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  3. New trends towards glaucoma treatment: Topical osmoprotective microemulsions loaded with latanoprost

New trends towards glaucoma treatment: Topical osmoprotective microemulsions loaded with latanoprost

  • Ocul Surf. 2023 Jun 7;S1542-0124(23)00055-1. doi: 10.1016/j.jtos.2023.05.013.
J J López-Cano 1,  M A González-Cela-Casamayor 1,  V Andrés-Guerrero 1,  M Vicario-de-la-Torre 1,  J M Benítez-Del-Castillo 2,  R Herrero-Vanrell 3,  I T Molina-Martínez 4
Affiliations

Affiliations

  • 1 Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy (UCM), Plaza Ramón y Cajal s/n, Madrid, 28040, Spain; Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, 28040, Spain.
  • 2 Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, 28040, Spain; Ocular Surface and Inflammation Unit, Ophthalmology Department, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, 28040, Spain.
  • 3 Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy (UCM), Plaza Ramón y Cajal s/n, Madrid, 28040, Spain; Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, 28040, Spain. Electronic address: rociohv@ucm.es.
  • 4 Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy (UCM), Plaza Ramón y Cajal s/n, Madrid, 28040, Spain; Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, 28040, Spain. Electronic address: iremm@ucm.es.
PMID: 37295473 DOI: 10.1016/j.jtos.2023.05.013
Abstract

The chronic use of hypotensive agents eventually leads to ocular surface damage and poor patient compliance during glaucoma management. Thus, new sustained drug delivery systems are needed. This work aimed to develop osmoprotective latanoprost-loaded microemulsion formulations as new potential glaucoma treatments with ocular surface protective properties. The microemulsions were characterized and latanoprost encapsulation efficacy determined. In-vitro tolerance, osmoprotective efficacy, cell internalization as well as cell-microemulsion interactions and distribution were performed. In vivo hypotensive activity was conducted in rabbits to assess intraocular pressure reduction and relative ocular bioavailability. Physicochemical characterization showed nanodroplet sizes within 20-30 nm being in vitro tolerance between 80 and 100% viability in corneal and conjunctival cells. Besides, microemulsions exhibited higher protection under hypertonic conditions than untreated cells. Cell fluorescence lasted for 11 days after short exposure to coumarin-loaded microemulsions (5 min) showing extensive internalization in different cell compartments by electronic microscopy. In vivo studies exhibited that a single instillation of latanoprost-loaded microemulsions reduced the intraocular pressure for several days (4-6 days without polymer and 9-13 days with Polymers). Relative ocular bioavailability was 4.5 and 19 times higher than the marketed formulation. These findings suggest the use of these microemulsions as potential combined strategies for extended surface protection and glaucoma treatment.

Keywords

Cell internalization; Glaucoma; Latanoprost; Microemulsion; Osmoprotection; Osmoprotective microemulsion.

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