{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:20:20Z","timestamp":1784204420668,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T00:00:00Z","timestamp":1622851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Starpharma Pty Ltd","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/100007819","name":"Allergan","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100007819","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Eye &amp; Ear Foundation of Pittsburgh","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH Core Grant for Vision Research","award":["EY08098"],"award-info":[{"award-number":["EY08098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u201cminimal\u201d to \u201cpractically non-irritating\u201d Draize scores in the ocular tolerability study. Further development of astodrimer sodium as a topical antiviral therapy for adenoviral ocular infections is indicated.<\/jats:p>","DOI":"10.3390\/molecules26113419","type":"journal-article","created":{"date-parts":[[2021,6,6]],"date-time":"2021-06-06T23:59:55Z","timestamp":1623023995000},"page":"3419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Topical Astodrimer Sodium, a Non-Toxic Polyanionic Dendrimer, Demonstrates Antiviral Activity in an Experimental Ocular Adenovirus Infection Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4246-3276","authenticated-orcid":false,"given":"Eric G.","family":"Romanowski","sequence":"first","affiliation":[{"name":"The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen A.","family":"Yates","sequence":"additional","affiliation":[{"name":"The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9981-421X","authenticated-orcid":false,"given":"Jeremy R. A.","family":"Paull","sequence":"additional","affiliation":[{"name":"Starpharma Pty Ltd., 4-6 Southampton Crescent, Abbotsford, VIC 3067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1852-5836","authenticated-orcid":false,"given":"Graham P.","family":"Heery","sequence":"additional","affiliation":[{"name":"Starpharma Pty Ltd., 4-6 Southampton Crescent, Abbotsford, VIC 3067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M. Q.","family":"Shanks","sequence":"additional","affiliation":[{"name":"The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,5]]},"reference":[{"key":"ref_1","first-page":"637","article-title":"Adenovirus-associated epidemic keratoconjunctivitis outbreaks\u2014Four States 2008\u20132010","volume":"62","author":"King","year":"2013","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.antiviral.2005.08.004","article-title":"Evaluation of dendrimer SPL7013, a lead microbicide candidate against herpes simplex viruses","volume":"68","author":"Gong","year":"2005","journal-title":"Antivir. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0166-3542(02)00054-2","article-title":"Evidence of dual sites of action of dendrimers: SPL-2999 inhibits both virus entry and late stages of herpes simplex virus replication","volume":"55","author":"Gong","year":"2002","journal-title":"Antivir. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tyssen, D., Henderson, S.A., Johnson, A., Sterjovski, J., Moore, K., La, J., Zanin, M., Sonza, S., Karellas, P., and Giannis, M.P. (2010). Structure Activity Relationship of Dendrimer Microbicides with Dual Action Antiviral Activity. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012309"},{"key":"ref_5","first-page":"561","article-title":"VivaGel\u2122 (SPL7013 Gel): A candidate dendrimer\u2014Microbicide for the prevention of HIV and HSV infection","volume":"2","author":"Rupp","year":"2007","journal-title":"Int. J. Nanomed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.antiviral.2011.03.186","article-title":"Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1","volume":"90","author":"Telwatte","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Paull, J.R.A., Heery, G.P., Bobardt, M.D., Castellarnau, A., Luscombe, C.A., Fairley, J.K., and Gallay, P.A. (2020). Virucidal and antiviral activity of astodrimer sodium against SARS-CoV-2 in vitro. bioR\u03c7iv.","DOI":"10.1101\/2020.08.20.260190"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1021\/mp050023q","article-title":"Dendrimers as Drugs: Discovery and Preclinical and Clinical Development of Dendrimer-Based Microbicides for HIV and STI Prevention","volume":"2","author":"McCarthy","year":"2005","journal-title":"Mol. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/aid.2005.21.207","article-title":"SPL7013 gel as a topical microbicide for prevention of vaginal transmission of SHIV89.6P in macaques","volume":"21","author":"Jiang","year":"2005","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/OLQ.0b013e3181bc0aac","article-title":"Safety, Tolerability, and Pharmacokinetics of SPL7013 Gel (VivaGel\u00ae): A Dose Ranging, Phase I Study","volume":"37","author":"Millwood","year":"2010","journal-title":"Sex. Transm. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1097\/QAD.0b013e328346bd3e","article-title":"Phase 1 randomized trial of the vaginal safety and acceptability of SPL7013 gel (VivaGel\u00ae) in sexually active young women (MTN-004)","volume":"25","author":"McGowan","year":"2011","journal-title":"AIDS"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cohen, C.R., Brown, J., Moscicki, A.-B., Bukusi, E.A., Paull, J.R.A., Price, C., and Shiboski, S. (2011). A Phase I Randomized placebo controlled trial of the safety of 3% SPL7013 gel (VivaGel\u00ae) in healthy young women administered twice daily for 14 days. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016258"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Waldbaum, A.S., Schwebke, J.R., Paull, J.R.A., Price, C.F., Edmondson, S.R., Castellarnau, A., McCloud, P., and Kinghorn, G.R. (2020). A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose-ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232394"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejogrb.2019.11.032","article-title":"Two phase 3, double-blinded, placebo-controlled studies of the efficacy and safety of Astodrimer 1% Gel for the treatment of bacterial vaginosis","volume":"245","author":"Chavoustie","year":"2020","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_15","first-page":"100121","article-title":"A phase 3, randomized, controlled trial of Astodrimer 1% Gel for preventing recurrent bacterial vaginosis","volume":"10","author":"Schwebke","year":"2021","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol. X"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1097\/00003226-199211000-00008","article-title":"Pretreatment with topical 0.1% (s)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine inhibits adenovirus type 5 replication in the New Zealand rabbit ocular model","volume":"11","author":"Gordon","year":"1992","journal-title":"Cornea"},{"key":"ref_17","first-page":"4135","article-title":"Topical HPMPC inhibits adenovirus type 5 in the New Zealand rabbit ocular replication model","volume":"35","author":"Gordon","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","first-page":"460","article-title":"Efficacy of topical cidofovir on multiple adenoviral serotypes in the New Zealand rabbit ocular model","volume":"41","author":"Romanowski","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0166-3542(01)00166-8","article-title":"Antiviral prophylaxis with twice daily topical cidofovir protects against challenge in the adenovirus type 5\/New Zealand rabbit ocular model","volume":"52","author":"Romanowski","year":"2001","journal-title":"Antivir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1167\/iovs.07-0491","article-title":"Efficacy of topical immunoglobulins (IG) against experimental adenoviral ocular infection","volume":"48","author":"Nwanegbo","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1167\/iovs.05-1270","article-title":"N\u2013Chlorotaurine is an effective antiviral agent against adenovirus in vitro and in the Ad5\/NZW rabbit ocular model","volume":"47","author":"Romanowski","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5295","DOI":"10.1167\/iovs.08-3286","article-title":"The in vitro and in vivo evaluation of ddC as a topical antiviral for ocular adenovirus infections","volume":"50","author":"Romanowski","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Romanowski, E.G., Hussein, I.T.M., Cardinale, S.C., Butler, M.M., Morin, L.R., Bowlin, T.L., Yates, K.A., Shanks, R.M.Q., and Kowalski, R.P. (2021). Filociclovir is an active antiviral agent against ocular adenovirus isolates in vitro and in the Ad5\/NZW rabbit ocular model. Pharmaceuticals, 15.","DOI":"10.3390\/ph14040294"},{"key":"ref_24","first-page":"377","article-title":"Methods for the study of irritation and toxicity of articles applied topically to the skin and mucous membranes","volume":"82","author":"Draize","year":"1944","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_25","first-page":"281","article-title":"Interpretation of eye irritation tests","volume":"13","author":"Kay","year":"1962","journal-title":"J. Soc. Cosmet. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0166-3542(91)90054-U","article-title":"Inhibitory effect of (S)-HPMPC, (S)-HPMPA, and 2\u2019-nor-cyclic GMP on clinical ocular adenoviral isolates is serotype-dependent in vitro","volume":"16","author":"Gordon","year":"1991","journal-title":"Antivir. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1586\/17469899.2013.831325","article-title":"Is there an anti-adenoviral drug on the horizon?","volume":"8","author":"Romanowski","year":"2013","journal-title":"Expert Rev. Ophthalmol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/11\/3419\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:11:08Z","timestamp":1760163068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/11\/3419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,5]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["molecules26113419"],"URL":"https:\/\/doi.org\/10.3390\/molecules26113419","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,5]]}}}