Evaluation of subconjunctival liposomal steroids for the treatment of experimental uveitis

Chee Wai Wong,Si Rui Ng,Tina T Wong,Josbert M Metselaar,Candice Ho,Bertrand Czarny,Gert Storm,Amutha Veluchamy Barathi

doi:10.1038/s41598-018-24545-2

Abstract

Non-infectious anterior uveitis (AU) is a potentially sight threatening inflammatory condition. The current gold standard for treatment is topical steroids, but low ocular bioavailability and compliance issues with the intensive dosing regimen limit the efficacy of this treatment. Liposomes as a drug delivery system may help to overcome these problems. We studied the efficacy of a PEG-liposomal formulation of liposomal steroids, administered as a single subconjunctival dose, in the treatment of experimental uveitis in rabbit eyes. Rabbits that received subconjunctival liposomal triamcinolone acetonide phosphate (LTAP) or liposomal prednisolone phosphate (LPP) had significantly lower mean inflammatory scores than untreated controls on Day 4 after induction of uveitis (LPP vs controls, p = 0.049) and 8 (LPP vs controls, p = 0.007; LTAP vs controls, p = 0.019), and lower scores than rabbits given topical PredForte1% 4 times a day on Day 8 (p = 0.03). After antigen rechallenge, the subconjunctival liposomal steroid groups continued to have greater suppression of inflammation than untreated controls on Day 11 (p = 0.02). Localization of liposomes in inflamed ocular tissue was confirmed by histology and immunostaining, and persisted in the eye for at least one month. Our study demonstrates that a single subconjunctival injection of liposomal steroids induces effective and sustained anti-inflammatory action.

Highlights

Non-infectious anterior uveitis (AU) represents a group of immune-related, sight-threatening inflammatory conditions that account for 60% of all cases of uveitis seen in eye centres[1,2,3,4,5]
We demonstrated that a single dose of liposomal steroid, injected subconjunctivally, was able to provide sustained anti-inflammatory action comparable to 2 weeks of eyedrop therapy with prednisolone acetate 1%
We found that liposomal prednisolone phosphate was able to suppress the initial inflammation better than eyedrops (p = 0.033)

Summary

Introduction

Non-infectious anterior uveitis (AU) represents a group of immune-related, sight-threatening inflammatory conditions that account for 60% of all cases of uveitis seen in eye centres[1,2,3,4,5]. Pegylated liposomal formulations of water-soluble corticosteroids have already shown promising results in human trials to treat systemic inflammatory diseases such as rheumatoid arthritis (Phase I/II) and ulcerative colitis (Phase IIa)[26,27]. When injected in the subconjunctival space, we postulate that, besides creating a local depot providing sustained release of the drug, the liposomes could enhance uptake of the drug by local inflammatory target cells in AU This is a therapeutic efficacy study with a GMP-liposomal corticosteroid formulation that has shown to be active in a variety of models of chronic inflammation after IV administration, by virtue of targeting to the inflamed target sites[26,27,29,30,31]. We compared the efficacy of subconjunctival liposomal prednisolone phosphate (LPP) and liposomal triamcinolone acetonide phosphate (LTAP) with topical prednisolone acetate 1% eyedrops and subconjunctival free prednisolone phosphate for the treatment of AU in a rabbit model of experimental uveitis

Methods

Results

Conclusion