Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, 5000, Argentina.
Pharmacol Res Perspect. 2021 Apr;9(2):e00723. doi: 10.1002/prp2.723.
Currently, biological drug therapy for ocular angiogenesis treatment is based on the administration of anti-VEGF agents via intravitreal route. The molecules approved with this purpose for ocular use include pegaptanib, ranibizumab, and aflibercept, whereas bevacizumab is commonly off-label used in the clinical practice. The schedule dosage involves repeated intravitreal injections of anti-VEGF agents to achieve and maintain effective concentrations in retina and choroids, which are administrated as solutions form. In this review article, we describe the features of different anti-VEGF agents, major challenges for their ocular delivery and the nanoparticles in development as delivery system of them. In this way, several polymeric and lipid nanoparticles are explored to load anti-VEGF agents with the aim of achieving sustained drug release and thus, minimize the number of intravitreal injections required. The main challenges were focused in the loading the molecules that maintain their bioactivity after their release from nanoparticulate system, followed the evaluation of them through studies of formulation stability, pharmacokinetic, and efficacy in in vitro and in vivo models. The analysis was based on the information published in peer-reviewed published papers relevant to anti-VEGF treatments and nanoparticles developed as ocular anti-VEGF delivery system.
目前，眼部血管生成治疗的生物药物治疗基于通过玻璃体内途径给予抗 VEGF 药物。为此目的批准用于眼部的分子包括培加他滨、雷珠单抗和阿柏西普，而贝伐单抗在临床实践中通常被超适应证使用。方案剂量包括重复玻璃体内注射抗 VEGF 药物，以在视网膜和脉络膜中达到并维持有效浓度，这些药物以溶液形式给药。在这篇综述文章中，我们描述了不同抗 VEGF 药物的特点、眼部递药的主要挑战以及作为它们的递药系统的纳米颗粒的开发。通过这种方式，探索了几种聚合物和脂质纳米颗粒来负载抗 VEGF 药物，目的是实现药物的持续释放，从而最大限度地减少所需的玻璃体内注射次数。主要挑战集中在加载分子上，这些分子在从纳米颗粒系统释放后保持其生物活性，然后通过研究制剂稳定性、药代动力学以及体外和体内模型中的疗效来评估它们。分析基于同行评议发表的与抗 VEGF 治疗和作为眼部抗 VEGF 递药系统开发的纳米颗粒相关的已发表论文中的信息。
