Original ArticleSelf-assembled DNA nanoparticles loaded with travoprost for glaucoma-treatment
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.
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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2021, Acta BiomaterialiaCitation Excerpt :Watson-Crick base pairing between DNA nanoparticles and drug-binding aminoglycoside-complexed aptamers have testified this general drug loading strategy using two kinds of antibiotics [71]. In 2020, de Vries and group applied this DNA-NP system for antiglaucoma drug delivery via aptamers that bound to travoprost via non-covalent interactions [16]. Compared to the pristine drug, the resulting nanoparticles showed additional residence time on the cornea for over 60 min in vivo and at least twice the amount of travoprost at every time-point detected.
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2021, Progress in Retinal and Eye ResearchCitation Excerpt :For glaucoma drug testing the model has several pitfalls, as readouts are inconsistent and not always correlate. In addition, studies show a high dropout rate (Turner et al., 2017) (Schnichels et al., 2020; under revision). Therefore, these variations and drop-outs need to be considered before designing a study with DBA/2J mice.
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.