2. Academic Validation
  3. Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents

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

  • Drug Deliv Transl Res. 2024 Apr 11. doi: 10.1007/s13346-024-01584-z.
Marco Brugnera 1 2 3,  Marta Vicario-de-la-Torre 1 2 3,  Miriam Ana González-Cela Casamayor 1 2,  José Javier López-Cano 1 2,  Irene Bravo-Osuna 1 2 3,  Fernando Huete-Toral 4,  María Luisa González Rubio 4,  Gonzalo Carracedo 4,  Irene Teresa Molina-Martínez 1 2 3,  Vanessa Andrés-Guerrero 5 6 7,  Rocío Herrero-Vanrell 8 9 10
Affiliations

Affiliations

  • 1 Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, Complutense University of Madrid (UCM), Madrid, Spain.
  • 2 Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, UCM; IdISSC, Madrid, Spain.
  • 3 University Institute of Industrial Pharmacy (IUFI), Faculty of Pharmacy, UCM, Madrid, Spain.
  • 4 Ocupharm Research Group, Department of Optometry and Vision, Faculty of Optics and Optometry, UCM, Madrid, Spain.
  • 5 Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, Complutense University of Madrid (UCM), Madrid, Spain. vandres@ucm.es.
  • 6 Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, UCM; IdISSC, Madrid, Spain. vandres@ucm.es.
  • 7 University Institute of Industrial Pharmacy (IUFI), Faculty of Pharmacy, UCM, Madrid, Spain. vandres@ucm.es.
  • 8 Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, Complutense University of Madrid (UCM), Madrid, Spain. rociohv@ucm.es.
  • 9 Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, UCM; IdISSC, Madrid, Spain. rociohv@ucm.es.
  • 10 University Institute of Industrial Pharmacy (IUFI), Faculty of Pharmacy, UCM, Madrid, Spain. rociohv@ucm.es.
PMID: 38602615 DOI: 10.1007/s13346-024-01584-z
Abstract

The 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.

Keywords

Glaucoma; Hyaluronic acid; Latanoprost; Liposomes; Ocular drug delivery; Osmoprotectants.

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