JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Xiaolin Li,Xunchan Jiang,Xiaolei Zhou,Yanju Cheng,Feng Cao
Many non-invasive novel nano-formulations were used for delivery from the ocular surface to posterior segment of the eye, while dexamethasone (DEX) ternary cyclodextrin (CD) aggregate suspension eye drops had recently entered phase III clinical trial . In this study, DEX quaternary CD aggregate suspension eye drops containing HPγCD as solubilizing CD, γCD as aggregating CD and poloxamer 407 were developed and easy for large-scale production. The permeability of DEX quaternary CD aggregate (DEX/γCD/HPγCD/P407) eye drops was better than that of DEX ternary CD (DEX/γCD/P407) eye drops in human corneal epithelial cells and human conjunctival epithelial cells. Ocular distribution revealed that the concentrations of DEX in the choroid-retina were still higher than the effective therapeutic concentration within12 h. DEX/γCD/HPγCD/P407 eye drops remained stable for 6 months in long-term testing and accelerated testing. In conclusion, DEX quaternary CD aggregate eye drops offer an efficient strategy for drug delivery from the ocular surface to posterior segment of the eye.
研究领域:
药剂学
·
眼科医学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Yan Liu,Xin-Xin Liu,Si-yu Wang,Xin-Yang Pan,Zi-Han Wang,Yu-Xin Wei,Zhi-Min Zhou,Kaihui Nan,Jing-Jie Wang
In situ gelling eye drops of tacrolimus (FK506 Gel) were developed to address the formulation challenge of tacrolimus for anterior ocular inflammatory diseases. Both in silico and in vitro investigations were conducted to screen a suitable cyclodextrin species to increase the drug solubility. Guanosine was employed as the gelator and combined with inclusion complexes of tacrolimus in the presence of borate anions to obtain FK506 Gel, which gelated when came into contact with cations in tear fluid and led to the formation of a nanofibrous hydrogel. The versatility of our design to improve the solubility and ocular retention of the hydrophobic drug was demonstrated in vivo with coumarin 6 as a model drug. A mouse dry eye model was used to evaluate the therapeutic effects of FK506 Gel, which, in combination with the biocompatibility study, suggested that FK506 Gel served as a superior treatment for anterior ocular inflammatory diseases.
研究领域:
药剂学
·
眼科医学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER SCIENCE SERIES A
·
2024
·
IF 1
Peng Liu,Dong Ling,Cai Tianqi,Liu Kai,Gao Xingtong,Sun Wenlong,Li Aixiang,Song Xinhua
In this study, the possibility of using hyaluronic acid (HA) modified lutein as the main component of eye drops for ophthalmic treatment was discussed. Firstly, hyaluronic acid grafted lutein (HA- g -lutein) was synthesized by hydrophilic modification of lutein by Steglich esterification. The grafted copolymer was self-assembled in water to form micelles and then loading unreacted lutein to prepare composite nanoparticles (denoted HA-lutein NPs). The findings from the FTIR, UV–Vis, and XRD analyses indicate that the graft copolymers were synthesized while preserving the structural integrity of lutein. Furthermore, the modification demonstrated efficient inhibition of lutein crystallization. TEM showed that HA-lutein NPs self-assembled into spherical micelles in water, the particle size of which was on the nanometer scale. The saturation solubility of HA-lutein NPs exhibits a 48-fold increase compared to that of free lutein. Then the cytotoxicity of HA-lutein NPs and the effect on in-vitro transcorneal permeation of excised-rabbit cornea, corneal hydration level, and in-vivo ocular irritation after topical administration of HA-lutein NPs in rabbit eyes were studied. The results indicated the ocular safety of HA-lutein NPs. The quantitative analysis of permeability parameters by HPLC showed that the apparent permeability coefficient and the cumulative penetration quantity within 360 minutes of the HA-lutein NPs group were 3.71 and 7.04 times higher compared to the free lutein group. In summary, the graft modification of lutein with HA to form nanoparticles is an effective method to improve the availability of lutein in the eye and has potential application in ocular therapy.
研究领域:
药剂学
·
眼科医学
·
生物材料科学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2020
·
IF 2.365
Guigang Li,Lingjuan Xu,Menglin Jiang,Xianggen Wu
The aim was to reveal the characteristic profiles of the marketed levofloxacin eye drops (5 mg/ml) and levofloxacin eye gel (3 mg/g) from the pharmacokinetics and pharmacodynamics views of rabbits’ eyes. A mild and a heavy bacterial keratitis models in rabbits were established. Different regimens of levofloxacin eye drops and eye gel, including phosphate buffer solution (the PBS group), the 4-Sol + 1-Gel group (rabbits were treated with 4 doses of levofloxacin eye drops and 1 dose levofloxacin eye gel per day), the 3-Sol + 1-Gel group (3 doses drops and 1 dose gel), the 4-Sol group (4 doses drops), the 4-Gel group (4 doses gel), the 3-Sol group (3 doses drops), and the 3-Gel group (3 doses gel), were applied to evaluate their efficacies. The ocular pharmacokinetics of levofloxacin eye drops and gel were also investigated. The results of mild infection groups showed that all treatment regimens significantly relieved the infection symptoms, and the treatment effect followed this order: 4-Gel > 4-Sol + 1-Gel > 3-Sol + 1-Gel > 4-Sol > 3-Gel > 3-Sol. In the heavy infection groups, all the treatment regimens significantly relieved the infection symptoms, and the treatment effect also followed the order with the mild infection results. All treatment regimens lowered the number of corneal colony forming units (CFU). Levofloxacin eye gel significantly increased intraocular penetration in rabbits’ eyes. It can be concluded that the levofloxacin eye gel was more effective in treating bacterial keratitis than the levofloxacin eye drops in rabbit keratitis model with a proper treatment regimen such as 4-Gel.
研究领域:
药理学
·
眼科医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Siying Wen,Xuemin He,Jiachen Wang,Zheyao Wen,Heying Ai,Mengyin Cai,Yi Yang,Hejun Li,Shasha Li,Guojun Shi,Aimin Xu,Zecong Xiao,Xintao Shuai,Yanming Chen
Retinal neovascularization is the main pathologic feature of ischemic retinopathy, which eventually leads to vision loss and even blindness. Current treatments like laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor A (VEGFA) drugs are invasive, expensive, and incompetent. Therefore, it is urgent to explore optimized therapies, particularly eye drops, to improve treatment effects. Our recent study reported that abnormal activation of the stimulator of interferon genes (STING) is closely associated with retinal vascular diseases, and it is highly enriched in retinal endothelial cells (ECs) with retinopathy. Thus, we evaluated whether endothelial STING affects retinal neovascularization. In addition, we constructed iRGD- and TAT-decorated nanoparticles (NPs) loaded with C-176 (I/T-C-NP), capable of penetrating the cornea and targeting retinal ECs. The I/T-C-NP eye drops were applied to the eyes of oxygen-induced retinopathy (OIR) mice, resulting in attenuated activation of the STING pathway. Consequently, retinal neovascularization and vascular tortuosity were effectively reduced, astrocyte activation was prohibited, and pericyte coverage was improved. These observations suggest that I/T-C-NP eye drops can be a potential solution for the treatment of retinal neovascularization.
研究领域:
眼科
·
分子生物学
·
药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Guang Xin,Ming Zhang,Zhihui Zhong,Li Tang,Yuliang Feng,Zeliang Wei,Shiyi Li,Youping Li,Junhua Zhang,Boli Zhang,Meng Zhang,Nelson Rowell,Zhen Chen,Hai Niu,Kui Yu,Wen Huang
There is a continuing, urgent need for an ophthalmic (eye) drop for the clinical therapy of age-related macular degeneration (AMD), a leading cause of blindness. Here, we report the first formulation of an eye drop that is effective via autophagy for AMD treatment. This eye drop is based on a single natural product derivative (ACD), which is an amphiphilic molecule containing a 6-aminohexanoate group (H2N(CH2)5COO−). We demonstrate that this eye drop reverses the abnormal angiogenesis induced in a primate model of AMD that has the pathological characteristics close to that of human AMD. The ACD molecule was self-assembled in an aqueous environment leading to nanoparticles (NPs) about 9.0 nm in diameter. These NPs were encapsulated in calcium alginate hydrogel. The resulting eye drop effectively slowed the release of ACD and displayed extended release periods in both simulated blood (pH 7.4) and inflammatory (pH 5.2) environments. We show that the eye drop penetrated both the corneal and blood–eye barriers and reached the fundus. With low cellular toxicity, the drop targeted S1,25D3-membrane-associated rapid response steroid-binding protein (1,25D3-MARRS) promoting autophagy in a dose-dependent manner. In addition, the drop inhibited cell migration and tubular formation. On the other hand, when protein 1,25D3-MARRS was knocked down, the eye drop did not exhibit such inhibition functionalities. Our study indicates that the 6-aminohexanoate group on self-assembled NPs encapsulated in hydrogel leads to the positive in vivo outcomes. The present formulation offers a promising approach for clinical treatment of human AMD.
研究领域:
眼科
·
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2016
·
IF 6.008
Tingting Xu,Jie Zhang,Huibo Chi,Feng Cao
To improve the ocular bioavailability of the model drug of pirenoxine sodium (PRN), organic-inorganic hybrid nanocomposites including layered double hydroxides (LDH) and chitosan derivatives (chitosan-glutathione (CG), chitosan-glutathione-valine (CG-V) and chitosan-glutathione-valine-valine (CG-VV)) were designed and characterized. In vivo precorneal retention study on rabbits showed that mean residence time (MRT) and area under the curve (AUC 0–6h ) of CG-PRN-LDH nanocomposite eye drop was up to 2.1-fold and 6.3-fold higher than those of commercial product, respectively. In vitro corneal penetration on rabbits demonstrated that the cumulative permeation of CG-VV-PRN-LDH nanocomposite dispersion was increased by 5.2 folds compared to that of commercial product, which may be due to the active transport effect of the nanocomposites by peptide transporter-1 (PepT-1). In addition, the ex vivo fluorescence imaging showed that fluorescent intensity of crystalline lens in rabbits was increased after the administration of PRN-LDH, CG-PRN-LDH, CG-V-PRN-LDH and CG-VV-PRN-LDH (in increasing order) nanocomposite eye drop. Finally, in vivo distribution evaluation in ocular tissues of rabbits revealed that AUC 0–8h and MRT in crystalline lens exhibited 14.7-fold and 2.2-fold increase in CG-VV-PRN-LDH nanocomposite eye drop group than those of commercial group, respectively. In summary, the organic-inorganic hybrid nanocomposites with multifunctional properties may be a promising ocular drug delivery system to achieve prolonged precorneal retention, better corneal permeability and enhanced ocular bioavailability. Statement of Significance Due to several structural and physiological intraocular barriers, drug delivery to the ocular mid-posterior segments still faces great challenges. In this manuscript, organic-inorganic hybrid nanocomposites based on chitosan derivatives and layered double hydroxides (LDH) were designed and constructed. Multifunctional properties of these hybrid nanocomposites were due to the possible active targeting to the peptide transporter-1 on the corneal epithelial cells, the bioadhesive ability and permeation enhancement of chitosan derivatives, and the electrostatic adsorption of LDH. Prolonged precorneal retention, better corneal permeability and enhanced ocular bioavailability of the model drug pirenoxine sodium were observed. Chitosan derivatives-LDH hybrid nanocomposites may be a promising ophthalmic drug system for the treatment of ocular diseases of mid-posterior segments.
研究领域:
药剂学
·
眼科医学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Yi Zhang,Chenglin Li,Qiuwen Zhu,Renjie Liang,Chang Xie,Shufang Zhang,Yi Hong,Hongwei Ouyang
Corneal injuries will cause corneal surface diseases that may lead to blindness in millions of people worldwide. There is a tremendous need for biomaterials that can promote corneal regeneration with practical feasibility. Here we demonstrate a strategy of a protein coating for corneal injury regeneration. We synthesize an o-nitrosobenzaldehyde group (NB)-modified gelatin (GelNB), which could adhere directly to the corneal surface with covalent bonding to form a thin molecular coating. The molecular coating could avoid rapid clearance and provide a favorable environment for cell migration, thereby effectively accelerating corneal repair and regeneration. The histological structure of the regenerated cornea is more similar to the native cornea. This molecular coating can be used conveniently as an eye drop solution, which makes it a promising strategy for corneal regeneration.
研究领域:
生物材料
·
组织工程
·
眼科
✓ 已验证
DOI
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Jiawei Li,Pengyue Liu,Yue Zhang,Fan Yang
Allergic conjunctivitis is a common ocular surface condition. Although corticosteroids are potent anti-inflammatory agents for its management, their use is often restricted by potential side effects. Conventional eye drops face challenges such as short retention time and poor corneal permeability, resulting in low drug bioavailability. To overcome these limitations, we developed a preservative-free synthetic high-density lipoprotein (sHDL) nanodisc eye drop containing dexamethasone palmitate. This novel formulation enhances drug stability and extends retention time on the ocular surface. In a mouse model of ovalbumin (OVA)-induced allergic conjunctivitis, the nanodisc eye drop significantly alleviated symptoms while reducing corticosteroid concentration, demonstrating excellent safety and biocompatibility. This innovative approach shows great promise for the treatment of allergic conjunctivitis and may lay the groundwork for new therapeutic strategies in anterior ocular disease management.
研究领域:
眼科
·
药物递送系统
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Lu Li,Shenghui Li,Sheng Wang,Xiaoli Xing,Yating Zhang,Lin Su,Xiaoli Wu,Hanjie Wang,Jin Chang,Xiaoqun Gong
Diabetic cataract (DC) is a kind of worrying ocular complications that eventually leads to blindness. However, there are a narrow range of pharmacological interventions to enable control the progression of DC, especially the eye drops based on noninvasive routes. In this work, we developed a kind of strong antioxidant Pt nanoclusters coated with cell-penetrating peptide (TAT) conjugated dextran (DTPNCs). The DTPNCs were dispersed in 0.1% Pluronic F127 (W/V) to form eye drops, which have the ability of corneal permeation. The results indicate that the presence of 0.1% Pluronic F127 (W/V) resists the clearance of tear film against DTPNCs and TAT-conjugated dextran contribute to the interaction and permeation with corneal barriers with the help of electrostatic interaction in vivo. More importantly, the DTPNCs possess effective antioxidant capacities and can protect the lens epithelial cells against oxidative stress by eliminating ROS and impose restrictions on the α-crystallin glycation and crosslinking in vitro, further to slow down the process of DC. We hope that our approach will provide a promising non-invasive and painless treatment to DC.
研究领域:
眼科学
·
纳米技术
·
药学
·
糖尿病研究
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Yiping Wu,Lulu Du,Xiaoning Xu,Yuhan Hu,Jia Liu,Jingwei Zhang,Lei Lei,Wenfang He,Zihao Sheng,Yuanao Ni,Jia Qu,Xingyi Li,Jun Jiang
Rapid corneal re-epithelialization is important for corneal wound healing. Corneal epithelial cell motility and oxidative stress are important targets for therapeutic intervention. In this study, we covalently conjugated the antioxidant caffeic acid (CA) with a bioactive peptide sequence (PHSRN) to generate a CA–PHSRN amphiphile, which was formulated into nanoparticular eye drops with an average size of 43.21 ± 16 nm. CA–PHSRN caused minimal cytotoxicity against human corneal epithelial cells (HCECs) and RAW264.7 cells, exhibited an excellent free radical scavenging ability, and remarkably attenuated reactive oxygen species (ROS) levels in H2O2-stimulated HCECs. The antioxidant and anti-inflammatory activities of CA–PHSRN were assessed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results show that CA–PHSRN treatment effectively prevented LPS-induced DNA damage and significantly reduced the levels of LPS-induced pro-inflammatory cytochemokines (i.e., iNOS, NO, TNF-α, IL-6, and COX-2) in a dose-dependent manner. Moreover, using a rabbit corneal epithelial ex vivo migration assay, we demonstrated that the proposed CA–PHSRN accelerated corneal epithelial cell migration and exhibited high ocular tolerance and ocular bioavailability after topical instillation. Taken together, the proposed CA–PHSRN nanoparticular eye drops are a promising therapeutic formulation for the treatment of corneal epithelial injury.
研究领域:
药学
·
眼科
·
纳米技术
·
药物递送系统
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-14
·
IF 10.6
Wu Han,Ye Jinfa,Zhang Minjie,Zhang Lingyu,Lin Sijie,Li Qingjian,Liu Yanbo,Han Yun,Huang Caihong,Wu Yiming,Cheng Yuhang,Cai Shundong,Ke Lang,Liu Gang,Li Wei,Chu Chengchao
Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
研究领域:
药学
·
纳米技术
·
眼科
·
药物递送系统
·
再生医学
✓ 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）