Allergan, Inc., 2525 Dupont Dr., Irvine, CA 92612, USA.
Pharm Res. 2010 Oct;27(10):2043-53. doi: 10.1007/s11095-010-0159-x. Epub 2010 Jun 10.
The safety and effectiveness of systemic and topical medical therapies for ocular disorders are limited due to poor ocular drug uptake, nonspecificity to target tissues, systemic side effects, and poor adherence to therapy. Intravitreal injections can enhance ocular drug delivery, but the need for frequent retreatment and potential injection-related side effects limit the utility of this technique. Sustained-release drug delivery systems have been developed to overcome these limitations; such systems can achieve prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure and side effects and improving patient adherence to therapy. A critical factor in the development of safe and effective drug delivery systems has been the development of biocompatible polymers, which offer the versatility to tailor drug release kinetics for specific drugs and ocular diseases. Ocular implants include nonbiodegradable and biodegradable designs, with the latter offering several advantages. The polymers most commonly used in biodegradable delivery systems are synthetic aliphatic polyesters of the poly-α-hydroxy acid family including polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid. The characteristics of these polymers for medical applications as well as the pharmacological properties, safety, and clinical effectiveness of biodegradable drug implants for the treatment of ocular diseases are reviewed herein.
由于眼部药物摄取不良、对靶组织的非特异性、全身副作用和治疗依从性差,全身和局部医学治疗眼部疾病的安全性和有效性受到限制。玻璃体内注射可以增强眼部药物递送,但需要频繁的重复治疗和潜在的注射相关副作用限制了该技术的应用。为了克服这些限制,已经开发了缓释药物递送系统;这些系统可以在限制全身暴露和副作用的同时,在眼部靶组织中实现延长的治疗药物浓度,从而提高患者对治疗的依从性。在开发安全有效的药物递送系统方面的一个关键因素是开发生物相容性聚合物,这些聚合物提供了针对特定药物和眼部疾病定制药物释放动力学的多功能性。眼部植入物包括不可生物降解和可生物降解的设计,后者具有几个优势。最常用于可生物降解递送系统的聚合物是聚-α-羟基酸家族的合成脂肪族聚酯,包括聚乳酸、聚乙醇酸和聚乳酸-乙醇酸共聚物。本文综述了这些聚合物作为医用材料的特性以及可生物降解药物植入物治疗眼部疾病的药理学特性、安全性和临床疗效。