Unveiling the Power of Gabapentin-Loaded Nanoceria with Multiple Therapeutic Capabilities for the Treatment of Dry Eye Disease

Yang, Chia-Jung; Anand, Anisha; Huang, Chih-Ching; Lai, Jui-Yang

doi:10.1021/acsnano.3c07817

Cited by 45 publications

(14 citation statements)

References 78 publications

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“…This implies that corneal cells may contribute to the enhanced tear production stimulated by GBP, working alongside the lacrimal glands to restore the tear film and reduce friction on the ocular surface, a known trigger for ocular pain. These results were further corroborated by a recent publication, in which a ceria-based nanocarrier system encapsulating GBP was designed to effectively alleviate dry eye symptoms [66]. Nanoceria eye drops are a type of ocular medication that utilizes nanotechnology to deliver cerium oxide nanoparticles (nanoceria) to the eye.…”

Section: Topical Formulation and Treatment With Gbp Eye Dropsmentioning

confidence: 59%

“…By encapsulating or attaching drugs to the surface of nanoceria particles, it may be possible to enhance drug stability, improve ocular bioavailability, and prolong drug release, leading to improved therapeutic outcomes. Therefore, a multifunctional nanoceria coated with thiolated gelatin and cross-linked with glutaraldehyde was developed [66], thus creating a nanocarrier that is biocompatible and exhibits antioxidant, anti-inflammatory, antiangiogenic, antiapoptotic, and neuroprotective properties. The abundant thiol groups on the gelatin significantly increased the cellular uptake of the nanocarrier by 2.3 times and enhanced its ability to bind mucin by 10 times, improving retention in the eye and boosting the efficacy of the treatment.…”

Section: Topical Formulation and Treatment With Gbp Eye Dropsmentioning

confidence: 99%

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Molecular Mechanisms and Therapeutic Potential of Gabapentin with a Focus on Topical Formulations to Treat Ocular Surface Diseases

Rusciano

2024

Pharmaceuticals

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Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases.

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Section: Topical Formulation and Treatment With Gbp Eye Dropsmentioning

confidence: 59%

Section: Topical Formulation and Treatment With Gbp Eye Dropsmentioning

confidence: 99%

Molecular Mechanisms and Therapeutic Potential of Gabapentin with a Focus on Topical Formulations to Treat Ocular Surface Diseases

Rusciano

2024

Pharmaceuticals

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“…The fluorescence intensity decreased by 98.7% after NS@lipid-PEG/CKC treatment, which was better than that in NS (42.3%), NS@lipid-PEG (80.9%), NS@lipid/CKC (83.1%), and commercial cationic nanoemulsion (91.6%) group (Figure A,C). Besides, the TUNEL assay was also used to evaluate the levels of DNA fragmentation and apoptosis. , Apoptotic cells decreased largely with the application of nanosuspensions and commercial cationic nanoemulsions, whereas the apoptosis cell in the cornea epithelium layer was significantly increased in the PBS group. NS@lipid-PEG/CKC showed the best ability to inhibit apoptosis (Figure B,D).…”

Section: Resultsmentioning

confidence: 99%

Combination of PEGylation and Cationization on Phospholipid-Coated Cyclosporine Nanosuspensions for Enhanced Ocular Drug Delivery

Ma,

Liu,

Wang

et al. 2024

ACS Appl. Mater. Interfaces

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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.

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“…A reactive oxygen species (ROS) generation assay was conducted by seeding cells in 96-well plates and treating with protection doses (750 nM melatonin (17.415 ng/100 μL) containing polydopamine nanoparticles, equivalent polydopamine nanoparticles, and 750 nM bare melatonin) of the formulation for 48 h against rotenone challenge by following the existing report . After treatment, DCFH-DA dyes (10 μM) were coincubated with cells for 45 min under a CO 2 incubator at 37 °C temperature.…”

Section: Methodsmentioning

confidence: 99%

Melatonin-Polydopamine Nanoformulation Prevents Retinal Neurodegeneration in a Preclinical Model of Diabetic Retinopathy

Sardoiwala,

Biswal,

Sahu

et al. 2024

ACS Appl. Nano Mater.

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Reactive oxygen species, inflammation, angiogenesis, and retinal neurodegeneration lead to diabetic retinopathy (DR) progression. The inhibition of VEGF and prevention from retinal neurodegeneration pave the way to developing DR treatment. Melatonin is a potent anti-inflammatory agent and a promising therapeutic candidate for DR therapy. However, melatonin has a lower absorption kinetic that limits its therapeutic efficiency. Recently, nanotechnology-based nanodrug delivery systems have gained attention to overcome limitations of existing potent drugs. Therefore, we have prepared melatonin-loaded polydopamine nanoparticles to improve the melatonin release profile that result in endowed therapeutic potential of melatonin. The evaluation of in vitro and in vivo DR studies have shown the protection efficiency of our nanoformulation. The mechanism of protection is attributed to downregulated vascular endothelial growth factor (VEGF), inhibited CASPASE3, and upregulated nerve/glial antigen 2 (NG2) and choline acetyltransferase (CHAT) that reflect the antiangiogenesis, antiapoptosis, and neuroprotective potential of our nanoformulation in the preclinical DR model. Thus, the antiangiogenesis and retinal neuroprotection efficiency of melatonin-loaded polydopamine nanoparticles suggests our nanoformulation as a promising nanotherapeutic agent for DR treatment.

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Unveiling the Power of Gabapentin-Loaded Nanoceria with Multiple Therapeutic Capabilities for the Treatment of Dry Eye Disease

Cited by 45 publications

References 78 publications

Molecular Mechanisms and Therapeutic Potential of Gabapentin with a Focus on Topical Formulations to Treat Ocular Surface Diseases

Molecular Mechanisms and Therapeutic Potential of Gabapentin with a Focus on Topical Formulations to Treat Ocular Surface Diseases

Combination of PEGylation and Cationization on Phospholipid-Coated Cyclosporine Nanosuspensions for Enhanced Ocular Drug Delivery

Melatonin-Polydopamine Nanoformulation Prevents Retinal Neurodegeneration in a Preclinical Model of Diabetic Retinopathy

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