One Single Eye Drop of Liposomes with Mucoadhesive Polymer Extends Hypotensive Effect of Latanoprost Compared to Marketed Formulation

Abstract

Purpose : The first-line treatment in glaucoma is decreasing intraocular pressure (IOP) by employing topical antihypertensive drugs such as the prostanoid selective receptor agonist latanoprost (LAT). Nanotechnology offers new versatile and well-tolerated solutions to increase antiglaucomatous drugs’ ocular bioavailability and decrease the frequency of their instillations. Our experimental study focuses on designing a new LAT-loaded liposomal formulation including hyaluronic acid (LIP) capable of lowering IOP, protecting corneal surface and being effective for a longer period of time compared to marketed LAT-ophthalmic solution (MF).

Methods : LIP were elaborated following the lipid film hydration method using a mixture of synthetic phospholipids and cholesterol. LAT was included in the lipid bilayer, whereas hyaluronic acid 0.2 % w/v was present in the aqueous dispersion. LIP were characterized by means of pH, size distribution, osmolarity, surface tension and viscosity. In vivo acute tolerance was tested in male albino New Zealand rabbits (n=6, 6 eyes) by topical administration of unloaded liposomes every 30 minutes for 6 hours (NaCl 0.9 % w/v in contralateral eye as control). LIP hypotensive effect was also evaluated up to 48 hours in normotensive rabbits (n=6, 12 eyes) using a tonometer after a single 25 µL instillation and compared to MF (n=6).

Results : LIP demonstrated suitable physicochemical properties, such as neutral pH (7.63 ± 0.01), unimodal vesicle size distribution (223.67 ± 86.10 nm), isotonicity (287.67 ± 2.08 mOsm/L), low surface tension (24.70 ± 0.50 mN/m) and viscosity (2.95 ± 0.02 mPa*s). No signs of alteration or discomfort were observed after 3, 6 and 24 hours after LIP administration in rabbits. LIP showed a longer IOP reduction (48 hours) in comparison to MF (24 hours), with the higher decrease at 3 hours for both formulations (LIP = 24.02 ± 8.26 %; MF = 21.94 ± 10.14 %). Their ocular bioavailability resulted statistically different (p < 0.001) when areas under the curve were compared (LIP = 382.13 ± 146.36 %*h; MF = 128.80 ± 43.85 %*h).

Conclusions : The liposomal formulation presented good tolerance with a 24-hour longer lasting effect compared to marketed formulation, which makes it a promising alternative to be considered for compliance-friendly antiglaucomatous eye drops.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.