July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Solid lipid nanoparticles for the delivery of a sustained-release small molecule antioxidant for RPE protection in dry AMD
Author Affiliations & Notes
  • Anthoula Arta
    Micro- and Nanotechnology, Technical University of Denmark, Kgs. Lyngby, Denmark
    Ophthalmology, Harvard Medical School,Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts, United States
  • Yu Su
    Ophthalmology, Harvard Medical School,Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts, United States
  • Franco Aparecido Rossato
    Ophthalmology, Harvard Medical School,Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts, United States
  • Gopalan Gnanaguru
    Ophthalmology, Harvard Medical School,Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts, United States
  • Patricia A. D'Amore
    Ophthalmology, Harvard Medical School,Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts, United States
  • Yin Shan Eric Ng
    Ophthalmology, Harvard Medical School,Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts, United States
  • Andrew J Urquhart
    Micro- and Nanotechnology, Technical University of Denmark, Kgs. Lyngby, Denmark
  • Footnotes
    Commercial Relationships   Anthoula Arta, None; Yu Su, None; Franco Aparecido Rossato, None; Gopalan Gnanaguru, None; Patricia D'Amore, None; Yin Shan Eric Ng, None; Andrew Urquhart, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1705. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Anthoula Arta, Yu Su, Franco Aparecido Rossato, Gopalan Gnanaguru, Patricia A. D'Amore, Yin Shan Eric Ng, Andrew J Urquhart; Solid lipid nanoparticles for the delivery of a sustained-release small molecule antioxidant for RPE protection in dry AMD. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1705. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Solid lipid nanoparticles (SLN) are a new class of lipid based drug delivery systems, able to incorporate poorly water soluble compounds and deliver them in a sustained manner to the tissue of interest. The goal of this work is to develop a SLN formulation loaded with a hydrophobic, very potent small molecule antioxidant, pentamethyl-6-chromanol (PMC), and evaluate its potential protective effects for retinal pigment epithelial cells (RPE) in an in vitro model of dry AMD: oxidized low-density lipoprotein (ox-LDL)-induced ROS production, lysosomal cholesterol accumulation and cell death of RPE cells.

Methods : PMC-loaded SLN (SLN:PMC) were prepared by high-shear homogenization and the particle size was characterized by light scattering. The loaded drug and the release profile were quantified by chromatography. The therapeutic potential of our system was assessed by treating ARPE-19 cells for 8-72 hours with ox-LDL (200µg/ml) in the presence or absence of different concentrations of PMC in the form of free drug (DMSO:PMC) or SLN:PMC and cell death was determined by lactate dehydrogenase (LDH) release assay, whereas intracellular ROS and total cellular cholesterol concentration was measured by fluorometric analysis.

Results : The SLN formulation had mean diameter of 185 nm, it exhibited PMC loading efficiency of approximately 51% and sustained PMC release. The SLN:PMC significantly protected ARPE-19 cells from ox-LDL-induced cell death for up to 72h of treatment in a similar manner as DMSO:PMC for concentrations as low as 1.3 µM (p < 0.001)(Fig). Ox-LDL (8h) uptake induced 5-fold increase in the ROS production compared to the control cells, an effect that was eliminated by SLN:PMC or DMSO:PMC treatment (p < 0.0001). Ox-LDL treatment for 8h significantly increased the total cholesterol levels in ARPE-19 cells, and PMC reduced cholesterol accumulation (p < 0.05), likely by facilitating the metabolism and efflux of the cholesterol from the lysosome.

Conclusions : We have successfully developed a sustained release SLN:PMC formulation which protects RPE cells from ox-LDL-induced cell death by suppressing ROS production and preventing lysosomal ox-LDL accumulation and destabilization. These preliminary data indicate SLN:PMC as a potential therapeutic formulation for protecting RPE in dry AMD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

RPE protection activity of free PMC or SLN encapsulated, against ox-LDL-induced cell death.

RPE protection activity of free PMC or SLN encapsulated, against ox-LDL-induced cell death.

×
×

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.

×