INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
·
IF 6.51
Jinfeng He,Jing Wang,Shoubei Gao,Yanshuai Cui,Xianbing Ji,Xiaoyu Zhang,Longgang Wang
Photothermal therapy uses photothermal agents (PTAs) to convert light energy to heat energy under near-infrared light to kill local tumors in cancer patients or speed up wound healing in diabetic patients. However, it is difficult to achieve high photothermal conversion efficiency for most of PTAs. Herein, daptomycin (Dap) micelles-stabilized palladium nanoflowers (Dap-PdNFs) were prepared for the first time. The palladium nanoflowers (PdNFs) inside of the Dap-PdNFs were 106 nm. The temperature of the Dap-PdNFs solution quickly rose from 26.8 °C to 52.0 °C within 10 min under irradiation with high photothermal conversion efficiency up to 38%. In addition, the cell viability of HeLa cells and HT-29 cells of Dap-PdNFs exceeded 95% in the absence of near-infrared light, indicating that Dap-PdNFs had good biocompatibility. Meanwhile, the inhibition rate of Dap-PdNFs on HeLa cells was as high as 71.2% under irradiation of 808 nm near-infrared light. More importantly, Dap-PdNFs had a good healing effect on wounds of diabetic mice under irradiation of 808 nm near-infrared light. In short, this research provides a facile method for the application of Dap-PdNFs in safe and efficient tumor treatment and wound healing.
研究领域:
生物医学工程
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Canadian Journal of Infectious Diseases & Medical Microbiology
·
2025
·Vol. 2025
·期 1
·5553355
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IF 2.6
Kai Ming Chow,Siu Kwan Wo,Simon Wai Yin So,Phyllis Mei Shan Cheng,Keary Rui Zhou,Wai Li Lim,Joan Zhong Zuo,Philip Kam Tao Li
Background: With emerging antibiotic resistance, many patients on peritoneal dialysis require newer antibiotic treatment such as daptomycin. Inadequate clinical information exists across different peritoneal dialysis solutions, including icodextrin, for the stability of intraperitoneal daptomycin. To guide the clinical practice of intraperitoneal daptomycin treatment, we need to establish the stability of daptomycin at dextrose concentration higher than 1.5% and icodextrin, as well as the duration of stability. Methods: We tested the stability of daptomycin in three types of peritoneal dialysis bags (UltraBag dextrose 2.5%, UltraBag icodextrin 7.5%, and Stay-Safe Balance 2.3%). Daptomycin was reconstituted with water for injection (50 mg/mL), followed by administration to peritoneal dialysis bags to obtain the final daptomycin concentrations of 70 μg/mL (equivalent to 140 mg/2L, the maintenance level) and 245 μg/mL (equivalent to 490 mg/2L, the loading level). The bags were then placed at ambient temperature (25°C) followed by withdrawing 5 mL samples at 0, 4, 8, 12, 24, and 48 h for UltraBag dextrose 2.5% and UltraBag icodextrin 7.5% and 0, 4, 8, 12, and 24 h for Stay-Safe Balance 2.3%. The concentrations of daptomycin in the collected samples were quantified by high-performance liquid chromatography with diode array detector (HPLC-DAD). Results: Under ambient condition, daptomycin was stable at maintenance level in UltraBag dextrose 2.5% for 48 h and in UltraBag icodextrin 7.5% or Stay-Safe Balance 2.3% for 24 h. For loading level, daptomycin was stable in UltraBag dextrose 2.5% and Stay-Safe Balance 2.3% for 12 h and in UltraBag icodextrin 7.5% for 48 h. Conclusions: Current stability results support and guide the use of intraperitoneal daptomycin in different dialysis solutions. Patients with peritonitis requiring icodextrin exchange and assisted preparation of daptomycin can benefit from nurses who provide daily home visit based on our stability results.
研究领域:
药理学
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临床医学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Dongliang Guan,Jian Li,Feifei Chen,Jiaqi Li,Xiaolei Bian,Yue Yu,Xinxin Feng,Lefu Lan,Wei Huang
Wide-spread use of daptomycin unavoidably resulted in the emergence of daptomycin-resistant pathogens. In the hunt for more active daptomycin derivatives through medicinal chemistry studies, we established a concise semisynthetic approach to modify the L-Kyn13 on daptomycin specifically and effectively. Here, 19 novel derivatives with certain diversity were designed and synthesized to perform a comprehensive SAR study on this underestimated position. The optimal compound, termed “hexakynomycin”, as the new generation of daptomycin-based antibiotic candidate exhibited 4->125-fold higher activity against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-intermediate resistant S. aureus (VISA), and vancomycin-resistant Enterococci (VRE), including daptomycin-resistant strains, compared with that of daptomycin. Greater membrane binding capacity rendered hexakynomycin better activity and special antibiotic property. Hexakynomycin also demonstrated a better pharmacokinetic profile, good safety features and good pharmacodynamics properties. This work provided an effective modification strategy aiming at daptomycin which provided significant insights and showed great promise for the next generation of daptomycin derivatives.
研究领域:
医药化学
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微生物学
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感染病学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Hongying Li,Qingtao Zeng,Limei Tan,Chenran Zhen,Xiaoyu Zhang,Longgang Wang,Xifa Lan,Haiyan Xiao
Traditional drugs face challenges due to low targeting efficiency and glioblastoma (GBM) cell resistance. Effective drug delivery is crucial to reduce the risk of postoperative recurrence in patients with glioma. A stable and multifunctional targeted nanodrug combining photothermal therapy and chemotherapy can be an effective approach to improve treatment outcomes. Herein, thiolated doxorubicin (SH-DOX), zwitterionic thiolated sulfobetaine (SB-SH), and targeting ligands c(RGDfC) were modified on the surfaces of zwitterionic daptomycin-mineralized gold nanoflowers (Au NFs) via Au–S bonds, and temozolomide (TMZ) was physically adsorbed onto the surfaces of daptomycin-mineralized Au NFs to prepare a multifunctional targeted nanodrug (SBDTC@Au NFs). SBDTC@Au NFs exhibit a flower-like morphology, with average particle size of 56.5 nm as shown in TEM images. These nanodrugs demonstrate high drug release in the weakly acidic tumor microenvironment and show good stability in complex media due to the presence of zwitterionic molecules on their surface. The drug showed an inhibition rate of 79.7 % against HS683 glioma cells, outperforming free DOX and TMZ. Cell uptake experiments confirmed that c(RGDfC) modification significantly enhanced targeting efficiency. In vivo experiments revealed that, after 14 days of treatment, the tumor inhibition rate in the SBDTC@Au NFs photothermal group reached 91.6 %. This study provides an innovative strategy for brain glioma treatment through multifunctional synergy and lays the foundation for the development of efficient and stable anti-tumor nanomedicines.
研究领域:
肿瘤学
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生物医学工程
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纳米医学
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药理学
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神经生物学
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产品关联
DOI
高影响因子
Polymers
·
2022
·Vol. 14
·期 14
·2787
·
IF 4.967
Jie Zhang,Jing Wang,Guixiu Fan,Bingjie Zhang,Guanglong Ma,Haiyan Xiao,Longgang Wang
Silver nanoparticles as photothermal agents have the problems of low stability and low photothermal conversion efficiency. Amphiphilic daptomycin can improve the stability of silver nanoparticles, thereby improving their photothermal conversion efficiency. Herein, daptomycin-biomineralized silver nanoparticles (Dap-AgNPs) were prepared by reducing silver nitrate with sodium borohydride in the presence of daptomycin as a stabilizer and biomineralizer. The Dap-AgNPs had good solution stability and peroxidase-like activity. Furthermore, the photothermal conversion efficiency of the Dap-AgNPs was as high as 36.8%. The Dap-AgNPs displayed good photothermal stability under irradiation. More importantly, the Dap-AgNPs showed good cell compatibility with HeLa cells and HT-29 cells without irradiation by 808-nanometer near-infrared light at a concentration of 0.5 mM, and the cell viability was greater than 85.0%. However, the Dap-AgNPs displayed significant anti-tumor ability with irradiation by 808-nanometer near-infrared light, which was due to the increasing temperature of the culture medium caused by the Dap-AgNPs. In conclusion, Dap-AgNPs have potential applications as photothermal agents in the treatment of tumors.Keywords:daptomycin;silver nanoparticle;biomineralization;anti-tumor;biocompatibility
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2021
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IF 4.539
Ying Liang,Hongchen Li,Liyuan Fan,Ruyu Li,Yanshuai Cui,Xianbing Ji,Haiyan Xiao,Jie Hu,Longgang Wang
Mimic enzymes , especially noble metal nanomaterials , replace natural horseradish peroxidase due to the artificial regulation of catalytic activity by adjusting particle size and morphology. However, the existing mimic enzymes still have disadvantages such as large particle size, easy clustering and poor biocompatibility . Herein, well-dispersed daptomycin stabilized palladium nanoparticles (Dap-Pd n NPs) were synthesized by using daptomycin as a biological template . The average particle size of palladium nanoparticles of Dap-Pd 0.25 NPs was 1.73 nm, the hydrodynamic size of Dap-Pd 0.25 NPs detected by DLS method was 49.97 nm, Dap-Pd 0.25 NPs were stable in fibrinogen solution. In addition, Dap-Pd 0.25 NPs had excellent peroxidase-like activity, which effectively catalyzed the colorimetric oxidation reaction of 3,3′,5,5′-tetramethylbenzidine (TMB) by H 2 O 2 . Dap-Pd 0.25 NPs were used to detect glucose concentration based on the colorimetric reaction of TMB, which had a wide detection range (0.02–1 mM) and low detection limit (5.6 μM) for glucose. Besides, fluorescence experiments proved that Dap-Pd n NPs catalyzed H 2 O 2 to generate·OH. Taken together, a simple, green and inexpensive synthesis method of palladium nanoparticles with enhanced peroxidase-like activity was proved in this research. Dap-Pd n NPs will have great application prospects in biological detection in the future.
研究领域:
生物化学
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纳米医学
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分析化学
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DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2021
·
IF 6.514
Quanling Guo,Lu Zhang,Mengmeng He,Xiaohua Jiang,Jingrui Tian,Qiurong Li,Zhiwei Liu,Longgang Wang,Haotian Sun
Development of a simple method to enhance targeting and anti-tumor effect of the chemotherapeutic agents in vivo is a major problem. Amphipathic and natural daptomycin is biocompatible antibacterial polypeptide used in clinical practice. Herein, doxorubicin (DOX) was stabilized by zwitterionic daptomycin (Dap) micelles in aqueous solution to form a zwitterionic nanodrug (Dap-DOX micelles). The hydrodynamic size and zeta potential of Dap-DOX micelles were 85 nm and −10 mV, respectively. The study on the controlled release showed that more DOX molecules were released from Dap-DOX micelles at acidic condition of tumor tissue than that at neutral condition of normal tissue which was due to pH responsiveness of Dap-DOX micelles. Dap-DOX micelles exhibited good stability in fibrinogen solution. Moreover, MTT studies showed that Dap-DOX micelles had higher cytotoxicity than free DOX. Notably, the results of flow cytometry indicated that the average fluorescence intensity of Dap-DOX micelle-treated cells was higher than that of free DOX-treated cells, and acidic conditions were more favorable for Dap-DOX micelles than normal pH in cell uptake assay. More importantly, Dap-DOX micelles were biocompatible in vivo based on the changes of weight and blood indexes of mice. Dap-DOX micelles were selectively accumulated at tumor sites in vivo through EPR effect , which reduced the toxicity of free DOX and achieved excellent tumor inhibition effect. The tumor inhibition rate of Dap-DOX micelles reached 96%. Dap-DOX micelles also effectively inhibited the growth of bacterial. Taken together, Dap-based drug delivery systems are promising and effective in cancer therapy.
研究领域:
药剂学
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肿瘤学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2023
·Vol. 19
·期 4
·282-288
·
IF 0.6
Zhang Hanzhi,Qin Feng,Sun Ning,Zheng Mengmeng,Luo Wenyan,Qiu Ya,Liu Hao,Zhang Xiangmin
Background: After the hydrolysis of daptomycin in deuterated hydrochloric acid, the deuterium-substituted kynurenine was found, but the structure of deuterium-substituted kynurenine has not been reported. Introduction: The deuterium-substituted kynurenines were simply synthesized
and confirmed to be tri- and tetra-substituted products by high resolution mass spectrum and NMR. In further, the deuterium-substituted kynurenines were used to determine the conformation of kynurenine to be L-type in daptomycin through conformation analysis combined with derivation and high
performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLCQ/ TOF-MS). Methods: In the present study, a simple synthesis method was developed for deuteriumsubstituted kynurenine, and its structure was confirmed by high resolution mass spectrometry and NMR. L-kynurenine
was mixed with the deuterated hydrochloric acid and heated at 110 °C for 7 h. The hydrogen/deuterium exchange products of L-kynurenine were obtained through the hydrogen/deuterium exchange method. After the derivation of deuterium-substituted L-kynurenine by Marfey’s reagent, the
conformation of kynurenine in daptomycin was deduced by HPLC-Q/TOF-MS. Results: The deuterium-substituted kynurenines were confirmed to be tri- and tetra-substituted products by high resolution mass spectrum. Further, Hydrogen NMR spectrum indicated that the deuterium-substitution positions
were β-position on amino acid and 3’ and 5’ positions on the benzene ring. Thus, the tri-deuterium-substituted product was L-[β, 3’, 5’-2H3] kynurenine-d3, while the tetra-deuterium-substituted product was L-[β, β, 3’,
5’-2H4] kynurenine-d4. Furthermore, the deuterium-substituted kynurenines were used to determine the conformation of kynurenine to be L-type in daptomycin through conformation analysis combined with derivation and HPLC-Q/TOF-MS. Conclusion: The synthesis, structures,
and application of tri- or tetra- deuterium-substituted kynurenine were reported in this study.
研究领域:
生物化学
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药物化学
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分析化学
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DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2026
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IF 5.2
Hong-Lan Wang,Lin-Yan Lu,Kai-Yuan Huang,Yi-Ming Zheng,Yang Yang,Zhi-Min Weng,Hao-Hua Deng,Wei Chen,Quan-Quan Zhuang
Yellow-green fluorescent AuNCs are synthesized by using 2-mercapto-1,3,4-thiadiazole (MTD) as a template. • Fluorescent MTD-AuNCs could be quenched by Ca 2+ via electrostatic interactions and sulfur coordination. • Daptomycin could restore the fluorescence of MTD-AuNCs by competitive Ca 2+ sequestration. • MTD-AuNCs can be applied as a fluorescence turn-off/on probe for sensing of Ca 2+ and daptomycin. • The limit detection of Ca 2+ and daptomycin are found to be 3.6 and 0.96 μM, respectively. Daptomycin's calcium-dependent antibacterial activity and significant pharmacokinetic variability necessitate therapeutic drug monitoring, yet current methods cannot simultaneously quantify pharmacodynamically critical Ca 2+ and daptomycin. To address this limitation, we developed fluorescent gold nanoclusters functionalized with 2-mercapto-1,3,4-thiadiazole (MTD-AuNCs) via a facile one-pot synthesis. The obtained MTD-AuNCs exhibit bright yellow-green fluorescence (quantum yield = 8.85%, emission at 545 nm) and exceptional stability. Crucially, they demonstrate a reversible fluorescence response: Ca 2+ induces quenching through aggregation caused by electrostatic interactions and sulfur coordination, while subsequent daptomycin addition triggers fluorescence recovery via competitive Ca 2+ sequestration. This dual-response enables sensitive detection of Ca 2+ and daptomycin with excellent selectivity over biological interferents. The assay was successfully validated in human urine samples, showing high accuracy and statistical equivalence to reference methods. This work presents the first nanocluster-based sensor for simultaneous Ca 2+ and daptomycin monitoring, offering a rapid, cost-effective platform for pharmacodynamically-informed antimicrobial therapy optimization. Download: Download high-res image (62KB) Download: Download full-size image
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DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2019
·
IF 2.931
Mengyao Wang,Honglin Yang,Yue Wu,Zhifeng Fu
A dual sites affinity protocol was developed for fluorescent analysis of Staphylococcus aureus ( S. aureus ) by employing daptomycin and immunoglobulin G (IgG) as the recognition elements . Pig IgG immobilized on microplate was employed as the first recognition element to capture S. aureus owing to the fact that the Fc segment of mammal IgG can selectively bind with protein A on the surface of the target bacteria. Meanwhile, fluorescein isothiocyanate-conjugated daptomycin was employed as the second recognition element as well as the signal tracer for the target bacteria utilizing the binding capability of daptomycin to Gram-positive bacteria. S. aureus can be analyzed within a concentration range of 5.0 × 10 3 –5.0 × 10 8 CFU mL −1 with a detection limit of 3.6 × 10 3 CFU mL −1 . The analytical process can be accomplished within 1.5 h by using a pre-coated microplate. The dual sites affinity protocol can exclude the interference led by Gram-negative bacteria and other common Gram-positive bacteria. We have successfully applied it to analyze S. aureus in spiked lake water and physiological saline injection samples, and the recovery values ranged from 88.0% to 120.0%. The results demonstrate its application potential for environmental sanitation and drug safety control.
研究领域:
微生物学
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分析化学
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环境科学
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药学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2016
·
IF 0
Hong Jiang,Meimei Xiong,Qiuyan Bi,Ying Wang,Chong Li
Considering that some antibacterial agents can identify the outer structure of pathogens like cell wall and/or cell membrane, we explored a self-enhanced targeted delivery strategy by which a small amount of the antibiotic molecules were modified on the surface of carriers as targeting ligands of certain bacteria while more antibiotic molecules were loaded inside the carriers, and thus has the potential to improve the drug concentration at the infection site, enhance efficacy and reduce potential toxicity. In this study, a novel targeted delivery system against methicillin-resistant Staphylococcus aureus (MRSA) pneumonia was constructed with daptomycin, a lipopeptide antibiotic, which can bind to the cell wall of S. aureus via its hydrophobic tail. Daptomycin was conjugated with N -hydroxysuccinimidyl–polyethylene glycol–1,2-distearoyl- sn -glycero-3-phosphoethanolamine to synthesize a targeting compound (Dapt–PEG–DSPE) which could be anchored on the surface of liposomes, while additional daptomycin molecules were encapsulated inside the liposomes. These daptomycin-modified, daptomycin-loaded liposomes (DPD-L[D]) showed specific binding to MRSA as detected by flow cytometry and good targeting capabilities in vivo to MRSA-infected lungs in a pneumonia model. DPD-L[D] exhibited more favorable antibacterial efficacy against MRSA than conventional PEGylated liposomal daptomycin both in vitro and in vivo . Our study demonstrates that daptomycin-modified liposomes can enhance MRSA-targeted delivery of encapsulated antibiotic, suggesting a novel drug delivery approach for existing antimicrobial agents.
研究领域:
药理学
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微生物学
·
药物递送系统
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DOI
PubMed
International Journal of Nanomedicine
·
2013
·
IF 3.463
Chong Li,Xiaolin Zhang,Xinliang Huang,Xiaoying Wang,Guojian Liao,Zhangbao Chen
The purpose of this study was to investigate flexible nanoliposomes for mediating topical delivery of daptomycin, and to document permeation rates and bacteriostatic activity towards skin infections. Response surface methodology was used to optimize the daptomycin-loaded flexible nanoliposomes (DAP-FL), and the amount of drug loaded into the particles was evaluated as the investigation index. The optimal lipid ratio was lecithin to sodium cholate 17:1 (w/w) and the lipid to drug ratio was 14:1 (w/w). The hydration temperature was set at 37°C and the duration of treatment with ultrasound was 20 minutes. The DAP-FL obtained had a small mean particle size (55.4 nm) with a narrow size distribution (polydispersity index 0.15). The mean entrapment efficiency was 87.85% ± 2.15% and the mean percent drug loading was 5.61% ± 0.14%. Using skin mounted between the donor and receptor compartments of a modified Franz diffusion cell, the percentage and quantity of cumulative daptomycin permeation from DAP-FL within 12 hours were measured at 96.28% ± 0.70% and (132.23 ± 17.73) μg/cm2 *5 = 661.15 ± 88.65 μg/cm2, directly, showing rapid and efficient antibacterial activity against Staphylococcus aureus. Following local administration of DAP-FL, daptomycin was detected in multilayer tissues within the skin and underlying structures in the dorsal skin of the mouse. Effective therapeutic concentrations were maintained for several hours, and significantly inhibited bacterial growth and injury-induced biofilms. These results demonstrate that the DAP-FL can enhance the ability of daptomycin to permeate the skin efficiently, where it has a powerful antibacterial action and activity against biofilms. This novel formulation of daptomycin has potential as a new approach in the clinical application of daptomycin.
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DOI
高影响因子
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