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Eric G Romanowski, Kathleen A Yates, Robert M Q Shanks, Oliver K Bernhard, Jeremy RA Paull, Regis P Kowalski; The Evaluation of Topical SPL, a Novel Dendrimer Antiviral, against Adenovirus in NZW Rabbit Ocular Models. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1872.
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© ARVO (1962-2015); The Authors (2016-present)
There is no FDA approved antiviral therapy for adenovirus (Ad) ocular infections. Dendrimers are novel nanoscale macromolecules that have the ability to be designed to interact polyvalently with a target and act as virucidal agents. SPL is a polyanionic dendrimer. SPL’s unique size, shape, and highly charged surface allow attachment to targets on viruses which then prevent viral attachment and/or adsorption to cells. The goals of the current study were to evaluate the ocular tolerability and anti-adenoviral efficacy of topical SPL in separate NZW rabbit ocular models.
Tolerability: 12 NZW rabbits were divided into 4 groups (n=3/group): 1) 5% SPL; 2) 3% SPL; 3) Vehicle (VEH); and 4) 0.5% Cidofovir (CDV). Rabbits were treated topically OU 4X/day for 5d except for CDV which was instilled 2X/day for 5d. Eyes were graded using the Draize scale on Days 1, 3, 5, 8, 10 and 12. Efficacy: 20 NZW rabbits were inoculated in both eyes after corneal scarification with 1.5 x 106 PFU/eye of Ad5. On day 1, rabbits were divided into 4 groups (n=5/group): 1) 5% SPL; 2) 3% SPL; 3) VEH; 4) 0.5% CDV. Rabbits were treated topically OU 8X/day for 4d, then 4X/day for 6d, except for CDV (2X/day for 7d). All eyes were cultured for virus on Days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Viral titers were determined.
Tolerability: There were no differences in Draize scores among 5% SPL, 3% SPL and VEH on any day (P>0.05, K-W). CDV produced higher Draize scores on Day 12 than SPL and VEH (P≤0.05, K-W). Efficacy: 5% SPL (Days 3, 5, 7, 9), 3% SPL (Days 3, 5, 7, 9) and CDV (Days 7, 9) reduced daily viral titers compared with VEH (P≤0.05, K-W). 5% SPL (7d), 3% (4.5d) and CDV (5d) reduced the Duration of Viral Shedding compared to VEH (9d) (P≤0.05, K-W). 3% SPL was more effective than 5% SPL in several outcome measures (Daily titers Day 5 and Duration of Viral Shedding) (P≤0.05, K-W).
5% SPL and 3% SPL demonstrated significant antiviral efficacy compared with VEH in the Ad5/NZW rabbit ocular model. Both 5% and 3% SPL demonstrated significantly better efficacy than CDV, during the Early Phase of Infection (Days 1-5). SPL induced “Minimal” to “Practically Non-Irritating” Draize scores in the NZW rabbit ocular tolerability model. Further development of SPL as a topical antiviral for adenoviral ocular infections is indicated.
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