Self-assembled DNA nanoparticles loaded with travoprost for glaucoma-treatment

Schnichels, Sven; Hurst, José; Vries, Jan Willem de; Ullah, Sami; Gruszka, Agnieszka; Kwak, Minseok; Löscher, Marina; Dammeier, Sascha; Bartz‐Schmidt, Karl Ulrich; Spitzer, Martin S.; Herrmann, Andreas

doi:10.1016/j.nano.2020.102260

Cited by 22 publications

(40 citation statements)

References 40 publications

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“…The eyes were moistened again with TBS buffer for about 30–45 s before application of the eye drops. We applied 40 µL of the drops to the cornea by pipette [ 35 , 36 ]. Drainage of the drops was not obstructed, resulting in additional contact of the drops with the sclera.…”

Section: Methodsmentioning

confidence: 99%

Corneal Penetration of Low-Dose Atropine Eye Drops

Austermann

Schaeffel

Mathis

et al. 2021

JCM

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Major studies demonstrating the inhibition of myopia in children and juveniles by low-dose atropine eye drops provide little information on the manufacturing process and the exact composition of the atropine dilutions. However, corneal penetration might significantly vary depending on preservatives, such as benzalkonium chloride (BAC), and the atropine concentration. Since there is a trade-off between side effects, stability, and optimal effects of atropine on myopia, it is important to gain better knowledge about intraocular atropine concentrations. We performed an ex vivo study to determine corneal penetration for different formulations. Atropine drops (0.01%) of different formulations were obtained from pharmacies and applied to the cornea of freshly enucleated pig eyes. After 10 min, a sample of aqueous humor was taken and atropine concentrations were determined after liquid–liquid extraction followed by high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). The variability that originated from variations in applied drop size exceeded the differences between preserved and preservative-free formulations. The atropine concentration in the anterior chamber measured after 10 min was only 3.8 × 10−8 of its concentration in the applied eye drops, corresponding to 502.4 pM. Obviously, the preservative did not facilitate corneal penetration, at least ex vivo. In the aqueous humor of children’s eyes, similar concentrations, including higher variability, may be expected in the lower therapeutic window of pharmacodynamic action.

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Section: Methodsmentioning

confidence: 99%

Corneal Penetration of Low-Dose Atropine Eye Drops

Austermann

Schaeffel

Mathis

et al. 2021

JCM

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“…Travoprost delivery with this NP system resulted in longer adhesion to the corneal surface, enhanced uptake, efficacy, and biocompatibility. For example, after four hours, the amount delivered in the eyes of albino rats via these NPs was four times higher, compared to pristine travoprost [130].…”

Section: Lipid Dna-based Nanoparticlesmentioning

confidence: 95%

Topical Drug Delivery to the Posterior Segment of the Eye

et al. 2022

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Topical drug delivery to the posterior segment of the eye is a very complex challenge. However, topical delivery is highly desired, to achieve an easy-to-use treatment option for retinal diseases. In this review, we focus on the drug characteristics that are relevant to succeed in this challenge. An overview on the ocular barriers that need to be overcome and some relevant animal models to study ocular pharmacokinetics are given. Furthermore, a summary of substances that were able to reach the posterior segment after eye drop application is provided, as well as an outline of investigated delivery systems to improve ocular drug delivery. Some promising results of substances delivered to the retina suggest that topical treatment of retinal diseases might be possible in the future, which warrants further research.

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“…In addition to vesicular systems and hydrogels, there are several novel nanotechnology-based drug delivery systems that may be promising, including in situ assembly systems, emulsomes, and gold nanoparticles [ 103 ]. Schnichels et al [ 145 ] developed an in situ assembly system leveraging DNA nanotechnology, in which micelle nanoparticles form themselves out of DNA molecules modified with lipid moieties. Previously, these kanamycin-loaded nanoparticles were used to treat acute corneal infection while optimising ocular adhesion [ 146 ].…”

Section: Emerging Technologiesmentioning

confidence: 99%

“…Previously, these kanamycin-loaded nanoparticles were used to treat acute corneal infection while optimising ocular adhesion [ 146 ]. When this same technology was loaded with travoprost, increased ocular residence time and improved biocompatibility were noted [ 145 ].…”

Section: Emerging Technologiesmentioning

confidence: 99%

Sustained release glaucoma therapies: Novel modalities for overcoming key treatment barriers associated with topical medications

et al. 2022

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Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness. The disease has conventionally been characterized by an elevated intraocular pressure (IOP); however, recent research has built the consensus that glaucoma is not only dependent on IOP but rather represents a multifactorial optic neuropathy. Although many risk factors have been identified ranging from demographics to co-morbidities to ocular structural predispositions, IOP is currently the only modifiable risk factor, most often treated by topical IOP-lowering medications. However, topical hypotensive regimens are prone to non-adherence and are largely inefficient, leading to disease progression in spite of treatment. As a result, several companies are developing sustained release (SR) drug delivery systems as alternatives to topical delivery to potentially overcome these barriers. Currently, Bimatoprost SR (Durysta TM ) from Allergan plc is the only FDA-approved SR therapy for POAG. Other SR therapies under investigation include: bimatoprost ocular ring (Allergan) (ClinicalTrials.gov identifier: NCT01915940), iDose ® (Glaukos Corporation) (NCT03519386), ENV515 (Envisia Therapeutics) (NCT02371746), OTX-TP (Ocular Therapeutix) (NCT02914509), OTX-TIC (Ocular Therapeutix) (NCT04060144), and latanoprost free acid SR (PolyActiva) (NCT04060758). Additionally, a wide variety of technologies for SR therapeutics are under investigation including ocular surface drug delivery systems such as contact lenses and nanotechnology. While challenges remain for SR drug delivery technology in POAG management, this technology may shift treatment paradigms and dramatically improve outcomes.

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Self-assembled DNA nanoparticles loaded with travoprost for glaucoma-treatment

Cited by 22 publications

References 40 publications

Corneal Penetration of Low-Dose Atropine Eye Drops

Corneal Penetration of Low-Dose Atropine Eye Drops

Topical Drug Delivery to the Posterior Segment of the Eye

Sustained release glaucoma therapies: Novel modalities for overcoming key treatment barriers associated with topical medications

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