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Cyclodextrin inclusion complex enhances solubility and antimicrobial activity of chlortetracycline hydrochloride

文献类型： 外文期刊

作者： Zhang, Chao 1 ; Yi, Lankun 1 ; Bai, Yubin 1 ; Yang, Xiaorong 1 ; He, Jian 1 ; Bai, Yuting 1 ; Zhang, Yong 2 ; Li, Bing 1 ; Zhang, Jiyu 1 ;

作者机构： 1.Chinese Acad Agr Sci, Minist Agr & Rural Affairs, Key Lab New Anim Drug Project Gansu Prov, Key Lab Vet Pharmaceut Dev,Lanzhou Inst Husb & Pha, Lanzhou 730050, Peoples R China

2.Gansu Agr Univ, Coll Vet Med, Lanzhou 730070, Gansu, Peoples R China

3.Hebei Univ Engn, Coll Life Sci & Food Engn, Handan 056038, Hebei, Peoples R China

关键词： Chlortetracycline hydrochloride; Hydroxypropyl-(3-cyclodextrin; Inclusion complex; Molecular docking; Freeze drying; Antibacterial activity in vivo and in vitro

期刊名称：TALANTA （ 影响因子：6.1； 五年影响因子：5.5 ）

ISSN： 0039-9140

年卷期： 2025 年 292 卷

页码：

收录情况： SCI

摘要： Chlortetracycline hydrochloride (CTC) is a broad-spectrum tetracycline antibiotic used to prevent or resist different bacterial infections. However, due to its poor aqueous stability and physicochemical instability, its clinical development is limited. To improve such properties, CTC complexation with (3-cyclodextrin ((3-CD) and 2hydroxypropanol-(3-cyclodextrin (HP-(3-CD) was performed using different preparation techniques (Freeze drying and ball milling). Inclusion complexes were comprehensively characterized using different analytical techniques and showed different properties distinct to pure CTC. In the presence of both CDs, CTC solubility was significantly improved. After ratio optimization, the optimal molar ratio after freeze-drying was determined to be 1:5. Compared to pure CTC powder (4 mg/mL), the solubility of CTC/HP-(3-CD improved approximately 9 times (36 mg/mL), and a new CTC injection was successfully prepared. The antibacterial activity (in vivo and in vitro) of the CTC/HP-(3-CD injection was then examined in natural infection chickens. Pathological tissue images showed that a 20 mg/kg CTC/HP-(3-CD dose increased antibacterial activity and therapeutic effects. Additionally, we determined five clinical strains and statistically verified that CTC/HP-(3-CD exhibits stronger antibacterial activity compared to CTC and other tetracycline drugs, with the most significant effect observed against Pseudomonas aeruginosa (MIC value of 2 mu g/mL). Thus, these findings suggest that CTC/HP-(3-CD inclusion complexes could be promising for pharmaceutical development, warranting further clinical evaluation, as solubility was significantly increased, and enhanced antibacterial activity was recorded in vivo and in vitro.

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