RSC Advances
·
2015
·Vol. 5
·期 111
·91398-91406
·
IF 3.84
Xiao Zheng,Dan Shao,Jing Li,Yubin Song,Yujing Chen,Yue Pan,Shoujun Zhu,Bai Yang,Li Chen
Carbon dots (CDs) have recently emerged as a new class of fluorescent nanomaterials and are already competitive in many respects to conventional semiconductor quantum dots (QDs). Despite CDs remarkable advantages in bioimaging, biosensing and other biomedical applications, their biosafety is still unclear. In the present study, the systematic single and repeated dose toxicity and biodistribution of two citric acid-based probes (CDs and a derivative, Et-IPCA) were investigated in vivo. For the single dose toxicity studies, the lethal dose 50 (LD50) of CDs was 391.615 mg kg−1 and 357.771 mg kg−1 for female and male mice, respectively, while Et-IPCA reached its saturation point in solution at 25 mg kg−1 and did not lead to the death of any mice at that concentration. For the repeated dose toxicity studies, although there were temporary changes in hematological parameters suggesting an acute inflammatory response after seven doses, the data on the body weight, organ coefficients, hematological parameters, blood biochemistry, and organ histopathology at the end of the 90 day recovery period suggested that both the CDs and Et-IPCA had low toxicity over the 90 day period. These findings will be useful for the future development of CDs-based drug delivery systems and for the development of clinical applications of these systems.
研究领域:
生物医学
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毒理学
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纳米材料科学
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产品关联
DOI
高影响因子
ACS Nano
·
2025
·
IF 16
Jiamin Deng,Zongmei Wang,Liqin Wu,Zhiyong Song,Hagar Shendy Bahlol,Xun Li,Ling Zhao,Heyou Han
Rabies, caused by rabies virus (RABV), is a zoonotic disease with a high mortality rate that has attracted global attention with the goal of eradication by 2030. However, rabies can only be prevented by appropriate and multiple vaccinations, which impede widespread vaccination in developing countries due to its high expenditure. Designing single-dose vaccines is a pressing challenge in the prevention of rabies and other infectious diseases. Herein, a metal–phenolic network (MPN)-based hydrogel vaccine (designated as CGMR) was developed to stimulate potent humoral immunity against RABV infection by a single immunization, resulting in 4.3-fold and 1.8-fold enhancements of virus-neutralizing antibody compared with that induced by inactivated RABV and alum adjuvant. The CGMR, cross-linked by phenol-modified chitosan with manganese ion, could prolong residence time by confining the antigen to the network of hydrogel, acting as a “hydrogel antigen depot”. It also stimulated the activation of the cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway, facilitating dendritic cell maturation and antigen presentation. The vaccine formulation recruited immunocytes and activated the germinal center, enhancing and sustaining humoral immune responses against the virulent RABV challenge. Collectively, this injectable manganese-based hydrogel vaccine provides a universal and ideal avenue for rabies and other infectious diseases.
研究领域:
免疫学
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生物医学工程
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病毒学
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产品关联
DOI
PubMed
高影响因子
Clinical Pharmacology in Drug Development
·
2020
·Vol. 10
·期 1
·57-67
·
IF 1.903
Lu-Ning Sun,Guo-Xian Sun,Yu-Qing Yang,Ye Shen,Feng-Ru Huang,Li-Jun Xie,Juan Cheng,Hong-Wen Zhang,Xue-Hui Zhang,Yun Liu,Yong-Qing Wang
Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single-dose and multidose cohorts and the effects of ABCB1, UGT1A1 , and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single-dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high-fat meal. The multidose study included 1 cohort receiving 100 mg of sitafloxacin granules once daily for 5 days. PK parameters were calculated using noncompartmental parameters based on concentration-time data. The genotypes for ABCB1 , UGT1A1 , and UGT1A9 single-nucleotide polymorphisms were determined using Sanger sequencing. Subsequently, the association between sitafloxacin PK parameters and target single-nucleotide polymorphisms was analyzed. Sitafloxacin granules were well tolerated up to 200 and 100 mg in the single-dose and multidose studies, respectively. Sitafloxacin AUC and C max increased linearly within the detection range, and a steady state was reached within 3 days after the administration of multiple oral doses. Our findings showed that C max was lower in the ABCB1 (rs1045642) mutation group, whereas t 1/2 was longer in the UGT1A1 (rs2741049) and UGT1A9 (rs3832043) mutation groups. In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However, ABCB1 (rs1045642), UGT1A1 (rs2741049), and UGT1A9 (rs3832043) genetic polymorphisms are likely to influence the C max or t 1/2 and thereby merit further clinical evaluation.
研究领域:
药理学
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遗传学
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临床研究
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF NUTRITION
·
2023
·
IF 3.6
Fan Du,Min Yan,Lili Duan,Guolong Xie,Xiuhua Yao,Wenjing Hu,Yu Liu,Min Meng,Jiepeng Chen,Di Shao
Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid–liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.
研究领域:
药理学
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营养学
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临床研究
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分析化学
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产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
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2021
·
IF 4.774
Chaoqun Cheng,Yuan Cheng,Sheng Zhao,Quan Wang,Sirong Li,Xiwen Chen,Xiaohan Yang,Hui Wei
Nanozymes are nanomaterials with enzyme-like activities, which have been developed for inflammatory disease therapy by reactive oxygen species (ROS) scavenging. The application of nanozymes in ulcerative colitis (UC) treatment not only inherits the merits of small molecular antioxidants (e.g., 5-aminosalicylic acid) to scavenge ROS but also achieves catalytic recycle instead of stoichiometric consumption. However, current therapies usually ignore the repair of mucosa, the first line of defense, whose damage increases the risk of infections. Herein, a multifunctional nanozyme hydrogel is designed and verified both as an ROS scavenger and a mucosal healing enhancer for UC therapy. The chitosan-coated CeO2 nanozyme (CCNZ) not only possesses excellent ROS-scavenging ability but also exhibits satisfactory antibacterial capacity. After gelation with alginate, the optimized CCNZ1:Alg1.5 nanozyme hydrogel exhibits multiple functions, including inflamed site targeting, supporting cell growth, ROS scavenging, and antibacterial activity, which alleviates UC better than a clinical medication 5-aminosalicylic acid by even a single-dose treatment. This study reveals that a nanozyme providing mucosal healing is promising for UC therapy with excellent potential for clinical application and enriches the nanozyme research of treatment for diseases.
研究领域:
纳米技术
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生物医学工程
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药学
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炎症性肠病
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DOI
PubMed
高影响因子
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