Nanomedicine and drug delivery to the retina: current status and implications for gene therapy

Tawfik, Mohamed M.; Chen, Fang; Goldberg, Jeffrey L; Sabel, Bernhard A.

doi:10.1007/s00210-022-02287-3

Cited by 31 publications

(25 citation statements)

References 252 publications

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“…Surgical or laser procedures are recommended when medication cannot sufficiently lower IOP (Schehlein and Robin, 2019 ; Rolim-De-Moura et al, 2022 ). In recent years, advances in surgery, drug delivery, and gene therapy have led to a new field of glaucoma treatment (Wan et al, 2021 ; Tawfik et al, 2022 ). However, the impaired visual function still becomes serious after lowering the IOP in some patients (Jayanetti et al, 2020 ; Baudouin et al, 2021 ) as RGCs and the optic nerve irreversibly degenerate (Jayanetti et al, 2020 ; Baudouin et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

A bibliometric analysis of apoptosis in glaucoma

Zhang

Wang²,

Tan³

et al. 2023

Front. Neurosci.

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BackgroundGlaucoma is the first irreversible and second blindness disease, which is characterized by the death of retinal ganglion cells (RGCs) and degeneration of the optic nerve. Previous works have indicated that apoptosis is the main reason for RGC death in glaucoma. Although many studies have investigated the mechanism of apoptosis and different strategies targeting apoptosis to protect the RGCs and finally recover the impaired vision in the glaucoma. However, the global trend and hotspots of apoptosis in glaucoma have not been well illustrated and discussed.MethodsDocuments were extracted from the Web of Science Core Collection on November 2, 2022. We selected articles and reviews published in English from January 1, 1999 to November 1, 2022 to perform visual analysis and statistical analysis of countries, institutions, authors, references and keywords by VOSviewer 1.6.18 and CiteSpace 5.8.ResultsThe publications about apoptosis in glaucoma show an increasing trend over time. Besides, the authors, institutions in the US and China published the most numbers of articles with the highest citation, which may be leading the research in the field of apoptosis in glaucoma. Last, series of advanced research results, technology and treatment for glaucoma, such as the discovery of key regulatory mechanisms on RGC apoptosis are emerging and will provide precise strategies for the treatment of glaucoma.ConclusionThis research will broaden our comprehension about the role of apoptosis in the process of glaucoma, and provide guidelines for us in basic research and disease treatment in the further.

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Section: Discussionmentioning

confidence: 99%

A bibliometric analysis of apoptosis in glaucoma

Zhang

Wang²,

Tan³

et al. 2023

Front. Neurosci.

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“…9,10 Intravitreal injection, the most prevalent method for ocular administration, carries risks including intraocular infection, vitreous hemorrhage, retinal detachment, and complications like glaucoma and cataracts. 8,9,11 Moreover, repeated intravitreal injections lead to poor patient compliance. 12 Researchers have been striving to develop noninvasive topical administration methods, but the presence of static barriers like the cornea and dynamic barriers like tears 13−15 severely restricts delivery efficiency to the retina.…”

Section: ■ Introductionmentioning

confidence: 99%

“…It is projected that by the year 2040, the number of affected individuals will reach 420 million. − The primary therapeutic strategies for retinal diseases focus on systemic administration , and ocular administration. ,− Traditional systemic administration routes such as intravenous injection or oral intake suffer from poor ocular bioavailability due to the blood–eye barrier, limiting treatment effectiveness. Increased dosages result in systemic toxicity and additional physical burden. , Intravitreal injection, the most prevalent method for ocular administration, carries risks including intraocular infection, vitreous hemorrhage, retinal detachment, and complications like glaucoma and cataracts. ,, Moreover, repeated intravitreal injections lead to poor patient compliance . Researchers have been striving to develop noninvasive topical administration methods, but the presence of static barriers like the cornea and dynamic barriers like tears − severely restricts delivery efficiency to the retina. , Therefore, finding an effective, noninvasive carrier for local retinal drug delivery is critically important.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Framework Nucleic Acid Eye Drops for Retinal Administration

Zhu,

Yan,

Wang

et al. 2023

ACS Appl. Bio Mater.

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Intravitreal injection is widely employed for the treatment of retinal diseases. However, it suffers from various drawbacks, including ocular trauma, risk of infection, and poor patient compliance due to frequent administrations. Due to the presence of barriers such as the cornea, it has been a challenge to develop efficient noninvasive ophthalmic eye drops that can reach the retina. Framework nucleic acids (FNAs), known for their excellent biocompatibility and precise, controllable shape and size, have been extensively utilized in drug delivery application. Here, we report the development of size- and shape-resolved fluorescent DNA frameworks for noninvasive retinal administration. Results show that tetrahedral DNA nanostructures (TDNs) with an edge length of 20 bp can reach the retina within 6 h with the highest efficiency. Moreover, this delivery method exhibits excellent biocompatibility. Our findings provide an approach for the development of localized treatment strategies for retinal diseases using FNA-based nanocarriers.

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“…Despite their advantageous properties, when in the vitreous, NPs can interact with anionic macromolecules, resulting in their retention at the injection site where they can be eliminated by hyalocytes or freely diffuse and be cleared from the vitreous, hampering their long-term efficacy and still requiring multiple injections [ 23 , 24 , 25 , 26 , 27 ]. Moreover, direct injection of NPs might cause toxicity due to poor biomimetic properties of the medium and poor control on drug release with high burst release [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Optimization of an Injectable Hydrogel Depot System for the Controlled Release of Retinal-Targeted Hybrid Nanoparticles

et al. 2022

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A drawback in the development of treatments that can reach the retina is the presence of barriers in the eye that restrain compounds from reaching the target. Intravitreal injections hold promise for retinal delivery, but the natural defenses in the vitreous can rapidly degrade or eliminate therapeutic molecules. Injectable hydrogel implants, which act as a reservoir, can allow for long-term drug delivery with a single injection into the eye, but still suffer due to the fast clearance of the released drugs when traversing the vitreous and random diffusion that leads to lower pharmaceutic efficacy. A combination with HA-covered nanoparticles, which can be released from the gel and more readily pass through the vitreous to increase the delivery of therapeutic agents to the retina, represents an advanced and elegant way to overcome some of the limitations in eye drug delivery. In this article, we developed hybrid PLGA-Dotap NPs that, due to their hyaluronic acid coating, can improve in vivo distribution throughout the vitreous and delivery to retinal cells. Moreover, a hydrogel implant was developed to act as a depot for the hybrid NPs to better control and slow their release. These results are a first step to improve the treatment of retinal diseases by protecting and transporting the therapeutic treatment across the vitreous and to improve treatment options by creating a depot system for long-term treatments.

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Nanomedicine and drug delivery to the retina: current status and implications for gene therapy

Cited by 31 publications

References 252 publications

A bibliometric analysis of apoptosis in glaucoma

A bibliometric analysis of apoptosis in glaucoma

Noninvasive Framework Nucleic Acid Eye Drops for Retinal Administration

Optimization of an Injectable Hydrogel Depot System for the Controlled Release of Retinal-Targeted Hybrid Nanoparticles

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