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Biomaterials Science · 2024 · IF 5.8

Bioactive electrospun polylactic acid/chlorogenic acid-modified chitosan bilayer sponge for acute infection wound healing and rapid coagulation

Huiling Zhong,Zhen Zhang,Mohong Wang,Yifei Fang,Ke Liu,Junqiang Yin,Jun Wu,Jianhang Du

Acute severe trauma is often associated with rapid blood loss and a high risk of infection. Based on these concerns, this study successfully constructed a multifunctional dual-layer bioactive sponge PCCT with rapid hemostatic and infection-preventing ability. Its external surface is an electrospun poly(lactic acid) (PLA) nanofiber thin film layer, which ensures its high air permeability and effectively protects against external bacterial invasion. In vitro results showed that the film is effectively resistant to invasion by typical Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. The inner sponge layer was formed by chlorogenic acid (CGA) grafted with chitosan (CS) and loaded with tranexamic acid (TA). The abundant cationic groups on the sponge interacted with negatively charged erythrocytes and achieved rapid hemostasis at the wound site under the action of TA. In addition, the high porosity and bioactivity of the CS-CGA sponge scaffold endowed the hydrogel with good water absorption, antibacterial properties and anti-inflammatory activity, which effectively accelerated the healing of acute infected wounds in rats and demonstrated favorable biosafety.

研究领域: 生物材料学 · 创伤修复 · 药剂学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Fabrication of PLGA-chitosan-tranexamic acid composite sponge and its mechanism for rapid hemostasis

Yue Zhu,Teng Chen,Xiujuan Wan,Guiqin Zhu,Zhiyong Chen,Zhoujie Yang,Jing Yang,Tingting Feng,Zuhua Wang,Ying Zhou

Persistent intraoperative hemorrhage is the major cause of trauma-related mortality, emphasizing the need for hemostatic dressings with improved efficacy. In this study, we designed a PLGA-CTS-TXA composite sponge, which was fabricated by grafting of poly (lactic- co -glycol acid) (PLGA) and hemostatic small molecule tranexamic acid (TXA) onto chitosan (CTS), for rapid hemostasis. The sponge integrates the advantages of CTS, PLGA and TXA, showcasing superior porosity (nearly 85 %) and water absorption capacity (3197 ± 105 % within 30 s). It also demonstrates good biocompatibility (hemolysis <1.2 %, RCV > 125 %), low blood clotting index (12.4 %) and abbreviated clotting times (<30 s). The incorporation of TXA substantially augmented the hemostatic capability of the composite sponge. Compared to CTS alone, PLGA-CTS-TXA demonstrated a significantly reduced hemostatic time in both rat tail and mouse liver hemostatic models. Its hemostatic mechanism was further analyzed from the perspective of the actual interface created by the interaction between the material and the biological fluid (ie., protein corona). The results demonstrated that the swift hemostatic mechanism involves modulation of erythrocyte and platelet aggregation/adhesion and fibrin degradation, etc. , thereby influencing the coagulation cascade. This research extends the utility of TXA in hemostasis and offers novel idea into the development and hemostatic mechanism of new high-efficiency hemostatic dressings.

研究领域: 生物材料学 · 医学工程 · 创伤治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2025 · IF 5.7

A supramolecular tranexamic acid with enhanced permeability and bioactivity

Zhenyuan Wang,Tie Dong,Jin Yang,Yiyu Wang,Mi Wang,Jiaheng Zhang

Due to its rich bioactivities, tranexamic acid (TA) has garnered significant attention in the biomedical and cosmetic fields. However, TA's hydrophilic nature impedes its penetration through the skin's stratum corneum. This limitation is addressed in the current study by designing a supramolecular TA, i.e., GATA, based on the non-covalent interactions between TA and glycolic acid (GA). The structure and formation mechanism of GATA are explored using multidimensional characterization techniques, including single crystal analysis and computer-aided simulations. In vitro, the supramolecular interactions within GATA facilitate deeper TA penetration into the skin, achieving >2.5 times improved transdermal permeability than pure TA. Notably, GATA does not damage the skin barrier, with the associated irritation and cytotoxicity significantly lower than that caused by GA. Moreover, compared with TA, GATA has comparable or superior thermal stability, water solubility, anti-glycation, antioxidant, and anti-inflammatory properties. GATA also exhibits excellent skin whitening efficacy. Hence, GATA is a promising alternative to TA, with enhanced permeability, bioactivity, and biosafety, as well as considerable application prospects in transdermal delivery.

研究领域: 药学 · 化妆品科学 · 生物医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF MOLECULAR STRUCTURE · 2024 · IF 4

Three-dimensional hierarchical porous biochar as an efficient adsorbent for simultaneous extraction of ametryn and benzo[a]pyrene from tea beverages

Qing Wang,Xue Ren,Shao-Feng Tang

Background Limits on ametryn and benzo[a]pyrene in tea beverages are becoming more stringent. To enhance detection efficiency and reduce analysis costs, it is critical to develop mixed-mode extractants for these two analytes with substantial differences in properties concurrently. Biochar (BC) is increasingly being used in the preparation of mixed-mode adsorbents, but there is a challenge in balancing adsorption capacity against adsorption rate. Therefore, it is of great significance to explore mixed-mode adsorbents that can simultaneously adsorb or extract analytes with different properties, such as ametryn and benzo[a]pyrene, and achieve rapid adsorption or extraction. Results The shells of Zizyphus jujuba seeds were used to synthesize K-H-BC, a three-dimensional hierarchical porous BC with a wide range of oxygen-containing functional groups. The synthesis technique included KOH activation and modification using a 1:3 vol ratio of HNO 3 /H 2 SO 4 . K-H-BC's mixed-mode adsorption properties resulted in various interactions with ametryn and benzo[a]pyrene. It exhibited rapid adsorption rates for ametryn and benzo[a]pyrene (reaching equilibrium in 15 min and 5 min, respectively) as well as high adsorption capacities (487.64 mg g −1 and 133.16 mg g −1 , respectively). Using K-H-BC as a dispersed solid-phase extraction adsorbent, combined with high performance liquid chromatography, a method for simultaneously detecting the two analytes in tea beverages was established. Ametryn displayed a linear range of 2–500 μg L −1 with a limit of detection of 0.20 μg L −1 , while benzo[a]pyrene showed a linear range of 25–500 μg L −1 with a limit of detection of 2.12 μg L −1 . Significance and novelty It provides a solution to the problem of high hydrophobicity in KOH-activated BC by modifying it with mixed acids. K-H-BC possesses a three-dimensional hierarchical porous structure and abundant surface oxygen-containing functional groups, allowing it to retain high adsorption capacity during rapid adsorption while co-adsorbing and co-extracting analytes with significantly different properties. This research provides a reference for using BC in sample pretreatment and the comprehensive utilization of non-medicinal parts of Zizyphus jujuba .

CAS / MDL: 834-12-8 50-32-8
研究领域: 环境科学 · 分析化学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2022 · IF 8.025

Preparation and characterization of tranexamic acid modified porous starch and its application as a hemostatic agent

Xinhong Zhao,Yunbo Sun,Zhiyun Meng,Zhiyuan Yang,Shan Fan,Tong Ye,Lei Yang,Tong Li,Ruolan Gu,Zhuona Wu,Hui Gan,Guifang Dou,Yongxiu Qi,Shuchen Liu

Effective bleeding control is essential for the reduction of traumatic deaths among civilians and military personnel, particularly for physical visceral and arteriovenous injuries. Materials with good hemostatic properties have recently attracted significant scientific attention. In this study, a novel material of tranexamic acid modified porous starch (TAMPS) was produced through esterification . The structure of the final product was characterized using Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis . The hemostatic effect of TAMPS was preliminarily analyzed via in vitro clotting time, mouse tail amputation model and liver injury model experiments. Hemostatic effect of TAMPS was found to be significantly better than that of the positive control Quickclean. Through the exploration of related hemostatic mechanisms , TAMPS can promote coagulation via rapid fluid absorption and high erythrocyte aggregation capacity. The in vitro cytotoxicity, acute toxicity, and hemolysis tests revealed that TAMPS is safe and nontoxic and has perfect blood compatibility. Therefore, the TAMPS has a great potential for future clinical application as a rapid and multitarget hemostatic material.

CAS / MDL: 9005-25-8
研究领域: 材料科学 · 医学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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RSC Advances · 2024 ·Vol. 14 ·期 47 ·34996-35004 · IF 3.9

Enhancing skin delivery of tranexamic acid via esterification: synthesis and evaluation of alkyl ester derivatives

Yutong Zeng,Mengrui Ma,Yongfeng Chen,Huichao Xie,Pingtian Ding,Keda Zhang

Tranexamic acid (TA) is widely used clinically as a skin whitening agent for treating melasma and hyperpigmentation. However, oral administration of TA is often associated with adverse effects. Topical application could mitigate these issues, but the hydrophilic nature of TA limits its topical use. To overcome this limitation, we explored the design of TA alkyl ester prodrugs to enhance skin absorption. Our study specifically focused on the butyl and octyl ester derivatives of TA. The results demonstrated that TA4 and TA8 significantly improved skin penetration and deposition, by approximately 2–3 times compared to unmodified TA. Furthermore, these derivatives were rapidly hydrolyzed to release the parent drug within less than 2 h in both skin homogenates and blood. Safety assessments indicated no significant skin irritation in mice and revealed low cytotoxicity in HaCaT cells when exposed to the TA ester derivatives. We also developed a hydrogel formulation incorporating the TA derivatives, using hydroxyethyl cellulose, propylene glycol, Tween 80, and chlorobutanol. This formulation exhibited good skin absorption, stability, and user experience, making it a promising candidate for topical application. To sum up, the alkyl esterification prodrug design provides a promising approach for enhancing the skin delivery of TA.

CAS / MDL: 30525-89-4 7647-14-5
研究领域: 药剂学 · 皮肤科学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Annals of Dermatology · 2024 · IF 1.5

Tranexamic Acid Ameliorates Skin Hyperpigmentation by Downregulating Endothelin-1 Expression in Dermal Microvascular Endothelial Cells

Lin-Xia Liu,Zhi-Kai Liao,Bing-Qi Dong,Shan Jiang,Tie-Chi Lei

Background Although reports suggest that tranexamic acid (TXA) has clinical benefits for melasma patients by oral, intralesional and topical treatment, the optimal route of TXA therapy and the underlying mechanism involved remain poorly defined. Objective To compare the skin lightening effect between oral TXA and topical TXA and to dissect the molecular mechanisms using ultraviolet B (UVB)-induced hyperpigmentation mouse model, ex vivo cultured human skin explant, and cultured melanocytes (MCs) and endothelial cells. Methods Melanin content and cluster of differentiation 31 (CD31)-positive cell numbers were measured in tail skins from UVB-irradiated mice treated by intragastral or topical TXA using immunofluorescent and Fontana-Masson staining. The conditioned medium (CM) was harvested from human umbilical vein endothelial cells treated with or without 3 mM TXA and was used to treat MCs for 48 hours. mRNA and protein levels of tyrosinase and microphthalmia-associated transcription factor were measured using quantitative real-time reverse transcription polymerase chain reaction and western blotting assays. HMB45- and CD31-positive cell numbers as well as melanin content were also examined in ex vivo cultured human skin explants. Results The hyperpigmented phenotype were significantly mitigated in UVB-irradiated tail skin plus intragastral TXA-treated mice compared with mice treated with UVB only or with UVB plus topical TXA. CD31-positive cell numbers correlated with the anti-melanogenic activity of TXA therapy. The data from cultured cells and skin tissues showed that suppression of endothelin-1 (ET-1) in vascular endothelial cells by TXA reduced melanogenesis and MC proliferation. Conclusion Oral TXA outperforms topical TXA treatment in skin lightening, which contributes to suppression of ET-1 in dermal microvascular endothelial cells by TXA.

CAS / MDL: 1197-18-8
研究领域: 皮肤病学 · 分子生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMACROMOLECULES · 2024 · IF 5.5

Hemostatic Tranexamic Acid-Induced Fast Gelation and Mechanical Reinforcement of Polydimethylacrylamide/Carboxymethyl Chitosan Hydrogel for Hemostasis and Wound Healing

Yi Wang,Peiyue Pan,Hao Liang,Jing Zhou,Chuan Guo,Lijuan Zhao,Jinrong Wu

The combinational properties with excellent mechanical properties, adhesive performance, hemostatic ability, antibacterial action, and wound healing efficacy are highly desirable for injectable hydrogels’ practical applications in hemorrhage control and wound closure, but designing one single hydrogel system integrating with such properties is still difficult. Herein, a simplified yet straightforward strategy is proposed to prepare an injectable and robust poly(N,N-dimethylacrylamide) (PDMAA)/carboxymethyl chitosan (CMCS) hydrogel induced by tranexamic acid (TXA). TXA not only promotes the rapid generation of free radicals but also introduces multiple hydrogen bonds into the hydrogel network. Moreover, as a common clinical hemostatic drug, TXA itself has excellent hemostatic effects. In addition, CMCS imparts sterilization and hemostasis effects to the hydrogel, thereby promoting wound healing. Besides, the amino and carboxyl groups on TXA molecules and the hydroxyl, amino, and carboxyl groups on CMCS molecules can form multiple hydrogen bonds with wet biological tissues, leading to good wet tissue adhesion of the hydrogel. As a result, the hydrogel with excellent mechanical properties (up to 1.83 MPa at 90% compression strain), adhesion performance (up to 18.7 kPa adhesion strength to porcine skin tissue), biocompatibility, hemostatic ability, antibacterial activity, and wound healing properties can be fabricated within several minutes. These combinational advantages enable the hydrogel to efficiently stop hemorrhage (blood loss amount: 110 mg; hemostasis time: 25 s) and promote the wound healing process (wound closure rate at 2 weeks: 83%), which can be verified using rat models of liver bleeding and infected full thickness skin defect. Overall, this facile strategy to design a hydrogel incorporating such unique advantages will greatly advance the hydrogel’s clinical application in rapid hemostasis and wound healing.

研究领域: 生物材料 · 医学工程 · 创伤修复
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Nanoscale · 2021 ·Vol. 13 ·期 21 ·9843-9852 · IF 7.79

Chestnut-like macro-acanthosphere triggered hemostasis: a featured mechanism based on puncturing red blood cells

Yang Liu,Kun Yu,Songmin Shang,Ruiqi Xie,Fei Lu,Rong Bao,Guangqian Lan,Enling Hu

Acute hemorrhage that occurs after trauma is a life-threatening condition. Hence, to halt massive bleeding, there is a critical need to develop a suitable therapy. In this study, we developed self-propelling chestnut-like particles (Pro-MAS) comprising a macro-acanthosphere (MAS) coated with calcium carbonate and protonated tranexamic acid to puncture red blood cells (RBCs) and thus activate hemostasis. In vitro assessments revealed that Pro-MAS was biocompatible, biodegradable, and nontoxic; furthermore, it was capable of puncturing RBCs to release procoagulants and activate platelet aggregation for hemostasis. Animal tests showed that self-propelling Pro-MAS effectively traveled through blood flow to the deep ends of wounds; hemorrhage was controlled within 90 s and 4 min in the injured liver and bleeding femoral artery, respectively. Compared with a commercial hemostat, superior hemostasis was achieved with Pro-MAS, which could be ascribed to its functional and structural features. Overall, traveling Pro-MAS possessed sufficient impact force to puncture RBCs and sufficient momentum to reach the targeted bleeding sites. The present study demonstrated the ability of a novel platform, self-propelling MAS particles, to trigger hemostasis by puncturing RBCs. To the best of our knowledge, this is the first trial in which the release of endogenous procoagulants is promoted without the addition of exogenous procoagulants for severe hemorrhage control.

研究领域: 医学 · 生物材料学
✓ 已验证 DOI PubMed 高影响因子
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Biomed Research International · 2021 · IF 3.411

The Topical Tranexamic Acid Have Potential Hazard of Promoting Biofilm Formation of Staphylococcus aureus in Microenvironment of the Prosthetic Joint

Feiyang Zhang,Wenjun Dong,Fengyan Wang,Jinlong Yu,Feng Jiang,Jin Tang,Yan Qian,Hao Shen

Background. Perioperative topical tranexamic acid as antifibrinolytic agent is often used for total joint replacement to reduce bleeding currently. Staphylococcus aureus was the most common isolates from perioperative infection of prosthetic joint. The influence of topical application with tranexamic acid on the incidence of acute prosthetic joint infection of Staphylococcus aureus has not been clarified. Methods. Mouse model of Staphylococcus aureus knee prosthesis infection was constructed. Tranexamic acid was intra-articular injected during the perioperative period. CFU counting from tissue and implant sample was evaluated 3 days and 7 days after inoculating of Staphylococcus aureus. Bacterial growth curve, biofilm formation, aggregation, and plasmin inhibition of Staphylococcus aureus were tested with tranexamic acid added to the synovial culture medium. Results. There were no significant differences of CFU counting from tissue and implant samples in knee prosthesis infection after a single local injection of tranexamic acid at the postoperative 3 or 7 days. The amount of bacterial colonization on the surface of implant increased after 3 days’ continuous local injection of tranexamic acid. Tranexamic acid has no effect on bacterial growth at the concentration (10 mg/ml) of clinical application, but it can inhibit bacterial aggregation and mildly inhibit biofilm formation. Plasmin can significantly inhibit biofilm formation which can be revised by adding tranexamic acid. Conclusion. Although continuous local injection of tranexamic acid can promote the biofilm formation of Staphylococcus aureus on the surface of articular implant, it has clinical safety for using one single local injection of tranexamic acid during the perioperative period.

研究领域: 微生物学 · 骨科 · 药理学
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CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS · 2015 · IF 2.321

Quantitative determination of ametryn in river water using surface-enhanced Raman spectroscopy coupled with an advanced chemometric model

Yao Chen,Zeng-Ping Chen,Jing-Wen Jin,Ru-Qin Yu

In this contribution, surface-enhanced Raman spectroscopy (SERS) coupled with an advanced chemometric method-multiplicative effects model (MEM SERS ) has been applied to quantitative analysis of ametryn in water samples of the Xiangjiang River (Changsha, China). The adoption of MEM SERS calibration model was to eliminate the detrimental effects caused by variations in the physical properties of enhancing substrates, the intensity and alignment/focusing of laser excitation source. Experimental results showed that the combination of SERS with MEM SERS can provide quite precise concentration predictions for ametryn in water samples of the Xiangjiang River with an average relative prediction error of about 4.8%. The combination of SERS with MEM SERS can compete with LC-MS/MS in terms of precision and accuracy of quantitative results. The limit of quantification was about 0.09   μM. More importantly, no laborious reference methods (e.g., HPLC) were needed to build the MEM SERS calibration model, since the MEM SERS calibration model built on the calibration samples prepared with ultrapure water could provide satisfactory quantification results for the test samples prepared with water collected from the Xiangjiang River. Therefore, it is reasonable to expect that SERS in combination with MEM SERS model would become a competitive alternative in routine quantitative analysis of ametryn in environmental water samples.

CAS / MDL: 834-12-8 106-45-6
研究领域: 环境科学 · 分析化学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2024 · IF 5.3

Prolonged joint cavity retention of tranexamic acid achieved by a solid-in-oil-in-gel system: A preliminary study

Ying Yu,Shuang Ren,Lixia Shang,Baoyan Zuo,Guofei Li,Jingxin Gou,Wei Zhang

Tranexamic acid (TXA) is an anti-fibrinolysis agent widely used in postoperative blood loss management. As a highly water-soluble drug, TXA is suffering from rapid clearance from the action site, therefore, large amount of drug is required when administered either by intravenously or topically. In this study, a TXA preparation with prolonged action site residence was designed using the nano-micro strategy. TXA nanoparticles were dispersed in oil by emulsification followed by lyophilization to give a solid-in-oil suspension, which was used as the oil phase for the preparation of TXA-loaded solid-in-oil-in-water (TXA@S/O/W) system. The particle size of TXA in oil was 207.4 ± 13.50 nm, and the particle size of TXA@S/O/W was 40.5 μm. The emulsion-in-gel system (TXA@S/O/G) was prepared by dispersing TXA@S/O/W in water solution of PLGA-b-PEG-b-PLGA (PPP). And its gelling temperature was determined to be 26.6 ℃ by a rheometer. Sustained drug release was achieved by TXA@S/O/G with 72.85 ± 7.52 % of TXA released at 120 h. Formulation retention at the joint cavity was studied by live imaging, and the fluorescent signals dropped gradually during one week. Drug escape from the injection site via drainage and absorption was investigated by a self-made device and plasma TXA concentration determination, respectively. TXA@S/O/G showed the least drug drainage during test, while more than 70 % of drug was drained in TXA@S/O/W group and TXA solution group. Besides, low yet steady plasma TXA concentration (less than 400 ng/mL) was found after injecting TXA@S/O/G into rat knees at a dosage of 2.5 mg/kg, which was much lower than those of TXA dissolved in PPP gel or TXA solution. In conclusion, sustained drug release as well as prolonged action site retention were simultaneously achieved by the designed TXA@S/O/G system. More importantly, due to the steady plasma concentration, this strategy could be further applied to other highly water-soluble drugs with needs on sustained plasma exposure.

研究领域: 药剂学 · 生物医学工程
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