已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Intravitreal injectable hydrogel rods with long-acting bevacizumab delivery to the retina

视网膜 贝伐单抗 材料科学 生物医学工程 眼科 医学 外科 化疗 神经科学 心理学 病理 替代医学
作者
Simin Lee,Hye Kyoung Hong,Jae Shin Song,Sae Im Jeong,Jae‐Yong Chung,Se Joon Woo,Ki Dong Park
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:171: 273-288 被引量:8
标识
DOI:10.1016/j.actbio.2023.09.025
摘要

Retinal vascular diseases such as neovascular age-related macular degeneration (nAMD) are the leading cause of blindness worldwide. They can be treated with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents by inhibiting VEGF which is a major agent of abnormal blood vessel growth. However, because of drug's short half-life, clinical treatment often requires monthly repeated intravitreal injections, causing treatment burden and undertreatment. Among various kinds of drug carriers, in situ forming hydrogels have been studied as potential intravitreal drug carriers for the high drug loading, easy injection, controlled drug release, and protection of encapsulated drugs from the environment. However, gelation time, crosslinking degree, and drug release patterns following injection of a liquid that will be subsequently gelled in situ are susceptible to be hindered by dilution of the hydrogel precursor solution with body fluids (e.g., blood or vitreous). Here, we report an injectable pre-crosslinked hydrogel rod to overcome the limitations of in situ forming hydrogels and to extend intravitreal half-life of anti-VEGF for reducing intraocular injection frequency. Hydrogel rods can be simply prepared using in situ forming hydrogels, and injectable using a designed rod injector. The adjustable crosslinking degree of hydrogel rods easily controlled bevacizumab release profiles in a sustained manner. Compared with in situ forming hydrogels, hydrogel rods effectively reduced initial burst release, and showed sustained release with long-term drug efficacy in vitro. From the 4-month in vivo pharmacokinetic analysis, following the intravitreal injection of hydrogel rods, the half-life of bevacizumab in the vitreous and retina was significantly extended, and drug elimination to aqueous humor was effectively reduced. Finally, intraocular stability, degradation, and inflammatory response of hydrogel rods were evaluated. We expect that the hydrogel rod can be a potential drug delivery system for the treatment of nAMD and other conditions that need long-term and local sustained drug administration. STATEMENT OF SIGNIFICANCE: Herein, we report an injectable pre-crosslinked hydrogel rod based on an in situ forming hydrogel to achieve intravitreal long-acting anti-VEGF delivery to reduce injection frequency and improve the long-term visual outcomes of patients with retinal vascular diseases. Hydrogel rods were readily prepared using removable molds and injected using customized injectors. Compared to the in situ forming hydrogel, hydrogel rods showed significantly reduced initial burst release, controllable release profiles for several months, physical stability, and a long-acting anti-angiogenic effect. Animal studies demonstrated that the hydrogel rods dramatically prolonged the intraocular drug half-life while significantly reducing drug elimination for up to four months. Moreover, the biodegradability and safety of the hydrogel rods suggest their suitability as an advanced intravitreal DDS for treating retinal vascular diseases.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
3秒前
Jasper应助ZQL采纳,获得10
4秒前
ppg123应助cheer采纳,获得30
4秒前
科目三应助qz采纳,获得10
5秒前
花花世界完成签到 ,获得积分10
6秒前
充电宝应助monica采纳,获得10
7秒前
斯文绿凝发布了新的文献求助10
8秒前
欢喜梦凡完成签到 ,获得积分10
12秒前
毛竹发布了新的文献求助10
14秒前
fufizzz完成签到,获得积分10
14秒前
hopen完成签到 ,获得积分10
14秒前
16秒前
L21发布了新的文献求助10
17秒前
iceink发布了新的文献求助200
18秒前
qz发布了新的文献求助10
23秒前
双黄应助不负韶华采纳,获得10
23秒前
26秒前
棕1完成签到 ,获得积分10
26秒前
27秒前
jj824完成签到 ,获得积分10
29秒前
欢呼妙彤发布了新的文献求助10
31秒前
李盼发布了新的文献求助10
32秒前
39秒前
39秒前
40秒前
Akim应助如意果汁采纳,获得10
41秒前
41秒前
nn发布了新的文献求助10
43秒前
123发布了新的文献求助10
44秒前
46秒前
doubleshake发布了新的文献求助10
46秒前
浮笙完成签到 ,获得积分10
47秒前
清爽的雨竹完成签到 ,获得积分10
49秒前
科研通AI2S应助万里采纳,获得10
52秒前
1111发布了新的文献求助10
52秒前
55秒前
双黄应助runzi采纳,获得10
56秒前
专一的绿茶完成签到,获得积分10
58秒前
59秒前
pathway完成签到 ,获得积分10
1分钟前
高分求助中
The late Devonian Standard Conodont Zonation 2000
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
Very-high-order BVD Schemes Using β-variable THINC Method 830
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3248577
求助须知:如何正确求助?哪些是违规求助? 2892044
关于积分的说明 8269473
捐赠科研通 2560089
什么是DOI,文献DOI怎么找? 1388851
科研通“疑难数据库(出版商)”最低求助积分说明 650913
邀请新用户注册赠送积分活动 627798