JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2023
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IF 5
Jing Su,Weijia Lu,Yexuan Guo,Zhuoyi Liu,Xu Wang,Hong Yan,Rui Xue Zhang
Periocular routes represent a promising approach to chronic eye therapy due to its unique exploitation of scleral structure. Especially, for ophthalmic infection requiring prolonged medication, sclera-traversing dosage forms capable of co-delivery of multiple drugs are highly desirable. Herein, phosphatidylcholine-based liposomes co-loading water soluble steroid dexamethasone and antibiotics moxifloxacin (LIP-DM) was developed for transscleral delivery of dual drugs. The size, mono-dispersity and drug entrapment of LIP-DM prepared by microfluidics were highly influenced by varying amounts of lipid composition. Final LIP-DM composing 63mol% phospholipid and 37mol% cholesterol was characterized of colloidal stable unilamellar structure with sub-100 nm size and entrapment of 0.412 mg and 1.21 mg for dexamethasone and moxifloxacin, respectively. Transport of LIP-DM using rabbit scleral tissues showed time-dependent particle penetration and accumulation from episcleral to intraocular side. Compared to immediate release of drugs in solution, LIP-DM exhibited differential release of dual drugs with fast antibiotics release and slow steroid release within 1 day, which in turn increased the transscleral contact time yet maintained effective permeability of dual drugs, leading to the rapid bacteriostatic onset and enhanced inhibition of proinflammatory cytokines in human retinal pigment epithelial cells. The results highlight liposomes as a potential transscleral depot of drug combination for the long-term vision care.
研究领域:
药剂学
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眼科学
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药物递送系统
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Yaxin Hu,Weixiong Weng,Yuxi Zhang,Ying Zhu,Xinyu Zhang
This study employed superficial ultrasound exposure of good ocular safety and a drug-loaded hydrogel of long residence time to enable transscleral delivery. First, we designed an acoustic adaptor to limit the ultrasound exposure depth to 1.59 mm to protect the posterior eye segments. Then, we optimized the alginate/polyacrylamide ratio (3:7) of a dual-crosslinked hydrogel to enable ultrasound-triggered release of model drug (70-kDa fluorescein isothiocyanate-conjugated dextran). Using fluorescence imaging to quantify the drug release, we showed that the developed method resulted in enhanced transscleral delivery in both ex vivo porcine scleras (2.6-fold) and in vivo rabbit scleras (2.2-fold). We also demonstrated that the method increased the drug penetration depth to the whole thickness of the sclera. In particular, the drug release efficiency increased with increasing ultrasound exposure time (1 and 3 min) and intensity (8, 19, 36, and 61 mW/cm 2 ). Using scanning electron microscopy, we revealed that ultrasound exposure resulted in rougher surfaces and microscale rupture of the hydrogel. Moreover, Masson staining of scleral slices showed that the integrity of the top scleral fibers was disturbed by ultrasound exposure, and this disturbance recovered 3 days later. Our work demonstrates that the developed method holds great potential for mediating ocular drug delivery.
研究领域:
药学
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生物医学工程
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眼科学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Shan He,Pei-Juan Wu,Li Zhang,Jia-Xue Wu,Hou-Li Li,Kun Yi,Qiu-Yun Sun,Zi-Yang Wang,Yu-Xin Yue,Dong-Sheng Guo,Ke Hu,Xiao-Bei Huang,Wen-Juan Wan
Myopia is one of the most common visual impairments worldwide. Recent studies suggest that scleral hypoxia may act as an early trigger for myopia, initiating oxidative stress (OS) that disrupts extracellular matrix (ECM) remodeling and, in turn, drives axial elongation. In this study, we constructed a novel hypoxia-responsive host-guest complex, DOX@SAC4A, by encapsulating doxycycline (DOX) within sulfonated azocalix[4]arene (SAC4A). In vitro, this system significantly reduced DOX cytotoxicity and enabled efficient hypoxia-triggered drug release. Moreover, the intrinsic activity of SAC4A synergistically enhanced the antioxidant and anti-apoptotic effects of DOX, helping to maintain ECM homeostasis. In vivo studies further confirmed that DOX@SAC4A selectively targeted hypoxic sclera and markedly increased local drug accumulation. Consequently, it effectively suppressed myopia progression in guinea pigs by delaying axial elongation and alleviating myopic refractive shift. In conclusion, DOX@SAC4A is a multifunctional drug delivery system that offers both therapeutic effects and targeted delivery. These results present a promising candidate and an improved delivery strategy for myopia prevention and control.
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DOI
PubMed
高影响因子
Cell Discovery
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2024
·Vol. 10
·期 1
·1-14
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IF 13
Li Hao,Du Yu,Cheng Kaiwen,Chen Yuxi,Wei Ling,Pei Yujun,Wang Xiaoyu,Wang Lan,Zhang Ye,Hu Xiaoxin,Lu Yi,Zhu Xiangjia
High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM’s gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.
研究领域:
眼科学
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微生物学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2025
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IF 5.7
Zi Fu,Yan Zhou,Ziyi Liu,Zhe Chen,Qiang Fu,Shiqun Lin,Rongping Dai,Huade Zheng
Pathological myopia, characterized by excessive axial elongation, posterior staphyloma (PS) and retinal-choroidal degeneration underlies sight-threatening conditions such as myopic traction maculopathy (MTM) and macular atrophy. Macular buckling (MB) surgery has demonstrated significant efficacy in managing MTM-associated pathologies, including macular schisis, macular holes, and macular retinal detachment. However, its widespread clinical adoption remains limited due to suboptimal material properties and geometrical design constraints of existing buckling devices. Advancements in imaging modalities-such as spectral-domain optical coherence tomography (SD-OCT), swept-source OCT (SS-OCT), ultrawidefield fundus imaging, and three-dimensional magnetic resonance imaging (3D-MRI)-have substantially enhanced the understanding and evaluation of MTM biomechanics. The future development of MB may lie in identifying superior biomaterials and creating customized buckling devices tailored to individual ocular morphology. Here, we developed a photo-curable polycaprolactone (PCL)-based non-isocyanate polyurethane acrylate (NIPUA) resin (PCL-NIPUA) for one-piece J-shaped 3D-printed MB devices. Structural characterization via Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Mass Spectrometry (MS) confirmed successful synthesis. Photocuring kinetics under 465 nm visible light achieved an optimal storage modulus within 82 s, coupled with minimal curing shrinkage (7.2%). By tuning flexible PCL segments, the material exhibited a tensile strength of 25 MPa and elongation at break of 32%, balancing strength and elasticity. The resin demonstrated environmental stability (water contact angle: 72°; water absorption: 8.8%; thermal decomposition: 420°C) and exceptional biocompatibility (hemolysis rate <0.5%; cell viability >97%). Liquid crystal display (LCD) 3D printing produced cost-effective MB devices that provided stable scleral indentation in rabbit models, with few complications, and no pathological structural changes in the optic nerve and retina，showing good biocompatibility and safety. This work establishes PCL-NIPUA as a synergistic platform combining green chemistry, rapid photocuring, mechanical adaptability, and biosafety, offering a clinically translatable solution for customized 3D-printed implants in MB surgery.
研究领域:
眼科
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生物材料
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组织工程
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转化医学
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生物医学工程
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眼底病学
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高分子医学材料
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Jinhui Lu,Xiaomeng Zhu,Meng Zhang,Xunchan Jiang,Wei Guo,Feng Jiang,Feng Cao
Investigating the structural integrity of carriers in transit from ocular surface to ocular posterior segment is essential for an efficient topical drug delivery system. In this study, dual-carrier hydroxypropyl-β-cyclodextrin [email protected] ( [email protected] ) nanocomposites were developed for the efficient delivery of dexamethasone . Förster Resonance Energy Transfer with near-infrared I fluorescent dyes and in vivo imaging system were used to investigate the structural integrity of [email protected] nanocomposites after crossing Human conjunctival epithelial cells (HConEpiC) monolayer and in ocular tissues. The structural integrity of inner HPCD complexes was monitored for the first time. The results suggested that 23.1 ± 6.4 % of nanocomposites and 41.2 ± 4.3 % of HPCD complexes could cross HConEpiC monolayer with an intact structure at 1 h. 15.3 ± 8.4 % of intact nanocomposites could reach at least sclera and 22.9 ± 1.2 % of intact HPCD complexes could reach choroid-retina after 60 min in vivo , which showed that the dual-carrier drug delivery system could successfully deliver intact cyclodextrin complexes to ocular posterior segment. In conclusion, in vivo assessment of structural integrity of nanocarriers is greatly significant for guiding the rational design, higher drug delivery efficiency and clinical transformation for topical drug delivery system to the posterior segment of the eye.
研究领域:
药学
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眼科
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纳米技术
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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
Nature Communications
·
2024
·Vol. 15
·期 1
·1-15
·
IF 14.7
Zhong Tianyan,Yi Hangjin,Gou Jiacheng,Li Jie,Liu Miao,Gao Xing,Chen Sizhu,Guan Hongye,Liang Shan,He Qianxiong,Lin Rui,Long Zhihe,Wang Yue,Shi Chuang,Zhan Yang,Zhang Yan,Xing Lili,Zhong Jie,Xue Xinyu
The proper axial length of the eye is crucial for achieving emmetropia. In this study, we present a wireless battery-free eye modulation patch designed to correct high myopia and prevent relapse. The patch consists of piezoelectric transducers, an electrochemical micro-actuator, a drug microneedle array, μ-LEDs, a flexible circuit, and biocompatible encapsulation. The system can be wirelessly powered and controlled using external ultrasound. The electrochemical micro-actuator plays a key role in precisely shortening the axial length by driving the posterior sclera inward. This ensures accurate scene imaging on the retina for myopia eye. The drug microneedle array delivers riboflavin to the posterior sclera, and μ-LEDs’ blue light induces collagen cross-linking, reinforcing sclera strength. In vivo experiments demonstrate that the patch successfully reduces the rabbit eye’s axial length by ~1217 μm and increases sclera strength by 387%. The system operates effectively within the body without the need for batteries. Here, we show that the patch offers a promising avenue for clinically treating high myopia.
研究领域:
眼科学
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
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