Hyaluronic acid based light responsive long acting hydrogel for the intraocular delivery of spironolactone.

IF 8.5 1区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sai Shreya Cheruvu, Shruthi Merugu, Manisha Malani, Onkar Kulkarni, Jayabalan Nirmal
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引用次数: 0

Abstract

Chorio-retinal diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), are responsible for irreversible vision loss worldwide. Non-VEGF pathways, such as the renin-angiotensin-aldosterone system (RAAS), show promise as therapeutic targets for retinal diseases to address the increasing non-responder population to anti-VEGF therapy for DR. Elevated renin levels in DR are linked to retinal angiogenesis and inflammation. Spironolactone (SPL) has demonstrated the potential to reduce angiogenesis. A sustained delivery approach could be beneficial for chronic ocular disorders by delivering the therapeutic dose over a longer duration, thus reducing the frequency of intravitreal administration. Hence, a light responsive methacrylated hyaluronic acid (MEHA) polymer was synthesised and used to develop an in situ gelling depot that provides sustained release of SPL upon UV crosslinking. The in vitro release of SPL from the light responsive in situ depot was seen over 90 days. Furthermore, the in vivo ocular residence studies have demonstrated the depot remaining for >60 days. The SPL-loaded light responsive hydrogel demonstrated in vivo safety and efficacy against DR, further supporting its potential as a long acting drug delivery platform for intravitreally injected drugs with reduced frequency of administration.

基于透明质酸的光反应长效水凝胶,用于眼内给药螺内酯。
绒毛膜视网膜疾病,如年龄相关性黄斑变性(AMD)和糖尿病性视网膜病变(DR),是世界范围内不可逆转的视力丧失的原因。非vegf途径,如肾素-血管紧张素-醛固酮系统(RAAS),有望成为视网膜疾病的治疗靶点,以解决DR中抗vegf治疗无反应人群的增加问题。螺内酯(SPL)已被证明具有减少血管生成的潜力。持续给药方法可以通过在较长的时间内给药治疗剂量,从而减少玻璃体内给药的频率,从而对慢性眼部疾病有益。因此,合成了一种光响应性甲基丙烯酸透明质酸(MEHA)聚合物,并用于开发一种原位凝胶库,该凝胶库在紫外线交联时提供持续释放的SPL。SPL从光响应原位库中体外释放超过90 天。此外,体内眼内滞留研究表明,储存库可维持100 - 60 天。负载spll的轻反应水凝胶在体内证明了抗DR的安全性和有效性,进一步支持了其作为玻璃体内注射药物的长效药物传递平台的潜力,减少了给药频率。
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来源期刊
International Journal of Biological Macromolecules
International Journal of Biological Macromolecules 生物-生化与分子生物学
CiteScore
13.70
自引率
9.80%
发文量
2728
审稿时长
64 days
期刊介绍: The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.
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