Abstract
Purpose :
To improve the controlled release delivery of molecules and proteins in a topical drug delivery system to the retina, several strategies have been explored to create a delivery system that maintains drug concentrations in their therapeutic range. Metal-organic frameworks (MOFs) are a novel strategy in ocular drug delivery since 2018 and provide many advantages such as large surface areas, tunable structures, and stability. We hypothesize that the incorporation of MOFs into our novel topical ocular drug delivery system can efficiently maintain drug levels in their therapeutic range.
Methods :
MOFs were prepared by crystallization of organic linkers and metal nodes, and loaded with an anti-VEGF antibody Fab fragment ranibizumab (RB; 48 kDa) and a surrogate, ovalbumin (OVA; 44kDa). Encapsulation efficiency (EE) and loading capacity (LC) were determined by microBCA assay after loading. In vitro release kinetics was performed in physiological buffer (PBS, pH 7.4) and quantified using microBCA assay. Particle size, porosity, and crystallinity were characterized. Additionally, cytotoxicity and ocular irritancy test were performed using human conjunctival epithelial cells and ex vivo bovine eyes. Permeability assays using porcine eyes in Franz Diffusion cells were performed over 5 hours and drug concentrations in the receptor chamber were measured using ELISA.
Results :
The MOF delivery vehicle showed LC of 28mg of RB per mg of MOF, and EE of 93.62% of total RB solution. This indicates that the internal porous structure is saturated with RB. In vitro release data shows no burst release and a cumulative release of 19.12 μg in 8 days. Within the first day, 4% of encapsulated RB was released and a total of 6% of encapsulated RB was released over 8 days. The therapeutic concentration threshold for RB is 27 ng/ml, and the in vitro measurements show an average 3.65 μg/ml released daily.
Conclusions :
MOFs are a favorable delivery vehicle in various applications due to their large surface areas, tunable porosity, and tailorable structures. The results of this study demonstrate a high loading capacity, a high encapsulation efficiency, and controlled release profiles favorable for topical ocular drug delivery applications. This new delivery vehicle has potential to be incorporated into existing delivery platforms and administration methods to treat anterior and posterior ocular diseases.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.