改性羟丙基壳聚糖/聚乙烯醇基水凝胶的合成及痛风性关节炎治疗微针的制备和性能

张鹏; 易宏; 俞豪杰; 王立

doi:10.11777/j.issn1000-3304.2026.26145

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改性羟丙基壳聚糖/聚乙烯醇基水凝胶的合成及痛风性关节炎治疗微针的制备和性能

研究论文 | 更新时间：2026-07-30

- 改性羟丙基壳聚糖/聚乙烯醇基水凝胶的合成及痛风性关节炎治疗微针的制备和性能
- Synthesis of Modified Hydroxypropyl Chitosan/Poly(vinyl alcohol)-based Hydrogel and Preparation and Properties of Their Microneedles for Gouty Arthritis Treatment
- 高分子学报 2026年页码：1-22
- 作者机构：
  
  1.浙江大学化学工程与生物工程学院化学工程与低碳技术全国重点实验室，杭州 310058
  2.浙江大学化学工程与生物工程学院浙江-俄罗斯光电磁功能材料联合实验室，杭州 310058
- 作者简介：
  
  E-mail: hjyu@zju.edu.cn
  E-mail: opl_wl@dial.zju.edu.cn
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2026.26145
  中图分类号：
- CSTR：32057.14.GFZXB.2026.7683
- 收稿：2026-05-05，
  
  录用：2026-07-15，
  
  网络首发：2026-07-30，
- 稿件说明：
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张鹏, 易宏, 俞豪杰, 王立. 改性羟丙基壳聚糖/聚乙烯醇基水凝胶的合成及痛风性关节炎治疗微针的制备和性能. 高分子学报, doi: 10.11777/j.issn1000-3304.2026.26145.

Zhang, P.; Yi, H.; Yu, H. J.; Wang, L. Synthesis of modified hydroxypropyl chitosan/poly(vinyl alcohol)-based hydrogel and preparation and properties of their microneedles for gouty arthritis treatment. Acta Polymerica Sinica (in Chinese), doi: 10.11777/j.issn1000-3304.2026.26145.
张鹏, 易宏, 俞豪杰, 王立. 改性羟丙基壳聚糖/聚乙烯醇基水凝胶的合成及痛风性关节炎治疗微针的制备和性能. 高分子学报, doi: 10.11777/j.issn1000-3304.2026.26145. DOI： CSTR： 32057.14.GFZXB.2026.7683.

Zhang, P.; Yi, H.; Yu, H. J.; Wang, L. Synthesis of modified hydroxypropyl chitosan/poly(vinyl alcohol)-based hydrogel and preparation and properties of their microneedles for gouty arthritis treatment. Acta Polymerica Sinica (in Chinese), doi: 10.11777/j.issn1000-3304.2026.26145. DOI： CSTR： 32057.14.GFZXB.2026.7683.

摘要

痛风性关节炎的临床治疗需兼顾急性期快速抗炎与长期持续降尿酸. 微针(microneedles，MNs)作为一种透皮给药方式，可高效穿透皮肤角质屏障，响应病灶部位存在特征性酸性微环境，通过多元化药物递送策略提升药物利用度，是痛风性关节炎极具潜力的治疗方案. 本研究制备了负载尿酸氧化酶(UOX)的聚多巴胺(PDA)修饰的ZIF-90 (PDA-ZIF-90@UOX)，PDA-ZIF-90@UOX兼具优异的光热转换性能与pH响应特性，可精准进行痛风性关节炎的治疗. 合成了苯硼酸改性甲基丙烯酰胺化羟丙基壳聚糖/聚乙烯醇水凝胶(HPCS-MA-FCPBA/PVA)，分别负载秋水仙碱(Col)和PDA-ZIF-90@UOX，通过两步离心模板法制备了核壳结构微针MN@PZUC. 该微针具有良好的pH响应释药性能，在pH=5.5条件下可释放总载药量57.9%的Col与63.1%的UOX. 体外实验证实，PDA-ZIF-90@UOX结合Col可使巨噬细胞M1型促炎亚群占比降低77%，展现出优异的抗炎活性. 在高尿酸血症痛风性关节炎SD大鼠模型中，使用MN@PZUC治疗的大鼠的血尿酸降低数值较疾病对照组提升68%，表明MN@PZUC具备良好的pH与光热双响应能力，抗炎效果显著，可有效缓解大鼠踝关节肿胀.

Abstract

The clinical treatment of gouty arthritis (GA) needs to balance rapid anti-inflammation in the acute phase and long-term sustained uric acid reduction. As a transdermal drug delivery method

microneedles can penetrate the skin barrier

respond to the acidic microenvironment of lesions

and enhance drug bioavailability through diversified drug delivery strategies

which show great potential for gouty arthritis treatment. In this study

uricase (UOX)-loaded polydopamine (PDA)-modified ZIF-90 (PDA-ZIF-90@UOX) was prepared. PDA-ZIF-90@UOX has both excellent photothermal conversion performance and pH-responsive dissociation characteristics

which can accurately match the therapeutic needs of GA. A phenylboronic acid-modified methacrylamidated hydroxypropyl chitosan/poly(vinyl alcohol) hydrogel (HPCS-MA-FCPBA/PVA) was synthesized

with colchicine (Col) and PDA-ZIF-90@UOX separately loaded into the shell and core hydrogel

and core-shell structured microneedles (MN@PZUC) were prepared

via

a two-step centrifugal template method. The prepared MN@PZUC had good pH-responsive drug release performance

releasing 57.9% of the total loaded Col and 63.1% of the total loaded UOX at pH=5.5.

In vitro

experiments confirmed that the combination of PDA-ZIF-90@UOX and Col reduced the proportion of M1-type pro-inflammatory macrophage subpopulation by 77%

showing excellent anti-inflammatory activity. In the SD rat model of hyperuricemia with gouty arthritis

the serum uric acid-lowering effect of MN@PZUC was 68% hi

gher than that of the disease control group. These results indicate that MN@PZUC has good pH and photothermal dual-responsive capabilities

a significant anti-inflammatory effect

and can effectively alleviate ankle swelling in rats.

关键词

Keywords

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