June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Combined protection for glaucoma and ocular surface diseases: New nanohybrid platforms with sustained in vivo hypotensive activity
Author Affiliations & Notes
  • José Javier López-Cano
    Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Madrid, Spain
    Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, Spain
  • Miriam Ana González-Cela Casamayor
    Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Madrid, Spain
    Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, Spain
  • Vanessa Andrés-Guerrero
    Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Madrid, Spain
    Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, Spain
  • Marta Vicario-de-la-Torre
    Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Madrid, Spain
    Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, Spain
  • José Manuel Benítez-del-Castillo
    Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Madrid, Spain
    Ocular Surface and Inflammation Unit, Ophthalmology Department, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, Madrid, Spain
  • Rocío Herrero-Vanrell
    Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Madrid, Spain
    Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, Spain
  • Irene Teresa Molina-Martínez
    Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Madrid, Spain
    Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), Madrid, Spain
  • Footnotes
    Commercial Relationships   José Javier López-Cano None; Miriam González-Cela Casamayor None; Vanessa Andrés-Guerrero None; Marta Vicario-de-la-Torre None; José Benítez-del-Castillo None; Rocío Herrero-Vanrell None; Irene Molina-Martínez None
  • Footnotes
    Support  Research Group UCM920415 (InnOftal), grants FEDER- CICYT (FIS-PI17/00079 and PI17/00466), ORBITAL–ITN (813440), PID2020-113281RB-C21 funded by MCIN/AEI/ 10.13039/501100011033 and ISCIII-FEDER RETICS (OFTARED) (RD16/0008/0009 and RD16/0008/0004) that funded the present research work. We also acknowledge the access to cryoEM CNB-CSIC facility in the context of the CRIOMECORR project (ESFRI-2019-01-CSIC-16). All the figures were created with BioRender (www.biorender.com). M.G. C. thanks for a PhD fellowship from the Spanish MECD (FPU18/03445).
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5080. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      José Javier López-Cano, Miriam Ana González-Cela Casamayor, Vanessa Andrés-Guerrero, Marta Vicario-de-la-Torre, José Manuel Benítez-del-Castillo, Rocío Herrero-Vanrell, Irene Teresa Molina-Martínez; Combined protection for glaucoma and ocular surface diseases: New nanohybrid platforms with sustained in vivo hypotensive activity. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5080.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Hypotensive topical formulations entail the first line for glaucoma treatment, eventually leading to poor patient compliance due to secondary ocular surface effects. This work aimed to develop osmoprotective latanoprost-loaded microemulsions (Lt-MEs) as a potential glaucoma treatment with extended activity.

Methods : Microemulsions (MEs) with or without hyaluronic acid (HA)/dextran (DX) were characterized and latanoprost entrapment efficacy (EE) assessed. In vitro tolerance and osmoprotective efficacy, cell internalization (coumarin-loaded) as well as cell-MEs distribution were carried out in human corneal (HCECs) and conjunctival epithelial cells (HcEpiC). In vivo hypotensive efficacy was conducted in New Zealand male albino rabbits to determine intraocular pressure reduction (△IOP), maximum percentage of △IOP (IOPmax), and relative ocular bioavailability (ROB). These experiments were carried out according to the ARVO Statement as well as the European community council directive (86/609/EEC) and Spanish regulations (PROEX 114.4/21).

Results : Developed hybrid MEs exhibited physicochemical properties suitable for ocular surface administration. Nanovesicles (inner phase) were 21.85±3.48nm for those without HA and 30.51±3.20nm with HA. Lt-MEs exhibited an EE ≥ 98%. High viability (>80%) at 1h and 4h exposure was obtained in HCECs and HcEpiC cells. Besides, all MEs avoided cell death in HCECs under hypertonic stress (470 mOsm/L) for 16h showing high cell survival (50.28±2.83%) in comparison with cells without receiving MEs (19.75±4.91%). Cell fluorescence was extended up to 11 days after 5-min exposure to all coumarin-loaded MEs. Also, extensive accumulation of nanovesicles was localized in different cellular regions. A single dose of Lt-MEs (25 µL) in rabbits decreased IOP between 4-6 (△IOPmax=23.39±5.23%) and 9-13 days (△IOPmax=29.78±4.96%) for those without and with polymers, respectively. MEs exhibited a ROB between 4.5 and 19 times higher than the marketed formulation. The MEs without mucoadhesive polymers presented AUC(0-t’)=139.31±15.92%●h increasing to AUC(0-t’)=271.50±38.25%●h (MEs-HA) and AUC(0-t’)=157.40±37.84%●h (MEs-DX).

Conclusions : New developed MEs were able to protect corneal cells under hypertonic stress and decrease IOP overtime, thus entailing a new potential strategy for the combined treatment of ocular surface diseases and glaucoma.

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×