Claro Carmen, Ruiz Rosa, Cordero Elisa, Pastor Ma Teresa, López-Cortés Luis Fernando, Jiménez-Castellanos Ma Rosa, Lucero Ma Jesús
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
Exp Eye Res. 2009 Mar;88(3):528-34. doi: 10.1016/j.exer.2008.11.015. Epub 2008 Dec 3.
The treatment of ocular diseases affecting the posterior segment of the eye, such as cytomegalovirus (CMV) retinitis, requires the access of the drugs to the vitreous humor. Foscarnet inhibits replication of herpesviruses, including CMV. The drug's encapsulation in liposomes is meant not only to increase activity and to prolong the effect of the drug, but also to reduce its toxicity. The aims of the present study were to evaluate foscarnet levels and its pharmacokinetic parameters in vitreous humor and retinal tissue of rabbits after the administration of an intravitreal injection of both liposomal foscarnet and foscarnet commercial solution. Liposomes were prepared by the reverse-phase evaporation method. The amount of encapsulated foscarnet (F) was 63% wt. The in vitro diffusion assays showed that F was released more slowly when formulated in liposomes than in the commercial solution. The in vivo studies showed that, as opposed to commercial solution F, liposomal F achieves stable and durable therapeutic levels in retina, going beyond 72h, reaching the vitreous humor with adequate levels to accomplish the aims of intravitreal therapy. Lyophilization also increased stability and dispersion of liposomes in aqueous medium, although not improving the pharmacokinetic results over those from non-lyophilized liposomes.
治疗影响眼后段的眼部疾病，如巨细胞病毒（CMV）视网膜炎，需要药物进入玻璃体液。膦甲酸可抑制包括CMV在内的疱疹病毒的复制。将该药物包封于脂质体中不仅是为了增强活性、延长药物作用时间，也是为了降低其毒性。本研究的目的是评估玻璃体内注射脂质体膦甲酸和膦甲酸商业溶液后，家兔玻璃体液和视网膜组织中膦甲酸的水平及其药代动力学参数。脂质体采用反相蒸发法制备。包封的膦甲酸（F）量为63%（重量）。体外扩散试验表明，与商业溶液相比，脂质体制剂中的F释放更慢。体内研究表明，与商业溶液F不同，脂质体F在视网膜中可达到稳定且持久的治疗水平，超过72小时，以足够的水平到达玻璃体液，实现玻璃体内治疗的目的。冻干也增加了脂质体在水性介质中的稳定性和分散性，尽管与未冻干的脂质体相比，药代动力学结果并未得到改善。
