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2014 Agenda and Abstracts | < Previous | Next >

2014 OMIG Abstract 16

The Evaluation of Topical SPL, a Novel Dendrimer Antiviral,
Against Adenovirus in NZW Rabbit Ocular Models

EG Romanowski1, KA Yates1, RMQ Shanks1, OK Bernhard2, JRA Paull2, RP Kowalski1
1The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center,
University of Pittsburgh, Pittsburgh, PA; 2Starpharma Pty Ltd., Melbourne, Australia

Purpose: Presently, there is no FDA approved antiviral therapy for treatment of adenovirus (Ad) ocular infections. Dendrimers are novel nanoscale macromolecules that have the ability to interact polyvalently with a target and act as virucidal agents. The drug under investigation, Starpharma compound, SPL, is a polyanionic dendrimer. SPL has a highly charged surface, which allows attachment to targets on viruses and thus prevention of viral attachment and/or adsorption to cells. SPL has also been shown to reduce viral replication in cells already infected with virus. 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.

Methods: 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 in both eyes 4X per day for 5 days except for CDV which was instilled twice daily for 5 days. Eyes were evaluated using the Draize scale on Days 1, 3, 5, 8, 10 and 12. Efficacy: 20 NZW rabbits were topically inoculated in both eyes, following 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 in both eyes 8X per day for 4 days, then 4X per day for 6 days, except for CDV which was instilled twice daily for 7 days. All eyes were cultured for virus on Days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Viral titers were determined using a standard plaque assay.

Results: Tolerability: There were no significant differences in Draize scores among 5% SPL, 3% SPL and VEH on any day (P>0.05, K-W).  CDV demonstrated significantly higher Draize scores on Day 12 than the SPL formulations 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) significantly reduced daily viral titers compared with VEH (P<0.05, K-W). 5% SPL (7 days), 3% (4.5 days) and CDV (5 days) significantly reduced the median Duration of Viral Shedding compared with VEH (9 days) (P<0.05, K-W). 3% SPL was significantly more effective than 5% SPL in several outcome measures (Daily titers Day 5 and Duration of Viral Shedding) (P<0.05, K-W).

Conclusions: 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.

Disclosure code: S       Support: Starpharma Pty Ltd

2014 Agenda and Abstracts | < Previous | Next >