Surface functionalized mesoporous silica nanoparticles for intravitreal application of tacrolimus

Paiva, Mayara Rodrigues Brandão de; Andrade, Gracielle Ferreira; Dourado, Lays Fernanda Nunes; Castro, Brenda Fernanda Moreira; Fialho, Sílvia Ligório; Sousa, Edésia Martins Barros de; Silva-Cunha, Armando

doi:10.1177/0885328220977605

Cited by 21 publications

(14 citation statements)

References 55 publications

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“…However, Chen et al reported that SiO 2 NPs led to cytotoxicity, ROS generation, and DNA damage in the human cornea [ 15 ]. SiO 2 NPs can be used as intravitreal drug carriers [ 38 , 41 ]; however, to the best of our knowledge, the retinal toxicity of SiO 2 NPs has not been investigated before now. Therefore, we conducted both in vitro and in vivo experiments to evaluate the retinal toxicity of SiO 2 NPs with sizes of 15 and 50 nm.…”

Section: Resultsmentioning

confidence: 99%

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Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

Zhang

Zhao

et al. 2022

J Nanobiotechnol

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Background Silica nanoparticles (SiO2 NPs) are extensively applied in the biomedical field. The increasing medical application of SiO2 NPs has raised concerns about their safety. However, studies on SiO2 NP-induced retinal toxicity are lacking. Methods We investigated the retinal toxicity of SiO2 NPs with different sizes (15 and 50 nm) in vitro and in vivo along with the underlying mechanisms. The cytotoxicity of SiO2 NPs with different sizes was assessed in R28 human retinal precursor cells by determining the ATP content and LDH release. The cell morphologies and nanoparticle distributions in the cells were analyzed by phase-contrast microscopy and transmission electron microscopy, respectively. The mitochondrial membrane potential was examined by confocal laser scanning microscopy. The retinal toxicity induced by SiO2 NPs in vivo was examined by immunohistochemical analysis. To further investigate the mechanism of retinal toxicity induced by SiO2 NPs, reactive oxygen species (ROS) generation, glial cell activation and inflammation were monitored. Results The 15-nm SiO2 NPs were found to have higher cytotoxicity than the larger NPs. Notably, the 15-nm SiO2 NPs induced retinal toxicity in vivo, as demonstrated by increased cell death in the retina, TUNEL-stained retinal cells, retinal ganglion cell degeneration, glial cell activation, and inflammation. In addition, The SiO2 NPs caused oxidative stress, as demonstrated by the increase in the ROS indicator H2DCF-DA. Furthermore, the pretreatment of R28 cells with N-acetylcysteine, an ROS scavenger, attenuated the ROS production and cytotoxicity induced by SiO2 NPs. Conclusions These results provide evidence that SiO2 NPs induce size-dependent retinal toxicity and suggest that glial cell activation and ROS generation contribute to this toxicity. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

“…Because the concentration of SiO 2 NPs used as a drug carrier was reported to be 100 μg/mL [ 38 ], we studied the in vivo retinal toxicity of SiO 2 NPs at a concentration of 80 μg/mL, which was the highest concentration used in our in vitro experiments. First, cell death and TUNEL assays were performed.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

Zhang

Zhao

et al. 2022

J Nanobiotechnol

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“…However, follow-up studies on ERGs indicated no changes in the retina cell function after 15 days of intravitreal injection, which were also proved by histopathologic examination, further supporting the biocompatibility, safety, and efficacy of the developed nanocarrier system in ocular therapy. Thus, the findings affirmed the considerable potential of MSNAPTES TAC to transport therapeutics in the ocular delivery for the treatment of eye diseases [ 53 ].…”

Section: Inorganic Npsmentioning

confidence: 55%

“…They evaluated the cell viability of MSNAPTES and TAC-loaded MSNAPTES (MSNAPTES-TAC) in the ARPE-19, and further, a chorioallantoic membrane (CAM) assay model was employed to show the biocompatibility and safety after intravitreal injection in vivo. Moreover, it was clinically examined based on measurement of intraocular pressure, ERG, and histopathological studies in rats’ eyes [ 53 ].…”

Section: Inorganic Npsmentioning

confidence: 99%

Drug Delivery Challenges and Current Progress in Nanocarrier-Based Ocular Therapeutic System

Akhter

Ahmad

Alshahrani

et al. 2022

Gels

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Drug instillation via a topical route is preferred since it is desirable and convenient due to the noninvasive and easy drug access to different segments of the eye for the treatment of ocular ailments. The low dose, rapid onset of action, low or no toxicity to the local tissues, and constrained systemic outreach are more prevalent in this route. The majority of ophthalmic preparations in the market are available as conventional eye drops, which rendered <5% of a drug instilled in the eye. The poor drug availability in ocular tissue may be attributed to the physiological barriers associated with the cornea, conjunctiva, lachrymal drainage, tear turnover, blood–retinal barrier, enzymatic drug degradation, and reflex action, thus impeding deeper drug penetration in the ocular cavity, including the posterior segment. The static barriers in the eye are composed of the sclera, cornea, retina, and blood–retinal barrier, whereas the dynamic barriers, referred to as the conjunctival and choroidal blood flow, tear dilution, and lymphatic clearance, critically impact the bioavailability of drugs. To circumvent such barriers, the rational design of the ocular therapeutic system indeed required enriching the drug holding time and the deeper permeation of the drug, which overall improve the bioavailability of the drug in the ocular tissue. This review provides a brief insight into the structural components of the eye as well as the therapeutic challenges and current developments in the arena of the ocular therapeutic system, based on novel drug delivery systems such as nanomicelles, nanoparticles (NPs), nanosuspensions, liposomes, in situ gel, dendrimers, contact lenses, implants, and microneedles. These nanotechnology platforms generously evolved to overwhelm the troubles associated with the physiological barriers in the ocular route. The controlled-drug-formulation-based strategic approach has considerable potential to enrich drug concentration in a specific area of the eye.

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“…The scientists did not detect any systemic or organ side effects connected to the topic treatment following a 12 week observation period after particle administration. Intravitreally injected silica nanoparticles showed anti-angiogenic effects inhibiting VEGFR phosphorylation after VEGF binding [95], while in another study, they showed promising results for the ocular delivery of tacrolimus [96].…”

Section: Inorganic Nanoparticlesmentioning

confidence: 98%

Nanomedicine for Treating Diabetic Retinopathy Vascular Degeneration

Bоrodinа

Kostyushev

Zamyatnin

et al. 2021

IJTM

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The incidence of diabetes and the pathological conditions associated with chronic hyperglycemia is increasing worldwide. Among them, diabetic retinopathy represents a leading cause of vision loss, causing a significant structural and functional impairment of the retinal and choroidal capillary network. Current therapies include anti-angiogenic and anti-inflammatory drugs administered through repetitive and invasive intraocular injections, and associated with significant adverse effects. The presence of ocular barriers affects the efficiency of topically administered therapeutics for treating the posterior segment of the eye. In this scenario, nanomedicine could improve current therapies for diabetic retinopathy by providing tools that can decrease the number of injections thanks to their controlled release properties, while some materials showed a natural ability to mitigate pathological neo-angiogenesis. Moreover, specific surface modifications could open new scenarios for the development of topical treatments. This review describes current advances in generating nanomedicine for diabetic retinopathy, focusing on the properties of the different materials tested explicitly for this purpose.

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Surface functionalized mesoporous silica nanoparticles for intravitreal application of tacrolimus

Cited by 21 publications

References 55 publications

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

Drug Delivery Challenges and Current Progress in Nanocarrier-Based Ocular Therapeutic System

Nanomedicine for Treating Diabetic Retinopathy Vascular Degeneration

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