基于高分子材料的降眼压药物递送系统

黄畅; 赵玉瑾; 徐建江; 孙兴怀; 孙建国

doi:10.14133/j.cnki.1008-9357.20210225001

基于高分子材料的降眼压药物递送系统

doi: 10.14133/j.cnki.1008-9357.20210225001

复旦大学附属眼耳鼻喉科医院，国家卫生健康委员会近视眼重点实验室，上海市视觉损害与重建重点实验室，上海200031

基金项目: 国家自然科学基金重点项目（82030027）；上海市自然科学基金（19ZR1408300）

详细信息

作者简介:
黄畅：黄　畅（1997—），女，硕士，主要研究方向为青光眼降眼压药物递送系统。E-mail：ievawong@126.com

孙建国，复旦大学附属眼耳鼻喉科医院副研究员，硕士生导师。主要从事眼部药物缓释系统及植入性医疗器械的应用基础研究，涉及青光眼、视网膜及角膜新生血管、眼内炎和葡萄膜炎等疾病。承担上海市科技支撑项目和自然科学基金等项目。在Angewandte Chemie International Edition, Biomaterials, ACS Applied Materials & Interfaces, Advanced Healthcare Materials等国际学术期刊发表论文20余篇，申报中国专利20多件，授权15件，其中1件专利已经成果转化。获江苏医学科技奖一等奖（2020年），第三十届上海市优秀发明金奖

通讯作者:
孙兴怀，E-mail：xhsun@shmu.edu.cn

孙建国，E-mail：jgsun@fudan.edu.cn

中图分类号: R319
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- 被引次数: 0
出版历程
- 收稿日期: 2021-02-25
- 刊出日期: 2021-06-01

Drug Delivery Systems Based on Polymer Materials for Lowering Intraocular Pressure

NHC Key Laboratory of Myopia, Shanghai Key Laboratory of Visual Impairment and Restoration, Eye & ENT Hospital of Fudan University, Shanghai 200031, China

摘要

摘要: 目前治疗青光眼降眼压药物面临着生物利用率低、给药不连续、患者依从性差及长期组织毒性等问题。为了更好地满足临床需要，材料工程化技术被逐渐用于新型降眼压药物递送系统的研发，其中有部分成果已经进入临床应用。基于前期工作及对新型眼部药物递送系统的理解，本文简要介绍了眼部生理结构和目前用药困境，简单归纳了可用于青光眼降眼压药物递送系统的高分子材料，系统总结了基于高分子材料研发的新型药物递送系统，并对其未来的发展进行了展望。
- 药物递送系统 /
- 高分子材料 /
- 眼压 /
- 青光眼
Abstract: Glaucoma drug therapy for lowering intraocular pressure suffers from some deficiencies, such as low bioavailability, discontinuous drug action, poor patient compliance and long-term tissue toxicity. To meet clinical needs more effectively, materials engineering technologies are gradually used for the development of novel intraocular pressure lowering drug delivery systems (DDSs), and some have been commercialized in clinical treatments. However, there is still a significant gap between commercial products and clinical needs in terms of safety and treatment efficacy. Based on our previous work and understanding of glaucoma treatment and novel ocular DDSs, we herein systematically summarize the recent research results of novel DDSs in lowering intraocular pressure. Initially, the physiological structure of the eye and the difficulties of drug therapy are introduced, and then polymer materials used to develop drug delivery systems for intraocular antihypertensive therapy are summarized. New DDSs based on polymer materials, such as solid implants, gel-based DDSs and nanocarrier-based DDSs are reviewed. Furthermore, we briefly introduce the DDSs developed by our group for improving intraocular pressure. After simply analyzing the limitations of commercial ocular drug delivery systems in clinical applications, we prospect the future development of intraocular pressure lowering DDSs in the directions of more effective, more targeted and more intelligent DDSs.
- drug delivery system /
- polymer material /
- intraocular pressure /
- glaucoma

HTML全文

图 1 眼球结构及眼部给药屏障

Figure 1. Eye structure and ocular barriers for drug delivery

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图 2 降眼压药物递送植入器件和用药位置^[42-44]

Figure 2. Basic shape and location of the solid implants for intraocular pressure-lowering treatments^[42-44]

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图 3 降眼压凝胶药物缓释系统^{[37, 66, 73]}

Figure 3. Schematic diagrams of gel-based drug sustained release systems for intraocular pressure-lowering treatment^{[37, 66, 73]}

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图 4 用于降眼压药物递送系统的高分子纳米粒子及其给药途径示意图^{[76, 77]}

Figure 4. Schematic diagrams of macromolecular nanoparticles used in intraocular pressure-lowering drug delivery systems and their administration routes^{[76, 77]}

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表 1 可用于制备降眼压药物递送系统的高分子材料

Table 1. Polymer materials used to develop drug delivery systems for lowering intraocular pressure

Type	Polymer materials	Drugs
Natural ｍaterials	Chitosan	Dorzolamide hydrochloride^[4], Timolol^[14], Brinzolamide^[15], Bimatoprost^[16], Latanoprost^[17]
	Hyaluronic acid	Dorzolamide hydrochloride & Timolol^[18]
	Sodium alginate	Carteolol^[19], Brimonidine^[20], Timolol^[21]
	Cellulose¹⁾	Timolol^[22], Dorzolamide hydrochloride^[23], Nimodipine^[24]
	Cyclodextrin²⁾	Methazolamide^[25]
	Gelatin	Timolol^{[26, 27]}
Synthetic materials	Polyester polymer （PLA、PCL、PLGA）	Forskolin^[28], Dorzolamide hydrochloride^[29], Dorzolamide^{[30, 31]}, Brinzolamide^[32], Prostaglandin analog DE-117^[33], Pilocarpine^[34], Brimonidine^[2], Acetylene acid^[35], Timolol^[36]
	Polyether polymer （PEG、PEO）	Brimonidine^[37]
	Polyaminoamine （PAMAM）	Timolol^[38], Tropikamide & Pilocarpine^[39], Carteolol^[40]
1）Composites made up with sodium hyaluronate, chitosan or acrylic hydrogel； 2） Branched supramolecular hydrogel formed with 4-arm PEG

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