Yu Yu, Lin Xingyan, Wang Qilin, He Mingguang, Chau Ying
Department of Chemical and Biological Engineering The Hong Kong University of Science and Technology Kowloon Hong Kong, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center Sun Yat-sen University Guangzhou China.
Bioeng Transl Med. 2019 Jun 10;4(2):e10128. doi: 10.1002/btm2.10128. eCollection 2019 May.
Wet age-related macular degeneration (wet-AMD) is a leading cause of irreversible blindness. Current treatment of AMD requires monthly intravitreal injection, which is difficult to be implemented in many parts of the world. In recent years, controlled release of anti-vascular endothelial growth factor (VEGF) therapeutics has attracted intense research interest aiming to reduce the injection frequency to one or two times per year. In this study, we evaluated the in vivo pharmacokinetics and the long-term therapeutic efficacy of an in situ hydrogel encapsulating an anti-VEGF antibody in nonhuman primates. We show that after a single injection of anti-VEGF controlled release hydrogel, a relatively constant concentration of drug can be maintained in the monkey eye for at least 5 months and the dose was sufficient for the treatment of recurrent choroidal neovascularization induced by repeat laser photocoagulation in monkeys. Our result suggested that when formulated into a controlled release formulation, a single dose of anti-VEGF may be sufficient for a half-year treatment and controlled release may be a suitable strategy to reduce the injection frequency in the treatment of AMD in human.
湿性年龄相关性黄斑变性(湿性AMD)是不可逆失明的主要原因。目前AMD的治疗需要每月进行玻璃体内注射,这在世界许多地区难以实施。近年来,抗血管内皮生长因子(VEGF)治疗药物的控释已引起了强烈的研究兴趣,旨在将注射频率降低至每年一到两次。在本研究中,我们评估了在非人灵长类动物中包裹抗VEGF抗体的原位水凝胶的体内药代动力学和长期治疗效果。我们表明,单次注射抗VEGF控释水凝胶后,可在猴眼中维持相对恒定的药物浓度至少5个月,且该剂量足以治疗猴重复激光光凝诱导的复发性脉络膜新生血管。我们的结果表明,当制成控释制剂时,单剂量抗VEGF可能足以进行半年的治疗,控释可能是降低人类AMD治疗中注射频率的合适策略。