巩膜对大分子物质的通透性研究

Permeability of sclera to macromolecules: a literature review

当前玻璃体腔注药已经成为治疗眼后段慢性疾病的主要给药途径。但限于玻璃体腔注药难以避免的多种副作用,临床上急需疗效相近且副作用较小的替代方案。眼表给药和全身给药因其作用强度不足和副作用过多等原因不能成为眼后段慢性疾病给药的理想方案,而眼球周围给药则因巩膜的种种特性而成为一种很有前景的给药方法。眼球周围给药,必需要穿透巩膜才能作用于眼内组织。影响巩膜通透性的因素包括药物自身因素,如分子量大小、分子形态、脂溶性及分子所带电荷等;巩膜自身因素,如巩膜厚度及巩膜是否老化等;以及巩膜周围条件因素,如眼内压、巩膜周围温度、巩膜周围电场、巩膜板层切除及胶原生物降解等。了解巩膜的通透性特点不但能够指导药物的开发和设计,还能更有效地指导临床根据患者自身特征及病情状态调整用药剂量,为眼后段慢性疾病提供更安全、有效的治疗方案。笔者仅对巩膜的解剖学特点、组织学特征、生理特点及巩膜通透性的影响因素进行综述。

Intra-vitrous injection has become the major treatment option of chronic posterior segment diseases of eye.However,this approach is associated with inevitable side-effects and it is urgent to develop alternative approaches with similar curative effects but fewer and less significant side-effects.While applying drugs onto the ocular surface or administering drugs systematically is not recommended due to the lack of strength and huge side-effects,periocular injection of drugs,which takes the advantage of the large surface area of the sclera, is being increasingly used in ophthalmology departments.The scleral macromolecular permeability is affected by numerous factors including drug features ( e.g., molecular weight, molecular structure,lipophilic property,and electric charge of the drug) ,scleral properties ( e.g.,scleral thickness and degree of degradation),periscleral features (e.g.,intra-ocular pressure,periscleral temperature,periscleral electric field,lamina sclerectomy,and collagen biodegradation) .Fully understanding the permeability of the sclera is essential not only to drug design and development but also to drug applications.This paper reviews the characteristics of sclera in anatomy, histology and physiology as well as factors that influence the permeability of the sclera.