JOURNAL OF BIOMATERIALS APPLICATIONS
·
2023
·
IF 2.9
Siyu Xiao,Aijie Ma,Yanzhuo Ma,Haiyan Bai,Binghong Zhang,Juan Li,Hongwei Zhou
Glaucoma is the leading cause of irreversible blindness, and its treatment is attracting widespread attention. Drug-loaded lacrimal suppositories can effectively treat xerophthalmia, but there is little research on the treatment of glaucoma with drug-loaded lacrimal suppositories. This article explored and expanded the non-pharmacological model of lacrimal suppository therapy for glaucoma by using a combination of lacrimal suppository and medication. The drug-loaded lacrimal suppository was rationally designed through the conjugation of gelatin with polyamide (PAM) via the formation of amide linkages, followed by Schiff base reaction grafting with latanoprost. In vitro drug release studies showed that latanoprost released from drug-loaded lacrimal embolus had sustained-release properties with a release time of 33 days and a drug release volume of 82.6%. The biological evaluation of drug-loaded lacrimal thrombus was carried out by IOP test, retinal potential test, and retinal H&E staining. The results showed that the IOP decreased to 27.125 ± 1.1254 mmHg, and the a and b waves of retinal potential increased to 4.39 ± 0.16 μV and 67.9 ± 2.17 μV, respectively. It indicated that latanoprost lacrimal suppository has a good therapeutic effect on glaucoma.
研究领域:
药剂学
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眼科医学
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DOI
PubMed
高影响因子
VIEW
·
2025
·
IF 8.5
Youjia Zhang,Ming Chen,Yi Tian,Bo Qin,Xiaoxiao Chen,Yiwen Zhou,Jinhai Huang,Mei Yang,Xinghuai Sun,Yuan Lei,Yuhong Chen
Elevated intraocular pressure (IOP) is a critical risk factor for the development and progression of glaucoma. However, current treatments focus primarily on mechanical stress relief, neglecting the underlying issue of diminished cellular energy production in patients. In this study, we investigated the impact of NAD + reduction on IOP regulation and explored the potential of NAD + precursors as a therapeutic strategy. We investigated the role of NAD + metabolism in glaucoma and revealed decreased nicotinamide phosphoribosyltransferase (NAMPT) expression in both patients and the human trabecular meshwork (HTM) cell model. Supplementation with NAD + precursors, nicotinamide (NAM) or nicotinamide mononucleotide (NMN), provided protective effects in H 2 O 2 -treated HTM cells and reduced IOP in ocular hypertension mouse models by mitigating senescence, extracellular matrix accumulation, and oxidative stress. To optimize drug delivery, we engineered the NAM@CeMOF-2 nanozyme system, which achieved a maximum IOP reduction in Cav1 ⁻/⁻ mice following 7 days of treatment. This localized treatment improved bioavailability and reduced systemic side effects. These findings suggest that NAD + deficiency plays a role in glaucoma development and propose novel therapeutic targets for addressing cellular dysfunction in glaucoma.
研究领域:
医学
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生物化学
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眼科研究
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产品关联
DOI
高影响因子
ACS Nano
·
2025
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IF 16
Xueyang Ren,Xuefei Zhu,Xiaodong Shao,Wen Yang,Yanmei Meng,Shiyu Chen,Yannan Wang,Jianqing Li,Qin Jiang,Benhui Hu
Elevated intraocular pressure (IOP) is a major risk factor for blindness in glaucoma patients, highlighting the critical need for continuous IOP monitoring. While traditional transpalpebral tonometers (TTs) circumvent corneal contact by adopting Goldmann applanation principles through impulsive corneal flattening forces, their measurement accuracy is inherently compromised by eyelid-induced cushion effects. In contrast, parallel-plate capacitive sensors employ constant compressive loading upon the eyelid, achieving palpebral compaction to mitigate the cushion effects. More recently, ion-pump-based capacitive sensors have emerged as promising alternatives, particularly due to their enhanced sensitivity. Nevertheless, these sensors exhibit sharp sensitivity deterioration at extended measurement ranges (0–10 kPa). This operational constraint originates from the strong hydrogen bond energies (between confining matrices and ions) and rigid block copolymer matrices’ steric hindrance. To address these limitations, we developed a transpalpebral tonometer featuring low-energy-barrier ion pumps, incorporating (3-aminopropyl)triethoxysilane (APTES)-silanized liquid metal nanoparticles (LM NPs) as confining matrices and an ionic liquid as an ion donor. The low-energy barrier arises from (1) weaker hydrogen bonds between the N–H of APTES and the F of the ionic liquid and (2) reduced crystallinity in the elastomeric matrices induced by LM NPs. Our sensor achieves a sensitivity of 24.88 kPa–1 with maintained linearity over 0–85 kPa. In vivo animal trials over 120 min validated its continuous IOP monitoring capability, reliably detecting elevated IOP states and demonstrating clinical potential for glaucoma management.
研究领域:
医学工程
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生物医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2019
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IF 7.901
Jiawen Xu,Ying Ge,Ruixuan Bu,Anan Zhang,Shasha Feng,Jian Wang,Jingxin Gou,Tian Yin,Haibing He,Yu Zhang,Xing Tang
Glaucoma is a group of irreversible ocular diseases which result in damage to the optic nerve and vision loss . The objective of the present work was to develop micelles-laden contact lenses (CLs-M) that could achieve the sustained release of timolol and latanoprost simultaneously for the treatment of glaucoma. CLs-M were obtained by free radical polymerization of HEMA monomer with timolol and latanoprost loaded mPEG-PLA micelles . The prepared CLs-M had a minimal impact on critical CLs properties, and could release timolol and latanoprost in simulated tear fluid for 144 h and 120 h individually, which is promising for extended drugs release applications. The in vivo PK study on rabbit eyes showed sustained timolol and latanoprost release for up to 120 h and 96 h in tear fluid, respectively. There was significant improvement of the mean residence time (79.6-fold and 122.2-fold) and bioavailability (2.2-fold and 7.3-fold) for both timolol and latanoprost delivered by CLs-M compared with eye drops. An in vivo PD study in a rabbit model with high IOP showed sustained reduction in the IOP for over 168 h. The relative pharmacological availability (PA) of CLs-M was 9.8 times as high as the eye drops. The protein adsorption, ocular irritation study and histological examination study indicated the safety of CLs-M. Therefore, this work has demonstrated the promising potential of micelles-laden CLs to co-deliver timolol and latanoprost for an extended period of time to treat glaucoma.
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
Drug Delivery and Translational Research
·
2020
·Vol. 11
·期 3
·1119-1132
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IF 2.664
Li Xuefei,Fang Jingwang,Xin Meng,Li Qiqi,Wang Jun,Yang Hui,Wu Xianggen
Nimodipine (NMD), a calcium channel blocker, has demonstrated benefits in treating glaucoma. However, its ocular therapeutic application remains limited due to its poor aqueous solubility, which restrains the development of an ophthalmic formulation. Thus, the present study aimed to formulate an NMD micelle ophthalmic solution to enhance the potential of NMD in an ocular topical formulation to treat glaucoma. The NMD micelle ophthalmic solution was formulated with nanocarriers composed of rebaudioside A and d -α-tocopheryl polyethylene glycol 1000 succinate. Spherical mixed micelles were optimized and obtained at a small micelle size 13.429 ± 0.181 nm with a narrow size distribution (polydispersity index 0.166 ± 0.023) and high encapsulation efficiency rate (99.59 ± 0.09%). Compared with free NMD, NMD in micelles had much greater in vitro membrane permeability and antioxidant activity. The NMD micelle ophthalmic solution was well tolerated in rabbit eyes. It profoundly improved the in vivo intraocular permeation of NMD, and in vivo intraocular pressure reduction and improved miosis were also observed. Accordingly, this NMD micelle ophthalmic solution might be a promising ocular formulation to treat glaucoma.
研究领域:
药剂学
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眼科
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2022
·
IF 6.819
Yujin Zhao,Chang Huang,Zhutian Zhang,Jiaxu Hong,Jianjiang Xu,Xinghuai Sun,Jianguo Sun
Glaucoma is the leading cause of irreversible vision loss worldwide, and reduction of intraocular pressure (IOP) is the only factor that can be interfered to delay disease progression. As the first line and preferred method to treat glaucoma, eye drops have many shortcomings, such as low bioavailability, poor patient compliance, and unsustainable therapeutic effect. In this study, a highly efficient brimonidine (BRI) silicone rubber implant (BRI@SR@TPU implant) has been designed, prepared, characterized, and administrated for sustained relief of IOP to treat glaucoma. The in vitro BRI release from BRI@SR@TPU implants shows a sustainable release profile for up to 35 d, with decreased burst release and increased immediate drug concentration. The carrier materials are not cytotoxic to human corneal epithelial cells and conjunctival epithelial cells, and show good biocompatibility, which can be safely administrated into rabbit’s conjunctival sac. The BRI@SR@TPU implant sustainably released BRI and effectively reduced IOP for 18 d (72 times) compared to the commercial BRI eye drops (6 h). The BRI@SR@TPU implant is thus a promising noninvasive platform product for long-term IOP-reducing in patients with glaucoma and ocular hypertension.
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
Expert Opinion on Drug Delivery
·
2024
·
IF 5
Zhutian Zhang,Qian Ma,Zhaoxing Dai,Jiaxu Hong,Jifeng Gu,Rong Shi,Jianjiang Xu,Yaling Ma,Xinghuai Sun,Jianguo Sun
Background Glaucoma is one of the major irreversible blinding eye diseases in the world. Reducing intraocular pressure (IOP) is the primary treatment option, and taking eye drops daily is the common method. However, short drug duration and poor bioavailability of eye drops may lead to unsatisfied therapeutic effects and inadequate patient compliance.Methods A brimonidine-loaded silicone rubber insert (BRI@SR@PT) was prepared by loading brimonidine into a surface-modified silicone rubber ring, followed by polydopamine/thermoplastic polyurethane coatings. The physical properties, in vitro cytocompatibility and drug release of BRI@SR@PT were investigated. The BRI@SR@PT was administrated in the conjunctival sac of rabbit eyes, and its in vivo drug release, IOP-lowering efficacy and biosafety were assessed.Results The BRI@SR@PT presented great thermal stability and excellent elasticity. The BRI@SR@PT was able to release BRI sustainably for 28 days with little toxicity in vitro. Compared to BRI eye drops, the BRI@SR@PT effectively lowered IOP for 21 days based on the sustained BRI release with great biosafety when administrated in conjunctival sac of rabbit eyes in a noninvasive fashion.Conclusions The conjunctival sac insert (BRI@SR@PT), as a promising drug-delivery platform, may provide a sustained IOP-lowering treatment for patients with ocular hypertension or glaucoma, without the need for invasive procedures.
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
Research
·
2025
·
IF 10.7
Yiling Han,Qiangwang Geng,Aimeng Dong,Menglu Jiang,Jingyi Ma,Wulian Song,Pan Fan,Yuanyuan Li,Jiawen Gao,Fenghua Zhang,Jinsong Leng,Huiping Yuan
Excessive fibrosis is the primary factor for the failure of glaucoma drainage device (GDD) implantation. Thus, strategies to suppress scar formation in GDD implantation are crucial. Although it is known that in implanted medical devices, microscale modification of the implant surface can modulate cell behavior and reduce the incidence of fibrosis, in the field of ophthalmic implants, especially the modification and effects of hydrogel micropatterns have rarely been reported. Here, we designed the patterned gelatin/acrylamide double network hydrogel and developed an innovative GDD with micropattern to suppress inflammatory and fibroblast activation after GDD implantation. Pattern topography suppressed F-actin expression and mitigated actin-dependent nuclear migration of myocardin-related transcription factor A (MRTF-A) during the proliferative phase after GDD implantation. Ultimately, the expression of α-smooth muscle actin (α-SMA), a key fibrosis-related gene product, was suppressed. Moreover, the modified GDD effectively controlled intraocular pressure (IOP), mitigated fibrous formation, and remodeled extracellular matrix (ECM) collagen distribution in vivo. Therefore, the novel GDD with surface patterning interventions provides a promising strategy to inhibit scar formation after GDD implantation and raise the efficacy of GDD implantation.
研究领域:
眼科
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生物材料学
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医学工程
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 5
·1281-1291
·
IF 7.59
Yanan Wang,Zikang Xu,Wenchi Li,Wei Wei,Mengqi Qin,Qun Li,Xuexia Liu,Xu Zhang,Xiaolei Wang
Excessive fibrosis is the major factor in the failure of glaucoma filtration surgery. So far, the dominant approach for inhibiting fibrosis is the use of an antimetabolite drug, but the complications it causes, such as filtering bleb leakage, bacterial endophthalmitis and ocular hypotony, are also inevitable. Herein, a multifunctional anti-scarring platform (PVA@rGO-Ag/5-Fu) integrated with outstanding photothermal, antibacterial and drug delivery abilities is developed. PVA@rGO-Ag shows favorable biocompatibility as well as an accurate regional photothermal killing ability on both conjunctival fibroblasts and bacteria under 808 nm near-infrared (NIR) irradiation. Furthermore, PVA@rGO-Ag/5-Fu improves bleb survival rates and results in the satisfactory reduction of intraocular pressure (IOP) by decreasing the fibrous reaction in vivo. In summary, PVA@rGO-Ag/5-Fu has promising potential as an efficacious and safe anti-scarring agent for filtering surgery.
研究领域:
生物医学工程
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眼科医学
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纳米医学
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2023
·
IF 6.7
Huang Chang,Shen Yuening,Zhao Yujin,Zhang Zhutian,Gao Shunxiang,Hong Jiaxu,Xu Jianjiang,Meng Qingtao,Sun Xinghuai,Sun Jianguo
Glaucoma is the leading cause of irreversible blindness, affecting 111 million people by 2040 worldwide. Intraocular pressure (IOP) is the only controllable risk factor for the disease and current treatment options seek to reduce IOP via daily taking eye drops. However, shortcomings of eye drops, such as poor bioavailability and unsatisfied therapeutic effects, may lead to inadequate patient compliance. In this study, an effective brimonidine (BRI)-loaded silicone rubber (SR) implant coated with polydimethylsiloxane (BRI@SR@PDMS) is designed and fully investigated for IOP reduction treatment. The in vitro BRI release from BRI@SR@PDMS implant reveals a more sustainable trend lasting over 1 month, with a gradually declined immediate drug concentration. The carrier materials show no cytotoxicity on human corneal epithelial cells and mice corneal epithelial cells in vitro. After administrated into rabbit’s conjunctival sac, the BRI@SR@PDMS implant releases BRI in a sustained fashion and effectively reduces IOP for 18 days with great biosafety. In contrast, BRI eye drops only maintain IOP-lowering effect for 6 h. Therefore, as a substitute of eye drops, the BRI@SR@PDMS implant can be applied as a promising non-invasive platform to achieve long-term IOP-lowering in patients suffering from ocular hypertension or glaucoma.
研究领域:
药学
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生物医学工程
·
眼科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Tao Wang,Yunran Zhang,Meiling Chi,Chen Zhao,Linlin Cao,Chutong Tian,K. Kamei,Ying Zheng,Qikun Jiang
Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration, poor efficacy and side effects. Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution (FC-TNL) has the ability to treat glaucoma by lowering the intraocular pressure (IOP) with great efficacy and improving patient compliance. However, the commercialized netarsudil dimesylate precipitated when the pH of the solution was above 5.4, or when maleic acid, the salt of commercial timolol maleate, was mixed with netarsudil dimesylate. Consequently, the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in pH 4.8–5.2 solution by synthesizing timolol mesylate. Next, the morphology of timolol mesylate was observed by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and powder X-ray diffraction. The prepared FC-TNL showed good stability during refrigeration storage. Additionally, FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study. Importantly, once-daily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells. The FC-TNL was stable, safe and effective, being a promising glaucoma therapeutic.
研究领域:
药理学
·
眼科医学
✓ 已验证
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Qiang Li,Cunrui Li,Yuanmin Chang,Mingzhi Su,Rilei Yu,Zhangjian Huang,Yue-Wei Guo,Xin Jin
The inhibition of Rho-associated coiled-coil kinase (ROCK) has emerged as a promising strategy for reducing intraocular pressure (IOP) and treating glaucoma. Here, we report the synthesis and evaluation of novel ROCK inhibitors, D25 and R3, which were designed to optimize selectivity, efficacy, and ocular bioavailability. D25 potently inhibited ROCK1/2 with IC50 values of 47.2 nM and 33.8 nM, respectively, surpassing Netarsudil. Compound R3 had weaker ROCK inhibition but demonstrated favorable lipophilicity (logP) and good selectivity to ROCKs, which enhances its potential and safety for ocular delivery. In human trabecular meshwork (HTM) cells, R3 showed lower cytotoxicity than Netarsudil and effectively mitigated oxidative damage, enhanced cellular integrity, and reduced inflammatory cytokine secretion. In rabbit models, D25 significantly lowered IOP, outperforming (S)-Netarsudil. R3 exhibited weaker IOP-lowering efficacy but better selectivity. D25 is a promising glaucoma treatment candidate, with R3 as a safer alternative for further optimization.
研究领域:
药理学
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眼科
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分子生物学
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DOI
PubMed
高影响因子
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