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

https://doi.org/10.1016/j.nano.2020.102260Get rights and content

Highlights

  • Lipid DNA NP as a drug delivery system can be easily tailored to different applications.

  • A novel aptamer was used to load the anti-glaucoma drug travoprost into the NP.

  • The uptake of the anti-glaucoma drug travoprost was at least doubled via Lipid DNA NP.

Abstract

Lipid DNA nanoparticles (NPs) exhibit an intrinsic affinity to the ocular surface and can be loaded by hybridization with fluorophore-DNA conjugates or with the anti-glaucoma drug travoprost by hybridizing an aptamer that binds the medication. In the travoprost-loaded NPs (Trav-NPs), the drug is bound by specific, non-covalent interactions, not requiring any chemical modification of the active pharmaceutical ingredient. Fluorescently labeled Trav-NPs show a long-lasting adherence to the eye, up to sixty minutes after eye drop instillation. Biosafety of the Trav-NPs was proved and in vivo. Ex vivo and in vivo quantification of travoprost via LC–MS revealed that Trav-NPs deliver at least twice the amount of the drug at every time-point investigated compared to the pristine drug. The data successfully show the applicability of a DNA-based drug delivery system in the field of ophthalmology for the treatment of a major retinal eye disease, i.e. glaucoma.

Graphical Abstract

Introducing hydrophobic chains at the nucleobase uracil enables the automated solid-phase synthesis of amphiphilic DNA strands, which self-assemble into spherical nano-objects. These lipid DNA nanoparticles (NPs) exhibit an intrinsic affinity to the ocular surface and were loaded with the anti-glaucoma medication travoprost by hybridizing a specific aptamer that binds the drug. The NPs were evaluated for adhesion, drug-uptake and biosafety with rats and mouse in vivo and ex vivo with porcine tissue. The NPs successfully delivered the drug to the ocular surface and revealed improved efficacy compared to the free drug.

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Section snippets

Preparation of DNA nanoparticles

The DNA NPs used as carrier were based on self-assembly of DNA amphiphiles, which were reported earlier. Moreover, the aggregation behavior of the NPs as well as the charge and size distribution was well explained.3,21 The amphiphilic nature of the DNA strand is imparted by the hydrophilic, anionic phosphodiester backbone and hydrophobic units, which are attached to the nucleobases (Figure 1, A). Alkylethyne moieties were incorporated at the 5-position of uracil. Employing an automated

Discussion

In order to improve glaucoma treatment or drug delivery via eye drops several different approaches are being followed. For several good reasons topical treatment is the first line therapy of glaucoma, since it is cheap and easy to apply and no surgical intervention is needed. Nevertheless, the efficiency of this approach is compromised by some difficulties. First, most eye drops contain preservatives and/or additives to increase adhesion to the ocular surface; both lead to blurred vision,

Acknowledgments

We thank Katharina Frößl and Felix Frößl for their assistance. The authors greatly acknowledge the University Eye Hospital Tübingen for their support.

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    Funding: This work was supported by the EXIST research transfer program of the Federal Ministry for Economic Affairs and Energy Germany (No. 03EFDBW075). A.H. greatly acknowledges support from the Zernike Institute for Advanced Materials.

    Conflicts of interest: A.H. M.S.S., J.W.d.V. and S.S. are Inventors of the presented technology. The patent (US10285939B2, EP3057572B1) is owned by the Medical Faculty of the University of Tübingen, Germany.

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