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用于微创手术止血的微通道传输药物释放系统。

Drug-release system of microchannel transport used in minimally invasive surgery for hemostasis.

作者信息

Huang Hong, Liu Houhe, Zhou Hua, Liang Zhiling, Song Dandan, Zhang Yun, Huang Wanqiu, Zhao Xiaotian, Wu Bo, Ye Guodong, Huang Yugang

机构信息

Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.

Key Laboratory of Molecular Target and Clinical Pharmacology of Guangdong Province, School of Pharmaceutical Sciences, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China,

出版信息

Drug Des Devel Ther. 2019 Mar 12;13:881-896. doi: 10.2147/DDDT.S180842. eCollection 2019.

DOI:10.2147/DDDT.S180842
PMID:30880920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6420104/
Abstract

BACKGROUND

Sucrose allyl ether (SAE) containing hemostatic drugs and a photoinitiator was established to treat mild postpartum hemorrhage or long-term continuous abnormal uterine bleeding in minimally invasive surgery (MIS) using a photopolymerization method.

METHODS AND RESULTS

Real-time infrared spectroscopy and rheological experiments showed that the SAE monomer with shear-thinning characteristics could polymerize rapidly into a transparent membrane. Cytotoxicity experiments in vitro showed that this system could elicit a long-term hemostatic effect. Tissue adhesion was also evaluated. The photo-stability of four delivered antifibrinolytic drugs (6-aminocaproic acid, ethylenediaminediacetic acid, tranexamic acid and p-(aminomethyl) benzoic acid) was tested by ultraviolet-photolysis experiments and illustrated by time-dependent density functional theory. Sustained-release experiments revealed that the formed film could be used as a drug carrier. Molecular docking and molecular dynamics were done to investigate the binding mechanism between hemostatic drugs as ligands and the human plasminogen kringle-1 (1HPK) as a target.

CONCLUSION

It has been suggested that SAE with tranexamic acid could be a drug-release system of microchannel transport used in MIS. This system could tackle the dilemma of fluidity and adhesion in MIS. The photo-stable tranexamic acid was the most suitable drug according to its satisfactory binding energy, good photo-stability, and sustained release.

摘要

背景

含止血药物和光引发剂的蔗糖烯丙基醚（SAE）被开发出来，用于在微创手术（MIS）中采用光聚合方法治疗轻度产后出血或长期持续性异常子宫出血。

方法与结果

实时红外光谱和流变学实验表明，具有剪切变稀特性的SAE单体能够迅速聚合成透明膜。体外细胞毒性实验表明该系统可产生长期止血效果。还评估了组织粘连情况。通过紫外光解实验测试了四种递送的抗纤溶药物（6-氨基己酸、乙二胺二乙酸、氨甲环酸和对（氨甲基）苯甲酸）的光稳定性，并通过含时密度泛函理论进行了说明。缓释实验表明形成的膜可作为药物载体。进行了分子对接和分子动力学研究，以探讨作为配体的止血药物与人纤溶酶原kringle-1（1HPK）作为靶点之间的结合机制。

结论

有人提出，含氨甲环酸的SAE可能是一种用于MIS的微通道运输药物释放系统。该系统可以解决MIS中的流动性和粘连问题。根据其令人满意的结合能、良好的光稳定性和缓释性能，光稳定的氨甲环酸是最合适的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/f92587b24a19/dddt-13-881Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/4b386a40fb5b/dddt-13-881Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/4b6f4d639967/dddt-13-881Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/404deab1d5ed/dddt-13-881Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/278c908ae0da/dddt-13-881Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/fa77fd583f0a/dddt-13-881Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/0f02b9e2bc61/dddt-13-881Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/cdbf9809f552/dddt-13-881Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/02621fb25878/dddt-13-881Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/f92587b24a19/dddt-13-881Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/4b386a40fb5b/dddt-13-881Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/4b6f4d639967/dddt-13-881Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/404deab1d5ed/dddt-13-881Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/278c908ae0da/dddt-13-881Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/fa77fd583f0a/dddt-13-881Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/0f02b9e2bc61/dddt-13-881Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/cdbf9809f552/dddt-13-881Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/02621fb25878/dddt-13-881Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be6/6420104/f92587b24a19/dddt-13-881Fig9.jpg

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