June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Active Transport of Cationic Liposomes Across the Retina
Author Affiliations & Notes
  • Anne Zebitz Eriksen
    Department of Healthtechnology, Danmarks Tekniske Universitet, Lyngby, Denmark
  • Fredrik Melander
    Department of Healthtechnology, Danmarks Tekniske Universitet, Lyngby, Denmark
  • Paul Joseph Kempen
    Department of Healthtechnology, Danmarks Tekniske Universitet, Lyngby, Denmark
    National Center for Nano Fabrication and Characterization, Danmarks Tekniske Universitet, Lyngby, Denmark
  • Andreas Kjaer
    cDepartment of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital – Rigshospitalet & Department of Biomedical Sciences, Kobenhavns Universitet, Kobenhavn, Denmark
  • Thomas Lars Andresen
    Department of Healthtechnology, Danmarks Tekniske Universitet, Lyngby, Denmark
  • Andrew James Urquhart
    Department of Healthtechnology, Danmarks Tekniske Universitet, Lyngby, Denmark
  • Footnotes
    Commercial Relationships   Anne Zebitz Eriksen None; Fredrik Melander None; Paul Kempen None; Andreas Kjaer None; Thomas Andresen None; Andrew Urquhart None
  • Footnotes
    Support  The Lundbeck Foundation, R322-2019-2611
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1851. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Anne Zebitz Eriksen, Fredrik Melander, Paul Joseph Kempen, Andreas Kjaer, Thomas Lars Andresen, Andrew James Urquhart; Active Transport of Cationic Liposomes Across the Retina. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1851.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Drug delivery to the retina remain a challenge, limiting the therapeutic possibilities for a myriad of blinding diseases. Ocular barriers and fast clearing of intravitreally injected drugs are recognized as the main obstacles for efficient retinal drug delivery. Encapsulation of drugs into nano-sized vehicles hold the promise of prolonging retention times and enhancing delivery to the retina, however, poor understanding of clearing mechanisms limits the clinical realization of nano-sized drug delivery systems (DDS) for intravitreal injection. Here we investigate the involvement of active transport in clearing intravitreally injected liposomes.

Methods : Liposomes were formulated with 10% cationic lipid (DSTAP) and 5% lipid anchored poly-ethylene-glycol (DSPE-PEG). The metal tracer drug Oxaliplatin (OxPt) was loaded in the core of the liposomes. Liposomes were intravitreally injected in 6-10-week-old female C57BL/6JrJ mice. A subset of 4 mice were pre-injected with chloroquine to inhibit active transport. 24h post injection eyes were harvested and dissected into tissue fractions. The amount of Pt in the tissues were quantified by induced coupled plasma mass spectrometry.

Results : The resulting liposomes were unilamellar, had a diameter of 120.2±2nm and slight positive zeta-potential of 7.6±2mV (Figure 1 A and B). The liposomes showed a clear tendency of retaining OxPt in the vitreous, compared to free OxPt (Figure 1C). Interestingly, free OxPt resulted in the highest retinal concentration of OxPt, while liposomal OxPt by-pass the retina and is transported to the RPE/Sclera. Pre-treatment with chloroquine, an inhibitor of active endosomal transport, significantly reduced the clearing of the cationic liposomes to the RPE/Sclera.

Conclusions : The liposomes enhanced the retention of OxPt after intravitreal injection, however, led to significant lower retinal concentrations compared to free drug, due to active transport from the vitreous to the RPE/Sclera. Active transport mechanisms significantly impact the biodistribution of intravitreally injected liposomes and needs consideration when designing DDS targeting the posterior eye.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Figure 1. Cationic liposomes for intravitreal injection. A) Liposome characteristics from Malvern Zeta-sizer. B) Cryo-EM image of liposomes. C) Distribution of OxPt 24h post intravitreal injection in mice. Significant differences from one-way ANOVA indicated(*=p<0.05, **=p<0.01)

Figure 1. Cationic liposomes for intravitreal injection. A) Liposome characteristics from Malvern Zeta-sizer. B) Cryo-EM image of liposomes. C) Distribution of OxPt 24h post intravitreal injection in mice. Significant differences from one-way ANOVA indicated(*=p<0.05, **=p<0.01)

×
×

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.

×