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

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

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Author(s): Hong Huang ¹ , Houhe Liu ² , Hua Zhou ¹ , Zhiling Liang ² , Dandan Song ² , Yun Zhang ² , Wanqiu Huang ² , Xiaotian Zhao ² , Bo Wu ² , Guodong Ye ² , Yugang Huang ²

Publication date (Electronic): 12 March 2019

Journal: Drug Design, Development and Therapy

Publisher: Dove Medical Press

Keywords: hemostasis, photopolymerization, minimally invasive surgery, molecular simulation

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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.

Most cited references 34

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Accurately extracting the signature of intermolecular interactions present in the NCI plot of the reduced density gradient versus electron density.

Corentin Lefebvre, Gaëtan Rubez, Hassan Khartabil … (2017)

An electron density (ED)-based methodology is developed for the automatic identification of intermolecular interactions using pro-molecular density. The expression of the ED gradient in terms of atomic components furnishes the basis for the Independent Gradient Model (IGM). This model leads to a density reference for non interacting atoms/fragments where the atomic densities are added whilst their interaction turns off. Founded on this ED reference function that features an exponential decay also in interference regions, IGM model provides a way to identify and quantify the net ED gradient attenuation due to interactions. Using an intra/inter uncoupling scheme, a descriptor (δg(inter)) is then derived that uniquely defines intermolecular interaction regions. An attractive feature of the IGM methodology is to provide a workflow that automatically generates data composed solely of intermolecular interactions for drawing the corresponding 3D isosurface representations.

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Tranexamic acid: a review of its use in surgery and other indications.

K Goa, C J Dunn (1999)

Tranexamic acid is a synthetic derivative of the amino acid lysine that exerts its antifibrinolytic effect through the reversible blockade of lysine binding sites on plasminogen molecules. Intravenously administered tranexamic acid (most commonly 10 mg/kg followed by infusion of 1 mg/kg/hour) caused reductions relative to placebo of 29 to 54% in postoperative blood losses in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), with statistically significant reductions in transfusion requirements in some studies. Tranexamic acid had similar efficacy to aprotinin 2 x 10(6) kallikrein inhibitory units (KIU) and was superior to dipyridamole in the reduction of postoperative blood losses. Transfusion requirements were reduced significantly by 43% with tranexamic acid and by 60% with aprotinin in 1 study. Meta-analysis of 60 trials showed tranexamic acid and aprotinin, unlike epsilon-aminocaproic acid (EACA) and desmopressin, to reduce significantly the number of patients requiring allogeneic blood transfusions after cardiac surgery with CPB. Tranexamic acid was associated with reductions relative to placebo in mortality of 5 to 54% in patients with upper gastrointestinal bleeding. Meta-analysis indicated a reduction of 40%. Reductions of 34 to 57.9% versus placebo or control in mean menstrual blood loss occurred during tranexamic acid therapy in women with menorrhagia; the drug has also been used to good effect in placental bleeding, postpartum haemorrhage and conisation of the cervix. Tranexamic acid significantly reduced mean blood losses after oral surgery in patients with haemophilia and was effective as a mouthwash in dental patients receiving oral anticoagulants. Reductions in blood loss were also obtained with the use of the drug in patients undergoing orthotopic liver transplantation or transurethral prostatic surgery, and rates of rebleeding were reduced in patients with traumatic hyphaema. Clinical benefit has also been reported with tranexamic acid in patients with hereditary angioneurotic oedema. Tranexamic acid is well tolerated; nausea and diarrhoea are the most common adverse events. Increased risk of thrombosis with the drug has not been demonstrated in clinical trials. Tranexamic acid is useful in a wide range of haemorrhagic conditions. The drug reduces postoperative blood losses and transfusion requirements in a number of types of surgery, with potential cost and tolerability advantages over aprotinin, and appears to reduce rates of mortality and urgent surgery in patients with upper gastrointestinal haemorrhage. Tranexamic acid reduces menstrual blood loss and is a possible alternative to surgery in menorrhagia, and has been used successfully to control bleeding in pregnancy.

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Photopolymerization kinetics of multifunctional monomers

Ewa Andrzejewska (2001)

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Author and article information

Journal

Journal ID (nlm-ta): Drug Des Devel Ther

Journal ID (iso-abbrev): Drug Des Devel Ther

Journal ID (publisher-id): Drug Design, Development and Therapy

Title: Drug Design, Development and Therapy

Publisher: Dove Medical Press

ISSN (Electronic): 1177-8881

Publication date Collection: 2019

Publication date (Electronic): 12 March 2019

Volume: 13

Pages: 881-896

Affiliations

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

[2 ]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, gzhygd@ 123456gzhmu.edu.cn ; hyug@ 123456gzhmu.edu.cn

Author notes

Correspondence: Guodong Ye; Yugang Huang, Key Laboratory of Molecular Target and Clinical Pharmacology of Guangdong Province, School of Pharmaceutical Sciences, The Fifth Affiliated Hospital of Guangzhou Medical University, No 621, Gangwan Road, Huangpu District, Guangzhou 511436, China, Tel +86 132 2949 4539, Email gzhygd@ 123456gzhmu.edu.cn ; hyug@ 123456gzhmu.edu.cn

[*]

These authors contributed equally to this work

Article

Publisher ID: dddt-13-881

DOI: 10.2147/DDDT.S180842

PMC ID: 6420104

SO-VID: db147e75-7acb-4223-a054-3ccf9503d262

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

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Abstract

Background

Methods and results

Conclusion

Most cited references 34

Accurately extracting the signature of intermolecular interactions present in the NCI plot of the reduced density gradient versus electron density.

Tranexamic acid: a review of its use in surgery and other indications.

Photopolymerization kinetics of multifunctional monomers

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Journal

Affiliations

Author notes

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