JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
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IF 5.062
Han Qiao,Zhuo Xu,Mengchi Sun,Shuwen Fu,Fangxue Zhao,Danping Wang,Zhonggui He,Yinglei Zhai,Jin Sun
Dry eye disease (DED) is a public health concern that cause ocular discomfort and visual disturbance, which seriously affect quality of life. Rebamipide (RBM) is one of the drugs used for DED treatment, the ophthalmic RBM suspension (Mucosta®) has been used to treat DED in Japan. However, due to the drug removing through the nasolacrimal duct, the residence time of suspension on the ocular surface is short. RBM in excess of the therapeutic dose irritate the ocular surface and cause more tear production. Moreover, the opaque and turbid appearance of the suspension can lead to blurred vision after administration. In this study, we designed RBM liposomal eye drops for the treatment of DED, which have great stability, good patient compliance and a slow-release rate. RBM liposomes were prepared by remote loading technique and optimized for different formulation parameters. The appropriate HSPC-to-Chol ratio, drug-to-lipid ratio, calcium acetate solution concentration, incubation time and temperature were selected according to the encapsulation efficacy of RBM liposomes. The encapsulation efficacy and in vitro release of RBM were evaluated. The retention, tolerability and therapeutic effect of RBM liposomes were evaluated in rats. The ocular distribution of RBM was evaluated in vivo in rabbits’ eyes. The retention time of RBM liposomes in the cornea is longer than that of suspensions. While reducing the drug dose and irritation to ocular surface, RBM liposomes maintain the same efficacy and increase the concentration in cornea and aqueous humor. RBM liposomes suggested a further application in ophthalmic therapy, especially for DED.
研究领域:
药学
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眼科
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Xiaopei Ma,Yaodong Liu,Jun Wang,Hui Liu,Gang Wei,Weiyue Lu,Yu Liu
Strong precorneal clearance mechanisms including reflex blink, constant tear drainage, and rapid mucus turnover constitute great challenges for eye drops for effective drug delivery to the ocular epithelium. In this study, cyclosporine A (CsA) for the treatment of dry eye disease (DED) was selected as the model drug. Two strategies, PEGylation for mucus penetration and cationization for potent cellular uptake, were combined to construct a novel CsA nanosuspension (NS@lipid-PEG/CKC) by coating nanoscale drug particles with a mixture of lipids, DSPE-PEG2000, and a cationic surfactant, cetalkonium chloride (CKC). NS@lipid-PEG/CKC with the mean size ∼173 nm and positive zeta potential ∼+40 mV showed promoted mucus penetration, good cytocompatibility, more cellular uptake, and prolonged precorneal retention without obvious ocular irritation. More importantly, NS@lipid-PEG/CKC recovered tear production and goblet cell density more efficiently than the commercial cationic nanoemulsion on a dry eye disease rat model. All results indicated that a combination of PEGylation and cationization might provide a promising strategy to coordinate mucus penetration and cellular uptake for enhanced drug delivery to the ocular epithelium for nanomedicine-based eye drops.
研究领域:
药剂学
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眼科医学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·Vol. 37
·期 19
·2415353
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IF 26.8
Ming Shao,Yu Chai,Yutong Jiang,Xinyi Wu,Wenjie Xie,Jiayi Lu,Xuehui Fu,Yao He,Xiaofeng Zhang,Han Zhang,Zhuang Liu
Dry eye disease (DED), the most prevalent ophthalmological condition worldwide, can cause severe ocular discomfort and even visual impairment. Effective yet safe therapeutics for severe DED are still highly demanded. Herein, considering the important role of excessive reactive oxygen species (ROS) in triggering DED, an eye-drop nano-formulation of catalase (CAT) self-assembled with cysteine-modified chitosan (CS-Cys) is designed for DED treatment. Upon eye-drop administration of CS-Cys/CAT nanoparticles, CS-Cys can form disulfide bonds with abundant thiols in the mucin layer of the tear film, anchoring catalase to the corneal surface. Thus the excess ROS accumulated on the ocular surface can be effectively eliminated, resulting in a regulated tear microenvironment. In mouse and rabbit models, it is verified that CS-Cys/CAT eye drops can offer excellent therapeutic effects, especially in promoting the recovery of damaged epithelium and increasing tear secretion. Remarkably, CS-Cys/CAT eye drops showed notably better therapeutic performance than clinically used cyclosporin and dexamethasone, as well as several new DED drugs in clinical trials. Thus, the work presents a unique nanoparticulate eye-drop-based ocular delivery system to allow prolonged ocular retention of protein therapeutics, and such nanoformulation formulated by fully biocompatible/biodegradable components possesses significant translational potential for effective and safe DED treatment.
研究领域:
药剂学
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眼科
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生物材料学
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产品关联
DOI
PubMed
高影响因子
ANALYST
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2025
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IF 3.3
Wei Wei,Yiwei Zhang,Mengdi Yu,Di Shen,Xiyu Sun,Mingshi Fu,Chi Zhang,Zhenzhen Jia,Mingzhen Zhang
Dry eye disease (DED) is a prevalent condition characterized by a multifaceted etiology, with its incidence exhibiting an upward trajectory. Consequently, it is imperative to develop a sensitive, straightforward, and convenient method for the analysis of biomarkers associated with DED to facilitate its auxiliary diagnosis. Lysozyme (LYZ), produced by the lacrimal gland, is a class of antibacterial enzymes believed to play a crucial role in immunity and is associated with DED. In this study, a novel fluorescent sensing platform utilizing neutral red-heparin sodium (NR-HS) was developed with LYZ as the target. The platform operates on the principle of static quenching, where HS effectively quenches the fluorescence of NR. As a hydrolase, LYZ can catalyze the hydrolysis of the glucoside bond in HS, thereby modulating the transformation of NR-HS fluorescence signal. This provides a straightforward fluorescent method for monitoring LYZ levels. Under optimal conditions, the developed "on-off-on" NR-HS sensing platform demonstrated the capability to detect LYZ within a range of 0.5 to 10 µg/mL, with a detection limit of 0.42 µg/mL, and exhibited enhanced specificity for LYZ. In conclusion, a cost-effective, rapid, and efficient LYZ sensing platform was established, which facilitates the diagnosis of DED and shows potential as a diagnostic detection technique.
研究领域:
医学诊断
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
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2023
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IF 3.8
Qiuhe Wang,Zheng Wu,Feifei Wang,Hua Zhang,Li Gan
Dry eye disease (DED) is a highly prevalent ocular surface disease that affects life quality and reduces productivity at work. The purpose of this study is to improve the efficacy of tacrolimus (FK506) in the treatment of DED using the special eye surface retention properties of cationic nanoemulsion (CNE) modified by thermosensitive in-situ gel (ISG) (CNE-ISG). The precorneal retention of CNE-ISG containing 0.05% FK506 (50 min) was longer than that of CNE containing 0.05% FK506 (25 min) and commercial suspension containing 0.1% FK506 (Talymus®) (10 min). Successfully modeled dry-eye rabbits were treated with 0.05% CNE-ISG (twice/day), 0.05% CNE and 0.1% suspension (Talymus®) (thrice/day). Schirmer's tear secretion test showed no significant difference between the CNE-ISG group and the healthy group after 5 days of treatment ( p > 0.05). The results of a tear ferning test (TFT) showed that the tear-fern-like crystal branches in the CNE-ISG group returned to normal after 5 days of treatment. Histological analysis showed that the number of goblet cells in the CNE-ISG group significantly increased. HET-CAM stimulation test showed that the CNE-ISG group had no ocular irritation. The above results indicated that CNE-ISG might be a promising delivery system and as an effective dosage form was employed for FK506 in the treatment of DED.
研究领域:
药剂学
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眼科医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
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IF 8.456
Sen Lin,Chaoxiang Ge,Doudou Wang,Qi Xie,Biao Wu,Jingjie Wang,Kaihui Nan,Qinxiang Zheng,Wei Chen
The sealed anatomical features of the eye and its physiological activity that rapidly removes drugs are called anatomical and physiological barriers, which are the cause of more than 90% of drug loss. This aspect remains a critical issue in eye surface medication. Thus, promoting tissue permeability of drugs as well as prolonging their retention on the eye surface can improve their bioavailability and enhance their therapeutic effects. Thanks to the existence of a negatively charged mucin layer on the eye surface, several peptide-decorated polymeric micelles were prepared to enhance the interaction between the micelle and eye surface, thus prolonging the drug retention on the eye surface and promoting its tissue permeability. Tacrolimus (also known as FK506) is a hydrophobic macrolide immunosuppressant used to treat dry eye syndrome and other eye diseases. However, its hydrophobic nature makes its delivery as a topical eye surface medication difficult, with the risk of side effects due to overdoses. Therefore, the aim of this work is to evaluate the ability of FK506 micelles in promoting their permeability on the eye surface. Our results showed that the positively charged nanomicelles could significantly prolong FK506 retention on the eye surface and enhance its corneal permeability in ex vivo and in vivo conditions. FK506 nanomicelles exhibited superior curing effects against dry eye diseases than the FK506 suspension and a commercial FK506 formula. It exerted better inhibitory effects on eye surface inflammation and corneal epithelium apoptosis when examined by a slip lamp and a transferase-mediated dUTP nick end labeling assay, respectively. Further assays revealed the higher suppressive effects on the expression of several inflammation-related factors at an mRNA and protein level. Hence, our results suggested that these positively charged nanomicelles might be a good drug delivery system for ocular surface medication.
研究领域:
药剂学
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眼科医学
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生物材料
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Ronggang Liu,Xiumin Zhang,Siyuan Fei,Mingqian Tan
The excessive production of reactive oxygen species (ROS) inside mitochondria is a significant factor in the perpetuation of dry eye disease (DED), and it may be a key target for DED treatment. In this work, we designed and prepared orally deliverable lutein nanoparticles formulated with phycocyanin, chitosan modified with triphenylphosphonium (TPP), and yeast β-glucan modified with 3-boronobenzoic acid. These nanoparticles possess dual-targeting abilities for microfold cells in Peyer’s patches and ocular cell mitochondria to intervene in DED. Our data demonstrated that the dual-targeted lutein nanoparticles effectively accumulated within Peyer’s patches and were endocytosed by resident immune cells. In vitro results demonstrated that dual-targeted lutein nanoparticles showed excellent mitochondrial targeting ability with a Pearson correlation value of 0.86 after incubation for 4 h. In vivo results showed that the accumulation of lutein in mouse eye mitochondria increased by 2.36 times. Furthermore, the dual-targeted lutein nanoparticles alleviated oxidative stress damage of the cornea by reducing ROS levels in the cornea, and reduced corneal inflammation and keratinization, thus alleviating DED. The novel lutein nanoparticles with dual abilities to improve absorption efficiency and target mitochondria can be used as a promising candidate for oral intervention in DED.
研究领域:
药学
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生物医学工程
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眼科
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
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2024
·Vol. 14
·期 49
·36804-36815
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IF 3.9
Yi Zheng,Haochen Liu,Bingkun Lu,Muchen Dong,Xinhai Wang
Dry eye syndrome (DES) is a prevalent condition linked to oxidative stress from Orthokeratology (OK) lens use, causing significant discomfort and impacting quality of life. Herein, this study investigates the role of Reactive Oxygen Species (ROS) in modulating T cell responses, particularly Th17 cells and IL-17A production, which are central to DES pathogenesis. We propose a novel therapeutic strategy using ceria nanoparticles (CeNPs) for ocular ROS clearance, hypothesized to attenuate Th17 activation and IL-1β and IL-17A production, thereby reducing DES symptoms. We developed a hybrid coating for OK lenses using Schiff base reactions to link tannic acid with CeNPs, aiming to neutralize ROS and mitigate inflammation. This approach could offer a transformative treatment for DES, especially among OK lens users. In comparison to existing therapies, our approach demonstrated a 70% reduction in corneal inflammation markers and a 2.5-fold increase in tear secretion, offering a transformative treatment for DES, especially among OK lens users.
研究领域:
免疫学
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眼科
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纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
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IF 8.5
Donghao Gu,Le Zhou,Yanming Zhang,Haochun Jin,Wenlong Nie,Minquan Zhang,Yidian Dong
Dexamethasone (Dex) is a primary medication for treating dry eye syndrome, and tobramycin-dexamethasone eye drops are commercially available. However, the eye's complex physiological environment reduces its bioavailability, and repeated use can lead to significant systemic toxicity and side effects. This study introduces a novel conjugate of chitosan (CS) and N -acetylcysteine (NAC), a bioadhesive material, which was grafted onto the surface of a Dex-supported nanostructured lipid carrier (NLC) to develop an innovative nanoparticle lipid ocular drug delivery system (CS-NAC@Dex-NLC). The enhancements afforded by CS-NAC, such as adhesion, osmotic, and targeting properties, address the limitations of traditional eye drops. NMR characterization confirmed the successful synthesis of the copolymer (CS-NAC). Particle size (PS), zeta potential, and transmission electron microscopy (TEM) verified the proper formation of the CS-NAC@Dex-NLC system. Cytotoxicity tests confirmed its excellent biocompatibility and safety. Cellular uptake studies showed that CS-NAC@Dex-NLC achieved the highest efficiency. Pharmacokinetic assessments revealed a significant increase in Dex's bioavailability in tears and aqueous humor. In vitro corneal penetration and in vivo imaging experiments demonstrated effective corneal penetration and retention, enhancing the drug's duration on the ocular surface and overcoming the barrier effect. Pharmacodynamic studies in rabbits with dry eye syndrome indicated that CS-NAC@Dex-NLC effectively alleviates symptoms, repairs corneal damage, and stabilizes the tear film. ELISA results showed a reduction in inflammation caused by dry eye. These findings suggest that CS-NAC@Dex-NLC is a promising vector for dry eye treatment, offering significant clinical relevance.
研究领域:
药剂学
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眼科
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Lin Mimi,Sun Xueqin,Ye Sihao,Chen Youyi,Gao Jing,Yuan Feng,Lin Na,Lawson Tom,Liu Yong,Deng Ruzhi
Dry eye disease is a common condition that affects the eyes. It is caused by problems with the tear film and the tear dynamics. Dry eye can be caused by an increase in the amount of reactive oxygen species (ROS) in the corneal epithelium. The treatment for dry eye typically focuses on relieving the uncomfortable symptoms by using eye drops such as artificial tears, antibiotics, and by using anti-inflammatory/immunosuppressive agents such as cyclosporine, and lifitegrast. However, the recovery of patients with dry eye can take several years particularly if the symptoms are severe. This is because the present treatment approaches for dry eye are not based on its cause, e.g., the oxidative stress arising from the rapid increase in ROS. This work describes a new type of antioxidant made from pterostilbene (PS) and carboxyl-chitosan modified graphene (CG). The use of a hydrophilic two-dimensional CG nanosheet to improve the properties of PS is reported. Superior enhanced properties including better cellular permeability, long sustained release period (over 30 h), and antioxidant properties, were realized by using PS-CG. A hyperosmotic (HS) damaged human corneal epithelial cell (HCEC) model was used for antioxidant tests. This model has an intracellular ROS level 4 times more than that of a control group. The ROS content was declined efficiently to the same amount as normal cells in the PS-CG treated HS group. There was a significant decline in the content of lactate dehydrogenase (LDH) and the apoptosis rate of HCEC in the PS-CG treated HS group when compared to that seen in the HS model. Real-time polymerase chain reaction (PCR) and western blots (WB) were used to understand the antioxidant mechanism of PS-CG. The results showed that the antioxidant was working by activating the Keap1-Nrf2-ARE signalling pathway. In vivo testing testing using a dry eye mouse model suggested that the PS-CG acted as an efficient antioxidant. More tear production and healthier corneal and conjunctival epithelial cells were achieved when PC-CG was applied to this model. The use of PS-CG could be a new strategy for treating dry eye and other ocular diseases caused by ROS.
研究领域:
眼科
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药理学
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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
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Lidan Zhang,Chengxin Tian,Chunying Zhao,Guangjie Wang,Miaomiao Pei,Changshan Sun,Tongying Jiang
The purpose of this study was to develop an ophthalmic preparation (LA/Res/HP-β-CD) containing alpha-lipoic acid (LA) and resveratrol (Res)/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex and to investigate the effect of LA/Res/HP-β-CD on medicating the dry eye disease. The inclusion complex of Res/HP-β-CD was prepared by solvent evaporation method to solve the poor water-solubility of Res, and the optimal proportion of resveratrol and lipoic acid in formulation was screened by hydroxyl radical scavenging test in vitro. Comparing with Res/HP-β-CD, the preparations of LA/Res/HP-β-CD had longer t 1/2 and larger AUC in tears, had more advantages in increasing Res concentration in cornea, conjunctiva and sclera, improving tear secretion and tear film stability, repairing the corneal epithelial and conjunctiva injury, improving mucin and inorganic salt components of tears, reducing pro-inflammatory factor IL-1β in the cornea, enhancing Vitamin D level of eyes. These results showed that LA improved the therapeutic effect of Res, and the combined preparations would exhibit a potential application prospect in treating dry eye disease.
研究领域:
药学
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眼科
✓ 已验证
DOI
高影响因子
BMC Ophthalmology
·
2018
·Vol. 18
·期 1
·1-11
·
IF 1.77
Li Shanshan,He Jiangnan,Chen Qiuying,Zhu Jianfeng,Zou Haidong,Xu Xun
Background Our study aimed to investigate the ocular surface health of Shanghai University students. Methods This is a cross-sectional study carried out among freshmen and sophomores on the main campus of Shanghai University. Questionnaires including the widely-used ocular surface disease index (OSDI) and the Zung Self-rating Anxiety Scale (SAS) were completed first, and then ocular examinations were conducted regarding height & weight, blood pressure and heart rate, optometry, intraocular pressure exam, vision and subjective refraction, Aladdin, Macular pigment density measurement, tear test, anterior segment examination, fundus photography, ophthalmologist check, TOPCON OCT check, and Collin’s fundus blood test. Results Totally 901 students were involved in our five-day study. The prevalence of myopia was 92% (the spherical equivalent refraction (SER) < − 0.50 D), and that of high myopia was 23% (SER < − 6.0D). The prevalence of dry eye disease (DED) was 10%. The corneal epithelial loss rate (corneal fluorescein staining > 1) was 10%, and corneal sensation decline rate (≤ 30 mm) was 12%. 4.5% of subjects ( n = 40) had moderate or severe anxiety, 78% were mild and a small portion (17.5%) didn’t have anxiety at all. No statistical significant association was found between anxiety with DED, fluorescein staining or with corneal sensation (all p > 0.05). However, subjects with DED had more symptoms of anxiety. Results also showed that students who kept eye strain for a long time were more inclined to have DED (12.5%: 6.9%, p = 0.0407, 95% CI); those who watched mobile phones and/or computers for over eight hours daily were more vulnerable to DED and fluorescein staining than others (14.1%: 8.6%, p = 0.0129; 13.0%: 8.3%, p = 0.0233, 95% CI). Conclusions Keeping eye strain or near work for a long time is associated with DED, while students with DED tend to encounter anxiety symptoms. The prevalence of myopia in Chinese university students is still high. We consider it necessary to provide education to university students about the good eye-using habits, and to diagnose anxiety for student patients with DED.
研究领域:
眼科学
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公共卫生
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流行病学
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视觉科学
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心理卫生
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屈光医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）