1. Academic Validation
  2. Topical Astodrimer Sodium, a Non-Toxic Polyanionic Dendrimer, Demonstrates Antiviral Activity in an Experimental Ocular Adenovirus Infection Model

Topical Astodrimer Sodium, a Non-Toxic Polyanionic Dendrimer, Demonstrates Antiviral Activity in an Experimental Ocular Adenovirus Infection Model

  • Molecules. 2021 Jun 5;26(11):3419. doi: 10.3390/molecules26113419.
Eric G Romanowski 1 Kathleen A Yates 1 Jeremy R A Paull 2 Graham P Heery 2 Robert M Q Shanks 1
Affiliations

Affiliations

  • 1 The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  • 2 Starpharma Pty Ltd., 4-6 Southampton Crescent, Abbotsford, VIC 3067, Australia.
Abstract

There is no approved Antiviral therapy for adenovirus (HAdV) ocular infections. Astodrimer sodium (SPL7013) is a polyanionic dendrimer with Antiviral activity. The current study evaluated the ocular tolerability and anti-adenoviral efficacy of topical SPL7013 in rabbit ocular models. In a tolerability study, rabbits were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Their eyes were graded using the Draize scale. In Antiviral efficacy studies, HAdV5 inoculated eyes were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Eyes were cultured for the virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Viral titers were determined. There were no differences in Draize scores between 3% SPL7013 and vehicle on any day. Cidofovir produced significantly higher Draize scores on day 12 than SPL7013 and vehicle. The 3% SPL7013 and 0.5% cidofovir significantly reduced daily viral titers and positive cultures per total compared with vehicle on several different days. The 3% SPL7013 and 0.5% cidofovir significantly reduced the duration of HAdV5 shedding compared to vehicle. The 3% SPL7013 demonstrated significantly more Antiviral activity compared with vehicle in the Ad5/NZW rabbit ocular model. The 3% SPL7013 induced "minimal" to "practically non-irritating" Draize scores in the ocular tolerability study. Further development of astodrimer sodium as a topical Antiviral therapy for adenoviral ocular infections is indicated.

Keywords

EKC; SPL7013; adenovirus; animal model; antiviral; astodrimer sodium; dendrimer; eye.

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