journal article·2021-03-03

Improved Treatment Options for Glaucoma with Brimonidine-Loaded Lipid DNA Nanoparticles

Sven Schnichels, José Hurst, Jan Willem de Vries, Sami Ullah, Katharina Frößl, Agnieszka Gruszka, Marina Löscher, Karl-Ulrich Bartz-Schmidt, Martin S Spitzer, Andreas Herrmann

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Abstract

Glaucoma is the second leading cause of irreversible blindness worldwide. Among others, elevated intraocular pressure (IOP) is one of the hallmarks of the disease. Antiglaucoma drugs such as brimonidine can lower the IOP but their adherence to the ocular surface is low, leading to a low drug uptake. This results in a frequent dropping regime causing low compliance by the patients. Lipid DNA nanoparticles (NPs) have the intrinsic ability to bind to the ocular surface and can be loaded with different drugs. Here, we report DNA NPs functionalized for loading of brimonidine through specific aptamers and via hydrophobic interactions with double stranded micelles. Both NP systems exhibited improved affinity toward the cornea and retained release of the drug as compared to controls both in vitro and in vivo. Both NP types were able to lower the IOP in living animals significantly more than pristine brimonidine. Importantly, the brimonidine-loaded NPs showed no toxicity and improved efficacy and hence should improve compliance. In conclusion, this drug-delivery system offers high chances of an improved treatment for glaucoma and thus preserving vision in the aging population.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Glaucoma and retinal disorders · Lipid Membrane Structure and Behavior · Molecular Sensors and Ion Detection

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Centre for Ophthalmology, University Eye Hospital Tübingen, Elfriede-Aulhorn-Straße 7, Tübingen D-72076, Germany

Clinic for Ophthalmology, University Medical Center Hamburg-Eppendorf (UKE), Martinistrasse 52, Hamburg D-20246, Germany

DWI − Leibniz Institute for Interactive Materials, Forckenbeckstrasse 50, Aachen 52056, Germany

Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, Aachen 52074, Germany

Funding

Bundesministerium f?r Wirtschaft und Energie · H2020 European Research Council

References (46)

Show source-provided references
1. 10.1021/ac010543710.1021/ac0105437 ↗
2. 10.1021/ar900101s10.1021/ar900101s ↗
3. 10.1016/j.nano.2020.10226010.1016/j.nano.2020.102260 ↗
4. 10.1373/clinchem.2006.08324610.1373/clinchem.2006.083246 ↗
5. 10.1016/j.biomaterials.2006.09.02110.1016/j.biomaterials.2006.09.021 ↗
6. 10.1016/j.bbrc.2007.04.00710.1016/j.bbrc.2007.04.007 ↗
7. 10.1002/cmdc.20080009110.1002/cmdc.200800091 ↗
8. 10.1208/s12248-010-9183-310.1208/s12248-010-9183-3 ↗
9. 10.1001/jama.2014.319210.1001/jama.2014.3192 ↗
10. 10.1016/j.ophtha.2014.05.01310.1016/j.ophtha.2014.05.013 ↗
11. 10.1016/j.ajo.2013.05.02710.1016/j.ajo.2013.05.027 ↗
12. 10.7326/0003-4819-158-4-201302190-0000810.7326/0003-4819-158-4-201302190-00008 ↗
13. 10.1097/00061198-199708000-0001010.1097/00061198-199708000-00010 ↗
14. 10.1001/archopht.1995.0110012004400610.1001/archopht.1995.01100120044006 ↗
15. 10.1016/S0161-6420(97)30349-210.1016/S0161-6420(97)30349-2 ↗
16. 10.1167/iovs.07-059310.1167/iovs.07-0593 ↗
17. 10.1016/j.jconrel.2004.07.00110.1016/j.jconrel.2004.07.001 ↗
18. 10.1055/s-0041-11044710.1055/s-0041-110447 ↗
19. 10.1097/IJG.0b013e3181f3eb4a10.1097/IJG.0b013e3181f3eb4a ↗
20. 10.1097/01.icu.0000193078.47616.aa10.1097/01.icu.0000193078.47616.aa ↗
21. 10.1016/j.ophtha.2009.06.02410.1016/j.ophtha.2009.06.024 ↗
22. 10.1038/sj.eye.670052010.1038/sj.eye.6700520 ↗
23. 10.1038/sj.eye.670144110.1038/sj.eye.6701441 ↗
24. 10.1007/s00347-017-0596-610.1007/s00347-017-0596-6 ↗
25. 10.1016/j.addr.2012.09.02610.1016/j.addr.2012.09.026 ↗
26. 10.1002/chem.20100181610.1002/chem.201001816 ↗
27. 10.1016/j.biomaterials.2017.11.04610.1016/j.biomaterials.2017.11.046 ↗
28. 10.1242/bio.02542910.1242/bio.025429 ↗
29. 10.1111/ceo.1299210.1111/ceo.12992 ↗
30. John S. W. · Invest. Ophthalmol. Vis. Sci. · 1998 · 39 · 951
31. 10.1017/S095252380522513010.1017/S0952523805225130 ↗
32. 10.1186/1471-2202-7-6610.1186/1471-2202-7-66 ↗
33. 10.1007/s00417-009-1146-y10.1007/s00417-009-1146-y ↗
34. 10.2147/IJN.S2495410.2147/IJN.S24954 ↗
35. 10.1186/1477-3155-2-310.1186/1477-3155-2-3 ↗
36. Subramanian N. · Molecular vision · 2012 · 18 · 2783
37. 10.4103/2230-973X.13834010.4103/2230-973X.138340 ↗
38. 10.1089/jop.2012.019310.1089/jop.2012.0193 ↗
39. 10.1016/j.exer.2008.02.00810.1016/j.exer.2008.02.008 ↗
40. 10.1167/iovs.07-074510.1167/iovs.07-0745 ↗
41. 10.1021/acsami.6b1650910.1021/acsami.6b16509 ↗
42. 10.1016/j.exer.2014.06.01310.1016/j.exer.2014.06.013 ↗
43. 10.1177/026119291984009210.1177/0261192919840092 ↗
44. 10.1016/j.preteyeres.2019.10079910.1016/j.preteyeres.2019.100799 ↗
45. 10.1016/j.preteyeres.2020.10088010.1016/j.preteyeres.2020.100880 ↗
46. Herrmann, A.; De, V. J. W.; Spitzer, M. S.; Schnichels, S. O., Means and Methods for Ocular Drug Delivery. EP3057572B1, 2015.