Topical siRNA delivery to the cornea and anterior eye by hybrid silicon-lipid nanoparticles

Baran-Rachwalska, Paulina; Torabi-Pour, Nissim; Sutera, Flavia Maria; Ahmed, Mukhtar H.; Thomas, Keith; Nesbit, M. Andrew; Welsh, Michael; Moore, Carrie; Saffie-Siebert, Suzanne

doi:10.1016/j.jconrel.2020.07.004

Cited by 37 publications

(41 citation statements)

References 61 publications

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“…Once arrived at the target cells, NPs have the great advantage to allow for an efficient cellular uptake of their therapeutic freight [ 8 ]. Macromolecular drugs in particular, such as siRNA, would otherwise be highly unstable and not be able to cross cellular membranes [ 9 ]. In a next step, we substantiated and quantified the cellular uptake in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to these small-molecule drugs, macromolecules, such as small interfering RNA (siRNA), are discussed as an innovative alternative to intervene disease progression [ 7 , 8 ]. However, their high molecular weight, inherent instability and strong negative charge currently prevent nucleic acids to reach a sufficiently high bioavailability in the anterior chamber of the eye [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy

et al. 2021

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In glaucoma therapy, nanoparticles (NPs) are a favorable tool for delivering drugs to the outflow tissues of the anterior chamber of the eye where disease development and progression take place. In this context, a prerequisite is an efficient enrichment of NPs in the trabecular meshwork with minimal accumulation in off-target tissues such as the cornea, lens, iris and ciliary body. We evaluated the optimal size for targeting the trabecular meshwork by using gold NPs of 5, 60, 80 and 120 nm with a bare surface (AuNPs) or coated with hyaluronic acid (HA-AuNPs). NPs were compared regarding their colloidal stability, distribution in the anterior chamber of the eye ex vivo and cellular uptake in vitro. HA-AuNPs demonstrated an exceptional colloidal stability. Even after application into porcine eyes ex vivo, the HA coating prevented an aggregation of NPs inside the trabecular meshwork. NPs with a diameter of 120 nm exhibited the highest volume-based accumulation in the trabecular meshwork. Off-target tissues in the anterior chamber demonstrated an exceptionally low gold content. Our findings are particularly important for NPs with encapsulated anti-glaucoma drugs because a higher particle volume would be accompanied by a higher drug payload.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy

et al. 2021

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“…Subsequently, luciferase-targeting siRNA packaged in ProSilic nanoparticles was topically applied daily in a reporter knock-in mouse model. A significant reduced luciferase expression could be observed within 24 hours after the first administration and lasting up to four days after the end of the treatment with a maximum inhibition of 41% at day 11 [69].…”

Section: Non-viral Vectorsmentioning

confidence: 92%

“…Baran-Rachwalska et al investigated topically applied biodegradable silicon/lipid nanoparticles (SiNPs; named ProSilic) to deliver (fluorescent) siRNA into corneal epithelial cells in mice [69]. Different lipid mixtures were explored (including DOPE and DC-chol).…”

Section: Non-viral Vectorsmentioning

confidence: 99%

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Challenges and strategies for the delivery of biologics to the cornea

Wels

Roels

Raemdonck

et al. 2021

Journal of Controlled Release

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Ocular Nanomedicine

et al. 2022

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Intrinsic shortcomings associated with conventional therapeutic strategies often compromise treatment efficacy in clinical ophthalmology, prompting the rapid development of versatile alternatives for satisfactory diagnostics and therapeutics. Given advances in material science, nanochemistry, and nanobiotechnology, a broad spectrum of functional nanosystems has been explored to satisfy the extensive requirements of ophthalmologic applications. In the present review, the recent progress in nanosystems, both conventional and emerging nanomaterials in ophthalmology from state-of-the-art studies, are comprehensively examined and the role of their fundamental physicochemical properties in bioavailability, tissue penetration, biodistribution, and elimination after interacting with the ophthalmologic microenvironment emphasized. Furthermore, along with the development of surface engineering of nanomaterials, emerging theranostic methodologies are promoted as potential alternatives for multipurpose ocular applications, such as emerging biomimetic ophthalmology (e.g., smart electrochemical eye), thus provoking a holistic review of "ocular nanomedicine." By affording insight into challenges encountered by ocular nanomedicine and further highlighting the direction of future studies, this review provides an incentive for enriching ocular nanomedicine-based fundamental research and future clinical translation.

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Topical siRNA delivery to the cornea and anterior eye by hybrid silicon-lipid nanoparticles

Cited by 37 publications

References 61 publications

Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy

Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy

Challenges and strategies for the delivery of biologics to the cornea

Ocular Nanomedicine

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