中国组织工程研究

中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (27): 4335-4339.doi: 10.12307/2022.834

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

姜黄素纳米粒对人视网膜色素上皮细胞增殖的影响

郑海生1，蓝育青2，钟兴武1，丁  辉1   

  1. 1中山大学中山眼科中心海南眼科医院(海南省眼科医院)，海南省眼科学重点实验室，海南省海口市  570311；2中山大学附属孙逸仙纪念医院，广东省广州市  510120
  • 收稿日期:2021-09-11 接受日期:2021-11-20 出版日期:2022-09-28 发布日期:2022-03-12
  • 通讯作者: 蓝育青，主任医师，中山大学附属孙逸仙纪念医院，广东省广州市 510120
  • 作者简介:郑海生，男，1983年生，海南省海口市人，汉族，硕士，副主任医师，主要从事眼科学研究。
  • 基金资助:
    海南省自然科学基金项目(819MS133)，项目负责人：郑海生

Effect of curcumin nanoparticles on proliferation of human retinal pigment epithelial cells

Zheng Haisheng1, Lan Yuqing2, Zhong Xingwu1, Ding Hui1   

  1. 1Hainan Eye Hospital, Zhongshan Eye Center, Sun Yat-sen University (Hainan Provincial Eye Hospital), Key Laboratory of Ophthalmology of Hainan Province, Haikou 570311, Hainan Province, China; 2Sun Yat-sen Memorial Hospital Affiliated to Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China 
  • Received:2021-09-11 Accepted:2021-11-20 Online:2022-09-28 Published:2022-03-12
  • Contact: Lan Yuqing, Chief physician, Sun Yat-sen Memorial Hospital Affiliated to Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
  • About author:Zheng Haisheng, Master, Associate chief physician, Hainan Eye Hospital, Zhongshan Eye Center, Sun Yat-sen University (Hainan Provincial Eye Hospital), Key Laboratory of Ophthalmology of Hainan Province, Haikou 570311, Hainan Province, China
  • Supported by:
    Natural Science Foundation of Hainan Province, No. 819MS133 (to ZHS)

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摘要：

文题释义：
纳米药物：药剂学中的纳米粒或称纳米药物，其尺寸界定于1-100 nm之间。纳米载体是指溶解或分散有药物的各种纳米粒。纳米药物是指直接将原料药加工成纳米粒。纳米药物涉及的给药途径包括口服、注射和眼部给药等。与传统药物相比，药物传输系统中的纳米粒及相关技术主要用于促进药物溶解，更容易通过血-视网膜屏障、血-脑屏障定向作用于视网膜及中枢神经，具有缓释性、靶向性，可提高药物疗效、减少不良反应等。
姜黄素：是从姜科、天南星科一些植物根茎中提取的一种二酮类化合物，为橙黄色结晶粉末，味稍苦，不溶于水，具有抗新生血管、抗炎、抗病毒、抗肿瘤、抗动脉粥样硬化等广泛的药理活性，且药源广泛、价格低廉、无明显毒副作用。


背景：姜黄素具有抑制人视网膜色素上皮细胞增殖及抗新生血管的作用，在防治眼底新生血管性病变中可以发挥重要作用，但其水溶性较差、体内半衰期短，需要长期、多次注射用药，因此研制姜黄素的新剂型具有重要临床意义。 
目的：探讨脱氧胆酸基接枝的壳聚糖衍生物负载姜黄素纳米粒的合成方法，以及其对人视网膜色素上皮细胞增殖的影响。
方法：首先制备壳聚糖-脱氧胆酸纳米粒，随后制备姜黄素/壳聚糖-脱氧胆酸纳米粒，检测姜黄素/壳聚糖-脱氧胆酸纳米粒的载药量、负载效率及体外释药性能。将人视网膜色素上皮细胞分别与姜黄素(5，10，20，40 mg/L)、壳聚糖-脱氧胆酸纳米粒(5，10，20，40 mg/L)、姜黄素/壳聚糖-脱氧胆酸纳米粒(5，10，20，40 mg/L)共培养，采用CCK-8法检测细胞增殖。
结果与结论：①姜黄素/壳聚糖-脱氧胆酸纳米粒的载药量、负载效率分别为27.5%，55%，体外前10 h内，该纳米粒存在药物突释现象，此后缓慢释放，至96 h后达到平衡，累积释放药物量为31.6%；②培养24，48 h，不同质量浓度的壳聚糖-脱氧胆酸纳米粒对人视网膜色素上皮细胞的增殖无明显影响；③不同质量浓度的姜黄素与姜黄素/壳聚糖-脱氧胆酸纳米粒均可抑制人视网膜色素上皮细胞的增殖，且具有时间与浓度依赖性；在相同质量浓度下，姜黄素/壳聚糖-脱氧胆酸纳米粒培养1-4 d的细胞增殖抑制率低于姜黄素组(P < 0.05)，两组培养5，6 d的细胞增殖抑制率比较差异无显著性意义(P > 0.05)；④结果表明，载姜黄素壳聚糖-脱氧胆酸纳米粒对人视网膜色素上皮细胞具有抑制作用，并且该纳米粒没有降低姜黄素原药成分的生物学活性。

https://orcid.org/0000-0002-9867-9423 (郑海生) 

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料;口腔生物材料;纳米材料;缓释材料;材料相容性；组织工程

关键词: 纳米粒, 姜黄素, 视网膜色素上皮细胞, 壳聚糖-脱氧胆酸, 细胞增殖

Abstract: BACKGROUND: Curcumin can inhibit the proliferation of human retinal pigment epithelial cells and anti-angiogenesis and can play an important role in the prevention and treatment of fundus neovascularization. However, its water solubility is poor and its half-life in the body is short. It requires long-term and multiple injections. Therefore, the development of a new dosage form of curcumin has an important clinical significance. 
OBJECTIVE: To study the synthesis of deoxycholic acid group grafted chitosan derivatives loaded curcumin nanoparticles and the effect of curcumin nanoparticles on the proliferation of human retinal pigment epithelial cells. 
METHODS: Chitosan-deoxycholic acid nanoparticles were prepared, and then curcumin/chitosan-deoxycholic acid nanoparticles were prepared to detect the drug loading, loading efficiency and in vitro drug release performance of curcumin/chitosan-deoxycholic acid nanoparticles. Human retinal pigment epithelial cells were co-cultured with curcumin (5, 10, 20, 40 mg/L), chitosan-deoxycholic acid nanoparticles (5, 10, 20, 40 mg/L), and curcumin/chitosan-deoxycholic acid nanoparticles (5, 10, 20, 40 mg/L). Cell proliferation was detected by the CCK-8 assay. 
RESULTS AND CONCLUSION: (1) The drug loading and loading efficiency of curcumin/chitosan-deoxycholic acid nanoparticles were 27.5% and 55%, respectively. Within the first 10 hours in vitro, the nanoparticles had a drug burst phenomenon, slowly released and then reached a balance until 96 hours later, and the cumulative amount of drug release was 31.6%. (2) The chitosan-deoxycholic acid nanoparticles of different mass concentrations had no significant effect on the proliferation of human retinal pigment epithelial cells after 24 and 48 hours of culture. (3) The curcumin of different mass concentrations and curcumin/chitosan-deoxycholic acid nanoparticles could suppress the proliferation of human retinal pigment epithelial cells in time- and mass-concentration-dependent manners. At the same mass concentration, the inhibition rate of cell proliferation of curcumin/chitosan-deoxycholic acid nanoparticles at 1-4 days of culture was lower than that of the curcumin group (P < 0.05). There was no significant difference in the inhibition rate of cell proliferation between the two groups cultured for 5 and 6 days (P > 0.05). (4) The results show that the curcumin-loaded chitosan-deoxycholic acid nanoparticles have an inhibitory effect on human retinal pigment epithelial cells, and the nanoparticles did not reduce the biological activity of the curcumin ingredients. 

Key words: nanoparticles, curcumin, retinal pigment epithelial cells, chitosan-deoxycholic acid, cell proliferation

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