading and sustained release, while the lubricative zwitterionic polymer outer layer prevents eyelid adhesion to ensure comfort. Following instillation, ALJN retains on ocular surface over 24 hours and reduces blinking frequency to normal level. Moreover, ALJN demonstrates remarkable therapeutic potential in mouse and rabbit models of corneal contusion and alkali burn. This work proposes a comfortable long-lasting topical delivery platform for treating various ocular diseases.
研究领域:
眼科
·
药剂学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Jia Liu,Yingni Xu,Yongrui Huang,Xiaomin Sun,Yuehai Peng,Wenjing Song,Jin Yuan,Li Ren
Corneal alkali burn is one of the most devastating ophthalmic emergencies correlated with remarkable morbidity resulting in severe visual impairment. Appropriate intervention in the acute phase determines the eventual outcome for later corneal restoration treatment. Since the epithelium plays an essential role in inhibiting inflammation and promoting tissue repair, sustained anti-matrix metalloproteinases (MMPs) and pro-epithelialization are the prior remedies during the first week. In this study, a drug-loaded collagen membrane (Dox-HCM/Col) that could be sutured to overlay the burned cornea was developed to accelerate the early reconstruction. Doxycycline (Dox), a specific inhibitor of MMPs, was encapsulated in collagen membrane (Col) through hydroxypropyl chitosan microspheres (HCM) to develop Dox-HCM/Col, affording a preferable pro-epithelialization microenvironment and an in-situ controlled release. Results showed that loading HCM into Col prolonged the release time to 7 days, and Dox-HCM/Col could significantly suppress the expression of MMP-9 and -13 in vitro and in vivo . Furthermore, the membrane accelerated the corneal complete re-epithelialization and promoted early reconstruction within the first week. Overall, Dox-HCM/Col was a promising biomaterial membrane for treating alkali-burned cornea in the early stage, and our attempt may provide a clinically feasible method for the ocular surface reconstruction.
研究领域:
眼科
·
生物材料
·
组织工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Manli Deng,Zhongxing Chen,Xiaomin Huang,Aodong Chen,Jiawei Li,Wei Wang,Qingyi Gao,Lingxin Chen,Qianfang Ye,Yue Wu,Jun Zou,Mei Yang,Bowen Tan,Zheyu Li,Lin Xu,Xingtao Zhou,Xiaoying Wang,Jinhai Huang
Corneal alkali burns (CAB) represent an ophthalmic emergency and pose a significant challenge due to extremely severe complications and poor prognosis. The CAB-induced vicious cycle that involves oxidative stress, sustained inflammation, limbal stem cell deficiency, and delayed epithelial healing critically disrupts ocular surface homeostasis, rendering conventional corticosteroid monotherapy insufficient. Herein, this study proposes a synergistic treatment approach regulating cellular stemness and oxidative microenvironment against CAB. The framework nucleic acids (FNAs) are developed to load L-ascorbic acid 2-phosphate (AA2P) with high loading capacity. The resulting FNAs-AA2P significantly inhibits the oxidative stress, mitochondrial membrane potential abnormality, and apoptosis of corneal epithelial progenitor cells (TKE2) under alkali conditions in vitro. Furthermore, FNAs-AA2P regulates the expression of critical markers (e.g., K14, P63, and SOX2), associated with enhanced proliferation and stemness of TKE2 cells. Therapeutically, the multifunctional FNAs-AA2P exhibits superior therapeutic efficacy in the CAB mouse model by accelerating epithelium recovery, mitigating corneal opacity, and suppressing corneal neovascularization. This synergistic treatment approach not only represents a promising candidate for CAB but also offers valuable insights for the management of other multifactorial disorders.
研究领域:
眼科学
·
分子生物学
·
纳米医学
·
干细胞生物学
·
氧化应激
·
炎症免疫
·
药物递送系统
·
转化医学
✓ 已验证
产品关联
DOI
高影响因子
CURRENT EYE RESEARCH
·
2022
·
IF 2.555
Xiaotian Liu,Shanjun Wu,Yan Gong,Lili Yang
Purpose To compare the therapeutic effects of different forms of nintedanib ophthalmic preparations on neovascularization corneal alkali burns in rats.Methods Forty rat models of left eye corneal alkali burns were constructed, and the five groups (N = 8) were treated with normal saline, dexamethasone ointment (dexamethasone), 0.2% nintedanib aqueous solution and nintedanib nano thermoreversible hydrogel (NNTH). A slit lamp microscope was used to observe the area of neovascularization. The levels of the inflammatory factors were detected by ELISA. HE staining was performed on the rat corneas. Vascular endothelial growth factor (VEGFA) was detected by immunohistochemistry, and the expression of corneal VEGFA and CD31 was detected by western blotting. An MTT assay was performed to detect the cytotoxicity of nintedanib on human corneal epithelial cells (HCECs) and human umbilical vein vascular endothelial cells (HUVECs). Cell migration was detected by a cell scratch assay, and the proportion of apoptotic cells was detected by Annexin/PI double staining. Immunofluorescence and western blotting were performed to detect the protein expression of VEGFA and CD31.Results NNTH had a stronger inhibitory effect on corneal neovascularization (CNV) in alkali-burned rats while reducing the level of inflammatory factors. NNTH had a longer drug duration of release than nanoformulations in vitro. Nintedanib at low concentrations (<8 μM) had no significant cytotoxicity to HCECs but significantly induced apoptosis and inhibited the expression of VEGFA and CD31 and the migration of HUVECs.Conclusions Nanomorphic thermoreversible hydrogel is superior among the nintedanib ophthalmic preparations, showing better inhibition of CNV in alkali-burned eyeballs and it blocked the migration and proangiogenic ability of HUVECs.
研究领域:
眼科学
·
药剂学
·
细胞生物学
·
炎症
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 7
·2531-2542
·
IF 6.6
Zongjian Sun,Mingxin Zhang,Yanjun Wei,Mengshuang Li,Xianggen Wu,Meng Xin
A simple but novel ophthalmic solution based on two approved drugs was developed to reposition existing drugs to treat new diseases. This nanoformulation was developed using the phytochemical drug glycyrrhizin as an amphiphilic nanocarrier to micellarly solubilize empagliflozin (EMP), an oral drug that is widely used to control high blood glucose but has poor water solubility. This novel nanoformulation, which we designated the EMP@glycymicelle ophthalmic solution, was obtained using a simple preparation process. The resulting solution was a clear solution with an EMP encapsulation efficiency of 97.91 ± 0.50%, a small glycymicelle size of 6.659 ± 0.196 nm, and a narrow polydispersity index of 0.226 ± 0.059. The optimized formulation demonstrated that EMP was soluble in water up to 18 mg ml−1 because of its encapsulation within glycymicelles. The EMP@glycymicelle ophthalmic solution exhibited excellent characteristics, including good storage stability, fast in vitro release profiles, improved in vitro antioxidant activity, and no ocular irritation. Ocular permeation evaluation showed that the EMP@glycymicelle ophthalmic solution had strong ocular permeation of EMP, and it reached the posterior segment of mouse eyes after ocular topical administration. The treatment efficacy evaluation showed that the EMP@glycymicelle ophthalmic solution had a significant effect against corneal alkali burns in mice, prompting corneal wound healing, recovering corneal sensitivity, reducing corneal haze, and relieving corneal NV invasion. The mechanism of inhibiting HMGB1 signaling was involved in this strong treatment effect. These results indicated that the EMP@glycymicelle ophthalmic solution provided a new concept of drug repurposing and a promising ocular system for the nano-delivery of EMP with significantly improved in vivo profiles.
研究领域:
药学
·
眼科
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Gels
·
2023
·Vol. 9
·期 9
·676
·
IF 4.6
Jun Zhang,Kun Xi,Guohua Deng,Xi Zou,Peirong Lu
Ocular alkali burns recruit neutrophils and triggers neutrophil extracellular trap (NET)-neovascularization cascade effects that limit ocular surface reconstruction and functional repair. However, effective inhibition of the release of neutrophil extracellular traps after a corneal chemical injury, coordination of intrinsic immunity with corneal repair, and exploration of more effective and non-invasive drug-delivery modes are still urgently needed. Using an in vitro coculture system, we found that an alkaline environment stimulates neutrophils to release NETs, which can be regulated by deoxyribonuclease I (DNase I). Inspired by this, we loaded DNase I, which effectively regulates NETs, onto chitosan nanoparticles and combined them with silk fibroin to construct a composite hydrogel that can sustainably regulate NETs. The hydrogel reduced neutrophil extracellular trap production by 50% and neovascularization by approximately 70% through sustained DNase I release after a corneal alkali burn. The complex hydrogel promotes ocular surface reconstruction by modulating the intrinsic immune-cascade neovascularization effect, providing a new research basis for the construction of nanobiomaterials that modulate pathological neovascularization.Keywords:composite hydrogel;neutrophil extracellular traps;corneal alkali burn;neovascularization
研究领域:
生物材料
·
免疫学
·
眼科学
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
·
2022
·Vol. 261
·期 3
·723-734
·
IF 3.535
Zhou Jin,Ding Yuanyuan,Zhang Yongqiang,Zheng Dehui,Yan Lifeng,Guo Mengxiang,Mao Yani,Yang Lihong
Purpose This study was aimed at exploring the function of Exosomes isolated from bone marrow-derived mesenchymal stem cells (BMSC-Exos) in corneal wound healing and at revealing the underlying mechanisms involving the p44/42 mitogen-activated protein kinase (MAPK) pathway. Methods The isolated BMSC-Exos were identified by transmission electron microscopy, Western blot, and nanoparticle tracking analysis. After coculture with BMSC-Exos, the proliferation and migration of human corneal epithelial cells (HCEs) were evaluated. The protein expression of p-MEK/MEK and p44/42 MAPK was detected by Western blot. A mouse model of alkali-burned cornea was established via NaOH exposure. After injection with BMSC-Exos, the pathological changes and expression of α-SMA (a fibrosis marker) and CD31 (a vascularization marker) in corneal tissues were detected. Results BMSC-Exos enhanced the proliferation and migration of HCEs in a dose-dependent manner. The p44/42 MAPK pathway was activated by the treatment of BMSC-Exos, and its blocking using U0126 partially abrogated the effects of BMSC-Exos on promoting the proliferation and migration of HCEs. In vivo , the injection of BMSC-Exos facilitated the remission of the pathological changes (inflammation) and weakened the upregulation of α-SMA (fibrosis) and CD31 (vascularization) in corneal tissues of mice with alkali-burn injury. Conclusion BMSC-Exos promoted the proliferation and migration of HCEs via activating the p44/42 MAPK pathway in vitro and also inhibited alkali burn-induced inflammation, fibrosis, and vascularization in corneal tissues in vivo . BMSC-Exos may be promising resources for promoting corneal wound healing.
研究领域:
眼科学
·
干细胞生物学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2024
·
IF 5.7
Wang Yanan,Shi Shaohua,Zhang Ling,Wang Songtao,Qin Hongqing,Wei Yanjun,Wu Xianggen,Zhang Mengmeng
Imatinib (IMB) is a type of tyrosine kinase inhibitor with great application potential for inhibiting corneal neovascularization (CNV), but its poor water solubility limits its application in eye disease treatment. In this study, novel IMB@glycymicelles entrapped in hydrogel (called IMB@glycymicelle-hydrogel) were prepared, characterized, and evaluated for their therapeutic effects on corneal alkali burn in mice. Imatinib could be successfully loaded in glycymicelles using glycyrrhizin as a nanocarrier with an optimized weight ratio of IMB:nanocarrier. The apparent solubility of IMB was significantly improved from 61.69 ± 5.55 μg/mL to bare IMB to 359,967.62 ± 20,059.42 μg/mL to IMB@glycymicelles. Then, the IMB@glycymicelles were entrapped in hydrogel fabricated with hydroxypropyl methylcellulose and sodium hyaluronate (HA) to prolong retention time on the ocular surface. Rabbit eye tolerance tests showed that IMB@glycymicelle-hydrogel possessed good ocular safety profiles. In a mouse model of corneal alkali burns, the topical administration of IMB@glycymicelle-hydrogel showed strong efficacy by prompting corneal wound healing, recovering corneal sensitivity, relieving corneal opacities, and inhibiting CNV, and these efficacy evaluation parameters were better than those of the positive drug HA. Overall, these results demonstrated that IMB@glycymicelle-hydrogel may be a promising candidate for the effective treatment of alkali ocular damage. Graphical abstract
研究领域:
药学
·
眼科
·
药物递送系统
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Xin Shi,Tong Zhou,Shenyu Huang,Yuejun Yao,Peifang Xu,Shaodan Hu,Chenxi Tu,Wei Yin,Changyou Gao,Juan Ye
s Ocular alkali burn is a serious ophthalmic emergency. Highly penetrative alkalis cause strong inflammatory responses leading to persistent epithelial defects, acute corneal perforation and severe scarring, and thereby persistent pain, loss of vision and cicatricial sequelae. Early and effective anti-inflammation management is vital in reducing the severity of injury. In this study, a double network biomaterial was prepared by compounding electrospinning nanofibres of thioketal-containing polyurethane (PUTK) with a reactive oxygen species (ROS)-scavenging hydrogel (RH) fabricated by crosslinking poly(poly(ethylene glycol) methyl ether methacrylate-co-glycidyl methacrylate) with thioketal diamine and 3,3′-dithiobis(propionohydrazide). The developed PUTK/RH patch exhibited good transparency, high tensile strength and increased hydrophilicity . Most importantly, it demonstrated strong antioxidant activity against H 2 O 2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH). Next, a rat corneal alkali burn model was established, and the PUTK/RH patch was transplanted on the injured cornea. Reduced inflammatory cell infiltration was revealed by confocal microscopy , and lower expression levels of genes relative to inflammation, vascularization and scarring were identified by qRT-PCR and western blot. Fluorescein sodium dyeing, hematoxylin and eosin (H&E) staining and immunohistochemical staining confirmed that the PUTK/RH patch could accelerate corneal wound healing by inhibiting inflammation, promoting epithelial regeneration and decreasing scar formation. Statement of significance Ocular alkali burn is a serious ophthalmic emergency, characterized with persistent inflammation and irreversible vision loss. Oxidative stress is the main pathological process at the acute inflammatory stage, during which combined use of glucocorticoids and amniotic membrane transplantation is the most widely accepted treatment. In this study, we fabricated a polyurethane electrospun nanofiber membrane functionalized with a ROS-scavenging hydrogel. This composite patch could be a promising amniotic membrane substitute, possessing with a transparent appearance, elasticity and anti-inflammation effect. It could be easily transplanted onto the alkali-burned corneas, resulting in a significant inhibition of stromal inflammation and accelerating the recovery of corneal transparency. The conception of ROS-scavenging wound patch may offer a new way for ocular alkali burn.
研究领域:
眼科学
·
生物材料科学
·
组织工程
·
伤口愈合
✓ 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）