Evaluation of subconjunctival liposomal steroids for the treatment of experimental uveitis

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.

Characterisation of the inflammatory cytokine and growth factor profile in a rabbit model of proliferative vitreoretinopathy

“…The procedures performed for histology and immunohistochemistry have been previously described by our group 8 . Eyes were enucleated and fixed in a mixture of 10% neutral buffered formalin solution (Leica Surgipath, Leica Biosystems Richmond, Inc.) for 24 hours.…”

Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations

“…Antidiabetics Insulin Diabetic retinopathy [193] Chemotherapeutics Carboplatin Retinoblastoma [194] Topotecan Folic acid analogues Methotrexate Granulomatous panuveitis [195] Corticosteroids Dexamethasone Uveitis [196] Thermo-responsive hydrogels are also systems that can be used to facilitate a sustained drug delivery. This pharmaceutical form turns into a gel when contacting with the injection area due to a temperature difference.…”

The availability of drug by liposomal drug delivery

“…Most probably, after uptake of liposomes by macrophages, PP is liberated in the endosomal/lysosomal compartment where it is dephosphorylated into P [29, 30]. Because of the previous observed efficacy [9, 29] and because P can easily pass membranes [46], it is assumed that the released P is not trapped in the lysosome, but can be available intra- and possibly also extracellularly [31]. Hence, the released P tissue concentrations shown in Figs.…”

“…Phosphatases are also overexpressed in tumor microenvironments [28]. Moreover, it is strongly believed that after liposome uptake by macrophages, the encapsulated drug is liberated in the endosomal/lysosomal compartment and hydrolyzed into P [29–31], because phosphatases are also present in macrophages and lysosomes [32]. Thus, it is assumed that PP is rapidly converted into P after release.…”