title: Formulation of cidofovir improves the anti-papillomaviral activity of topical treatments in the CRPV/rabbit model.
abstract: Current topical treatments for papillomas use ablative, cytotoxic and immunomodulating strategies and reagents. However, the effectiveness of topical treatments using different formulations has not been examined in preclinical models or clinical trials. The purpose of this study was to determine whether formulation of the small molecule acyclic nucleoside, cidofovir (CDV), could lead to improved therapeutic endpoints following topical treatment of papillomas using the cottontail rabbit papillomavirus (CRPV)/rabbit model. Different formulations with a set dose of 1% cidofovir were tested to establish comparative data. The results demonstrated that anti-papilloma treatments with topical CDV were greatly enhanced when formulated versus unformulated. Best results were obtained with CDV formulated in cremophor, then in Carbomer 940, and then in DMSO. Further studies indicated that effective formulations led to complete cures of papillomas at dilutions less than 0.3% CDV. These studies together with previous observations demonstrated that unformulated CDV under the same treatment regime required doses of 2% to achieve cures demonstrating that much less compound can be used when properly formulated.
authors.affiliation: Department of Pathology, Penn State College of Medicine, Hershey, PA 17033, United States; Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, United States. Electronic address: ndc1@psu.edu.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Christensen
authors.affiliation: Department of Pathology, Penn State College of Medicine, Hershey, PA 17033, United States.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Cladel
authors.affiliation: Department of Pathology, Penn State College of Medicine, Hershey, PA 17033, United States.
authors.forename: Jiafen
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology, Penn State College of Medicine, Hershey, PA 17033, United States.
authors.forename: Karla K
authors.initials: KK
authors.lastname: Balogh
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000737:chemistry / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D000077404:Cidofovir; D012777:Cottontail rabbit papillomavirus / Q000187:drug effects*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D005079:Excipients / Q000737:chemistry; D063065:Organophosphonates / Q000737:chemistry / Q000627:therapeutic use*; D030361:Papillomavirus Infections / Q000662:veterinary* / Q000821:virology; D011817:Rabbits; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000662:veterinary* / Q000821:virology
chemical_list: D000891:Anti-Infective Agents, Local; D005079:Excipients; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir
keywords: Anti-tumor treatments; Antiviral compound; CRPV/rabbit model; Cidofovir; Formulation; Papillomavirus