INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Xuejiao Wang,Yinling Ma,Xiaodan Qi,Xi Ruan,Deying Cao,Feng Zhao
The development of dissolving microneedles (DMNs) has brought light to the transdermal delivery of biomolecules that are released into the skin through the rapid dissolution of the matrix material to enter the systemic circulation and exert therapeutic effects. Herein, we aimed to prepare, characterize, and analyze the effectiveness of a glucagon-loaded DMN system that rapidly increases blood sugar levels in rats with diabetic hypoglycemia. The stability and content of biological drugs following DMNs preparation was assessed using circular dichroism and bicinchoninic acid kit for protein determination kits(BCA kits). The maximum drug loading capacity of DMNs was approximately 140 μg in each patch, and the microneedles could be stored for up to 14 days under dry storage conditions. In vitro skin permeation studies were conducted using a Franz diffusion cell apparatus for glucagon-loaded DMNs. To investigate the efficacy of transdermal drug delivery, drug-laden DMNs were administered to rats with hypoglycemic diabetes. Compared to subcutaneous injections , microneedle drug release demonstrated comparable efficacy in raising blood glucose levels in vivo. Therefore, this study demonstrated that glucagon-loaded DMNs may be a promising approach for efficient transdermal drug delivery as an alternative to subcutaneous injection for the treatment of severe hypoglycemia in patients with diabetes.
研究领域:
药剂学
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生物医学工程
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内分泌学
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2020
·Vol. 40
·期 9
·1284-1296
·
IF 2.997
Zhangjian Chen,Shuo Han,Pai Zheng,Shupei Zhou,Guang Jia
Titanium dioxide nanoparticles (TiO 2 NPs) were usually consumed with a high content of sugar, and children were identified as having the highest exposures due to sweet food preferences. Research on the combined effect of ingested TiO 2 NPs and glucose has great significance, particularly in young people. We examined young Sprague-Dawley rats administered TiO 2 NPs (0, 2, 10 and 50 mg/kg) orally with and without glucose (1.8 g/kg) for 90 days. Blood glucose homeostasis was assessed by monitoring blood glucose and detecting glycoproteins. Glucose tolerance was also evaluated by the oral glucose tolerance test. The levels of blood glucose-related hormones such as insulin, C-peptide and glucagon were measured. We found that subchronic co-exposure of TiO 2 NPs and glucose caused slight imbalance of blood glucose homeostasis in vivo. Mild and temporary hypoglycemia, impaired glucose tolerance and changes of glucose-regulating hormones were shown in the exposure groups. The combined effect of TiO 2 NPs and glucose was more apparent than that of TiO 2 NPs alone, which may be due to the effects of excess glucose and the interactions between TiO 2 NPs and glucose. The antagonistic effect of TiO 2 NPs with glucose did exist in the level of glycosylated hemoglobin in female rats. Gender differences were apparent in these effects induced by TiO 2 NPs and glucose. Female rats seemed to be more susceptible for blood glucose disorders. Co-exposure of TiO 2 NPs and excessive glucose could induce gender-dependent imbalance of blood glucose homeostasis in rats. It may be the reason that these consumers face greater health risks glycosylated hemoglobin.
研究领域:
毒理学
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内分泌学
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营养科学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Xiang Yu,Xueyu Wen,Jianchen Xu,Qiao Zhou,Yingrong Chen,Fengli Qu,Min He,Hao Chang,Chao Zheng
The timely administration of glucagon is a standard clinical practice for the treatment of severe hypoglycemia. However, the process involves cumbersome steps, including the reconstitution of labile glucagon and filling of the syringe, which cause considerable delays in emergency situations. Moreover, multiple dosages are often required to prevent the recurrence of the hypoglycemic episode because of the short half-life of glucagon in plasma. Herein, we develop a glucagon-loaded long-dissolving microneedle (GLMN) patch that exhibits the properties of fast onset and sustained activity for the effective treatment of severe hypoglycemia. Three types of MN patches were fabricated with different dimensions (long, medium, and short). The longer MN patch packaged a higher dosage of glucagon and exhibited supreme mechanical strength compared to the shorter one. Additionally, the longer MN patch could insert more deeply into the skin, resulting in higher permeability of glucagon across the skin tissue and more rapid systemic absorption as compared with the shorter MN patch. The GLMN patch was observed to reverse the effects of hypoglycemia within 15 min of application in animal models (specifically, rat and rhesus monkey models) and maintained long-term glycemic control, owing to highly efficient drug permeation and the drug reservoir effect of the MN base. The current study presents a promising strategy for the rapid reversal of severe hypoglycemia that exhibits the desirable properties of easy use, high efficiency, and sustained action.
研究领域:
生物医学工程
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药剂学
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内分泌学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2020
·
IF 6.306
Qi-Wu Zhong,Tao-Shun Zhou,Wen-Hui Qiu,Ya-Kun Wang,Qiao-Li Xu,Song-Ze Ke,Si-Jia Wang,Wei-Hua Jin,Jian-Wei Chen,Hua-Wei Zhang,Bin Wei,Hong Wang
The brown seaweed Undaria pinnatifida polysaccharides show various biological activities, but their hypoglycemic activity and the underlying mechanism remain unclear. Here, three fractions of sulfated polysaccharides Up-3, Up-4, and Up-5 were prepared by microwave-assisted extraction from U. pinnatifida . In vitro assays demonstrated that Up-3 and Up-4 had strong α-glucosidase inhibitory activity, and Up-3, Up-4, and Up-5 could improve the glucose uptake in insulin-resistant HepG2 cells without affecting their viability. In vivo studies indicated Up-3 and Up-4 markedly reduced postprandial blood glucose levels. Up-U (a mixture of Up-3, Up-4, and Up-5), reduced fasting blood glucose levels, increased glucose tolerance and alleviated insulin resistance in HFD/STZ-induced hyperglycemic mice. Histopathological observation and hepatic glycogen measurement showed that Up-U alleviated the damage of the pancreas islet cell, reduced hepatic steatosis, and promoted hepatic glycogen synthesis. These findings suggest that Up-U could alleviate postprandial and HFD/STZ-induced hyperglycemia and was a potential agent for diabetes treatment.
研究领域:
海洋生物学
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药理学
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糖尿病研究
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Yi Chen,Xiaowen Jiang,Junnan Wang,Zhengxiu Wu,Yuchen Wu,Zhonghua Ni,Hong Yi,Rongsheng Lu
The clinical challenge of high-accuracy blood glucose detection schemes is to overcome the detection error caused by the background interferences in different individuals. H2O2 as the specific product of glucose oxidation can be involved in the Fe2+/Fe3+ conversion and detected by the time-domain nuclear magnetic resonance (TD-NMR) method sensitively. But, in clinical applications, the oxidation of Fe2+ is susceptible to the complex sample substrates. In this work, we sorted out two kinds of possible interference mechanisms of Fe2+ oxidation in the NMR blood glucose detection method and proposed a feasible scheme that uses sorbitol to weaken the adverse effects of interference. We found that sorbitol-mediated Fe2+ can greatly enhance the sensitivity of the T2 value to H2O2. The chain reaction caused by sorbitol can significantly amplify the efficiency of Fe2+ oxidation at the same concentration of H2O2. Thereby, we can achieve the higher dilution multiple of serum samples to reduce the amount of interfering substances involved in the Fe2+/Fe3+ conversion. We justified the accuracy and availability of our method by successfully detecting and confirming the correlation between the T2 decrease and glucose concentration of the serum samples collected from 16 subjects. The sorbitol–Fe2+ glucose detection method with high sensitivity can be further combined with miniature NMR analyzers to satisfy the calibration requirements of glucose monitoring in diabetic patients instead of frequent medical visits.
研究领域:
医学诊断
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生物化学
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临床医学
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DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Muhammad Mazhar,Zhu Yong,Wen Anyan,Liu Na,Qin Likang
Regular consumption of low-glycemic index (GI) foods is a common strategy for type 2 diabetes patients. To evaluate the potential application of adzuki beans in low-GI foods, the phenolic profile and alpha-amylase inhibitor (α-AI) activity of four varieties of adzuki beans (G24, Te Xiao Li No. 1, Gui Nong No. 1, and Qian Xiao Hei) were determined. The starch digestibility properties and in vitro glycemic index (IVGI) of these beans were also evaluated using the in vitro digestion model coupled with 3,5-dinitrosalicylic acid colorimetry. The results indicated that these adzuki beans, containing numerous phenolics, showed inhibitory activities to alpha-amylase with the α-AI activities between 1.760 ± 0.044 and 3.411 ± 0.186 U/g. The resistant starch (RS) contributed predominantly to the total starch with proportions between (69.78 ± 2.45%) and (81.03 ± 0.06%); Te Xiao Li No. 1 was the highest compared with the other varieties. The adzuki beans were categorized into low- or medium-GI foods, and the IVGI ranged from (39.00 ± 0.36) to (56.76 ± 4.21). These results suggested that adzuki beans can be used as a component of low-GI foods.
研究领域:
营养学
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食品科学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 16
·
IF 11.7
Jing Bai,Dingyao Liu,Xinyu Tian,Yan Wang,Binbin Cui,Yilin Yang,Shilei Dai,Wensheng Lin,Jixiang Zhu,Jinqiang Wang,Aimin Xu,Zhen Gu,Shiming Zhang
Continuous glucose monitoring systems (CGMs) are critical toward closed-loop diabetes management. The field’s progress urges next-generation CGMs with enhanced antinoise ability, reliability, and wearability. Here, we propose a coin-sized, fully integrated, and wearable CGM, achieved by holistically synergizing state-of-the-art interdisciplinary technologies of biosensors, minimally invasive tools, and hydrogels. The proposed CGM consists of three major parts: (i) an emerging biochemical signal amplifier, the organic electrochemical transistor (OECT), improving the signal-to-noise ratio (SNR) beyond traditional electrochemical sensors; (ii) a microneedle array to facilitate subcutaneous glucose sampling with minimized pain; and (iii) a soft hydrogel to stabilize the skin-device interface. Compared to conventional CGMs, the OECT-CGM offers a high antinoise ability, tunable sensitivity and resolution, and comfort wearability, enabling personalized glucose sensing for future precision diabetes health care. Last, we discuss how OECT technology can help push the limit of detection of current wearable electrochemical biosensors, especially when operating in complicated conditions.
研究领域:
生物医学工程
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材料科学
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糖尿病健康管理
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiangxing Meng,Rui Liu,Jiao Xie,Liwei Li,Yu Kai,Jianhui Liu,Ye Zhang,Hao Wang
The objective of this study was to investigate the impact of anthocyanin-rich black currant extract (BCE) on the structural properties of starch and the inhibition of glycosidases, gathering data and research evidence to support the use of low glycemic index (GI) foods. The BCE induced a change in the starch crystal structure from A-type to V-type, resulting in a drop in digestibility from 81.41 % to 65.57 %. Furthermore, the inhibitory effects of BCE on glycosidases activity ( α -glucosidase: IC 50 = 0.13 ± 0.05 mg/mL and α -amylase: IC 50 = 2.67 ± 0.16 mg/mL) by inducing a change in spatial conformation were confirmed through in vitro analysis. The presence of a 5′-OH group facilitated the interaction between anthocyanins and receptors of amylose, α -amylase, and α -glucosidase. The glycosyl moiety enhanced the affinity for amylose yet lowered the inhibitory effect on α -amylase. The in vivo analysis demonstrated that BCE resulted in a reduction of 3.96 mM·h in blood glucose levels (Area Under Curve). The significant hypoglycemic activity, particularly the decrease in postprandial blood glucose levels, highlights the potential of utilizing BCE in functional foods for preventing diabetes.
研究领域:
营养学
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药理学
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食品科学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Nature Biomedical Engineering
·
2023
·
IF 28.1
Zhang Juan,Wei Xiangqian,Liu Wei,Wang Yanfang,Kahkoska Anna R.,Zhou Xianchi,Zheng Huimin,Zhang Wentao,Sheng Tao,Zhang Yang,Liu Yun,Ji Kangfan,Xu Yichen,Zhang Peng,Xu Jianchang,Buse John. B.,Wang Jinqiang,Gu Zhen
Glucose-responsive formulations of insulin can increase its therapeutic index and reduce the burden of its administration. However, it has been difficult to develop single-dosage formulations that can release insulin in both a sustained and glucose-responsive manner. Here we report the development of a subcutaneously injected glucose-responsive formulation that nearly does not trigger the formation of a fibrous capsule and that leads to week-long normoglycaemia and negligible hypoglycaemia in mice and minipigs with type 1 diabetes. The formulation consists of gluconic acid-modified recombinant human insulin binding tightly to poly- l -lysine modified by 4-carboxy-3-fluorophenylboronic acid via glucose-responsive phenylboronic acid–diol complexation and electrostatic attraction. When the insulin complex is exposed to high glucose concentrations, the phenylboronic acid moieties of the polymers bind rapidly to glucose, breaking the complexation and reducing the polymers’ positive charge density, which promotes the release of insulin. The therapeutic performance of this long-acting single-dose formulation supports its further evaluation and clinical translational studies.
研究领域:
药理学
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糖尿病研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2022
·Vol. 35
·期 10
·2208648
·
IF 32.086
Tao Sheng,Rui Jin,Changwei Yang,Ke Qiu,Mingyang Wang,Jiaqi Shi,Jingyu Zhang,Yuman Gao,Qing Wu,Xin Zhou,Hao Wang,Juan Zhang,Qin Fang,Neng Pan,Yanan Xue,Yue Wang,Rong Xiong,Fei Gao,Yuqi Zhang,Haojian Lu,Jicheng Yu,Zhen Gu
Timely administration of key medications toward patients with sudden diseases is critical to saving lives. However, slow transport of first-aid therapeutics and the potential absence of trained people for drug usage can lead to severe injuries or even death. Herein, an unmanned aerial vehicle (UAV)-mediated first-aid system for targeted delivery (uFAST) is developed. It allows unattended administration of emergency therapeutics-loaded transdermal microneedle (MN) patches toward patients to relieve symptoms by a contact-triggered microneedle applicator (CTMA). The implementability and safety of the uFAST for first aid is demonstrated in a severe hypoglycemic pig model by automatically delivering a glucagon patch with immediate and bioresponsive dual release modes. This platform technique may facilitate the development of UAV-mediated first-aid treatments for other sudden diseases.
研究领域:
生物医学工程
·
急诊医学
·
药学
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DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 46
·期 3
·e13686
·
IF 2.72
Wanxiu Cao,Xin Chen,Yaoxian Chin,Jinkai Zheng,Phaik Eem Lim,Changhu Xue,Qingjuan Tang
Natural compounds have tremendous potential to regulate glucose metabolism, but conventional methods for studying their bioactivities are usually labor intensive. Here, hypoglycemic properties in 22 selected food-derived compounds were examined using molecular docking. The results indicated that curcumin is an inhibitor of both α-glucosidase and dipeptidyl-peptidase 4 (DPP-4), which are important for glycemic control. These effects of curcumin were also confirmed by enzymatic determination in vitro. Furthermore, curcumin significantly improved diet-induced hyperglycemia (e.g., fasting plasma glucose levels and glycogen storage in muscle or liver) in mice. This might be attributed to its inhibitory effects on the activities of α-glucosidase and DPP-4 in vivo. Curcumin also upregulated the expression of genes (e.g., glucagon-like peptide 1) related to DPP-4 activity in the small intestine. In conclusion, curcumin is a potential ingredient of functional foods used for diet-induced hyperglycemia management. Practical applications Curcumin has been widely used as a colorant in the food industry. Moreover, a growing number of studies have described its diverse biological functions, such as anti-inflammatory, anti-oxidant, and anti-angiogenic activities. Thus, curcumin is regarded as a potential ingredient in functional foods. Our results highlighted the hyperglycemic effect of curcumin, suggesting that curcumin may be included in food products for hyperglycemic patients.
研究领域:
药理学
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营养学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Jinsong Shao,Lingzi Feng,Qingyu Zhao,Chao Chen,Jia Li,Qian Ma,Xiaohan Jiang,Ying Sun,Yanguang Yang,Haiying Gu,Yong Hu,Donglin Xia
Exogenous insulin (INS) is critical for managing diabetes. However, owing to its short in vivo half-life, frequent injection of INS is un-avoidable, which is both painful and inconvenient, compromising the quality of life. Herein, we developed a laser-regulated INS release system ( [email protected] hydrogel) that allowed an on-demand release of INS from the subcutaneous INS reservoir by remote laser control without the frequent injection of INS. The amino acid hydrogel functions as a hydrogel 3D scaffold material, which offers increased subcutaneous stability of drug loaded erythrocytes (ER). This [email protected] hydrogel would release INS due to the elevated content of reactive oxygen species (ROS), generated by ICG under laser irritation. Conversely, the ROS would be scavenged without the laser irradiation and stopped the release of INS from [email protected] hydrogel. Furthermore, the release of INS from [email protected] hydrogel could be regulated by laser irradiation. The [email protected] hydrogels could control the hyperglycemia within 2 h in diabetic mice and maintained their normal blood glucose level (BGL) for up to 6 days with laser irradiation 30 min prior to meals avoiding the frequent injection of free INS. This delivery system is an effective method that offers a spatiotemporally controlled release of INS to control the glucose level in vivo.
研究领域:
生物医学工程
·
药学
·
糖尿病研究
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产品关联
DOI
PubMed
高影响因子
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