The effect of parasitic ions on riboflavin permeability and cross-linking effectiveness in iontophoresis-assisted scleral cross-linking_Journal of Biomedical Engineering

Authors：

WANG Jing ,  LI Xiaona , GAO Zhipeng , CHEN Lingfeng ,  CHEN Weiyi , WU Tingting

College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, P.R.China;

Corresponding author：

LI Xiaona, Email: lixiaona@tyut.edu.cn; CHEN Weiyi, Email: chenweiyi@tyut.edu.cn

Keywords：

riboflavin-ultraviolet A; iontophoresis; parasitic ions; permeability; scleral mechanical properties

DOI：

10.7507/1001-5515.202104034

Video：

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The effect of parasitic ions on the results of ultraviolet A (UVA) cross-linking in iontophoresis was still not clear. In this work, the porcine sclera was cross-linked by riboflavin lactate Ringer’s solution (group A) and riboflavin normal saline (group B) in vitro, respectively. The concentration of parasitic ions in the solution was calculated. In addition, the average fluorescence intensity, penetration depth and concentration after the introduction of riboflavin and the mechanical properties of cross-linked sclera tissue were measured. The ranges of diffusion coefficient of the two solutions were also calculated, respectively. The results showed that more kinds of parasitic ions were detected in group A compared with group B, while the average fluorescence intensity, penetration depth and concentration of riboflavin and scleral elastic modulus in group B were significantly higher than those in group A when the penetration time was 10 minutes. Besides, the diffusion coefficient of riboflavin in group B was about 1.5 times larger than that in group A. The results suggested that the species of parasitic ions has a great impact on the permeability of riboflavin, and affects the mechanical properties of cross-linked sclera. The above results could provide a reference for improving the efficiency of riboflavin introduction and optimizing the formula of riboflavin in iontophoresis scleral cross-linking.

Citation： WANG Jing, LI Xiaona, GAO Zhipeng, CHEN Lingfeng, CHEN Weiyi, WU Tingting. The effect of parasitic ions on riboflavin permeability and cross-linking effectiveness in iontophoresis-assisted scleral cross-linking. Journal of Biomedical Engineering, 2021, 38(5): 869-876. doi: 10.7507/1001-5515.202104034 Copy

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2.	Li X X, Wu M Q, Zhang L Y, et al. Riboflavin and ultraviolet A irradiation for the prevention of progressive myopia in a guinea pig model. Exp Eye Res, 2017, 165: 1-6.
3.	Xiao B, Chen Y H, Wang H Y, et al. Minimally invasive repetitive UVA irradiation along with riboflavin treatment increased the strength of sclera collagen cross-linking. J Ophthalmol, 2017, 2017: 1-6.
4.	Dotan A, Kremer I, Gal-Or O, et al. Scleral cross-linking using riboflavin and ultraviolet-A radiation for prevention of axial myopia in a rabbit model. J Vis Exp, 2016, 2016(110): e53201.
5.	Zhang Y, Li Z, Liu L, et al. Comparison of riboflavin/ultraviolet-A cross-linking in porcine, rabbit, and human sclera. Biomed Res Int, 2014, 2014(1): 194204.
6.	张亚丽, 李志伟, 牟国营, 等. 核黄素/紫外线 A 诱导的胶原交联对兔和人巩膜生物力学性能的影响. 中华眼视光学与视觉科学杂志, 2014, 16(5): 279-281.
7.	刘太祥, 吴君舒, 顾宇伟, 等. 京尼平诱导猪眼巩膜胶原交联后生物力学性能变化. 中华眼视光学与视觉科学杂志, 2014, 16(5): 274-278.
8.	Cassagne M, Laurent C, Rodrigues M, et al. Iontophoresis transcorneal delivery technique for transepithelial corneal collagen crosslinking with riboflavin in a rabbit model. Invest Ophthalmol Vis Sci, 2016, 57(2): 594-603.
9.	Rong S, Wang C, Han B, et al. Iontophoresis-assisted accelerated riboflavin/ultraviolet A scleral cross-linking: a potential treatment for pathologic myopia. Exp Eye Res, 2017, 162: 37-47.
10.	Mastropasqua L, Nubile M, Calienno R, et al. Corneal cross-linking: intrastromal riboflavin concentration in iontophoresis-assisted imbibition versus traditional and transepithelial techniques. Am J Ophthalmol, 2014, 157(3): 623-630.
11.	Perez V L, Wirostko B, Korenfeld M, et al. Ophthalmic drug delivery using iontophoresis: recent clinical applications. J Ocul Pharmacol Ther, 2020, 36(2): 75-87.
12.	马红霞. 木材表面胶粘剂渗透性能研究进展//第二届全国生物质材料科学与技术学术研讨会论文集. 呼和浩特: 中国林学会, 2008: 419-423.
13.	葛勇, 樊杰, 袁杰, 等. 混凝土水压法渗透性与氯离子扩散系数的关系//超高层混凝土泵送与超高性能混凝土技术的研究与应用国际研讨会论文集: 中文版. 广州, 2008: 396-400.
14.	Schumacher S, Mrochen M, Wernli J, et al. Optimization model for UV-riboflavin corneal cross-linking. Invest Ophthalmol Vis Sci, 2012, 53(2): 762-769.
15.	McQuaid R, Mrochen M, Vohnsen B. Rate of riboflavin diffusion from intrastromal channels before corneal crosslinking. J Cataract Refract Surg, 2016, 42(3): 462-468.
16.	张学敏, 赵旭, 张丰菊, 等. 核黄素在巩膜组织内渗透性的实验研究. 中华眼科杂志, 2015, 51(6): 450-454.
17.	朱莹. 超声介导药物经巩膜递送的方法研究. 深圳: 深圳大学, 2019.
18.	姜良柱. 改良角膜紫外线交联术在圆锥角膜治疗中的基础与临床研究. 济南: 山东大学, 2018.
19.	Baiocchi S, Mazzotta C, Cerretani D, et al. Corneal crosslinking: riboflavin concentration in corneal stroma exposed with and without epithelium. J Cataract Refract Surg, 2009, 35(5): 893-899.
20.	Shoeibi N, Mahdizadeh M, Shafiee M. Iontophoresis in ophthalmology: a review of the literature. Rev Clin Med, 2014, 1(4): 183-188.
21.	Güngör S, Delgado-Charro M B, Ruiz-Perez B, et al. Trans-scleral iontophoretic delivery of low molecular weight therapeutics. J Control Release, 2010, 147(2): 225-231.
22.	吴闽枫. 直流电离子导入的治疗技术和方法简介. 中国电子商情: 科技创新, 2014: 86.
23.	Seiler T, Hafezi F. Corneal cross-linking-induced stromal demarcation line. Cornea, 2006, 25(9): 1057-1059.
24.	贾洪真, 庞旭, 李刚, 等. 应用两种不同核黄素溶液的离子导入交联治疗进展期圆锥角膜后基质分界线深度比较. 解放军医学院学报, 2017, 38(9): 824-826, 849.
25.	Wollensak G, Spoerl E. Collagen crosslinking of human and porcine sclera. J Cataract Refract Surg, 2004, 30(3): 689-695.
26.	张学敏, 张丰菊. 角巩膜胶原交联中核黄素渗透性的研究进展. 中华眼视光学与视觉科学杂志, 2015, 17(3): 189-192.

1. Sun M, Zhang F, Ouyang B, et al. Study of retina and choroid biological parameters of rhesus monkeys eyes on scleral collagen cross-linking by riboflavin and ultraviolet A. PLoS One, 2018, 13(2): e0192718.
2. Li X X, Wu M Q, Zhang L Y, et al. Riboflavin and ultraviolet A irradiation for the prevention of progressive myopia in a guinea pig model. Exp Eye Res, 2017, 165: 1-6.
3. Xiao B, Chen Y H, Wang H Y, et al. Minimally invasive repetitive UVA irradiation along with riboflavin treatment increased the strength of sclera collagen cross-linking. J Ophthalmol, 2017, 2017: 1-6.
4. Dotan A, Kremer I, Gal-Or O, et al. Scleral cross-linking using riboflavin and ultraviolet-A radiation for prevention of axial myopia in a rabbit model. J Vis Exp, 2016, 2016(110): e53201.
5. Zhang Y, Li Z, Liu L, et al. Comparison of riboflavin/ultraviolet-A cross-linking in porcine, rabbit, and human sclera. Biomed Res Int, 2014, 2014(1): 194204.
6. 张亚丽, 李志伟, 牟国营, 等. 核黄素/紫外线 A 诱导的胶原交联对兔和人巩膜生物力学性能的影响. 中华眼视光学与视觉科学杂志, 2014, 16(5): 279-281.
7. 刘太祥, 吴君舒, 顾宇伟, 等. 京尼平诱导猪眼巩膜胶原交联后生物力学性能变化. 中华眼视光学与视觉科学杂志, 2014, 16(5): 274-278.
8. Cassagne M, Laurent C, Rodrigues M, et al. Iontophoresis transcorneal delivery technique for transepithelial corneal collagen crosslinking with riboflavin in a rabbit model. Invest Ophthalmol Vis Sci, 2016, 57(2): 594-603.
9. Rong S, Wang C, Han B, et al. Iontophoresis-assisted accelerated riboflavin/ultraviolet A scleral cross-linking: a potential treatment for pathologic myopia. Exp Eye Res, 2017, 162: 37-47.
10. Mastropasqua L, Nubile M, Calienno R, et al. Corneal cross-linking: intrastromal riboflavin concentration in iontophoresis-assisted imbibition versus traditional and transepithelial techniques. Am J Ophthalmol, 2014, 157(3): 623-630.
11. Perez V L, Wirostko B, Korenfeld M, et al. Ophthalmic drug delivery using iontophoresis: recent clinical applications. J Ocul Pharmacol Ther, 2020, 36(2): 75-87.
12. 马红霞. 木材表面胶粘剂渗透性能研究进展//第二届全国生物质材料科学与技术学术研讨会论文集. 呼和浩特: 中国林学会, 2008: 419-423.
13. 葛勇, 樊杰, 袁杰, 等. 混凝土水压法渗透性与氯离子扩散系数的关系//超高层混凝土泵送与超高性能混凝土技术的研究与应用国际研讨会论文集: 中文版. 广州, 2008: 396-400.
14. Schumacher S, Mrochen M, Wernli J, et al. Optimization model for UV-riboflavin corneal cross-linking. Invest Ophthalmol Vis Sci, 2012, 53(2): 762-769.
15. McQuaid R, Mrochen M, Vohnsen B. Rate of riboflavin diffusion from intrastromal channels before corneal crosslinking. J Cataract Refract Surg, 2016, 42(3): 462-468.
16. 张学敏, 赵旭, 张丰菊, 等. 核黄素在巩膜组织内渗透性的实验研究. 中华眼科杂志, 2015, 51(6): 450-454.
17. 朱莹. 超声介导药物经巩膜递送的方法研究. 深圳: 深圳大学, 2019.
18. 姜良柱. 改良角膜紫外线交联术在圆锥角膜治疗中的基础与临床研究. 济南: 山东大学, 2018.
19. Baiocchi S, Mazzotta C, Cerretani D, et al. Corneal crosslinking: riboflavin concentration in corneal stroma exposed with and without epithelium. J Cataract Refract Surg, 2009, 35(5): 893-899.
20. Shoeibi N, Mahdizadeh M, Shafiee M. Iontophoresis in ophthalmology: a review of the literature. Rev Clin Med, 2014, 1(4): 183-188.
21. Güngör S, Delgado-Charro M B, Ruiz-Perez B, et al. Trans-scleral iontophoretic delivery of low molecular weight therapeutics. J Control Release, 2010, 147(2): 225-231.
22. 吴闽枫. 直流电离子导入的治疗技术和方法简介. 中国电子商情: 科技创新, 2014: 86.
23. Seiler T, Hafezi F. Corneal cross-linking-induced stromal demarcation line. Cornea, 2006, 25(9): 1057-1059.
24. 贾洪真, 庞旭, 李刚, 等. 应用两种不同核黄素溶液的离子导入交联治疗进展期圆锥角膜后基质分界线深度比较. 解放军医学院学报, 2017, 38(9): 824-826, 849.
25. Wollensak G, Spoerl E. Collagen crosslinking of human and porcine sclera. J Cataract Refract Surg, 2004, 30(3): 689-695.
26. 张学敏, 张丰菊. 角巩膜胶原交联中核黄素渗透性的研究进展. 中华眼视光学与视觉科学杂志, 2015, 17(3): 189-192.

Journal of Biomedical Engineering

The effect of parasitic ions on riboflavin permeability and cross-linking effectiveness in iontophoresis-assisted scleral cross-linking

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