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壳聚糖纳米复合材料共轭氯喹-藏红花对恶性疟原虫3D7和K1株的体外抗疟活性

In Vitro Antimalarial Activity of Chloroquine-Crocus Sativus Conjugated to Chitosan Nanocomposits against 3D7 and K1 Strains of .

作者信息

Khezri Aram, Nateghpour Mahdi, Motevali Haghi Afsaneh, Elmi Taher, Rahimi Foroushani Abbas, Shafii Ardestani Mehdi, Hanifian Haleh

机构信息

Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Center for Research of Endemic Parasites of Iran, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Parasitol. 2025 Apr-Jun;20(2):213-226. doi: 10.18502/ijpa.v20i2.19027.

Abstract

BACKGROUND

The use of nanocarriers in combination with other treatments shows significant promise in addressing drug-resistant diseases, particularly malaria. Given the high prevalence of drug-resistant malaria, research into innovative therapies is crucial. This study focuses on a nanoform of chitosan, a biodegradable polymer, combined with (saffron) and chloroquine to enhance their antimalarial effects.

METHODS

Saffron extract and chloroquine were separately conjugated with chitosan, followed by confirmation tests to determine conjugation efficiency. Both chloroquine-resistant and sensitive strains of were cultured to calculate the IC50 values of various treatments in vitro. This study was conducted at the School of Public Health, Tehran University of Medical Sciences, Tehran, Iran in 2024.

RESULTS

Confirmation tests (FTIR, DLS, Zeta potential, TEM) verified proper drug conjugation to nanocomposites, with observed nanosize, the percentage of conjugation was 64.4% for chloroquine and 42.9% for saffron. Toxicity and hemolysis tests confirmed safe doses. The IC50s values for Chloroquine, Nanoparticle-Chloroquine, Saffron, and Nanoparticle-Saffron were 0.3, 0.8, 42.5, and 6.24 μg/ml, respectively, for the sensitive strain, and 5, 1, 12.5, and 3.12 μg/ml, respectively, for the resistant strain. Combination therapy with the fixed ratio method showed synergistic effects. Statistical analysis revealed synthesized nanocomposites' superior inhibition of growth compared to non-nano. Significant differences were observed in some cases (< 0.05).

CONCLUSION

Utilizing nanocarriers and combination therapy is an appropriate strategy for addressing drug resistance. Saffron's anti-malarial effects on were notably increased when linked to chitosan nanocomposites. Furthermore, employing a fixed ratio technique enhanced the therapeutic effectiveness of saffron when combined with chloroquine and chloroquine-nanocomposites across all concentrations.

摘要

背景

纳米载体与其他治疗方法联合使用在治疗耐药性疾病,特别是疟疾方面显示出巨大潜力。鉴于耐药性疟疾的高流行率,对创新疗法的研究至关重要。本研究聚焦于壳聚糖的纳米形式(一种可生物降解的聚合物)与藏红花和氯喹联合使用,以增强它们的抗疟效果。

方法

藏红花提取物和氯喹分别与壳聚糖共轭,随后进行确认试验以确定共轭效率。培养氯喹耐药和敏感菌株以计算各种处理在体外的半数抑制浓度(IC50)值。本研究于2024年在伊朗德黑兰医科大学公共卫生学院进行。

结果

确认试验(傅里叶变换红外光谱、动态光散射、zeta电位、透射电子显微镜)验证了药物与纳米复合材料的正确共轭,观察到纳米尺寸,氯喹的共轭百分比为64.4%,藏红花为42.9%。毒性和溶血试验确认了安全剂量。对于敏感菌株,氯喹、纳米颗粒 - 氯喹、藏红花和纳米颗粒 - 藏红花的IC50值分别为0.3、0.8、42.5和6.24μg/ml,对于耐药菌株分别为5、1、12.5和3.12μg/ml。采用固定比例法的联合疗法显示出协同作用。统计分析表明,合成的纳米复合材料对疟原虫生长的抑制作用优于非纳米材料。在某些情况下观察到显著差异(<0.05)。

结论

利用纳米载体和联合疗法是解决耐药性的合适策略。当与壳聚糖纳米复合材料结合时,藏红花对疟原虫的抗疟作用显著增强。此外,采用固定比例技术提高了藏红花与氯喹和氯喹纳米复合材料在所有浓度下联合使用时的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4980/12307787/6470060b6332/IJPA-20-213-g001.jpg

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