Abstract
Purpose :
Our drug delivery platform based on lipid-modified DNA nanoparticles (NPs) was already presented in previous years showing improved topical delivery of antibiotics and travoprost and general biosafety of the carrier. Lipid DNA-NPs have an intrinsic affinity to the ocular surface and can be used as broadly functionalizable carriers for enhanced drug delivery. Here, the anti-glaucoma drug brimonidine (Brim) was loaded into the NP (NP-Brim) to attain an improved therapy option.
Methods :
Two loading strategies: 1. incorporation of Brim using hydrophobic interaction; 2. aptameric interactions via self-designed aptamers were established and evaluated. Next, the safety profile of the Brim-NPs was measured on primary corneal epithelial cells. Furthermore, the Brim-NPs were evaluated in-vivo with different dosing regimen and corneal sections were then screened for apoptosis. Afterwards, fluorescently labeled NP-Brim eye drops were applied onto ex-vivo pig eyes and in-vivo on rats. After different incubation times, the adhesion to the corneas was assessed via fluorescent microscopy and fluorophotometry. Finally, the Brim-NPs and brimonidine were dropped on healthy rats and DBA/2J-mice to evaluate the IOP lowering effect and compared to the commercially available formulation.
Results :
Both loading strategies proved excellent loading and release profiles of the drugs. An optimized Brim aptamer was selected. Brim-NPs showed a long-lasting adherence to ex-vivo and in-vivo corneas and were present on the in-vivo corneas for up to 60 minutes from eye drop installation. Quantification after fluorophotometry confirmed these results showing a significant higher adhesion even 2 hours after dropping. Both in-vitro and in-vivo experiments proved the biosafety of the Brim-NPs. Finally efficacy of the Brim-NPs was proven by the IOP lowering effect in-vivo on glaucoma-affected DBA/2J mice.
Conclusions :
Our data successfully proves the functionality of our DNA-based NP carrier system as anti-glaucoma drug delivery vehicle. We confirmed that the drug formulated with DNA NPs remained functional with both loading strategies, that they are non-toxic and even showed higher efficacy. This is the first time that we show successful delivery to the anterior segment with hydrophobic loading. These findings allow further investigation with our NP carrier system to improve glaucoma-treatment by delivering drugs more efficiently.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.