scholarly journals In vivo activity and low toxicity of the second-generation antimicrobial peptide DGL13K

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0216669 ◽  
Author(s):  
Sven-Ulrik Gorr ◽  
Craig M. Flory ◽  
Robert J. Schumacher
Keyword(s):  
Antimicrobial Peptide ◽  
Second Generation ◽  
Low Toxicity

Models of In-Vivo Bacterial Infections for the Development of Antimicrobial Peptide-based Drugs

2016 ◽  
Vol 17 (5) ◽  
pp. 613-619 ◽  
Author(s):  
Jlenia Brunetti ◽  
Chiara Falciani ◽  
Luisa Bracci ◽  
Alessandro Pini
Keyword(s):  
Antimicrobial Peptide ◽  
Bacterial Infections

scholarly journals Construction of hollow polydopamine nanoparticle based drug sustainable release system and its application in bone regeneration

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lu Wang ◽  
Shuwei Liu ◽  
Chunxia Ren ◽  
Siyuan Xiang ◽  
Daowei Li ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Load Capacity ◽  
Good Prospect ◽  
Alizarin Red ◽  
Drug Load ◽  
Load Rate ◽  
Low Toxicity

AbstractNanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.

scholarly journals GMP-compliant fully automated radiosynthesis of [18F]FEPPA for PET/MRI imaging of regional brain TSPO expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chi-Wei Chang ◽  
Chuang-Hsin Chiu ◽  
Ming-Hsien Lin ◽  
Hung-Ming Wu ◽  
Tsung-Hsun Yu ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Western Blotting ◽  
Second Generation ◽  
Mrna Levels ◽  
Automated Radiosynthesis ◽  
Lps Challenge ◽  
Tnf Α ◽  
The Brain ◽  
Tspo Expression

Abstract Background Expression of translocator protein (TSPO) on the outer mitochondrial membrane of activated microglia is strongly associated with neuroinflammation. The second-generation PET ligand [18F]FEPPA specifically binds TSPO to enable in vivo visualization and quantification of neuroinflammation. We optimized a fully automated radiosynthesis method and evaluated the utility of [18F]FEPPA, the second-generation PET ligand specifically binds TSPO, in a mouse model of systemic LPS challenge to detect TSPO-associated signals of central and peripheral inflammation. In vivo dynamic PET/MR imaging was performed in LPS-induced and control mice after [18F]FEPPA administration. The relationship between the [18F]FEPPA signal and the dose of LPS was assessed. The cytokine levels (i.e., TNF-α, Il-1β, Il-6) in LPS-induced mice were measured by RT-PCR. Standard uptake value (SUV), total volume of distribution (VT) and area under the curve (AUC) were determined based on the metabolite-uncorrected plasma input function. Western blotting and immunostaining were used to measure TSPO expression in the brain. Results The fully automated [18F]FEPPA radiosynthesis produced an uncorrected radiochemical yield of 30 ± 2% within 80 min, with a radiochemical purity greater than 99% and specific activity of 148.9‒216.8 GBq/µmol. Significant differences were observed in the brain after [18F]FEPPA administration: SUV, VT and AUC were 1.61 ± 0.1, 1.25 ± 0.12 and 1.58 ± 0.09-fold higher in LPS-injected mice than controls. TNF-α, Il-1β and Il-6 mRNA levels were also elevated in the brains of LPS-injected mice. Western blotting revealed TSPO (p < 0.05) and Iba-1 (p < 0.01) were upregulated in the brain after LPS administration. In LPS-injected mice, TSPO immunoactivity colocalized with Iba-1 in the cerebrum and TSPO was significantly overexpressed in the hippocampus and cerebellum. The peripheral organs (heart, lung) of LPS-injected mice had higher [18F]FEPPA signal-to-noise ratios than control mice. Conclusions Based on the current data on ligand specificity and selectivity in central tissues using 7 T PET/MR imaging, we demonstrate that [18F]FEPPA accumulations significant increased in the specific brain regions of systemic LPS-induced neuroinflammation (5 mg/kg). Future investigations are needed to determine the sensitivity of [18F]FEPPA as a biomarker of neuroinflammation as well as the correlation between the PET signal intensity and the expression levels of TSPO.

scholarly journals A Second Generation of Carbamate-Based Fatty Acid Amide Hydrolase Inhibitors with Improved Activity in vivo

ChemMedChem ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. 1505-1513 ◽  
Author(s):  
Jason R. Clapper ◽  
Federica Vacondio ◽  
Alvin R. King ◽  
Andrea Duranti ◽  
Andrea Tontini ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Second Generation ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Evaluation of Paclitaxel Nanocrystals In Vitro and In Vivo

Drug Research ◽  
2017 ◽  
Vol 68 (04) ◽  
pp. 205-212 ◽  
Author(s):  
Wanqing Li ◽  
Zhiguo Li ◽  
Lisha Wei ◽  
Aiping Zheng
Keyword(s):  
Drug Concentration ◽  
Antitumor Effects ◽  
High Drug ◽  
High Drug Concentration ◽  
Low Toxicity ◽  
Nanoparticle Drug Delivery ◽  
Antitumor Evaluation ◽  
Mcf 7

AbstractWe created a novel paclitaxel (PTX) nanoparticle drug delivery system and compared this to acommercial injection preparation to evaluate the antitumor effects for both formulations in vivo and in vitro.PTXnanocrystals were 194.9 nm with potential of −29.6 mV. Cytotoxicity tests indicated that both formulations had similar effects and cytotoxicity was dose- and time-dependent.Pharmacodynamics indicated that the drug concentration at the tumor was greater with PTX nanocrystals compared to commercial injection (P<0.01) and that drug accumulated more and for a longer duration. In vivo antitumor evaluation indicated significant antitumor effects and low toxicity of PTX nanocrystals. Moreover, bioimaging indicated that the PTX retention time in MCF-7-bearing mice was longer, especially at the tumor site, and this high drug concentration was maintained for a long time.Overall, PTX nanocrystalsare feasible and superior to traditional injection formulation chemotherapy.

Graphene: Insights on Biological, Radiochemical and Ecotoxicological Aspects

2021 ◽  
Vol 17 (1) ◽  
pp. 131-148
Author(s):  
Xing Haixia ◽  
Aline Oliveira da Silva de Barros ◽  
Francisco do Vale Chaves e Mello ◽  
Fan Sozzi-Guo ◽  
Cristina Müller ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Graphene Quantum Dots ◽  
Covalent Bonds ◽  
Cell Internalization ◽  
Functional Density Theory ◽  
Ecotoxicological Evaluation ◽  
Plasmatic Membrane ◽  
Low Toxicity ◽  
The Impact

Graphene, including graphene quantum dots, its oxide and unoxidized forms (pure graphene) have several properties, like fluorescence, electrical conductivity, theoretical surface area, low toxicity, and high biocompatibility. In this study, we evaluated genotoxicity (in silico analysis using the functional density theory-FDT), cytotoxicity (human glioblastoma cell line), in vivo pharmacokinetics, in vivo impact on microcirculation and cell internalization assay. It was also radiolabeled with lutetium 177 (177Lu), a beta emitter radioisotope to explore its therapeutic use as nanodrug. Finally, the impact of its disposal in the environment was analyzed using ecotoxicological evaluation. FDT analysis demonstrated that graphene can construct covalent and non-covalent bonds with different nucleobases, and graphene oxide is responsible for generation of reactive oxygen species (ROS), corroborating its genotoxicity. On the other hand, non-cytotoxic effect on glioblastoma cells could be demonstrated. The pharmacokinetics analysis showed high plasmatic concentration and clearance. Topical application of 0.1 and 1 mg/kg of graphene nanoparticles on the hamster skinfold preparation did not show inflammatory effect. The cell internalization assay showed that 1-hour post contact with cells, graphene can cross the plasmatic membrane and accumulate in the cytoplasm. Radio labeling with 177Lu is possible and its use as therapeutic nanosystem is viable. Finally, the ecotoxicity analysis showed that A. silina exposed to graphene showed pronounced uptake and absorption in the nauplii gut and formation of ROS. The data obtained showed that although being formed exclusively of carbon and carbon-oxygen, graphene and graphene oxide respectively generate somewhat contradictory results and more studies should be performed to certify the safety use of this nanoplatform.

scholarly journals The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

2018 ◽  
Vol 51 (2) ◽  
pp. 647-663 ◽  
Author(s):  
Bobin Mi ◽  
Jing Liu ◽  
Yi Liu ◽  
Liangcong Hu ◽  
Yukun Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Wound Healing ◽  
Antimicrobial Peptide ◽  
Structural Stability ◽  
Cell Counting ◽  
Sprague Dawley ◽  
Skin Wound Healing ◽  
High Sodium

Background/Aims: Antimicrobial peptides are effective promoters of wound healing but are susceptible to degradation. In this study, we replaced the GIGDP unit on the N-terminal of the endogenous human antimicrobial peptide hBD-2 with APKAM to produce A-hBD-2 and analyzed the effect on wound healing both in vitro and in vivo. Methods: The effects of A-hBD-2 and hBD-2 on cytotoxicity and proliferation in keratinocytes were assessed by Cell Counting Kit-8 assay. The structural stability and antimicrobial activity of hBD-2 and A-hBD-2 were evaluated against Staphylococcus aureus. RNA and proteins levels were evaluated by real-time PCR and western blotting, respectively. Cell migration was evaluated using a transwell assay. Cell cycle analysis was performed by flow cytometry. Wound healing was assessed in Sprague-Dawley rats. Epidermal thickness was evaluated by hematoxylin and eosin staining. Results: We found that hBD-2 exhibited cytotoxicity at high concentrations and decreased the structural stability in the presence of high sodium chloride concentrations. A-hBD-2 exhibited increased structural stability and antimicrobial activity, and had lower cytotoxicity in keratinocytes. A-hBD-2 increased the migration and proliferation of keratinocytes via phosphorylation of EGFR and STAT3 and suppressed terminal differentiation of keratinocytes. We also found that A-hBD-2 elicited mobilization of intracellular Ca2+ and stimulated keratinocytes to produce pro- and anti-inflammatory cytokines and chemokines via phospholipase C activation. Furthermore, A-hBD-2 promoted wound healing in vivo. Conclusion: Our data suggest that A-hBD-2 may be a promising candidate therapy for wound healing.

scholarly journals Cucurbitacin B, a novel in vivo potentiator of gemcitabine with low toxicity in the treatment of pancreatic cancer

2010 ◽  
Vol 160 (4) ◽  
pp. 998-1007 ◽  
Author(s):  
Gabriela B Iwanski ◽  
Dhong H Lee ◽  
Shlomit En-Gal ◽  
Ngan B Doan ◽  
Brandon Castor ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cucurbitacin B ◽  
Low Toxicity
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