眼内色素在眼部药物传递中的作用

Role of ocular melanin in ocular drug delivery

眼内色素主要存在于葡萄膜（包括虹膜、睫状体、脉络膜）和视网膜色素上皮（RPE）层,它能与很多不同类型的药物结合,如抗生素、麻醉剂、β-受体阻滞剂、糖皮质激素和抗疟药等,结合的关键在于药物的酸碱度和脂溶性.通过研究药物在不同给药途径中的药代动力学和药效学,发现眼内色素与药物的结合在眼部药物传递中起重要的作用.它不仅可以提高药物在组织中的初始浓度,而且色素与大部分药物的结合是可逆的,使得药物可以从色素中缓慢释放而延长药物的作用时间,产生有利或不利的影响.由于不同的药物与色素的结合力不同,且在不同的物种和种族,甚至同一组织的不同区域中眼内色素的含量都有区别,使得药物与色素的结合存在个体差异,因此进一步研究不同药物与眼内色素结合的特点和量化关系,可以为科研和临床用药,特别是经巩膜给药的研究和药物递放系统的开发提供更多的科学依据和指导意义.

Ocular melanin is mainly distributed in the uveal tract （including iris,ciliary body and choroid） and the retina pigmented epithelial （RPE） layer.Many drugs from different therapeutic classes can bind to melanin.Examples include antibiotics,anesthetics,β-blockers,corticosteroids,antimalarial drugs and so on.The critical factors are the acid/base status and the lipophilicity of the molecule.Lots of literatures,which refer to pharmacokinetic and pharmacodynamics of drugs from different administration routes,have demonstrated that the binding of drugs to melanin plays an important role in the drug delivery.Not only it may increase initial concentration of drug in the tissues,but also the reversible binding of most drugs to melanin result in a slow release of drugs from melanin,thus it would prolong the action time to potentially beneficial or adverse effects.In addition,the melanin content differs by species and races,even by regions of an eye,which results in different binding capacity of a drug in each individual.Nonetheless,further understanding the melanin-drug binding can provide scientific insight and guideline for transscleral ocular drug delivery.