Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents

• DOI: 10.1007/s13346-024-01584-z
• Publication Date: 2024-04-11T15:01:51Z
• Authors: Marco Brugnera; Marta Vicario-de-...; Miriam Ana Gonzál...; José Javier López...; Irene Bravo-Osuna; Fernando Huete-Toral; María Luisa Gonzá...; Gonzalo Carracedo; Irene Teresa Moli...; Vanessa Andrés-Gu...; Rocío Herrero-Van...
• Keywords: Ocular drug delivery; Male; 0301 basic medicine; Hyaluronic acid; 2209.15 Optometría; Osmoprotectants; Glaucoma; Optica (Medicina); Cell Line; 617.75; 03 medical and health sciences; Liposomes; Phosphatidylcholines; Latanoprost; Humans; Animals; 2209 Óptica; Original Article; Rabbits; Hyaluronic Acid; Óptica y optometría; Antihypertensive Agents; Intraocular Pressure

AbstractThe first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L−1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m−1) and viscosity (2.69 ± 0.15 mPa s−1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment. Graphical abstract