Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment

J Control Release. 2023 Sep:361:534-546. doi: 10.1016/j.jconrel.2023.08.004. Epub 2023 Aug 15.

Abstract

Glaucoma is the third leading cause of blindness worldwide and is primarily characterized by elevated intraocular pressure (IOP). Common risk factors such as age, myopia, ocular trauma, and hypertension all increase the risk of elevated IOP. Prolonged high IOP not only causes physiological discomfort like headaches, but also directly damages retinal cells and leads to retinal ischemia, oxidative imbalance, and accumulation of reactive oxygen species (ROS) in the retina. This oxidative stress causes the oxidation of proteins and unsaturated lipids, leading to peroxide formation and exacerbating retinal damage. While current clinical treatments primarily target reducing IOP through medication or surgery, there are currently no effective methods to mitigate the retinal cell damage associated with glaucoma. To address this gap, we developed a novel nanoemulsion to co-delivery latanoprost and α-tocopherol (referred to as LA@VNE later) that prolongs ocular retention and enhances retinal permeability through localized administration. By encapsulating latanoprost, an IOP-lowering drug, and α-tocopherol, a potent antioxidant, we effectively reduced ROS accumulation (>1.5-fold in vitro and 2.5-fold in vivo), retinal ganglion cell (RGC) apoptosis (>9 fold), and inflammatory cell infiltration (>1.6 fold). Our approach showed strong biocompatibility and significant potential for clinical translation, providing a promising platform for the treatment of glaucoma.

Keywords: Antioxidant; Glaucoma; Latanoprost; RGC protection; α-Tocopherol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • Antioxidants / therapeutic use
  • Glaucoma* / drug therapy
  • Humans
  • Intraocular Pressure
  • Latanoprost / therapeutic use
  • Prostaglandins F, Synthetic* / therapeutic use
  • Reactive Oxygen Species
  • alpha-Tocopherol

Substances

  • Latanoprost
  • Antioxidants
  • Reactive Oxygen Species
  • alpha-Tocopherol
  • Antihypertensive Agents
  • Prostaglandins F, Synthetic