{"title":"基于透明质酸的光反应长效水凝胶,用于眼内给药螺内酯。","authors":"Sai Shreya Cheruvu, Shruthi Merugu, Manisha Malani, Onkar Kulkarni, Jayabalan Nirmal","doi":"10.1016/j.ijbiomac.2025.146451","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"146451"},"PeriodicalIF":8.5000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hyaluronic acid based light responsive long acting hydrogel for the intraocular delivery of spironolactone.\",\"authors\":\"Sai Shreya Cheruvu, Shruthi Merugu, Manisha Malani, Onkar Kulkarni, Jayabalan Nirmal\",\"doi\":\"10.1016/j.ijbiomac.2025.146451\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":333,\"journal\":{\"name\":\"International Journal of Biological Macromolecules\",\"volume\":\" \",\"pages\":\"146451\"},\"PeriodicalIF\":8.5000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Biological Macromolecules\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ijbiomac.2025.146451\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biological Macromolecules","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/j.ijbiomac.2025.146451","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Hyaluronic acid based light responsive long acting hydrogel for the intraocular delivery of spironolactone.
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.
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.