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

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.

Keywords:

• hemostasis
• photopolymerization
• minimally invasive surgery
• molecular simulation

Acknowledgments

This research was funded by the National Natural Science Foundation of China (21274032 and 51403043) and Natural Science Foundation of Guangdong Province (2014A030313500). It was also funded by a project of the high-level University of Guangdong Province and municipal college research program of the Guangzhou Education Bureau (1201610202). The general director and corresponding author, Guodong Ye, gratefully acknowledges the support for this study by the organizations mentioned previously. We also express our sincere gratitude to Professor Eric Hénon for detailed help using IGMPlot. Hong Huang, Houhe Liu, and Hua Zhou are co-first authors.

Disclosure

The authors report no conflicts of interest in this work.

Supplementary materials

Figure S1 Photopolymerization reaction process of SAE with HMPP. The structure of four hemostatic drugs, AMCHA, EACA, EDDA and PAMBA.

Abbreviations: AMCHA, tranexamic acid; EACA, 6-aminocaproic acid; EDDA, ethylenediaminediacetic acid; HMPP, 2-hydroxy-2-methyl-1-phenyl-1-propanone; PAMBA, p-(aminomethyl) benzoic acid; PSAE, poly(sucrose allyl ether); SAE, sucrose allyl ether.

Figure S2 The illustration of excited energies.

Abbreviations: GS, ground state; PES, potential energy surface.