Single subconjunctival injection formulation with a 5-fluorouracil-poly(lactic) acid controlled-release system for glaucoma filtration surgery.

IF 1.8 4区医学 Q2 OPHTHALMOLOGY

International journal of ophthalmology Pub Date : 2025-10-18 eCollection Date: 2025-01-01 DOI:10.18240/ijo.2025.10.02

Jing-Jing Zhang, Feng Gao, Kai-Xin Deng, Wen-Xue Guan, Yao-Yao Sun

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引用次数: 0

Abstract

Aim: To develop a 5-fluorouracil (5-FU) mesoporous poly(lactic) acid (PLA) delivery system for glaucoma filtration surgery suitable for a single subconjunctival implantation.

Methods: The 5-FU was infiltration-loaded into mesoporous PLA. In vitro and in vivo release experiments and ocular toxicology evaluation of the formulation were performed. The antiproliferative effect of this 5-FU-PLA tablet after glaucoma filtration surgery in rabbits was evaluated. Pathology, immunohistochemistry, and Western blot were used to further validate the inhibitory effect of this sustained release system.

Results: Various drug formulations were tested, and two 5-FU-PLA tablets, namely 1.5P15 (5-FU 1.5 mg+PLA 15 000 Da) and 2.5P15 (5-FU 2.5 mg+PLA 15 000 Da), had the most suitable release profiles in vitro. Further in vivo studies confirmed the safety and sustained-release profiles of both drugs. Both 5-FU-PLA tablets, relative to the free drugs, significantly inhibited tissue proliferation after glaucoma filtration and improved surgical success. Western blot showed that transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) were inhibited by 5-FU after filtration surgery, with the effects of the 5-FU-PLA tablets being more lasting.

Conclusion: The tested 5-FU-PLA tablets provide a sustained release of 5-FU, which may be used for a single subconjunctival implantation to inhibit proliferation after filtration surgery.

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青光眼滤过手术单次结膜下注射配方与5-氟尿嘧啶聚乳酸控释系统。

目的：研制一种适用于单次结膜下植入术青光眼滤过手术的5-氟尿嘧啶（5-FU）介孔聚乳酸（PLA）给药系统。方法：将5-FU渗透到PLA中孔中。进行了体外、体内释放实验和眼毒理学评价。评价5-FU-PLA片在兔青光眼滤过术后的抗增殖作用。通过病理、免疫组织化学和Western blot进一步验证该缓释系统的抑制作用。结果：对不同剂型的药物进行了试验，发现1.5 p15 （5-FU 1.5 mg+PLA 15 000 Da）和2.5 p15 （5-FU 2.5 mg+PLA 15 000 Da）两种5-FU-PLA片体外释放谱最合适。进一步的体内研究证实了这两种药物的安全性和缓释特性。与游离药物相比，两种5-FU-PLA片均能显著抑制青光眼滤过后组织增殖，提高手术成功率。Western blot结果显示，滤过术后5-FU对转化生长因子-β (TGF-β)和结缔组织生长因子（CTGF）均有抑制作用，且5-FU- pla片作用更持久。结论：所制备的5-FU- pla片具有5-FU的缓释作用，可用于单次结膜下植入术，抑制滤过术后角膜的增殖。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International journal of ophthalmology Medicine-Ophthalmology

CiteScore

2.50

自引率

7.10%

发文量

3141

审稿时长

4-8 weeks

期刊介绍： · International Journal of Ophthalmology-IJO (English edition) is a global ophthalmological scientific publication and a peer-reviewed open access periodical (ISSN 2222-3959 print, ISSN 2227-4898 online). This journal is sponsored by Chinese Medical Association Xi’an Branch and obtains guidance and support from WHO and ICO (International Council of Ophthalmology). It has been indexed in SCIE, PubMed, PubMed-Central, Chemical Abstracts, Scopus, EMBASE , and DOAJ. IJO JCR IF in 2017 is 1.166. IJO was established in 2008, with editorial office in Xi’an, China. It is a monthly publication. General Scientific Advisors include Prof. Hugh Taylor (President of ICO); Prof.Bruce Spivey (Immediate Past President of ICO); Prof.Mark Tso (Ex-Vice President of ICO) and Prof.Daiming Fan (Academician and Vice President, Chinese Academy of Engineering. International Scientific Advisors include Prof. Serge Resnikoff (WHO Senior Speciatist for Prevention of blindness), Prof. Chi-Chao Chan (National Eye Institute, USA) and Prof. Richard L Abbott (Ex-President of AAO/PAAO) et al. Honorary Editors-in-Chief: Prof. Li-Xin Xie(Academician of Chinese Academy of Engineering/Honorary President of Chinese Ophthalmological Society); Prof. Dennis Lam (President of APAO) and Prof. Xiao-Xin Li (Ex-President of Chinese Ophthalmological Society). Chief Editor: Prof. Xiu-Wen Hu (President of IJO Press). Editors-in-Chief: Prof. Yan-Nian Hui (Ex-Director, Eye Institute of Chinese PLA) and Prof. George Chiou (Founding chief editor of Journal of Ocular Pharmacology & Therapeutics). Associate Editors-in-Chief include: Prof. Ning-Li Wang (President Elect of APAO); Prof. Ke Yao (President of Chinese Ophthalmological Society) ; Prof.William Smiddy (Bascom Palmer Eye instituteUSA) ; Prof.Joel Schuman (President of Association of University Professors of Ophthalmology,USA); Prof.Yizhi Liu (Vice President of Chinese Ophtlalmology Society); Prof.Yu-Sheng Wang (Director of Eye Institute of Chinese PLA); Prof.Ling-Yun Cheng (Director of Ocular Pharmacology, Shiley Eye Center, USA). IJO accepts contributions in English from all over the world. It includes mainly original articles and review articles, both basic and clinical papers. Instruction is Welcome Contribution is Welcome Citation is Welcome Cooperation organization International Council of Ophthalmology(ICO), PubMed, PMC, American Academy of Ophthalmology, Asia-Pacific, Thomson Reuters, The Charlesworth Group, Crossref,Scopus,Publons, DOAJ etc.