Christensen Neil D, Cladel Nancy M, Hu Jiafen, Balogh Karla K
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.
Department of Pathology, Penn State College of Medicine, Hershey, PA 17033, United States.
Antiviral Res. 2014 Aug;108:148-55. doi: 10.1016/j.antiviral.2014.06.001. Epub 2014 Jun 16.
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.
目前针对乳头瘤的局部治疗采用消融、细胞毒性和免疫调节策略及试剂。然而,使用不同配方的局部治疗效果尚未在临床前模型或临床试验中得到检验。本研究的目的是确定小分子无环核苷西多福韦(CDV)的配方在使用棉尾兔乳头瘤病毒(CRPV)/兔模型对乳头瘤进行局部治疗后是否能改善治疗终点。测试了固定剂量为1%西多福韦的不同配方以建立比较数据。结果表明,与未配方化的情况相比,局部使用CDV进行抗乳头瘤治疗时,配方化后的效果大大增强。在聚氧乙烯蓖麻油中配方化的CDV效果最佳,其次是在卡波姆940中,然后是在二甲基亚砜中。进一步研究表明,有效的配方在CDV稀释度低于0.3%时可使乳头瘤完全治愈。这些研究与之前的观察结果共同表明,在相同治疗方案下,未配方化的CDV需要2%的剂量才能治愈,这表明正确配方化后可以使用少得多的化合物。