Abstract
Purpose :
A novel solid lipid nanoparticulate (SLN) drug delivery system has been developed to deliver drugs into the posterior segment of the eye via topical application. The purpose of this study was to investigate the safety and efficacy of SLN loaded atorvastatin (SLN-ATS) in a high-fat atherogenic mouse model of thickened Bruch’s membrane (a pathological feature of age-related macular degeneration, AMD).
Methods :
Mice of C57BL/6J strain (6 weeks old; n=30) were divided into 6 groups of normal pellet diet (n=5), high-fat diet (HFD, n=5), HFD+atorvastatin (ATS) free suspension prevention (n=5), HFD+SLN-ATS prevention (n=5), HFD+ATS free suspension regression (n=5), HFD+SLN-ATS regression group (n=5). Both eyes received the formulations (0.25%) twice daily via topical route from day 0 for the prevention group or from week 15 for the regression group. Animals were monitored and weighed weekly during the experimental period. Retinal structure and function were examined at baseline, and at weeks 15 and 30 after treatment using optical coherence tomography and electroretinography (ERG), respectively. Eye tissues were collected at termination for gross histology and transmission electron microscopy of Bruch’s membrane (BM).
Results :
There was no ocular abnormalities or systemic adverse effect noticed with the treatment. At week 30, the body weight was not significantly reduced in SLN groups as compared to HFD control group (p = 0.145). In mice treated with SLN+ATS, BM thickness was significantly reduced both in the prevention (0.55±0.38µm; p<0.01) and regression groups (0.96±0.28µm; n = 8 eyes; p<0.05) as compared to HFD group (1.98±0.46µm). There was no difference in ERG responses between SLN+ATS treated and control groups (p>0.05).
Conclusions :
SLN safely delivers drug to the posterior segment via topical application. These findings suggest that SLN topical application could potentially be an alternative method for treating chronic retinal diseases such as neovascular AMD.
This is a 2020 ARVO Annual Meeting abstract.