Controlled release delivery of penciclovir via a silicone (MED-4750) polymer: kinetics of drug delivery and efficacy in preventing primary feline herpesvirus infection in culture.
Controlled release delivery of penciclovir via a silicone (MED-4750) polymer: kinetics of drug delivery and efficacy in preventing primary feline herpesvirus infection in culture.
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DOI：
10.1186/1743-422x-11-34
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发表时间：
2014-02-22
期刊：
影响因子：
4.8
通讯作者：
Margulies BJ
中科院分区：
文献类型：
--
作者：
Semenkow SL;Johnson NM;Maggs DJ;Margulies BJ
疱疹病毒是普遍存在的病原体，可感染多种动物并引起复发性疾病。猫疱疹病毒 1 (FHV-1) 是α疱疹病毒家族的成员，可引起呼吸道疾病和结膜炎，大约 80% 的家猫是潜伏感染者。在隐蔽、安慰剂对照的前瞻性试验中，口服泛昔洛韦或局部应用西多福韦可减少实验接种猫的临床症状和病毒脱落。然而，据作者所知，其他药物尚未经过类似评估或不安全或有效。同样，据我们所知，还没有以安慰剂对照的方式对患有复发性疱疹病的猫进行药物评估。控释装置将允许长期服用这些药物并提高依从性。因此，我们设计了由浸渍喷昔洛韦的硅胶 (MED-4750) 制成的可植入圆柱形装置，用于长期、稳态输送该药物。我们的数据显示，这些设备在释放第十天之前以爆发式药物输送方式释放喷昔洛韦，然后在接下来的 50 天内以每天 5.063± 1.704 μg 的平均速率释放喷昔洛韦，动力学接近零级（与 MED-4750-阿昔洛韦设备相比，MED-4750-阿昔洛韦设备显示出相同的爆发动力学和平均此后为 2.236±±0.625 微克/天）。此外，这些装置还可抑制细胞培养系统中 FHV-1 的初次感染。这些硅胶喷昔洛韦装置的临床部署可能允许通过单一干预措施长期治疗 FHV-1 感染，从而延长宿主猫的生命。
Herpesviruses are ubiquitous pathogens that infect and cause recurrent disease in multiple animal species. Feline herpesvirus-1 (FHV-1), a member of the alphaherpesvirus family, causes respiratory illness and conjunctivitis, and approximately 80% of domestic cats are latently infected. Oral administration of famciclovir or topical application of cidofovir has been shown in masked, placebo-controlled prospective trials to reduce clinical signs and viral shedding in experimentally inoculated cats. However, to the authors’ knowledge, other drugs have not been similarly assessed or were not safe or effective. Likewise, to our knowledge, no drugs have been assessed in a placebo-controlled manner in cats with recrudescent herpetic disease. Controlled-release devices would permit long-term administration of these drugs and enhance compliance. We therefore engineered implantable cylindrical devices made from silicone (MED-4750) impregnated with penciclovir, for long-term, steady-state delivery of this drug. Our data show that these devices release penciclovir with a burst of drug delivery until the tenth day of release, then at an average rate of 5.063 ± 1.704 μg per day through the next 50 days with near zero-order kinetics (in comparison to MED-4750-acyclovir devices, which show the same burst kinetics and average 2.236 ± 0.625 μg/day thereafter). Furthermore, these devices suppress primary infection of FHV-1 in a cell culture system. The clinical deployment of these silicone-penciclovir devices may allow long-term treatment of FHV-1 infection with a single intervention that could last the life of the host cat.