Exploring the Extended Benefits: Long-term Study on the Safety and Efficacy of Mucoadhesive Latanoprost-Loaded Liposomes for Glaucoma Treatment

Abstract

Purpose : Glaucoma patients subjected to repeated topical administrations of hypotensive eye drops may trigger dry eye disease’s symptoms due to tear film destabilization and secondary effects associated to antiglaucomatous formulations. We hypothesize that daily instillations of unpreserved latanoprost-loaded liposomes dispersed in the mucoadhesive polymer sodium hyaluronate (0.2%w/v), containing the osmoprotective substances betaine and leucine (LL), are able to maintain healthy conditions of the tear film, be well-tolerated and reduce intraocular pressure (IOP) in normotensive rabbits during long-term treatments.

Methods : In addition to the already stated ingredients, synthetic phospholipids and cholesterol were LL main components, which were prepared by the lipid film hydration protocol. LL (25µL) was instilled once per day for 15 days (according to EMA/CHMP/SWP/2145/2000) in male albino New Zealand rabbits (n=14 eyes); 0.9%w/v NaCl (NC) was used as control (n=6 eyes). Ocular tolerance was evaluated daily according to the Draize test scoring system. Tears’ osmolarity was measured with an osmometer. Tear breakup time (TBUT), Schirmer’s test (ST) and grading of corneal and conjunctival fluorescence staining evaluated through the Oxford scale (OS) were the parameters tested during a 25-day follow-up. IOP was measured for 15 days using a rebound tonometer just before and 3 hours after each instillation up to normal IOP values.

Results : Our results showed that no signs of discomfort or ocular damage were observed during the long-term study. Similar values were observed for LL and NC for ST (10.29±3.00 mm LL, 9.83±2.64 mm NC at 25 days) and OS (1.86±0.86 LL, 1.33±0.52 NC at 25 days) and slightly increased for osmoprotective LL regarding TBUT (7.00±0.78 sec LL, 6.00±0.63 sec NC at 15 days) at all timepoints. There was no statistical difference considering rabbits tears’ osmolarity (320.07±15.22 mOsm/L LL, 320.33±10.56 mOsm/L NC at 15 days). Hypotensive effect started from day 1; IOP mean value was 81.27±8.49 % for LL for 5-15 days interval. Maximum IOP decrease was registered at day 14 (72.76±8.89 % LL, 103.25±8.46 % NC, p<0.001).

Conclusions : The well-tolerated formulation effectively lowered IOP within the therapeutic window during a simulated chronic administration. This promising outcome positions it as a potential candidate for an antiglaucomatous eye drop.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.